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Medical Finals Revision
Welcome from the Manchester Oncology Society
Welcome from The Christie Hospital
Dear Conference Delegates
On behalf of The Christie Hospital Foundation Trust may I welcome
you to Manchester. We are delighted to have been invited by the
Manchester Oncology Society to be involved in this inaugural National
Aspiring Oncologist Conference and I would like to take this opportunity to
congratulate the organising team on producing what is clearly going to be
a highly successful day.
The Manchester Oncology Society takes great pleasure in welcoming
you to the National Aspiring Oncologists Conference at this prestigious
venue. The response to the day has been overwhelming and
demonstrates a high level of interest in the field of oncology amongst
medical students and junior doctors.
The aim of the conference is to enable delegates to showcase high
quality research, to stimulate debate and to inspire and empower those
interested in oncology through lectures and careers advice. As far as we
are aware this is the first event of its kind and we hope you will take full
advantage of the opportunities on offer.
Thank you for coming. If you have any questions or comments
throughout the day please don’t hesitate to contact one of the
committee members.
Best Wishes
The MOS committee
The Christie hospital has a rich pioneering heritage in the field of
cancer and it is fitting that this first such conference should take place at
this institute.
Delegates have come from all over the UK and what unites us is our
passion for oncology. Oncology is unique in that it touches on all
branches of medicine and surgery, it is a field that is at the cutting
edge of scientific research and as oncologists we bring our knowledge
and skills to help our patients at a very vulnerable time in their lives.
Thank you for joining us and enjoy the day
Dr Richard Cowan
Saturday 17th September 2011
The Manchester Oncology Society
Executive committee
The Manchester Oncology Society was formed in 2009 by Benjamin
Hunter, a medical student at the University of Manchester. We aim to
foster an interest in clinical aspects of oncology, academic research
in general and all facets of cancer care among the undergraduate
community in Manchester and beyond. Our ongoing programme
involves building links between local universities and teaching
hospitals in order to deliver symposia, conferences, competitions
and careers advice to students. Our logo was created by graphic
designer Ben Seary; the interlinked rings symbolise the joining together
of students with clinicians and researchers. Over the next year the
society is planning an ambitious expansion of its educational mission
to take full advantage of our new website by providing open-access
study resources including booklets, “pod-casts” and videos. Our
programme of events this year will be stronger than ever with symposia
to complement Manchester Medical School’s problem-based
learning course and a repeat of the extremely successful oncology
careers evening. The society has a strong tradition of recognising and
showcasing excellence among medical undergraduates. We have
held two essay competitions with prizes generously donated by Christie
Hospital consultants. At our educational events, undergraduates have
had the opportunity to deliver educational talks alongside leading
cancer experts so that we can simultaneously provide exam-tailored
content and raise awareness of cutting-edge developments.
Dr. Benjamin Hunter, MBChB, MRes.
Society founder
President 2009-2011
Ben graduated from Manchester medical school in 2011, and is
currently working as an academic foundation doctor at The University
Hospital of South Manchester. He founded the Manchester Oncology
Society in the summer of 2009, and was the society President from
2009-2011. Ben undertook a Masters in Research at the Paterson
Institute of Cancer Research exploring methods of targeting the
breast cancer stroma. His work was presented at the National Cancer
Research Institute conference in November 2010. Other research
interests include how diet affects the breast tumour stroma. Ben has
worked closely with the Christie to increase the presence of oncology in
Manchester medical school, and was a student member of the Christie
Undergraduate Board for the academic year 2010-2011. He was also
involved in the first Christie careers day, giving a lecture on life as a
medical student to encourage college students to consider medicine.
Career wise, Ben hopes to progress from the academic foundation
programme into core medical training. Following that, his goal is to
gain an academic clinical fellowship in clinical oncology and to work
towards a PhD.
Christopher Howarth M.A. (Oxon), M.Res.
MOS President 2011-2012
Conference team member 2010-2011
Christopher is a final-year student at Manchester Medical School.
Originally from Stockport, he read Biology at St Peter ’s College Oxford,
where he developed particular interests in experimental design,
comparative neurophysiology and bioethics. On discovering that he
had a vocation for medicine, he worked for a year as a care assistant
at the John Radcliffe Hospital in Oxford while applying to study in
Manchester. During his medical studies he developed a passion for
cancer research and spent his intercalated masters at the Paterson
Institute for Cancer Research. Christopher joined an international
collaboration between Manchester and the University of Nebraska
(USA), researching the use of archival tissue samples to understand
the molecular pathology of diffuse large B-cell lymphoma. He is also
passionate about medical education, he represented students as part
of the Curriculum Innovation Group during the recent redevelopment
of the medical course at Manchester. Outside medicine, Christopher
has an interest in computers and is a keen musician, activities
he combined by building his own audio workstation to record his
compositions. Christopher hopes to pursue a career in medical
oncology and to be involved in translational medical research.
Annie Alves
MOS Vice president 2011-2012
Annie has just completed her fourth year of medical school at the
University of Manchester and is under-taking an intercalated degree this
year. She will be studying a Masters of Research in Oncology which is
based at The Christie and also at the adjoining Cancer Research funded
Paterson Institute. Throughout medical school, Oncology has always
interested Annie. She has just completed an audit on the treatment
of stage III non-small cell lung cancer in the Greater Manchester
region under the supervision of a clinical oncologist at The Christie. Her
recommendations will hopefully benefit patients being treated in the
area. In Annie’s spare time she enjoys spending time with her friends,
organising extra-curricular events with other Manchester medical
societies and enjoys travelling during the holidays. She joined the MOS
committee in 2010 as a fund-raising representative but is thrilled to
have a more pivotal role this year. Annie provided the link between two
medical societies this year to produce the ever so popular oncology
careers evening which is now set to become an annual event. She
hopes to be able to collaborate with the rest of the team to create even
more oncology events for the students at Manchester this year as she
herself hopes to pursue a career in the field in the future.
Andrew Davies BSc (Hons)
Conference team lead 2011-2012
Conference team member 2010-2011
Andrew is a final year medical student at the University of Manchester
and holds a degree in Anatomical Sciences. He is the current
Conference Lead for the Manchester Oncology Society and has been
delighted by the enthusiastic response to the event over recent months.
He has an interest in medical education and has enjoyed teaching
and mentoring a group of medical students at the Wythenshawe
Hospital. Outside the field of oncology Andrew is currently studying the
impact of a new management technique in the paediatric emergency
department and he has recently presented work at a national
anaesthetics meeting. Andrew is a keen sportsman and rowed in a
successful Manchester University 1st VIII crew at Henley Royal Regatta
for two consecutive years. He is a qualified windsurfing instructor and is
currently learning Spanish in preparation for his elective in Ecuador.
Mr Navraj S Nagra
Events Lead 2010-2011
Conference and Educational Resources
Team 2011-2012
Navraj is currently a 4th year medical student at Manchester. He has
been involved with the Manchester Oncology Society since its
inception and is eager to further knowledge of oncology amongst
medical students. Navraj will also be spearheading the oncology
podcast series which will hopefully be available from the MOS website
very soon. Career wise, Navraj maintains an open mind, however he
is keen to undertake the MSc in Biomechanics and potentially pursue
a career in orthopedics.
Agenda
09.00 Registration
12.45 Lunch & Exhibitions
09.30 Introduction to the Conference
Consultant Palliative Medicine & Undergraduate Lead
Dr Richard Berman
14.00 Careers Panel
(Chair: Dr Richard Berman)
09.40 Plenary lecture
Consultant Clinical Oncologist & Director of Education
The Christie
Dr Richard Cowan
10.05 Preaching to the Converted
Consultant in Medical Oncology
The Christie
Dr Was Mansoor
Dr Richard Cowan
Miss Christina Lo
SpR - Surgical Theatres The Christie
Dr Emma Dean
Research Registrar The Christie
Dr Alastair Greystoke
SpR - Medical Oncology The Christie
Dr Was Mansoor
10.30 Coffee & Exhibitions
11.00 Morning Presentation Sessions
(Chair: Dr Richard Cowan)
11.00 Uptake of risk reducing oophorectomy in BRCA1
and BRCA2 mutation carriers
Lauren Sidon
11.13 An unusual presentation of ovarian carcinoma
with paraneoplastic dermatomyositis
Callum Harmer
11.26 A clinical audit on the use of G-CSF prophylaxis
in patients with lymphoma
Leslie Cheng
11.39 Supporting ‘Bert’ during head & neck radiotherapy:
developing a ‘contract of care’ for patients with dementia
Tsun Mak
11.52 CD133 as a cancer stem cell marker in small cell lung cancer
Anna Cowell
12.05 Rare case of childhood malignant melanoma:
a case report
Melody Tsai
12.18 Expression of the copper export transporter ATPase
7B correlates with FOLFOX induced tissue injury
Asef Zahed
12.31 Audit of hospital acquired thromboembolism
in spinal surgery
Antony Sorial
Dr Rob Metcalf
ST5 - Medical Oncology The Christie
Dr Catherine Woolley-Stafford
ST1 - Palliative Care St Annes Hospice
Dr Martin McCabe
Honorary Consultant Paediatric Oncologist The Christie
14.40 Afternoon Presentation Sessions
(Chair: Dr Nick Slevin)
14.40 Evaluation of in home palliative care strategies for patients with
terminal illnesses
Victoria Connor
14.53 Polymorphisms in the genes Carbonic Anhydrase-9 (CA-9)
and Hypoxia Inducible Factor 1-alpha (HIF1a) as predictors of
response to high-dose Interleukin-2 in Metastatic Renal Cell
Carcinoma patients.
Chris Jacobs
15.06 mTORC1 is an important downstream mediator of WNT signalling
activation in the intestinal epithelium
Helen Casey
15.19 Using the internet for information about breast cancer
Sophie Littlechild
15.30 Coffee & Exhibitions
15.50 Quiz
Consultant Clinical Oncologist with an Interest in Lung Cancer
and Lymphoma
The Christie
Dr Margaret Harris
16.20 Closing remarks, prize presentation & evaluations of the day
Dr Richard Cowan
Dr Richard Berman
Dr Emma Dean
Dr Berman is a Consultant in Palliative Medicine, and Honorary Senior
Lecturer and Undergraduate Medical Tutor at the School of Oncology in
The Christie, which is Europe’s largest cancer centre.
His specialist interests are: complex pain control in cancer,
management of complex symptoms in cancer, malignant bowel
obstruction, communication skills and undergraduate medical education.
Dr Dean graduated with BMedSci MB BS from the University of
Nottingham in 2001 and undertook her general medical training at
hospitals across the UK, before deciding to specialise in
medical oncology.
She was appointed as a Specialist Registrar at The Christie in
2005, gaining her PhD from the University of Manchester in 2009 at
the Paterson Institute for Cancer Research under Professor Caroline
Dive and the Derek Crowther Phase 1 clinical trials unit under Professor
Malcolm Ranson. Her research focussed on pre-clinical research and
early clinical ‘first in human’ trials of novel apoptosis-targeting therapies.
Dr Dean is now a Specialist Registrar and NIHR Clinical Lecturer
in Medical Oncology, dividing her time between translational clinical
research combining novel apoptosis-inducing agents with chemoradiotherapy, and the completion of her medical oncology training.
Dr Richard Cowan
Dr Cowan qualified in London where he stayed for his initial medical
postgraduate training before moving to Sheffield and later Manchester.
After spending two years in research, he was appointed as Consultant
in Clinical Oncology at the Christie Hospital in 1992. Dr Cowan’s
clinical practice encompasses the management of patients with
malignant lymphoma and urological cancer. He is active in clinical
research in both these areas and sits on a number of national
research committees. Between 2006 and 2011, he was Chair of the UK
Cutaneous Lymphoma Group.
In 2009 Dr Cowan became Director of Education at The Christie
and a Senior Lecturer in the School of Cancer and Enabling Sciences
at the University of Manchester. As Director of Education he has been
responsible for the launch of The Christie School of Oncology. The
aim of the school is to deliver undergraduate and postgraduate
educational opportunities in oncology across the whole spectrum of
professionals involved in cancer and palliative care. Between 2005 and
2011 Dr Cowan was an examiner in clinical oncology for the Royal
College of Radiologists.
Dr Catherine Woolley-Stafford
Dr Woolley-Stafford studied medicine at the University of Manchester
and qualified in 2007. Whilst a medical student she worked as a
healthcare assistant and medical secretary, with time spent working at
The Christie, introducing her to oncology as a specialty. After qualifying
she completed a voluntary research internship with Cancer Research
UK, prior to commencing foundation training. This experience helped
her to decide to aim for a career in oncology or palliative medicine.
Dr Woolley-Stafford completed foundation training at Stepping
Hill Hospital in Stockport in 2010, and in order to gain further clinical
experience in oncology, has spent the last year as a Junior Oncology
Fellow at The Christie working for both clinical and medical oncology
teams. She commenced core medical training this August and is
currently working in palliative care at St. Ann’s Hospice.
Dr Was Mansoor
Dr Mansoor originally started training to become a gastroenterologist in
the mid to late 1990s. He came to the Christie Hospital in 1998
after becoming interested in the oncology aspects of the GI tract.
He did a PhD exploring various aspects of GI cancer immunology
before taking up a consultant post within the department of Medical
Oncology. He now specializes in upper GI malignancies as well as rarer
neuroendocrine cancers.
He leads the upper GI department and is the Greater Manchester
Cancer Network Upper GI Research Lead. The upper GI team is very
research active focusing mainly on phase II and III trials, many of which Dr
Mansoor is in charge of running.
He is also the Training Program Director for Medical Oncology for
Manchester and sits on the National Specialty Accreditation Committee
for Medical Oncology.
Dr Rob Metcalf
Dr Metcalf trained at the University of Manchester Medical School,
graduating in 2004. He is currently working as a final year Specialty
Registrar in Medical Oncology, having trained at The Christie since
2008. Throughout this training he has gained a broad experience in
clinical research, being a sub-investigator on many clinical trials. He
has been awarded a CRUK/Astra Zeneca Research Fellowship at the
Paterson Institute of Cancer Research, Manchester, where he will study
toward a PhD with the Clinical and Experimental Pharmacology Group.
His area of research is the study of circulating tumour cells in non-small
cell lung cancer.
Dr Nick Slevin
Dr Slevin is a Consultant in Clinical Oncology at The Christie with special
interest in non surgical management of head and neck cancer. He is
also the current Director of chemotherapy and radiotherapy services at
The Christie.
Dr Slevin has had over 100 publications, and was formerly the NCRI
Chair of the Head and Neck subgroup, and a previous RCR examine.
Dr Alastair Greystoke
Dr Greystoke graduate from the University of Edinburgh in 2000 with an
intercalated degree in Pharmacology. He has been undertaking
medical oncology training since 2003 and has worked at The
Christie, the Royal Marsden, the Western General in Edinburgh and in
New Zealand. During this time, he alsocompleted an online MSc in
Oncology through the University of Newcastle.
Dr Greystoke was the first member of a joint scheme ran by CRUK
and AstraZeneca to develop medical oncologists with the skills and
experience to run drug development programmes. This led to a PhD in
Cancer Studies through the University of Manchester.
His present role is as a Clinical Lecturer and honorary SpR in
Medical Oncology, with a special interest in the development of
mechanism based agents and the use of blood borne biomarkers of
cell death, to speed drug development and individualise patient care.
Dr Margaret Harris
Dr Harris graduated from Nottingham University in 1994 and after
obtaining her MRCP came to The Christie to train as a Clinical
Oncologist in 1998. She was appointed as a consultant in 2003. Her
specialist interests are in lung cancer and lymphoma, and is heavily
involved in undergraduate teaching and training.
The Christie - A Profile
History
The Christie is the largest cancer centre in Europe, treating more than
40,000 patients a year. We were the first UK centre to be officially
accredited as a comprehensive cancer centre. We are based in
Manchester and serve a population of 3.2 million across Greater
Manchester & Cheshire, but as a national specialist around 25%
patients are referred to us from other parts of the country. Our annual
turnover is £180 million and we have 2,500 staff, 400 volunteers and
20,000 public members.
We have achieved world firsts since the Christie was established in 1901. It
was named The Christie in recognition of the pioneering work of both
Richard Copley Christie and his wife Mary Ellen Christie. At this time there
were 30 beds and 463 patients a year.
NHS services
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We provide:
Radiotherapy through one of the largest radiotherapy
departments in the world, both on our main site in south
Manchester and via The Christie radiotherapy centres in Oldham
and Salford
Chemotherapy in the largest chemotherapy unit in the UK on
our main site, with 17% provided locally via other hospitals as
well as offering breast cancer drug Herceptin at home
Highly specialist surgery for complex and
rare cancer
A wide range of support and diagnostic services
Research & Education
We are also an international leader in research, with world first
breakthroughs for over 100 years. Our clinical trials unit is the largest
early phase trials unit in the world, with around 200 trials ongoing at any
one time. We are part of the Manchester Cancer Research Centre with
The University of Manchester and Cancer Research UK and also one of
seven partners in the Manchester Academic Health Science Research
Centre. Cancer research in Manchester has been officially ranked the
best in the UK. The Christie School of Oncology provides undergraduate
education, clinical professional and medical education and is the first
of its kind in the UK.
Joint ventures
We provide private patient services through The Christie Clinic, our joint
venture with HCA International. These services help increase income for
our NHS developments.
Charity
Our charity is the second largest hospital charity in the country. Over
2,000 fundraisers and 20,000 supporters help bring in £13 million a
year, which helps fund additional patient services and vital research.
Milestones throughout the 20th century include:
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1901 - use of X-rays for therapy
1905 - use of radium for therapy
1932 - development of the “Manchester Method” of radium
treatment
1944 - world’s first clinical trial of Stilboestrol a breast cancer drug
1970 - world’s first clinical use of Tamoxifen a breast cancer drug
1986 - world’s first use of cultured bone marrow for leukaemia
treatment
1991 - world’s first single harvest blood stem-cell transplant
1996 - inventing photo-dynamic therapy for skin cancer
….and ‘world firsts’ are still continuing in the 21st century.
Surgery was suspended in 1915 because of First World War work,
and during the Second World War Christie staff had to keep the radium
safe from potential bombing whilst they carried on treating patients.
From 1931 The Christie was linked with the Holt Radium Institute which
gave radium treatments for patients in local hospitals. The two
institutions then moved from Stanley Grove to a new building
in Withington, south Manchester, where The Christie’s main site
remains to this day.
In the 1930s and onwards, Dr Ralston Paterson built a team of
physicists and clinicians who turned the hospital into a world recognised
centre for the treatment of cancer by radiation. The Christie set the first
international standards for radiation treatment in 1932.
Dr Paterson’s wife, Dr Edith Paterson, started research work at the
Christie in 1938 - initially alone, unpaid and having to provide her
own equipment. She too became a world-renowned pioneer in
biological dosimetry, childhood cancers and anti-cancer drug
treatment methods.
In 1948 The Christie became part of the newly created NHS.
Dr Eric Easson was appointed Director of The Christie following
Dr. Paterson’s retirement in 1962, and remained as Director until his
retirement in 1979. His initial interest was in leukaemia and he became
internationally known for his work on curability. Early detection of
cancer was his abiding concern and for eight years he was chairman
of the Commission on Cancer Control of the International Union against
Cancer (the UICC). He was also the President of the Royal College of
Radiologists from 1975 until 1977, and was awarded the CBE in 1978.
Many subsequent clinical and scientific staff members have
made significant contributions to research, education and
clinical developments - lending their expertise to the broader UK
and world community.
For over 100 years The Christie has played a crucial role in the
advancement of cancer treatment and care.
We are one of Europe’s leading cancer centres but have always
retained our treasured ‘family spirit’, with the patient being at the very
heart of everything we do.
National Essay Competition 2011 Results
Title: ‘Hitting cancer where it hurts: How have targeted therapies
improved our approach?’
Congratulations to Karin Purshouse of Newcastle University
for her winning essay.
Second place was awarded to Christopher Jacobs
of Manchester University.
Ganiy Opeyemi Abdulrahman, Jnr of Cardiff University
received the award for third place.
The Manchester Oncology Society would like to thank all the authors
who submitted essays to the competition. Details of the National Essay
Competition 2012 will be available on our website: www.manchesteroncology.org in the New Year. We look forward to receiving you entries!
Oral Presentation 1:
Uptake of Risk Reducing Oophorectomy in BRCA1 and BRCA2
Mutation Carriers
Lauren Sidon (The Medical School, University of Manchester), Gareth
Evans (Department of Clinical Genetics, St Mary ’s Hospital, Manchester)
Background: Mutations in the genes BRCA1 and BRCA2 are associated
with high lifetime risk of developing breast and/or ovarian cancer. Risk
to the age of 70 of developing ovarian cancer is estimated at 39%
with a BRCA1 mutation and 11% with a BRCA2 mutation. Screening for
ovarian cancer is ineffective. Bilateral risk reducing salpingooophorectomy (BRRSO) is therefore the only effective way of reducing
ovarian cancer risk, and can also reduce breast cancer risk in premenopausal women.
Objectives: To analyse uptake of BRRSO in 731 women from greater
Manchester with a BRCA1 or BRCA2 mutation. Three variables will be
considered: type of BRCA mutation, age and previous history of breast
cancer.
Methods: Carriers of a BRCA1 or BRCA2 mutation were identified and
dates of BRRSO were then obtained from family files (by looking at
referral letters, clinic letters and recall letters). These were entered on a
database and a Kaplan Meier analysis was run commencing at the date
of the genetic mutation report.
Results: Cumulative percentage uptake of BRRSO was greater in BRCA1
mutation carriers (61.1% at 10 years) compared with BRCA2 mutation
carriers (50.4% at 10 years). The 40 to 59 years age group shows the
greatest uptake of BRRSO, the under 40s show a delay in a few years
before opting for surgery and the over 60s show significantly lower
uptake. Finally, women with a personal history of breast cancer have
a lower uptake (28%) than women with no breast cancer history (46%).
Conclusion: Uptake of BRRSO is dependent on several factors: cancer
risk, age and personal history of breast cancer. With screening being
ineffective, uptake of surgery should ideally be greater:especially
in the over 60s and in women with a breast cancer history. Regular
counselling regarding risk-reducing options is a key step in ensuring this.
Oral Presentation 2:
An Unusual Presentation of Ovarian Carcinoma with Paraneoplastic
Dermatomyositis.
Callum Harmera (Brighton and Sussex Medical School), Dr Kate
Lankesterb (Royal Sussex County Hospital)
Background: Paraneoplastic syndromes are rare conditions which
occur due to the presence of cancer in the body rather than a direct
local effect of cancer cells. Symptoms develop either because cancer
cells produce hormones, cytokines or as a result of an autoimmune
response. One such manifestation is dermatomyositis, characterised
by proximal myopathy with dermatological features. We present a case
of a patient presenting with dermatomyositis due to an occult epithelial
ovarian cancer.
Case: A 62 year old woman presented with a two-week history of
tender bilateral arm swelling, with left axillary lymphadenopathy. She had
no abdominal symptoms; no early satiety or abdominal bloating. On
examination she had a generalised erythematous macular
rash on the dorsum of the hands, chest and face and proximal
muscle weakness of all limbs. She was provisionally diagnosed with
dermatomyositis and started on dexamethasone. Highly elevated
creatinine kinase levels and skin biopsy confirmed the diagnosis.
Fine Needle Aspiration of the left axillary lymph nodes demonstrated
adenocarcinoma cells and CT imaging revealed a complex ovarian
mass. Biopsies of the ovarian mass and the left axillary lymph node were
reported as poorly differentiated ovarian carcinoma with left
axillary metastasis. The patient was subsequently palliated with
carboplatin chemotherapy and debulking surgery.
Conclusion: The pathophysiology behind dermatomyositis has not
been fully elucidated but is thought to be due to disregulation of
the immune response. When associated with cancer, autoimmune
reactions against molecularly similar antigens occur in both cancer cells
and those tissues affected in dermatomyositis. However, further research
is required to determine why this crossover reaction does not occur in all
patients. There are no guidelines concerning screening for malignancy
after diagnosis of dermatomyositis but a careful history and examination
to elucidate symptoms and signs of cancer plus imaging and tumour
markers is advised.
Oral Presentation 3:
A Clinical Audit on the use of G-CSF Prophylaxis in Patients with
Lymphoma
Leslie Cheng (The Medical School, University of Manchester),
Dr Kim Linton, Dr Adam Gibb, Prof John Radford (The Christie NHS
Foundation Trust)
Background: Febrile neutropaenia (FN) is a life-threatening
condition and is common in patients undergoing myelosuppressive
chemotherapy. Granulocyte colony stimulating factors (e.g.
pegfilgrastim) stimulates the bone marrow to produce more
neutrophils, and thus, are used in patients at high risk of developing FN.
Objectives: To quantify the use of pegfilgrastim in lymphoma
patients during the year 2009, the FN rate, compliance with
pegfilgrastim indications published in the 2009 Manchester
Lymphoma Group Network Guidelines, and pegfilgrastim usage
under new proposed indications.
Method: Data of all patients who were prescribed pegfilgrastim in
the year 2009 were extracted from the electronic database, and
compared with pegfilgrastim indications under current guidelines.
Results & Conclusions: 118 patients received pegfilgrastim in the year
2009. There were 403 prescriptions. 5 patients were excluded from the
audit, leaving 113 patients considered. Most patients were prescribed
pegfilgrastim due to advanced age (28.3%), followed by those
prescribed as a result of having developed FN (27.4%). There was an
almost equal weighting (53.18% vs 54.9%) of pegfilgrastim prescriptions
between indications proposed in the network guidelines and those of
the extended guidelines. The FN rate in elderly patients who received
G-CSF prophylaxis is 11.8%, remarkably lower than the rate reported
in research studies of patients who did not receive G-CSF support
(>20%). There were 8 (7.1%) guideline violations in pegfilgrastim
prescriptions, mostly due to clinical decisions to provide G-CSF support
in patients with low neutrophil counts, but were not severe enough
(grade 4) to require G-CSF use under the guidelines. There is a possibility
of extending the existing guidelines to incorporate the indications
proposed in the SACT 30 day mortality review to optimise patient care
and treatment. An observation supporting this proposal is that the FN
rate of elderly patients given G-CSF prophylaxis is considerably lower
(11.8%) than historical rates of above 20%.
Oral Presentation 4:
Supporting ‘Bert’ during head and neck radiotherapy: developing a
‘contract of care’ for a person with dementia
Mak Tsun (School of Medicine, University of Manchester); Mackereth
Peter; Tomlinson Lynne; Mehrez Anita; Hackman Eileen, Younger
Jane; Booth Adam; Sellar Katy; Lee Lip (The Christie NHS Foundation
Trust).
Background: Over 750,000 people in the UK have some form of
dementia; this figure should rise steadily over the next 25 years4. With
early diagnosis, more cases of cancer patients with dementia will have to
be treated. For head and neck (H&N) cancers, immobilization masks are
routinely used to ensure accurate and safe radiotherapy. MRI scans and
mask making have been documented as causing severe anxiety and
claustrophobia in up to 58% of patients, even for those without
mental problems3. CALM service was developed at The Christie to
assist patients in managing severe anxiety with positive results for those
undergoing H&N cancer radiotherapy.
Purpose: The case study reports on the care and support provided to
a dementia patient and his carer during H&N cancer treatment. The
study highlighted ethical and practical issues for the Multidisciplinary
Team (MDT), including getting ongoing consent, respecting autonomy,
doing good and avoiding harm.
Interventions: ‘Bert’, a 62 year-old patient with a left buccal mucosa
lesion, was referred for 20 fractions of post-operative radiotherapy. His
dementia, diagnosed 10 years ago, had now progressed to
a moderate/severe stage. Lorazepam was used prior to the first
radiotherapy procedure, but Bert got so confused that treatment was
abandoned. The CALM service was asked to provide support. Assessing
and verifying Bert’s ongoing consent was crucial. It was observed
that interaction with Bert was enhanced via a structured and tailored
‘contract of care’, teamwork, observing non-verbal cues, the use of
relaxation techniques (Progressive Muscle Relaxation) and through
positive behavioral re-enforcement and Validation Therapy. A calmer and
more focus state was achieved with Bert successfully completed 17 out of
20 planned radiotherapy sessions.
Conclusion: Bert’s story illustrates how an individualized ‘contract of
care’ could be developed to help maximize interactions, ensure
ongoing consent and maintain his dignity during difficult and
challenging medical procedures.
The exact biological behaviour of such lesions under the age of 10
years is under debate, with some studies suggesting a better prognosis
than conventional adult melanoma. However, other reports suggest an
increased mortality in up to 66% of cases due to delayed diagnosis.
Here, we present a rare case of childhood malignant melanoma
arising de novo in an otherwise healthy seven-year-old girl.
Case presentation: A seven-year-old girl presented to her general
practitioner with a 7 mm diameter scaly skin lesion on the right lower
back, which was catching on her clothes and had bled. The lesion was
initially diagnosed by several clinicians as molluscum contagiosum and
subsequently, atypical dermatofibroma. After excision of the lesion and
on review at a multidisciplinary team meeting, a diagnosis of severely
atypical dermal melanocytic tumour, best regarded as malignant
melanoma of childhood was made by a specialist dermatopathologist.
The tumour had a Breslow thickness of 3.5mm and Clark’s Level of
IV. Further re-excision with possible sentinel lymph node biopsy was
advised and the patient was referred to a paediatric plastic surgeon.
Conclusion: This case illustrated that although rare, malignant
melanomas can occur in children and are often diagnosed at more
advanced stages as compared to adult cases. Both clinicians and
pathologists should be aware of the potential diagnosis when faced with
a changing mole. More importantly, a multi-disciplinary team
approach to compensate for our current lack of experience in such cases
could avoid delay in diagnosis and further maximize the benefits of
treating this disease at an earlier stage.
Oral Presentation 5:
CD133 as a Cancer Stem Cell Marker in Small Cell Lung Cancer
Anna Cowell, Sana Sarvi, Alison MacKinnon (University of Edinburgh);
Tariq Sethi ( Kings College, London)
Oral Presentation 7:
Expression of the Copper Export Transporter ATPase 7B Correlates with
FOLFOX induced Tissue Injury
Cancer stem cell theory hypothesises that only a small subset of
cancer cells have the capacity to initiate and sustain tumour growth.
The chemoresistance of this subset to current therapies may explain
the inevitable relapse and therefore poor prognosis of small cell lung
cancer (SCLC). These cells have been called Cancer stem cells (CSCs),
and may represent a novel target for future cancer therapies. Many
markers to identify CSCs have been suggested, this study evaluates the
cell surface protein CD133 as a possible marker of CSCs in the H69 cell
line of SCLC.
Flow cytometry and cell sorting were used to sort the cells
in to those expressing high, medium and low levels of CD133.
The characteristics of these groups were then compared in 3
assays; Expression of the stem cell marker Oct-4 by western
blot, chemoresistance to conventional chemotherapy by a
colourimetric MTT assay and tumorigenicity between the groups by
xenotransplantation in mice.
In this cell line, CD133 expression displays a Gaussian distribution,
with 15% of cells expressing high levels. CD133high cells also express
stem cell marker Oct-4. The CD133high group were also more resistant
to topoisomerase II inhibitor, Etoposide. (IC50 value of CD133high
was 123.43±22.5μg/ml, significantly higher than the IC50 value of
CD133low cells at 11.56±1.94μg/ml (p<0.001).) A preliminary in vivo
experiment found that 1×105 CD133high cells formed tumours in nude
mice within 5 days, whereas in 50 days, no tumours were seen where
5×105 CD133low cells were injected.
In conclusion, CD133 is a marker for Oct-4 expressing cells, which
display increased chemoresistance to Etoposide, and have higher
tumorigenic potential than CD133low cells in nude mice. Further work will
continue to investigate the characteristics of CD133high cells, and evaluate
CD133 as a potential CSC marker.
Zahed A, White SA, Mann DA, Robinson SM (Institute of Cellular
Medicine, Newcastle University)
Oral Presentation 6:
Rare Case of Childhood Malignant Melanoma: a Case Report
Melody Tsai, Amani Evans (School of Medicine, University of
Manchester); Iskander Chaudhry (Department of Pathology,
Manchester Royal Infirmary)
Background: Malignant melanoma in childhood is exceptionally rare.
Diagnosis of such lesions can be a challenge to clinicians as well as
pathologists, leading to a delay in diagnosis and subsequent treatment.
Chemotherapy associated liver injury is a cause for significant
concern when undertaking liver resection for metastatic colorectal
cancer. The use of oxaliplatin regimens e.g. FOLFOX has been linked
to the development of hepatic sinusoidal obstruction syndrome with
subsequent increases in perioperative morbidity and mortality.
When FOLFOX is administered to healthy mice the major site or organ
toxicity appears to be the spleen rather than liver. Cellular platinum
uptake is determined by the copper transporters CRT1 and CRT2 and
its export by ATPases 7A and 7B. The aim of this study was to determine
what effect tissue specific expression of these transporters has on
FOLFOX related tissue injury.
Methods: RNA was extracted from the liver and spleen of healthy
C57/Bl 6 mice and experimental colorectal liver metastases
(established with the MCA38 cell line). RT-PCR was performed
to determine expression of genes encoding the transport proteins.
Tissue injury following FOLFOX treatment was determined by H&E.
Immunohistochemistry was performed to assess the extent of drug
induced DNA damage (H2AX) and cell death (cleaved caspase 3).
Results: Copper uptake transporters were expressed in all tissues.
There was however reduced expression of the export transporter
ATP7B in spleen and tumour tissue as compared to the liver.
In keeping with high tissue platinum levels there was an increase
in H2AX positive cells in the spleen (p<0.05) and tumour tissue
(p<0.01) of FOLFOX treated mice.
Conclusion: Expression levels of the transporter protein ATPase 7B may
play a role in determining tissue specific toxicity of platinum based
chemotherapy regimens. Numerous polymorphisms exist in the ATP7B
gene and are associated with impaired export of copper from cells. It
may be polymorphisms in the gene encoding ATP7B or variations in its
expression, may play a role in the development FOLFOX induced liver
injury and are worthy of further investigation.
Oral Presentation 8:
Audit of Hospital Acquired Thromboembolism in Spinal Surgery
Antony Sorial, Katherine Armstrong (The Medical School, University of
Manchester); Parmjit Sian, John Brad Williamson (Salford Royal
Foundation Trust)
Introduction: Surgical decompression and posterior instrumentation is
one of the management options available for both primary and
secondary spinal tumours. In oncology patients the hypercoagulable
state can increase the risk of thromboembolism and therefore
fatal pulmonary embolism. Thromboembolism can be treated with
chemical thromboprophylaxis (TP) however the vascular nature of
tumours increases the risk of post-operative bleeding and epidural
haematoma, which can cause paralysis.
Objectives: In our unit we have an evidence-based policy for spinal
thromboprophylaxis, an audit was undertaken in 2011 to determine
adherence to this policy.
Methods: We conducted a retrospective audit of this policy in fifty
consecutive spinal ward admissions
Results: 100% of surgical patients received appropriate hospital
acquired thromboembolism assessments, of these 52% were
administered Tinzaparin. Only 48% were documented to have received
all thromboprophylaxis within the correct time period. All surgical
tumour patients received chemical TP but only 14% received this within
the timeframe outlined by policy (<8 hours post-operatively). This was,
in part, caused by the concern of a potential coagulopathic patient.
100% of patients had mechanical intermittent calf compression but
whilst conducting our audit we observed this was at times stopped for
>20 minutes in recovery.
Conclusion: This audit has highlighted areas where we can improve
the adherence to spinal TP policy. We have presented the audit to
the Harm Free Care committee, a poster has been produced to
improve both awareness and adherence to TP and the policy has
been simplified. The new policy allows 24 hours for administration of
TP. A potential trial of an automated prescription service has been
investigated to improve adherence; once clotting is normal the chemical
TP prescription becomes active. New systems are in place to ensure there
is no interruption in calf compression. A re-audit has been arranged and
will be undertaken in October 2011.
Oral Presentation 9:
Evaluation of in home palliative care strategies for patients
with terminal illnesses
satisfaction, quality of life and readmission time. Finally, palliative care
services in patients home tended to cost less than in hospital stays
which would allow savings to the health care system.
Conclusion: At home palliative care services seem lead to better
patient outcomes and could reduce health care costs. However, we
need to ensure that staff need to work in multidisciplinary teams and
are trained in palliative care methods to ensure that the best patient
outcomes are achieved.
Oral Presentation 10:
Polymorphisms in the genes Carbonic Anhydrase-9 (CA-9) and Hypoxia
Inducible Factor 1-alpha (HIF1a) as predictors of response to high-dose
Interleukin-2 in Metastatic Renal Cell Carcinoma patients.
C.D Jacobs (The Medical School, University of Manchester), A.
Molassiotis (School of Cancer and Supportive Care, University of
Manchester)
Introduction: Treatment options in metastatic renal cell carcinoma
(MRCC) are limited. High-dose Interleukin-2 is a potentially
curative agent, although highly toxic, achieving a response rate
of approximately 27% in unselected patients, many of which are
complete and durable. Establishing predictive markers of response is
especially important in this field. We assessed single nucleotide
polymorphisms in the CA9 and HIF1a genes and their association with
IL-2 response in 38 patients with MRCC.
Methods: Patients were treated with at least 2 cycles of IL-2 and
response assessed after 3 months by radiology using the RECIST criteria.
Genomic DNA was extracted from formulin-fixed-paraffin-embedded
(FFPE) tumour blocks or peripheral blood. The relevant exons of CA-9 and
HIF-1a were amplified by polymerase chain reaction (PCR) using specific
primer pairs and then sequenced.
Results: CA9 polymorphisms rs2071676, rs12553173, rs3829078 and
rs1048638 were present in 53%, 21%, 19% and 41% of patients
respectively. HIF1a polymorphism G1790A was present in 22% of
patients. 24 out of 38 (63%) patients in the cohort responded to
treatment. All 8 Patients expressing the G allele of rs3829078 responded to
treatment making this polymorphism significantly associated with
response to IL-2 (p=0.0324). No other polymorphisms were significantly
associated with treatment response.
Conclusions: The polymorphism rs3829078 present in 19% of patients is
predictive of treatment response. Genotyping patients together with
histological criteria may have the potential to improve the selection of
patients for treatment with high-dose IL-2.
Victoria Connor (University of Liverpool)
Background: A recent survey estimated that in the UK 11% of patients
die in a hospice and over half of patients with terminal illness die in
hospital beds. However, extensive evidence has concluded that over
50% of patients when faced with a terminal disease would prefer to
be cared for and die at home. Unfortunately, patients choices depend
greatly on the quality of care available at home and the
costs involved.
Objectives: The clinical effectiveness of different types of home
palliative care will be assessed and the costs of these services will be
compared to the alternatives available.
Method: A computer aided search was conducted using four
major electronic databases namely, Scopus, Medline, PubMed and
Cochrane, hand searching of high impact journals was undertaken and
reference lists of studies were examined. Relevant studies were critically
appraised using the CASP tool to ensure that only the most robust studies
were discussed in this structured review.
Results: None of the studies reviewed showed that palliative care at
home negatively impacted patients and their caregivers. Overall results
from the studies reviewed showed that patients who were cared for at
home showed better outcomes specifically when evaluating patient
Oral Presentation 11:
mTORC1 is an important downstream mediator of WNT signalling
activation in the intestinal epithelium
Helen Casey, William Faller, Sorina Radulescu, Rachel Ridgway, Julia
Cordero (The Beatson Institute for Cancer Research, Glasgow); Michael
Hall (Biozentrum, University of Basel, Switzerland); Owen Sansom (The
Beatson Institute for Cancer Research, Glasgow).
Colorectal cancer is the third most common cancer in the UK and
the second most common cause of death from cancer. Deletion
mutations of the tumour suppressor gene APC (Adenomatous Polyposis
Coli) gene are present in over 70% of sporadic colorectal cancers.
Furthermore, germline mutation of the APC gene can also lead to
an autosomal dominant inherited disorder, Familial adenomatous
polyposis (FAP), which is characterized by the early onset of hundreds to
thousands of adenomatous polyps throughout the colon. Functionally,
APC acts as a tumour suppressor by negatively regulating Wnt
signalling. We have previously shown that APC deletion in the mouse
intestinal epithelium causes a hyper proliferative phenotype. We have
also shown that this proliferation is dependent on Mammalian Target
of Rapamycin Complex 1 (mTORC1) signalling. Both genetic deletion
of Raptor, an essential component of mTORC1, and treatment with
the mTORC1 inhibitor Rapamycin cause an almost complete block
in Wnt-driven proliferation, while not affecting the proliferation of
normal intestine. To test whether established tumours show the same
response to rapamycin, we treated APC (Min/+) mice with rapamycin
after they showed signs of illness. We treated the mice for 6, 24, 48
and 72 hours and then assessed the expression of several relevant
proteins using immunohistochemistry. We observed a drastic decrease
in tumour proliferation as a result of treatment. As expected, levels of
phospho S6K, a downstream effector of mTORC1, were diminished,
while phospho AKT and phospho 4E-BP1was unchanged. Finally, we
have previously observed that KRas mutation conveys resistance to
Rapamycin in this context. Therefore, we compared the proliferation
of the intestinal epithelium following APC deletion and KRas mutation,
both with and without Raptor deletion. Raptor deletion caused a
significant decrease in proliferation, suggesting that KRas driven
proliferation is partially dependent on S6K-independent mTORC1
signalling. These results suggest that mTORC1 may be an attractive
target for therapy in colorectal cancer.
Oral Presentation 12:
Using the Internet for Information about Breast Cancer
Sophie Littechild (University of Manchester), L Barr (Consultant Breast
Surgeon, University Hospital of South Manchester)
Introduction: Breast cancer patients are known to have particularly
high informational needs; if these are not met by health professionals,
patients will endeavour to find this information elsewhere. The most
commonly used source for this is the Internet.
Objectives: This study aimed to identify the proportion of women that used
the Internet for breast cancer information, whether there was a specific
sub-group based on age, ethnicity and annual household
income that were more likely to do so, and the particular problems and
benefits that patients experienced.
Methods: A 10-item questionnaire was given to 209 patients that
attended the Nightingale Centre between 9th May and 6th June 2011
following breast cancer treatment within the last 5 years.
Results: 200 questionnaires were completed (96%). 50.5% of patients
had used the Internet for breast cancer information. Patients were more
likely to do so if they were younger (p<0.001) with a higher household
income (p<0.001). However, ethnicity did not have any affect
(p=0.128). 63% chose websites on their own initiative, with Macmillan
being most frequently used (41%). Only 8% of patients accessed
websites because they were recommended by health professionals.
The Internet was deemed to be beneficial by a considerable majority
(73%) of patients; with most stating that it increased their general
understanding (79%). 31% of patients experienced problems when
using the Internet:- anxiety was the problem most frequently reported
(68%). Ethnicity affects the likelihood of experiencing problems with
white patients experiencing fewer problems (25%) compared to nonwhite patients (64%) (p=0.008).
Conclusion: Health professionals need to be aware that over 50% of
their patients may use the Internet for information about breast cancer,
the majority conducting searches using entirely their own initiative.
Certain sub-groups are less likely to access the Internet,
and patients from minority ethnic backgrounds are more likely to
encounter problems.
Poster Presentation 1:
Initial toxicity and compliance evaluation for consolidation pemetrexed
following concurrent chemoradiotherapy (cCTRT) in stage III non-small cell
lung cancer (NSCLC): a phase II trial.
Jonathan Helbrow (The School of Cancer and Enabling Sciences, The
University of Manchester), Corinne Faivre-Finn, Neil Bayman, Paul A.
Burt, Abbas Chittalia, Maggie A. Harris, Helen Lander, Lip W. Lee,
Laura Pemberton, Hamid Sheikh (Department of Clinical Oncology, The
Christie NHS Foundation Trust), Paul Taylor, Fiona Blackhall
(Department of Medical Oncology, The Christie NHS Foundation Trust)
Linda Ashcroft (Clinical Trials Co-ordination Unit, The Christie NHS
Foundation Trust) and Gareth Webster (North West Medical Physics, The
Christie NHS Foundation Trust).
Background: Lung cancer is the leading cause of cancer-related
mortality worldwide. cCTRT is the standard treatment for good
performance status stage III NSCLC and is associated with 5 year
survival of 20-25%. Strategies to improve on the efficacy of cCTRT with
cisplatin/etoposide are required. Here we evaluate the compliance
and acute toxicity of cCTRT followed by consolidation pemetrexed.
Methods - This was a single-institution phase II study. Treatment
comprised cisplatin (50 mg/m2 days 1, 8, 29, 36), etoposide (50 mg/
m2 days 1-5 and 29-33) and concurrent thoracic radiotherapy (66 Gy
in 33 daily fractions) followed by consolidation pemetrexed (500 mg/
m2 on days 71, 92 and 133).
Results: 35 patients were recruited. Median age=61 years (range
42-75), M:F=23:12, ECOG performance status=0 (n=11) or 1 (n=24).
All 35 patients received cCTRT: 33 patients (94%) received full dose
concurrent chemotherapy, 32 patients (91%) received the planned
dose of 66Gy (range 56-66 Gy). Number of patients who received
pemetrexed: cycle 1=25 (71%), cycle 2=21 (60%), cycle 3=16 (46%).
Reasons for omitting cycle 1 pemetrexed: 7 patients had not recovered
from cCTRT-related adverse events, 2 patients withdrew and 1 patient
died on study. Oesophagitis and pneumonitis were unassessable for
one patient. 10 patients experienced grade 3 oesophagitis (29%), and
1 patient grade 4 (3%). 1 patient experienced grade 3 pneumonitis
(3%), no grade 4. 8 patients experienced grade 3 fatigue (23%), no
grade 4. 2 patients with central disease suffered grade 5 haemoptysis.
Conclusion - The addition of consolidation pemetrexed following cCTRT
for stage III lung cancer does not appear to worsen the incidence
or severity of treatment-related side effects. However, the full dose of
consolidation therapy was not feasible in half of patients. This study
highlights the challenges of adding further systemic therapy to cCTRT
in locally advanced NSCLC, and will inform the design of future trials
involving consolidation treatment.
Poster Presentation 2:
CYP2C40/55 metabolites and their role in colon cancer
Michael Albert (University of Nottingham), Prof Andrew Bennett (Faculty of
Medicine & Health Sciences, University of Nottingham)
Background: Certain Cytochrome P450 (CYP)-dependent arachidonic
acid (AA) metabolites are thought to induce therapeutic effects in the
colon via activation of peroxisome proliferator activated receptors
(PPARs), specifically the PPAR-α subtype. The activation of PPAR-α leads
to changes in the expression and activity of target genes and other
transcription factors such as COX-2, NF-KB and AP-1, resulting in antiinflammatory and anti-tumorigenic effects. CYP2C40 and CYP2C55 are
two recently discovered CYPs, isolated from the murine intestinal tract.
Their metabolites include 16-,HETE, 8,9-EET and 14,15-EET which have
been shown to have anti-inflammatory effects both in vitro and in vivo.
Evidence suggests that CYP2C40 and CYP2C55 may have a potential
therapeutic role to play in colon tumorigenesis. This study aims to
determine whether PPAR activation leads to an up-regulation in the
expression of CYP2C40 and CYP2C55.
Methods: CYP2C40 and CYP2C55 promoter regions were isolated from
murine DNA via PCR and inserted into a luciferase plasmid (pGL4.10).
Plasmid DNA was cloned following transfection into highly competent cells
and purified via Midi-Prep recovery. Purified plasmids were
transfected into COS-7 and HCA-7 cells and the cells were treated with
PPAR-α, α and α ligands Wy14643, GW0742 and Rosiglitazone (COS-7
cells had PPAR-α/α/α over-expressed). Cells were harvested after 24 hours
incubation and luciferase activity (equivalent to gene expression) was
measured in relative light units (RLU) using a reporter assay system.
Results- In COS-7 cells PPAR-α, α and α ligands led to a significant
increase in CYP2C40 RLU from a baseline measurement of (mean
(± SD)) 235 (20) to 726 (45), 458 (61) and 466 (42) for PPAR-α, α and α
respectively. CYP2C55 showed a significant increase from 154 (6) to 263
(10) and 354 (21) for PPAR-α and α respectively (p=0.001). HCA-7 cells
were shown to only express endogenous PPAR0-α and following
incubation with PPAR-α, α and α ligands a significant RLU increase was
observed in CYP2C40 from 55 (13) to 126 (17) and in CYP2C55 from 62 (11)
to 111 (4) for PPAR α (p=0.001).
Conclusion: The results suggest that a functional peroxisome
proliferator response element (PPRE) exists within the promoter regions of
CYP2C40 and CYP2C55 and that activation of PPAR-α within the HCA7 cell line leads to a significant increase in CYP2C40 and CYP2C55
expression. Given the beneficial properties of PPAR-α and CYP derived AA
metabolites it seems that CYP2C40 and CYP2C55 may become important
future therapeutic targets in colon cancer.
Poster Presentation 3:
Copying Clinical Letters to Oncology Patients
Omar Taha (Bart’s and The London Medical School), Dr Ihsaan AlHadad (Charring Cross Hospital), Muhammad Najim (Imperial College
Medical School), Dr Rula Najim (Northwick Park Hospital), Dr Chris
Gallagher (Bart’s and The London Hospital)
Introduction: After the NHS Plan of 2000, guidelines state that ‘letters
between clinicans about an individual patient’s care will be copied to
the patient as of right’. A study was done at the oncology
department, Barts Hospital, London, to analyse whether patients still
wanted copies of their clinical letters, and also whether doctors were in
fact copying letters.
Methodology: The study involved distributing questionnaires to patients
and oncologists during outpatient clinics and on wards over a period of
one week throughout August 2009.
Results: Return rates of 89% (107/120) and 76% (23/30) from the
patients and oncologists respectively was achieved. Key findings
included; 87% of clinicians ask for consent only on the first consultation,
occasionally or even never, and the most frequent reason is forgetting
to. Only 37% of patients had ever been given the option of obtaining
a copy of their clinical letter, with 54% of these still not being consented
after every consultation. Most patients, 77%, still wanted a copy of their
clinical letter.
Conclusion : The majority of patients still want a copy of their clinical
letter; however most doctors fail to take consent of the patient at every
consultation, the main reason being they forget to.
Poster Presentation 4:
Burkitt’s Lymphoma : A Case Report
Katarina Bray (University of Manchester), Dr Mark Grey (Royal Bolton
Hospital)
Burkitt’s lymphoma (BL), a sub-type of the non-Hodgkin group of
lymphomas, is defined as a neoplasm formed of non-cleaved B-cells
of small size and extremely aggressive, highly proliferative nature.
First described in 1958 in the equatorial African region, this highly
aggressive sarcoma commonly affects the jaw and abdomen, with
its manifestation often rapid in nature. The presentation of BL within
adults is deemed an infrequent occurrence and many of its disease
characteristics, including management and aetiology are considered
to be distinct. Three sub-types of BL are recognised clinically, namely
endemic, sporadic and immunodeficient, of which lymphomagenesis
across variants is based upon chromosomal alterations of the c-MYC
oncogene. The case presented demonstrates a previously healthy
male who developed sporadic BL with B symptoms of night sweats
and weight loss. It highlights the rapidity with which disease progression
occurs and the importance of rapid, intense chemotherapeutic
intervention on disease prognosis.
Poster Presentation 5:
A pilot study on the use of a cancer-specific comprehensive geriatric
assessment tool in older women with primary operable breast cancer
Ruth Mary Parks (University of Nottingham), Prof Karen Cox (School of
Nursing, University of Nottingham), Mr Kwok-Leung Cheung (Division of
Breast Surgery University of Nottingham)
Context: Comprehensive geriatric assessment (CGA) is an analytical
tool measuring physical and psychosocial function. Breast cancer
is primarily a disease of the elderly. A pilot study, contributing also
to a BMedSci project of the undergraduate medical curriculum, was
conducted evaluating a cancer-specific CGA tool in older women
with primary operable breast cancer.
Methods: Newly diagnosed women attending the Primary Breast
Cancer Clinic for Older Women in Nottingham were invited to
participate. CGA was completed within 6 weeks. The decision of
primary treatment followed consultation with the clinical team and was
not guided by CGA. 47 patients were recruited (surgery n=29, primary
endocrine therapy (PET) n=17, primary radiotherapy n=1).
Results: Patients were mostly widowed (52%); living with someone
(54%); retired (96%); of white ethnicity (91%); had completed primary/
secondary education (65%), with a mean age of 80 (range 68-92),
Body Mass Index (BMI) of 27.4, and good scores for Activities of Daily
Living (21/34), Karnofsky self-reported (6/8) and physician-rated (80/100)
performance, mood measured by the Hospital Anxiety and Depression
Scale (79/102), social activities (14/20) and support (49/60) measured
by the Medical Outcomes Study Social Activity Limitations measure.
On average participants took 4 daily medications and scored 5 (out
of 51) on the Physical Health Section measuring comorbidity. 25% had
experienced a fall in the last 6 months and 2 had signs of cognitive
impairment based on the Blessed Orientation-Memory-Concentration
test. Average completion of the timed ‘up and go’ (TUG) was 16
seconds. Statistically significant association was found between
PET (as opposed to surgery) and increasing age (p=0.001), greater
comorbidity (p=0.022), more daily medications (p=0.002) and slower
TUG (p=0.014). Logistic regression showed only age to
be independently significant (p=0.016; odds ratio=12.69, 95%
CI 1.60-100.69).
Conclusions: There was an association between CGA factors and
treatment patterns in this cohort of older adults with breast cancer.
The study is still ongoing.
Poster Presentation 6:
Traction force microscopy of focal adhesions
Jerome Goffin (The University of Edinburgh), Boris Hinz (Laboratory of
Tissue Repair and Regeneration (University of Toronto, Canada)
Background: The tumour microenvironment is believed to play an
important role in tumour progression. This complex system is made
of several cell types including myofibroblasts which are therefore
seen as an important target for anti-cancer therapies. In fact,
cancerogenesis is characterised by an increase in the number of
differentiated myofibroblasts. Myofibroblasts are contractile cells
exhibiting a smooth muscle phenotype and best known for promoting
dermal wound closure but also pathological contractures such as
organ fibrosis.
Objective(s): The aim of this project is to better understand the
differentiation of myofibroblasts by measuring the cell-generated forces
transmitted to the extra-cellular matrix via anchor points known as focal
adhesions.
Method: Compliant substrates were designed in a microtechnology
center in order to embed a lattice of micrometre-sized markers made
of fluorescent resin in a thin substrate of PDMS, a biocompatible
polymer. REF-52 cells which were stably transfected with GFP-α3 integrin
(a marker of focal adhesions) were cultured on this substrate. Due
to the contraction, the cells deformed the substrate. The resulting
displacement field was computed by registration of the confocal
images of the substrate before and after relaxation of the cytoskeleton
(with cytochalasin D, an inhibitor of actin polymerisation) using an
ImageJ plugin.
A new algorithm was implemented in order to compute cellgenerated forces corresponding to the displacement field calculated.
Result(s)We show that supermature focal adhesions typical of
myofibroblasts exhibit stresses fourfold higher (α12 nN/μm2) than
classical focal adhesions with a length below 6 micrometres.
We also show that our newly implemented algorithm to retrieve forces
is more accurate than the gold-standard Fourier Transform Traction
Cytometry algorithm.
Conclusion: This result contradicts the current belief that stresses are
constant across the whole range of focal adhesion sizes and sheds a
light on the myofibroblastic phenotype.
Poster Presentation 7:
The Prevalence of long term side effects in patients treated with radical
radiotherapy for pelvic malignancies within the Sussex Cancer Network.
Sarah Winnett (Brighton and Sussex Medical School), Dr Kate Lankester
and Dr Fiona McKinna (Sussex Cancer Centre)
Background: Approximately 12,000 patients in the UK are treated
with radical radiotherapy for pelvic cancers annually. Survival rates
are increasing and many of the side effects of radiotherapy are
underreported. The aim of this study was to estimate the prevalence of
long term side effects of patients treated with radical radiotherapy for
pelvic cancers within the Sussex Cancer Network and
determine whether levels of anxiety and depression correlated
with a patient’s symptoms.
Methods : The VISIR database was used to identify suitable patients
who had completed a course of radical radiotherapy to the pelvis in
2008 or 2009. After confirmation from the patient’s GP and oncologist
that the patient met the inclusion criteria they were sent an information
pack containing a copy of a pelvic toxicity questionnaire, which has
been devised and validated by the Christie Hospital, Manchester and a
copy of the HAD scale.
Results: 124 responses were received made up of 105 males and
19 females. 44 patients (35.8%) reported at least one symptom
representative of bowel toxicity of which rectal bleeding was the
most prevalent. 66 patients (53.2%) reported at least one symptom
representative of bladder toxicity. Of these symptoms frequency was
the most commonly reported followed by retention. Sexual dysfunction
was particularly prevalent with 67.6% of men and 36.8% of women
believing that treatment had affected their ability to have a sexual
relationship 14.2% of patients gave answers suggestive of anxiety
disorder. 1 patient was highlighted as suffering from severe anxiety.
5% of patients gave answers suggestive of depressive disorder with 2
patients reporting severe depression. There was no clear correlation
seen between levels of anxiety or depression and levels of bowel or
bladder toxicity.
Conclusions: Long term side effects affecting the bowel, bladder and
sexual function are common and often under reported in patients who
have been treated with radical radiotherapy to the pelvis.
Poster Presentation 8:
Is the Modified Early Warning Score an effective tool for use in oncology
patients?
Emma Kitlowski (University of Manchester)
Background: Track and trigger systems such as the Modified Early
Warning Score (MEWS) are used to identify patients at risk of critical
illness or deterioration. There are a variety of these systems in use,
however most have been developed based on clinical intuition rather
then evidence.
Aims : The validation and evidence for the effectiveness of these
systems is limited and so far studies have been restricted to general
medical patients. This study, carried out at The Christie Hospital,
Manchester aims to assess if the scoring system used is effective in
identifying ‘at risk’ oncology patients. Can this tool be used to identify
the patients that will benefit from intervention on the critical care unit
(CCU) and if not what variables can?
Methods : Data was collected from electronic proformas completed
for all patients seen by the Outreach Team from April 2009 to January
2011. The raw physiology was used to calculate a MEWS score for
each patient and the measured outcomes were CCU admission and
mortality within 30 days.
Results: The MEWS score was statistically significant in predicting
outcome (CCU admission p=0.037, 30 day mortality p= 0.0046).
However the median score in the outcome groups was just one point
higher then that in the control group and no score demonstrated
satisfactory sensitivity and specificity for predicting either critical care
admission or mortality. The variables identified statistically as being
predictive of critical care admission are capillary refill time, fraction of
inspired oxygen and disease group, none of which are included in the
current scoring systems.
Conclusions: Despite the statistical significance, the MEWS score in not a
clinically useful tool for oncology patients. Further studies are needed in
this patient group to identify which variables can be used to develop a
more effective scoring system.
Poster Presentation 9:
An audit to calculate the pre-operative diagnosis rate for symptomatic
breast cancer patients
A. Alves (University of Manchester), A. Warner (University of Manchester),
Dr N. Barr (University Hospital of South Manchester)
Background: Guidelines on the management of breast cancer
recommend that a diagnosis should be made with non-operative
techniques such as the triple assessment. These guidelines also suggest
that at least 90% (target ≥95%) of invasive cancers and 85% (target
≥90%) of non-invasive cancers should be detected pre-operatively.
Objective : The aim of this audit was to calculate the pre-operative
diagnosis rate for invasive and non-invasive breast cancer patients at the
University hospital of South Manchester (UHSM) and how many needle
biopsies were needed to obtain the diagnosis. The reasons for having no
pre-operative diagnosis were also analysed.
Method: Patients who were diagnosed with breast cancer at the
UHSM between April 2009 and March 2010 were identified. Diagnoses
identified by screening and recurrence breast cancers were excluded.
A hospital database of diagnostic procedures was used to establish
whether the eligible patients had a diagnosis before surgery or not.
Results. 368 cases (including 8 patients with bilateral carcinomas)
were entered into the audit. 6.5% were ductal carcinoma in situ (noninvasive), with the remainder as invasive carcinomas. 88% (21/24) of
non-invasive and 98% (336/344) of invasive carcinomas had a preoperative diagnosis. Reasons for not having a preoperative diagnosis
included technical limitations with radiological equipment, inconclusive
biopsies, co-existing illnesses and patient wishes. 38.6% of patients
who had a pre-operative diagnosis only had to have 1 biopsy but 12
patients had to have 3 biopsies before a diagnosis could be made.
Conclusions: This audit has shown that the breast unit at the UHSM
does follow the recommended guidelines for the management of
breast cancer by reaching the minimum standards set for invasive
and non-invasive cancer. In particular, it has an excellent preoperative diagnosis rate for invasive breast cancers by exceeding the
recommended target. Many patients only needed 1 biopsy in order to
obtain a diagnosis.
Poster Presentation 10:
The treatment of stage III non-small-cell lung cancer (NSCLC): an
analysis of current practice
A. Alves, C. Faivre-Finn & N. Bayman
Background: Stage III non-small-cell lung cancer (NSCLC) is a
heterogeneous group and therefore the treatment of it remains a hotly
debated topic. Curative options include surgery as well as radical
radiotherapy or combined chemoradiotherapy for unresectable
tumours. Issued guidelines recommend gold standard treatments
for stage III disease but implementation of the guidelines has been
variable across the UK.
Objective : The purpose of this study is to assess the current
management practice of stage III NSCLC in Greater Manchester and in
particular how many patients receive the gold standard concurrent
chemoradiotherapy. An evaluation will also be made into the factors
which influence treatment decisions.
Method: Patients who were diagnosed with stage III NSCLC,
discussed at a multidisciplinary team (MDT) meeting during JulySeptember 2010 were entered into the audit. Various details from
each eligible patient were collected such as patient demographics
and details of the disease e.g. the histological subtype of the tumour.
The intended treatment (as per MDT decision) and actual treatment
received were compared.
Results: Overall, 85 patients were eligible to be included into the study. In
24.5% of cases there was a difference between the MDT decision and the
actual treatment received. 8.2% of patients were treated with surgery,
16.5% with chemoradiotherapy and 30.6% with palliative care. Only 5
patients received concurrent chemoradiotherapy.
Conclusions: The management of stage III NSCLC in Greater
Manchester is in line with the guidelines. However few actually receive
concurrent chemoradiotherapy. Age and performance status are
factors that influence a MDT decision. Data recorded at MDT may not
always be accurate, therefore causing the discrepancy between the
actual treatment and the option that was advised by the MDT. Further
studies are needed into patient characteristics at treatment initiation
and why so few patients are considered eligible to be treated with
concurrent chemoradiotherapy.
Poster Presentation 11:
Seven year follow up of patients treated with hypofractionated IMRT for
localised carcinoma of the prostate: late toxicity and outcome
Sophie Merrick (University of Manchester), Ananya Choudhury,
David Thomson, Ric Swindell, Joanna Coote, James Wylie, Richard
Cowan, Tony Elliott, John Logue and Jacqueline Livsey (Christie NHS
Foundation Trust)
Background: Hypofractionation results in reduced treatment times,
and should be biologically advantageous given the low alpha-beta
ratio for prostate cancer. However this may lead to increased toxicity.
IMRT allows dose escalation with hypofractionation, while achieving
acceptable levels of toxicity. We report 7 year late toxicity data in
patients treated with two such regimens within the HIPRO study.
Methods : Sixty men, median age 75 years (50-87), with localised
adenocarcinoma of prostate (T1-3NOMO) and either Gleason score
≥7 or PSA 20-50ng/l received 57Gy in 19 fractions (n=30) or 60Gy in 20
fractions (n=30) using 5-field inverse-planned IMRT. All patients received
neoadjuvant hormone therapy, continuing for up to 6 months. Late
toxicity was assessed at 7 years follow-up using RTOG criteria and a
validated LENT/SOMA patient questionnaire. Overall survival, causespecific survival and biochemical progression-free survival (bPFS) were
assessed at 5 years.
Results: Forty-four (73%) patients were alive at 7 years. Nine patients
(21%) reported RTOG grade 1 bowel or bladder toxicity; there was no
grade 2 toxicity or above and no difference between the fractionation
schedules. LENT/SOMA questionnaires were returned by 31/44 patients.
Mean and median scores were less than one for bowel and urinary
symptoms. When compared with pre-treatment, the proportion of
patients with significant (maximum LENT/SOMA ≥2) urinary symptoms
remained similar (75% vs. 76%), problems with sexual function had
decreased (84% vs. 98%) but bowel symptoms increased (62% vs.
25%). At 5 years, overall survival was 83% and 74%, cause-specific
survival 83% and 84% and bPFS 50% and 58% in the 57Gy and 60Gy
groups respectively. There was no significant difference in survival
between the two fractionation schedules.
Conclusions: Dose-escalated hypofractionated IMRT for prostate
cancer appears well tolerated with acceptable levels of late toxicity.
Studies to assess long term disease control with these regimens
are on-going.
Poster Presentation 12:
Case report: Pseudomyxoma Peritonei imitates ovarian carcinoma;
the importance of early recognition for a favourable outcome
Rupal Patel (University of Manchester)
Introduction: Pseudomyxoma peritonei (PMP) is an extremely rare
condition, characterised by the progressive accumulation of mucinous
fluid in the peritoneal cavity and predominantly arises from the rupture of
an appendiceal mucocele.
Its rarity and similarity in presentation with other conditions, in
particular ovarian carcinoma, presents a diagnostic challenge.
Case presentation: A 46-year-old woman presented with a 12-month
history of abdominal bloating, discomfort and iliac fossa pain. An
ultrasound scan showed a part solid, part cystic mass on the left ovary,
ascites and possible peritoneal deposits.
Suspicion of ovarian carcinoma led to further gynaecological
investigations. Tumour markers were found to be elevated, ultrasound
guided biopsy found samples to have a gelatinous consistency, and
a CT scan revealed mild to moderate ascites with diffuse ill-defined
nodularity throughout the peritoneum; all findings consistent with PMP.
The patient was referred to the Peritoneal Tumour Service at The Christie
within 3 weeks of presentation. Cytoreductive surgery with hyperthermic
intraperitoneal chemotherapy (HIPEC); 90 minutes of intraperitoneal
mitomycin C, heated to 41.5αC, was performed, with promising results.
Discussion: This case illustrates a very common presenting picture of
PMP. It is important to recognise this syndrome early to improve patient
prognosis, however the presenting symptom is often caused as a
result of disease progression; the most common presenting symptoms
include suspected acute appendicitis, ovarian mass, abdominal pain
and increasing abdominal girth (30-50% of patients).1
This patient’s symptoms led to further gynaecological investigations
on suspicion of ovarian carcinoma, however consequently led to the
diagnosis of PMP.
Initial recognition that the disease features and distribution were
not characteristic of ovarian carcinoma led to a quick referral to the
national treatment centre within 3 weeks of presentation, and most
probably a more favourable patient outcome.
Poster Presentation 13:
Using DNA copy number as novel biomarkers of malignant melanoma
Mohamed Zahir Mughal, Gerald Saldanha, David Moore, James
Howard Pringle (Department of Cancer Studies and Molecular
Medicine, University of Leicester)
Introduction: Melanoma has a remarkable propensity to metastasize
at an early stage. DNA copy number changes are a hallmark of virtually all
melanomas, and thus could be developed into biomarkers. Novel Real
Time PCR assays developed by our group are able to detect DNA copy
number in fixed tissue. The aim of this study was to establish proof of
concept that our assays can detect DNA copy number changes in fixed
primary and metastatic melanoma tissue. The assays were
evaluated for biomarkers of progression.
Method: Seven novel Real Time PCR assays, known as duplex ratio tests
(DRT), were designed to detect DNA copy number at chromosomal
regions frequently gained or lost in melanoma. DRTs were tested on
ten fixed benign tonsils to assess measurement reliability. DRTs were
validated on 35 fixed benign skins and lymph nodes from 20 patients
to generate a diploid reference range using 95% Z scores. DRTs were
tested on 20 fixed primary cutaneous melanomas and 20 fixed
matched lymph node metastases from the same patients. DRT results
outside the diploid range indicated DNA copy number change.
Results: Three DRTs targeting the following pairs of genes
RREB1(6p)|MYB(6q), TBX2(9p)|HIC1(9q) and BRAF(7q)|PTEN(10q),
detected DNA copy number changes in primary melanoma at
frequency of 13/20, 12/20 and 7/20, respectively; and in metastatic
melanoma at frequency of 10/20, 8/20 and 13/20, respectively. These
three DRTs together identified 19/20 primary melanomas and 18/20
metastatic melanomas, whilst the other DRTs were not additive.
CONCLUSIONS: This study provides proof of concept that DRTs can
determine DNA copy number changes in fixed primary and metastatic
melanoma. These assays are tissue biomarkers of melanoma
progression. Development of a blood assay may be useful for
detecting the recurrence or progression of disease in an outpatient
setting. DRTs may also be diagnostic and prognostic biomarkers.
Poster Presentation 14:
Niclosamide, an anti-helminthic, as a novel anti-myeloma therapy that
also reduces FLC production.
Blair Merrick, Farhat Khanim, Hannah Giles, Monica Jankute,
Mark Drayson, Chris Bunce (Department of Biosciences, University of
Birmingham)
Background: Multiple myeloma (MM) remains an incurable
haematological malignancy with poor median survival of 4-6 years. Up to
50% patients will develop renal impairment, the predominant cause of
this being free light chain (FLC) mediated nephrotoxicity. Current
treatments such as bortezomib and lenalidomide, whilst improving patient
outcome, are limited in their use due to; high cost, the need for
prolonged maintenance therapy, and combined toxicities.
Objective : There is a need for effective anti-myeloma therapies that
kill the malignant plasma clone, reduce FLC production, are costeffective, and offer tolerable toxicity to the predominantly elderly
population afflicted by this disease.
Method: Niclosamide, an anti-helminthic, emerged from a screen
of 100 off-patent drugs (encompassing a broad range of classes),
as a future anti-MM therapy. The effect of niclosamide on cell viability
was assessed with multiple assays. And its mode of action at the level
of the mitochondrion and cellular pathways by FACS, Western blot,
and immunohistochemistry. FLC production was assessed using
intracellular FACS and secretion by Luminex immunoassay. Looking
at the effect of niclosamide on CD34+ progenitor cell viability served
as a marker for toxicity.
Results: Niclosamide induces uncoupling of oxidative phosphorylation
leading to the generation of mitochondrial superoxide. This correlated
with a loss in malignant cell viability. Niclosamide also inhibited NF-αB
and STAT3 signaling in addition to its mitochondrial mode of action.
The importance of these pathways in the survival of the malignant cell
has been well demonstrated. This anti-tumour action was seen at levels
of minimal toxicity. In addition sub-lethal doses were able to reduce
FLC production and secretion from both MM cell lines and some
primary MM clones.
Conclusion : Niclosamide has emerged as a drug for future
redeployment in MM, earmarking it for further experimentation as
either a single agent, or probably more successfully as part of a
combination therapy.
Poster Presentation 15:
Evaluation of in home palliative care strategies for patients with
terminal illnesses
Victoria Connor (University of Liverpool)
Background: A recent survey estimated that in the UK over half of
patients with terminal illnesses die in hospital beds and approximately
11% of patients will die in a hospice. Contrary to this, extensive
evidence has concluded that over 50% of patients when faced with
a terminal disease would prefer to be cared for and die at home.
Unfortunately, patients’ choices depend greatly on the quality of care
available at home and the costs involved in this type of service.
Objectives: The clinical effectiveness of home palliative care will be
assessed and the costs of these services will be compared to the
alternatives available.
Method: A computer aided search was conducted using four
major electronic databases namely, Scopus, Medline, PubMed and
Cochrane, hand searching of high impact journals was undertaken and
reference lists of studies were examined. Relevant studies were critically
appraised using the CASP tool to ensure that only the most robust studies
were discussed in this structured review.
Results: Overall results from the studies reviewed showed that patients
who were cared for at home showed better outcomes specifically when
evaluating patient satisfaction, quality of life and re-admission rates. In
addition none of the studies showed that at home strategies lead to any
negative outcomes for patients or their carers. Finally, in home palliative
care services tended to cost less than in hospital stays which would
allow savings to the health care system.
Conclusion: At home palliative care services appear to lead to better
patient outcomes and could reduce health care costs. However, to
ensure that the best patient outcomes are achieved, staff providing
at home care must be trained in specific palliative care methods and
need to work in multidisciplinary teams.
Poster Presentation 16:
Assessing body composition using computed tomography imaging:
findings in UK patients with thoracic cancer
Pettit C (University of Nottingham), Maddocks M (University of
Nottingham and Nottingham University Hospitals) , Pointon K
(Nottingham University Hospitals), Wilcock A (University of Nottingham
and Nottingham University Hospitals)
Introduction: Cancer cachexia adversely affects survival, treatment
response and quality of life. Effective treatments are lacking and
progress is hindered in part by the lack of reliable assessments of body
composition. The use of computed tomography (CT) images for body
composition analysis is one potential way forward. This study examined
the inter- and intra-observer reliability of this technique and findings in a
UK cohort of patients with thoracic cancer.
Methods : CT scans were analysed using Slice-O-Matic software to
calculate cross-sectional area of skeletal muscle and adipose tissues
at the level of the third lumbar vertebrae, from which whole-body fat
and fat-free mass were estimated. Intra- and inter-observer reliability
were assessed in the first ten of 100 patients examined. Intra- and
inter-class correlation coefficients and descriptive statistics were used to
assess reliability and the cohort findings respectively.
Results: CT image analysis was found to be highly reliable both within
and between observers for the assessment of all tissue types with intraand inter-class correlation coefficients of 1.00 (lower 95% confidence
intervals 0.98−1.00). Of 100 patients (52 female, mean (SD) age 70(9)
years, BMI 25.0(4.6) kg/m2) one fifth were sarcopenic. Of this group,
only one-third were classified as malnourished using clinical criteria.
Conclusion: CT image analysis is a highly reliable method of assessing
body composition in patients with thoracic cancer. It can be used to
accurately identify patients with severe muscle wasting, who may be
overlooked by current clinical criteria, and may play an important role in
the future management of cancer cachexia.
Poster Presentation 17:
Investigations on the Molecular Mechanisms Underpinning the
Development of Myeloproliferative Neoplasms
Sarah-Lindsay Jones (University of Manchester), Dr Andrew Pierce and
Professor Anthony Whetton (School of Cancer and Enabling Sciences,
University of Manchester)
Background: Polycythaemia Vera (PV), Essential Thrombocythaemia
(ET) and Primary Myelofibrosis (PMF) are clinically distinct yet genetically
similar myeloproliferative neoplasms (MPNs). JAK2V617F, JAK2K539L
and MPLW515L are gain of function mutations affecting the
haematopoietic stem cell implicated in the development of PV, ET and
PMF. Previous research within this field has suggested that these
oncogenic mutations result in constitutive activation of the JAK-STAT
cellular signalling pathway. It is through the activation of this pathway
that increased gene transcription occurs, resulting in proliferation of an
affected myeloid lineage and the development of myeloproliferative
neoplasms. This report hypothesises that increased expression of
proteins involved with the JAK-STAT pathway will be seen among cells
harbouring oncogenic mutations associated with MPNs.
Methods and Results: Protein expression profiles for STAT3, STAT5,
Src, C-myc and FOXO3a were assessed by western blot analysis
to compare expression between control and oncogenic cell lines.
Oncogenic cell lines demonstrated the ability to maintain cellular
growth independent of cytokine signalling. STAT5 expression was even
between all cell lines in both the whole cell lysate and cytoplasmic
fraction, but increased among the oncogenic cell lines in the nuclear
fraction. Src expression was seen exclusively in Janus Kinase 2 (JAK2)
containing cell lines.
Conclusion : JAK2V617F, JAK2K539L and MPLW515L mutations are
implicated in the development of PV, ET and PMF. These mutations
lead to activation of the JAK-STAT pathway resulting in up-regulation
of downstream signalling proteins, such as STAT5. An expansion of this
project could include running a series of western blot analyses using
phospho-STAT3 and phospho-STAT5 to further understanding of JAK-STAT
pathway involvement. Future research within this field is currently aimed
at developing molecular targeted therapies, such as JAK2 inhibitors,
which at present are in preclinical trials. This is an exciting prospect that
could potentially alter the clinical picture of PV, ET and PMF.
Poster Presentation 18:
Inhibition of Rho-associated kinase reduces mammary fibroblast
activation and mammosphere formation.
Benjamin Hunter, Christina Lo, Susann Busch, Nigel Bundred, Göran
Landberg (Breakthrough Breast Cancer Research Unit, University of
Manchester, Paterson Institute for Cancer Research, Manchester)
Background: Stromal-epithelial signalling plays an important role
in cancer development. Cancer-associated fibroblasts (CAFs),
characterised by alpha-smooth muscle actin (α-SMA) expression, are
associated with a poorer prognosis and earlier metastasis in breast
cancer. CAF activation is induced by tumour-secreted transforming
growth factor beta (TGF-α1) via the Rho-pathway. Rho-associated kinase
(ROCK) is increased by TGF-α1. Inhibition of ROCK has been shown to
prevent fibroblast activation in scleroderma and to prevent metastasis in
breast cancer models. However, the effects of ROCK inhibition on CAFs
and cancer initiating cells are unknown. We sought to determine whether
ROCK-inhibition can prevent or reverse fibroblast activation
and reduce mammosphere formation and renewal.
Method: Human immortalised mammary fibroblasts were treated
with the ROCK-inhibitors Fasudil or Y27632 prior to or concurrently
with TGF-α1 treatment. Western blotting was used to analyse α-SMA
expression and cell growth was assessed using Sulforhodamine B
assays. Cancer initiating properties were delineated using non-adherent
mammosphere cultures.
Results: TGF-α1 treatment caused increases in fibroblast α-SMA
expression. Interestingly, ROCK-inhibition (during and after TGF-α1
treatment) caused phenotypical changes to the fibroblasts which were
accompanied by reductions in α-SMA expression. We also observed
dose-dependent reductions in fibroblast and MCF7 cell growth as well
as a significant reduction in MCF7 mammosphere-forming efficiency.
Conclusion : ROCK inhibition affects the activation of human
mammary fibroblasts and reduces the proportion of epithelial cells with
cancer initiating properties. Therefore, ROCK inhibitors would provide an
attractive therapeutic option for targeting both tumour cells and the
associated stroma simultaneously.
Poster Presentation 19:
Audit of Cervical Cancer Reporting in the University Hospitals Bristol NHS
Foundation Trust in two cohorts of women: those above and below 35
Catherine Rowan BSc (University of Bristol), Jennifer Rootes BA (University
of Bristol), Dr Joya Pawade (Universities Hospitals Bristol)
are managed appropriately. A recent National Chemotherapy Advisory
Group (NCAG) report1 suggests a target of 1 hour from presentation to
administration of antibiotics.
Objectives: Recognise shortcomings in assessment and treatment of
oncology patients with neutropenic sepsis, with a future aim to improve
service provision. To record whether assessment and subsequent
antibiotic treatment occurs within 1h, how quickly investigations such as
blood cultures are implemented, and investigate whether admission
department has an effect on the timeliness of the patient’s treatments and
their outcome.
Method: A retrospective study collecting data about all oncology
patients presenting to the Royal Derby Hospital with neutropenic sepsis
over two 2 week periods: 2/10/10-15/10/10 and 1/11/10-14/11/10, giving
a sample size of 22 patients.
Results: The average time from initial assessment to antibiotics was
2.68h with the average time to blood cultures being 2.82h. 7 patients
(32%) had blood cultures taken after receiving antibiotics. When only
considering patients fulfilling exact hospital criteria2 of neutropenic
sepsis on presentation, they waited on average 1.42h for antibiotics
and 0.82h for blood cultures. When considering all patients diagnosed
with neutropenic sepsis, CDU treated more swiftly, however when only
considering patients fulfilling exact hospital criteria ward 303 were
slightly more prompt. In both data sets, ward 303 had a significantly
longer length of admission and the only patient who died was admitted
through ward 303. 15 patients (68%) received antibiotics within 2h of
assessment.
Introduction: Audit has been crucial to the development of the
Cervical Screening Programme which has reduced the number of
deaths from cervical cancer since its introduction in 1988. As one
of the most expensive screening programmes in the UK, subject
to controversy over the age at which to start screening; it must be
continually assessed for its effectiveness. This is the first audit examining
the quality of cervical cancer reporting in the Bristol University Hospitals.
Accurate reporting is essential to patient care with factors such as
stage directly affecting prognosis. Additional data on cervical cancer,
particularly in women below 35 is essential to monitor the evolving
nature of this disease.
Conclusions: Only 3 patients presenting with neutropenic sepsis were
treated within 1h, but all patients presenting with raised temperature and
low neutrophil count were treated within 2h. Ward 303 took longer to
treat with a corresponding poorer outcome, suggesting CDU has a better
system in place.
Methods: Retrospective audit of 111 case notes of women diagnosed
and treated for cervical cancer in UH Bristol between 2005 and 2007,
divided into two cohorts- those above and below 35. Medical notes
were examined for recording of histological diagnosis; staging; health
outcomes; screening history and discussion at an MDT meeting.
Standards were derived from the Royal College of Pathologists guidelines
and the target was 100% throughout.
Lok Chi Angie Chan (University of Manchester), Dr Anand Methuku,
Judith Eelloo, Dr Jacqueline Berry, Dr Chris Chaloner, Dr Susan M
Huson, Dr Zulf Mughal.
Results: 4 out of 6 standards were met. The standards failed included
recording of histological diagnosis (86%) and health outcomes (92%).
The sample included three women below 25 and hence outside the
screening programme. The majority of histological diagnosis were
squamous cell carcinoma (U35 70%, >35 74%) but with an increased
proportion of U35 presenting with adenocarcinoma (U35 30% and >35
20%). Women under 35 who’d had a greater number of smears tended to
present with a lower stage of cancer.
Conclusion: The majority of standards were met with areas of
improvement identified. Epidemiological data was consistent with the
bimodal distribution of cervical cancer, an increasing incidence of
adenocarcinoma in younger women and the additional benefit of the
programme in down-staging cervical cancer.
Poster Presentation 20:
An audit of assessment and treatment times for oncology patients
presenting with neutropenic sepsis
Eleanor Keene (University of Nottingham), Rhiann Anderson (University
of Nottingham), Alison Launchbury (Derby Hospitals NHS), Dr Mojca
Persic (Derby Hospitals NHS)
Background: Neutropenic sepsis is a common and potentially fatal
complication of chemotherapy, thus it is vital that susceptible patients
Poster Presentation 21:
A study into vitamin D status of adults with Neurofibromatosis type I (NF1)
and its association with the number of neurofibromas
Aims: To determine if adults with NF-1 had lower serum 25(OH)D
concentrations in comparison to age-matched controls unaffected by
NF-1. The second aim was to determine if there was a relationship
between the number of dermal neurofibromas on NF-1 patients their
serum 25(OH)D concentrations.
Method: A total of 28 white Caucasian adults aged between 30 and
60 (14 NF1 subjects and 14 age-matched controls) took part in this
study. Questionnaires were used to access the dietary vitamin D and
calcium intake, as well as sun exposure time and body surface area.
Total number of neurofibromas was counted on each NF1 subjects.
Serum concentrations of 25(OH)D, 1,25(OH)2D, Calcium, Phosphate,
alkaline phosphatase and parathyroid hormone were measured.
Results: The median serum 25(OH)D concentration in NF1 subjects
was significantly lower (p=0.026) in comparison to controls. There with
no significant difference in dietary vitamin D and calcium intake, sun
exposure time and body surface area exposed in comparison
to control subjects. The number of neurofibromas in NF subjects
were not associated with the serum 25(OH)D concentrations (r=0.28
p=0.35), The daily sun exposure time (r=0.52 p=0.06) was almost
significantly correlated with the serum 25(OH)D levels in the controls
but the NF1 subjects.
Conclusion: Adults with NF1 have lower body stores of vitamin D and
might benefit from oral vitamin D supplements. The lack of association
between sunshine exposure and serum 25(OH)D levels in NF1 suggests
that cutaneous vitamin D synthesis in NF1 might be impaired, and a
further study is required to confirm this.
Poster Presentation 22:
Outcomes for Choroid Plexus Tumours diagnosed in the North West
region during 1954-2008
Danielle Ormandy (University of Manchester), Robert D. Alston, Jilian M
Birch (Cancer Research UK Paediatric and Familial Cancer Research
Group, University of Manchester), Edward J, Estlin (Dept of paediatric
Oncology, Royal Manchester Children’s Hospital)
upregulation of pro-apoptotic proteins), intracellular protein transport
and the DNA damage response2. Defects in its function result in
increased susceptibility to malignancies, radiosensitivity and premature
death of neurones, especially cerebellar Purkinje cells.
References
• Su Y, Swift M. Mortality rates among carriers of ataxia telangiectasia
mutant alleles. Ann Intern Med. 2000;133:770-8.
•
Purpose: Choroid plexus tumours (CPTs); namely choroid plexus
papilloma (CPP) and choroid plexus carcinoma (CPC) are rare
neoplasms of the central nervous system (CNS), accounting for 0.40.6% of all brain tumours and 1-4% of childhood brain tumours. This
study was undertaken to provide further insight into the epidemiology,
natural history and outcomes in relation to changes in treatment
emphasis for these rare tumours, over the last 56 years in the NW
of England and determine the relative importance of possible
contributory factors.
Methods: Data relating to presentation, management and survival
for 57 patients diagnosed with CPT between 1954-2008 was extracted
from the North West Children’s Tumour Registry and hospital records.
Results: Data collated showed a male predilection for choroid plexus
carcinomas (22 male, 6 female) and an equal distribution of CPP
and CPC (29 and 28 respectively). 5 year Kaplan-Meier estimates
demonstrate significant improvements in survival for papillomas
over the last 56 years. Carcinomas show no significant improvement
in survival over the last 56 years with 5 year survival fluctuating
by 10% over the last 40 years. However, overall survival (OS) is
improved by adjuvant treatment with both chemotherapy and
radiotherapy (P<0.05).
Conclusion: Our study shows that CPC is more commonly diagnosed
in males and that CPP and CPC arise in equal proportions: This is
in contention with the previous descriptions of these tumours in the
literature. OS for CPC has improved with the use of radiotherapy and
chemotherapy. To the author ’s knowledge, this report characterises and
provides survival data for choroid plexus tumours over a longer period
of time than any other large single-institution series currently available.
Poster Presentation 23:
Ataxia Telangiectasia: A rare cause of childhood malignancy
Maria Shumbusho (University of Warwick), Graeme Mattison (University of
Warwick)
MA is an 8 year old boy with ataxia telangiectasia (A-T),
immunodeficiency and non-Hodgkin’s lymphoma. MA’s first symptom
was ataxia, which began before the age of 1. This manifested as
difficulty sitting unaided, loss of balance on standing, and walking with
a fast, unsteady gait. His parents didn’t think anything of it for a few
years, until he went on to develop frequent unrelenting fevers, recurrent
chest infections, reduced appetite and failure to thrive. He was thought
to have tuberculosis, and received a full course of anti-TB medication,
which had little effect. He continued to deteriorate, and a lung biopsy
confirmed that he had Non-Hodgkin’s lymphoma. It was only after this
diagnosis and chromosomal analysis that he was diagnosed with A-T at
8 years old.
Currently MA is on low doses of Vincristine and Doxorubicin,
Prednisolone, IVIG infusions and several analgesics and anti-emetics. He
has deteriorated post-chemotherapy, and now requires assistance with
most of his activities of daily living.
A-T is a rare, degenerative, autosomal recessive childhood
disorder with an estimated incidence of 1 in 100,000 births and an
equal sex incidence1. Characteristic features of A-T are progressive
ataxia, oculocutaneous telangiectasia, repeated bronchopulmonary
infections and malignancy. The incidence of malignancy is 60300 times higher than in the general population1. Patients with A-T
demonstrate two patterns of malignancy : haematological (leukaemia
and non-Hodgkin’s lymphoma) and solid tumour development (in the
oral cavity, breast, stomach, pancreas, ovary and bladder).
A-T results from defects in the ataxia telangiectasia mutated (ATM)
gene, identified on chromosome 11q22-23. The ATM gene encodes
protein kinase ATM, a key regulator of cell cycle control (through
Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm
for cell signalling and cancer.
Nat Rev Mol Cell Biol. 2008;9:759-69.
Poster Presentation 24:
The effect of a ‘false positive’ recall on intention to re-attend for
screening mammography.
Dr Emma De Sousa (Nightingale Centre & Genesis Prevention Centre,
University Hospital of South Manchester, Wythenshawe, Manchester),
Lester Barr (Hospital of South Manchester, Wythenshawe, Manchester).
Background: The balance of risks and benefits of screening
mammography continues to be a subject of debate. Critics argue
that the screening programme causes unnecessary intervention and
anxiety in women who are subsequently found not to have cancer.
Some previous studies have shown a drop in re-attendance rates
following such a ‘false positive’ recall. Our study was designed to
discover the factors that might cause women not to re-attend for
subsequent rounds of screening following a ‘false positive’ recall.
Method: All patients attending Recall Assessment Clinics at our
centre during the calendar month March 2010 were identified. Those
diagnosed with breast cancer or DCIS were excluded, leaving 106
patients who were subsequently discharged to routine screening after
benign results. Postal questionnaires were sent to all these women in
January 2011.
Results: 73 questionnaires were completed (69%). Of these women
96% reported that their opinion of breast screening was ‘very good’ or
‘good’ BEFORE the experience of a false positive recall. This rose to 98%
AFTER that experience. 100% said they would come again for another
mammogram (93% ‘definitely ’ and 7% ‘probably ’). Feedback from
free-text parts of the questionnaire indicated that the most frequent
reasons for satisfaction were the speed of the service (18 replies), the
general experience (15 replies), reassurance (13 replies), and good
explanations received (10 replies). Feedback on negative aspects
included insufficient information in recall letter (4 replies), waiting time
too long (3 replies) and pain of mammography (2 replies).
Conclusion: Contrary to our expectations, the experience of a ‘false
positive’ recall following a routine mammogram increased rather than
decreased the perception of the value of breast screening. The
intention of women to re-attend for subsequent rounds was
100%. Despite the limitations of a questionnaire based study our results
suggest that an efficient and caring clinical service with good
explanation and reassurance, results in high patient satisfaction rates
and does not reduce intention to re-attend.
Poster Presentation 25:
Metaplastic breast carcinoma: A case report and systematic review of the
literature
Zaher Toumi, Caroline Bullen (Department of General Surgery,
Tameside General Hospital), Albert C. S. Tang (TheUniversity of
Manchester), Neha Dalal (Department of Pathology, Tameside General
Hospital) and Simon Ellenbogen (Department of General Surgery,
Tameside General Hospital).
Abstract: A 78-year-old retired woman was diagnosed with metaplastic
breast carcinoma (MBC), a rare tumor, in our hospital. We reviewed 15
articles with a total of 1328 patients to determine the epidemiology,
clinical features, biomarkers, histology, management and outcome
of patients with this tumor. The mean age at presentation is 58.5 years
(range 32:83). Eighty-one percent of patients presented either with
a breast mass or abnormal mammographic finding. Twenty three
percent of patients had a family history of breast cancer. Estrogen
receptors were only found in 12%, progesterone receptors in 10%
and HER2 in 6% of patients. The main method of treatment was
mastectomy (66.9%) in combination with chemotherapy (57%) and
radiotherapy (47%). Five-year disease-free survival ranged between
40% and 84% and 5-year overall survival ranged between 64 and
83%. We have further reviewed the nature of this disease in the light of
advancement in genetics, such as microarray gene expression profiling.
The relationship of MBC with triplenegative tumor and basallike tumor is discussed. It is hoped that advances in genetics and
biomarkers will bring forward the era of personalized medicine in the
treatment of breast carcinoma.
Poster Presentation 26:
Maintenance of high-affinity memory B cells induced by conjugate
cancer vaccines requires T-cell help
Natalia Savelyeva (Genetic Vaccine Group, Cancer Sciences
Division, School of Medicine, University of Southampton), Michael
Shipton (Genetic Vaccine Group, Cancer Sciences Division, School of
Medicine, University of Southampton and University of Manchester),
Amy Suchacki, Gavin Babbage and Freda K. Stevenson (Genetic
Vaccine Group, Cancer Sciences Division, School of Medicine,
University of Southampton)
Most tumour antigens are weakly immunogenic due to the tendency to
induce tolerance rather than immunity. A lack of CD4+ T-cell
help is generally responsible for the inability to elicit protective
antibody responses, which is a common scenario in haematological
malignancies. Conjugate vaccines composed of tumour antigen
bound to an immunoenhancing protein designed to induce T-cell
help, such as Fragment C of tetanus toxin, have been successful in
providing immunity. However, we previously demonstrated that release of
tumour-derived antigen lacking this exogenous T-cell help (“helpless”
antigen) during relapse can suppress the majority of vaccine-induced
immunoglobulin G-positive (IgG+) memory B cells. We have now found
that, in contrast, most vaccine-induced IgM+ memory B cells survive
exposure to “helpless” lymphoma-derived antigen.
To better understand these differing effects on IgG and IgM
memory we used the model hapten NP (4-hydroxy-3-nitrophenyl)
acetyl, conjugated to keyhole limpet haemocyanin (KLH), an
immunoenhancing protein, which provides T-cell help. Adoptive transfer
experiments indicated that “helpless” antigen permanently silenced
high-affinity IgG+ memory B cells, whereas low-affinity IgG+ and IgM+
memory B cells survived. Furthermore, whilst IgM+ memory B cells
had similar Ig gene usage, they possessed fewer somatic mutations,
accounting for the decreased affinity for antigen compared to IgG+
memory B cells. Although IgM+ memory B cells had entered the
germinal centre, they failed to class switch. Overall, these
data indicate that memory B-cell survival on exposure to “helpless”
antigen is dependent on the affinity, rather than isotype, of the
antibody produced.
This effect could be responsible for the inability to maintain protective
responses against many tumour antigens. Conjugate vaccines may be
efficacious only in patients in remission as release of “helpless” antigen
during relapse could suppress high-affinity memory B cells. However,
maintenance of T-cell help via regular injections of conjugated antigen
may be sufficient to overcome this issue.
Poster Presentation 27:
An Audit of the Incidence, Treatment and Survival Outcomes of those
diagnosed with Peripheral T-cell Lymphoma at The Christie NHS Trust
from January 1st 2005 to December 31st 2010.
Katy Will (University of Manchester), Prof John Radford (The Christie
NHS Trust)
lymphoma (T-cell lineage). An audit was carried out to look at the
incidence, treatment and survival outcomes of those who were
diagnosed with peripheral T-cell lymphoma at The Christie NHS Trust
between January 1st 2006 and December 31st 2010. It included all
those patients who had received their first line treatment for the disease
at The Christie NHS Trust. 50 patients were included in the study.
The results showed that at The Christie NHS Trust patients with peripheral
T-cell lymphoma tend to be male, over the age of 50 years and usually
present late. First line treatment was found to be CHOP chemotherapy
in 88% of patients and 6 of these patients were part of a national
clinical trial. Although 80% of patients were found to respond to first
line treatment, the relapse rate was high with over 40% of patients
who had responded to treatment relapsing within 2 years. The study
found that the overall survival rate at 2 years was 53.7%. IPI score was
found to be useful prognostic factor for peripheral T-cell lymphoma.
Patients with an IPI score of 0 or 1 were found to have a better survival
outcome than patients with an IPI score of 2 or above. The findings in
this study at The Christie NHS Trust are similar to the results published by
the International T-cell Lymphoma Project in 2008. The study concludes
that with the poor survival outcomes of patients with current therapies,
new treatments need to be developed. This highlights the importance
of clinical trials for patients with peripheral T-cell lymphoma.
Poster Presentation 28:
How effective is the gynaecology Rapid Access Clinic?
S Littlechild, M Dinsdale (University of Manchester) R Khan, R Bhalla, M
Ravagan (University Hospital of South Manchester, Wythenshawe).
Introduction: Patients are referred to the Rapid Access Clinic if there is a
high clinical suspicion of carcinoma. NICE guidelines state patients
referred to the Rapid Access Clinic must be seen within two weeks
and have their first treatment within 62 days. These guidelines also
outline those presenting complaints deemed appropriate for referral to
this clinic.
Objectives: This study was conducted to access the efficiency
of the Rapid Access Clinic in the gynaecology department at the
University Hospital of South Manchester. Efficiency was measured
in three ways: firstly is the clinic meeting the National Targets?
Secondly, are the referrals appropriate? Thirdly, are there any areas
requiring improvement?
Methods: A prospective audit was carried out from 1st June to
31th August 2010.
Results: 85 patients were included; 76% were seen in the clinic
within two weeks and 79% were treated within 62 days. The study
demonstrated that 89% of referrals were appropriate, with the most
common presenting complaint being post-menopausal bleeding
(65%) and 9% of these patients receiving a diagnosis of endometrial
carcinoma. Additionally, this study revealed that only 25% of patients
were having an ultrasound scan organised by their GP before attending
clinic, therefore delaying their treatment time. It has also highlighted
how few endometrial samplings are being carried out in clinic (32%)
and how unsuccessful these are (63% failure rate). Consequently, a
high number of hysteroscopies (51%) had to be carried out.
Conclusion: As a result of this study a one-stop clinic is proposed
with nurse-led triage, ultrasound, pipelle and hysteroscopy facilities
all available. This aims to reduce both patient waiting times, thus
improving National Target figures, and also patient anxiety levels as
they would receive a provisional result the same day.
Poster Presentation 29:
An audit on treatment and survival rates for medulloblastoma patients
C. Higgins, Dr F Alam, Dr N Thorpe
Peripheral T-cell lymphoma (PTCL) is a rare aggressive type of nonHodgkin’s lymphoma. There are several subtypes of which the most
common are peripheral T-cell lymphoma-not otherwise specified,
angioimmunoblastic T-cell lymphoma and anaplastic large cell
Context/background: Medulloblastoma is the most common brain
tumour in children and accounts for approximately 40 percent of all
tumours in the posterior fossa of the brain and is the second most
common form of cancer of childhood after leukaemia.
The clinical presentation of medulloblastoma is as follows; an
increase in head circumference (in children whose fontanelles are still
open), morning headaches with associated vomiting and lethargy as
well as unsteadiness.
The treatment options available for medulloblastoma are surgical
resection, chemotherapy and radiotherapy.
discovery and other microarray experiments. More specifically, FFPE
may be useful for producing better prognostic models of diffuse large
B-cell lymphoma. However, microarray analysis is not suitable for routine
clinical assessments; the next stage of this work should involve the
development of inexpensive tests to guide clinical decision-making.
Objectives: To look at the survival rates of medulloblastoma patients
post treatment and also look at the percentage of patients that
relapsed post treatment.
Poster Presentation 31:
The Role of Axillary Clearance in Positive Sentinel Lymph Nodes with
Micrometasases: a Case Report and Literature Review
Method: A literature review and retrospective audit was carried out in
which a sample of twenty-one patients files, all who had suffered from a
medulloblastoma tumour were reviewed and from which data was
extracted and analysed. Journal searches were carried out using the
“Medline” database and the most recent articles were reviewed. To
review the patient files, a table was constructed for data extraction and
the relevant information filled in for each patient.
Tsai Melody (University of Manchester), Ooi Jane (Department of Breast
Surgery, Royal Bolton Hospital, Manchester)
Results: Out of the files used for data extraction, six of the patients had
passed away, two of the patients were terminally ill and thirteen of the
patients were still alive. Survival rates of the patients were then looked at
into further depth and broken down into six divisions indicating the
survival rates after the start of treatment per year.
Conclusion: To conclude, the results from this study showed that from
the sample of patients the data was taken from, 57% of the patients
survived more than five years post treatment. The data also showed
that one third of the patients suffered relapse.
Poster Presentation 30:
Gene Expression Analysis of Formalin-Fixed Lymphoma Biopsies: Can
we unlock the Tissue Archives?
Christopher Howarth (The University of Manchester), Kim Linton
(Manchester Cancer Research Centre), Mark Wappett, Gillian Newton
(The Paterson Institute for Cancer Research) Cynthia Lachel, Javeed Iqbal
(The University of Nebraska) Stuart Pepper (The Paterson Institute for
Cancer Research), Richard Byers (Manchester Cancer Research Centre),
Wing (John) Chan (The University of Nebraska) and John
Radford (The University of Manchester).
Introduction: Microarray gene expression profiling is a technology
which has opened up many avenues of cancer research. Formalinfixed, paraffin embedded (FFPE) tissue is the standard method for
processing routine clinical biopsies. However, RNA from FFPE is badly
degraded and it is widely regarded as being unsuitable for gene
expression profiling using microarrays. The use of formalin-fixed archival
tissues would be an attractive prospect for cancer research, especially in
rarer diseases. However, data generated from FFPE samples must be
validated to determine whether it is biologically meaningful. This study
assessed whether it would be feasible to re-profile diffuse large B-cell
lymphoma using fixed archival samples.
Methods: 40 paired FFPE and unfixed lymphoma biopsies were
processed for gene expression microarrays. The FFPE samples were
clustered using both a published 90 gene list discriminatory for
ABC/GCB subtypes (Alizadeh et al) and a new list of the top 100
differentially-expressed genes identified within the new data set using
difference mapping and false-discovery analysis.
Results: Twenty paired biopsies showed good global correspondence of
transcripts called present (61%) and absent (83%). Unsupervised
hierarchical clustering of unselected present probe-sets allowed
classification of known ABC/GCB molecular subtypes with high
accuracy. A Baysean classifier correctly classified 32/36 cases with
90% probability.
Conclusion: These results support the robust nature of existing
molecular classifications using modern microarray platforms. Faithful
retention of gene expression patterns in fixed samples attest to the
biologically meaningful nature of gene expression data from fixedtissue archives. These findings have promising implications for the
use of fixed archival samples in classification of diseases, biomarker
Background: The optimum management of positive sentinel lymph
nodes (SLN) with micrometastases presents challenges to both
clinicians and patients. The current standard approach is to offer
further axillary clearance (AC).1 However, this technique has debatable
impact on survival as well as significant postoperative morbidities.2
In the era of improved histopathological and molecular analysis
techniques, there are emerging data, which suggest sentinel lymph
node biopsy (SLNB) to be the better, less invasion option.3 To further
explore this topic, we present a case of a 54-year-old woman with a
positive SLN with micrometastases. We also examined current evidence
on similar cases.
Case Presentation: A 54-year-old patient presented with a right upper
quadrant mass, which was subsequently diagnosed as grade 1 invasive
tubular carcinoma with neither lymphovascular space invasion nor
in situ component. The patient received right wide local excision
and SLNB. The final pathology revealed a 10 mm grade 1 tubular
carcinoma. A total of one of the five axillary lymph nodes examined was
found to have micrometastasis with a tumor size of 0.7mm. The patient
was otherwise healthy with no family history of breast cancer noted. This
patient’s case was discussed in a multidisciplinary team
meeting. However, whether further axillary clearance should be offered
remained a controversial debate.
Conclusion: This case illustrates a common scenario that often leads to
conflicting point of views during multidisciplinary team discussions. This is
reflected by the lack of firm results from studies that compared SLNB alone
and SLNB with further AC.4-7 With ambiguous benefits of offering further
AC, our guideline for the management of these patients should be
patient-tailored and reviewed. Clinicians are urged to contribute to this
debate and further provide level-1 evidence to yield a clearer role of AC in
positive SLN with micrometastasis.
Poster Presentation 32:
Re-audit of Neutropenic Sepsis at Weston General Hospital
Louisa Wilson (Bristol University)
Background: Neutropenic sepsis is a potentially life-threatening
medical emergency that commonly occurs as a side-effect of
chemotherapy. Unfortunately, however, there are often delays in starting
treatment which can lead to increased mortality. This problem has
previously been identified at Weston General Hospital, and changes
have since been made to try and reduce the time elapsed between
presentation and treatment, with the ultimate aim of reducing mortality.
Objectives: To re-evaluate the time taken for patients presenting with
neutropenic sepsis to be assessed by a doctor and given treatment in
light of the recent changes made at Weston General Hospital.
Methods: All patients with neutropenia who were admitted to
Weston General Hospital during a 6-month period were identified
retrospectively. Details including admission time, time of doctor review
and time of treatment were recorded for each episode of neutropenic
sepsis and compared to the results of the initial audit.
Results: The proportion of patients that were assessed by a doctor within
one hour of admission has increased from 28% to 66% since the initial
audit and the proportion of patients receiving treatment within this time
has increased from 14% to 31%. The proportion of patients admitted
that died on the same admission has fallen from 39% to
14% as a result.
Conclusion: The improvements made at Weston General Hospital
have led to an overall reduction in the time taken for patients with
neutropenic sepsis to receive treatment. However, some delays still
exist due to factors such as lack of awareness of trust policy and failure to
recognise the condition. It is therefore important to continue the staff
education programme and poster displays to keep staff aware of
neutropenic sepsis and its management. A Patient Group Directive and
patient education programme might further reduce the time taken before
treatment is given in future.
Poster Presentation 33:
Sarcoma Recurrence: West of Scotland registry.
Morhij R (University of Glasgow), Jane M (Glasgow Royal Infirmary), Prof
Hart A (Canniesburn Plastic Surgery Unit & college of Medical veterinary &
life sciences University of Glasgow)
Poster Presentation 34:
Analysis of Serum TGF-α1 in Healthy Volunteers and Prostate Cancer
patients.
Morhij R (University of Glasgow), Tot B (Analytic service Unit, Beatson
Institute), McKillop A, Tait G (Beatson West Of Scotland Cancer Centre),
Ullah R, MacCormick C, Walker J, Appleton K, D’Hondt E (Analytic
service Unit, Beatson Institute), Macpherson I (Beatson West Of Scotland
Cancer Centre).
Introduction: Aberrant growth factor signalling is a common driving
event in cancer. Transforming growth factor beta 1 (TGF-α1) has
previously been linked to the progression of prostate cancer. However,
both the normal range of circulating TGF-α1 in healthy individuals and
the range of circulating TGF-α1 in patients with prostate cancer are
not well documented. We therefore aimed to determine the normal
physiological range of serum Transforming growth factor beta 1 in
healthy individuals and in prostate cancer patients across different
stages of the disease.
Methods: Blood samples were collected from healthy volunteers
and from patients treated for prostate cancer at the Beatson West
of Scotland Cancer Centre. Demographic data collected included
tumour stage, Gleason score, prior treatment history, current PSA and
current disease status. Serum TGF-α1 was measured by ELISA and
these were carried out to standards commensurate to GCP for clinical
laboratories.
Results: To ensure our data is robust we have validated an ELISA- based
assay and demonstrated low intra- and inter- operator variability
(coefficient of variation < 10%). We are now analysing data from the first
50 healthy volunteers (median age 34, range 18- 60, male 26, female 24)
and 50 prostate cancer patients (median age 72,
range 51- 84 ) and these data will be presented.
Poster Presentation 35:
An Audit of the management of breakthrough cancer pain
Rachel Heard (The University of Manchester Medical School) Dr
Richard Berman, Dr Andrew Davies (The Christie NHS Foundation Trust).
Background: Breakthrough cancer pain has a prevalence of
approximately 66%. Although there has been research surrounding
the management, there are no set guidelines. The Association
for Palliative Medicine of Great Britain and Ireland (APM) science
committee devised 12 recommendations on optimal management of
breakthrough cancer pain but these are based on limited evidence.
Aim: To assess the management of breakthrough cancer pain in a
tertiary oncology centre.
Objectives: The objectives focussed on comparing current practice
at The Christie NHS Foundation Trust with standards developed with
reference to the APM guidelines.
Method: It was a retrospective case note audit.
Results: 52% were male, 48% were female with an age range from
21-96 years. The most common cancer diagnoses were head and neck
(50 patients), lung (44 patients) and breast (40 patients). 56% of patients
were experiencing pain; of these 43% had an assessment for
breakthrough cancer pain. 52% of patients who had an assessment
were experiencing breakthrough cancer pain. Compliance
percentages: consideration of treatment of the underlying cause
(85%), consideration of avoidance of trigger (95%), reviewing of the
background analgesia (95%), consideration of non-pharmacological
(51%), consideration of non-opioids (97%), consideration of
interventional technique (21%), reassessment of management (100%).
Conclusion: Breakthrough cancer pain is a significant issue for The
Christie NHS Foundation Trust with few patients being assessed for this.
Management for many patients is not ideal. However, Palliative Care
Support Team and Pain Team involvement improve patient outcomes
regarding pain. The results advocate the need to increase education
throughout the trust.
Poster Presentation 36:
Anal Cancer, Are We Treating It Fast Enough?
Tim Jackson, Suzanne Linsdall (Brighton and Sussex Medical School),
Dr Joanna Stokoe (Sussex Cancer Centre, Royal Sussex County Hospital,
Brighton)
Background: Anal cancer is an uncommon malignancy of the anal
canal and perianal skin area.
There are around 750 new cases in the UK each year. It is
mostly a loco-regional disease at diagnosis, with metastasis in
only 15% of patients.
Methods: The audit was carried out over a period of 10 months and
incorporated patients treated for anal cancer at the Sussex Cancer
Centre from January 2004 to December 2010. Data were collected
from patient notes, radiotherapy treatment records and patient
correspondence letters. Details including, date of histopathology
report, date of birth and sex, dose of radiotherapy intended and then
delivered, HIV status, disease relapse and management of relapse,
and cause of death were recorded and analysed using Microsoft Excel.
Results: 98 patients were identified in the audit. 89% of patients
received the total intended dose of radiotherapy prescribed. In total
83% were prescribed 50.4 Gray in 28 fractions; 78% of patients being
prescribed this dose between 2004-2008 and 90% of patients between
2008-2010. 9 patients in the audit did not complete the total intended
dose of radiotherapy. 50% of the patients started radiotherapy
treatment between 6-10 weeks of diagnosis. 70% of the patients are
alive and 26% died. Of those who died 60% were due to anal cancer,
12% due to an unrelated cause and for 28% the cause of death is
unknown (3% of patients were lost to follow up and 1% of patients the
current status is unknown).
Conclusions: 70% of patients were cured after radiotherapy. The
majority of patients completed the intended radiotherapy dose, with
increasing standardisation of radiotherapy dose prescribed (50.4
Gray in 28 fractions). However there was a prolonged time between
pathology report and start of radiotherapy with less than 10% of
patients receiving radiotherapy within the recommendation of 31 days.
Additionally, the presence of an elevated C-reactive protein
(CRP>5mg/L vs. CRP<5mg/L (odds ratio 3.0, 95%CI 1.0 to 8.9 p=0.04))
was predictive of lymph node spread.
Poster Presentation 37:
Case Report: Carcinoma ex-pleomorphic adenoma
Jessica Ball (Manchester Royal Infirmary), Robert TM Woodwards (North
Manchester General Hospital)
Introduction: Pleomorphic adenomas are the most common benign
tumour of the parotid gland. With time, an extremely small number
undergo malignant change into a carcinoma
ex-pleomorphic adenoma.
Method: We report an 80 year old Ukrainian lady who presented with
a painful, rapidly-growing mass anterior to the right tragus. CT scanning
confirmed a large 3.7 x 3.1cm mass involving the superficial lobe of
the parotid gland with level II lymphadenopathy and the patient had
a rapidly progressive facial nerve palsy that raised suspicions of a
malignant lesion. Despite the scheduling of early surgery, by the time
of operation the patient had a House-Brackmann grade VI palsy.
Results: A right total parotidectomy with a selective level I-IV neck
dissection was performed. The facial nerve was encased in tumour so
had to be sacrificed and post-operative radiotherapy was indicated.
Post-operatively the facial palsy which had not improved was treated
with an ipsilateral lateral tarsorrhaphy to prevent ocular complications.
Conclusion: A literature review of carcinoma ex-pleomorphic adenoma
is presented, with the features suggestive of malignancy and
difficulties regarding investigation and management of this rare
and aggressive condition.
Poster Presentation 38:
Title: Do systemic inflammatory markers correlate with poor prognosis in
early breast cancer?
Table 2 shows haematological variables and their relationship to
oestrogen receptor (ER) status.
ER
Negative
SD
ER
Positive
SD
p-value
Monocyte
Count(*109/L)
0.59
0.18
0.50
0.15
0.06(n/s)
Neutrophil
Count(*109/L)
5.26
1.71
3.91
1.26
0.001
Leucocyte
Count(*109/L)
8.31
1.87
6.73
1.74
0.004
No significant correlations were found between serological variables
and either tumour size or tumour grade.
Conclusion: The systemic inflammatory response is increased in early
breast cancer patients with lymph node positive and oestrogen
receptor negative disease.
Systemic inflammatory markers may have a prognostic role in early
breast cancer.
Poster Presentation 39:
Multiple Endocrine Neoplasia type 1 (MEN1): Genetics and Issues
surrounding genotyping, a case report
Hilary Graffy (Manchester University Medical School)
Iain McKevitt (University of Manchester), Mr Hudhaifah Shaker, Professor
Nigel Bundred, Miss Cliona Kirwan (Department of Academic Surgery,
University Hospital of South Manchester.)
Background: The systemic inflammatory response has been shown to
correlate with reduced survival in patients with colorectal cancer and
metastatic breast cancer. The prediction of prognostic outcome in
patients with early breast cancer remains problematical. Studies of
systemic inflammatory markers in early breast cancer are limited and
have not investigated differential leucocyte cell counts.
Objective: To determine whether serological inflammatory markers
correlate with established prognostic markers in early breast cancer.
Methods: Eighty four patients with early invasive breast cancer
were studied. Prior to breast surgery the following serological variables
were recorded:
• C-reactive protein concentration.
• Total leucocyte counts (summative neutrophil, eosinophil, basophil,
lymphocyte and monocyte counts).
• Differential leucocyte counts for neutrophils and monocytes. The
correlations between serological inflammatory markers and key
clinicopathological variables (lymph node invasion, tumour size, grade
and ER status) were analysed using univariate analysis.
Results: Table 1 shows haematological variables and their relationship to
lymph node (LN) positivity.
LN
Negative
SD
LN
Positive
SD
p-value
Monocyte
Count(*109/L)
0.49
0.14
0.58
0.21
0.04
Neutrophil
Count(*109/L)
3.99
1.32
4.45
1.65
0.19(n/s)
Leucocyte
Count(*109/L)
6.75
1.56
7.57
2.40
0.07(n/s)
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal
dominant condition characterised by a “P-triad” of neuroendocrine
tumours; affecting the parathyroid glands, the pituitary gland and
the pancreas. In 1997, positional cloning was used to identify the
responsible gene, localising it to chromosome 11q13, which encodes the
protein menin. MEN1 can be either familial (90%) or sporadic
(10%). In the familial disease, the individual has one germline mutation
and one somatic mutation, whereas in the sporadic disease, both
mutations are somatic. Genotyping is currently available for MEN1 and
requires a single peripheral blood sample for DNA analysis. Whilst the
introduction of the test has provided patients with a definitive diagnosis, it
has in turn created a series of ethical dilemmas.
Here we report a case of a 47-year-old man who was diagnosed
with MEN1 15 years ago. Since his diagnosis his already complex medical
management has been complicated by issues at home over the
genotyping of his immediate family. This report aims to discuss some of
the practical and ethical implications surrounding genotyping in MEN1
syndrome, by demonstrating one family ’s conflict.
Poster Presentation 40:
A 69 year old man with Advanced Oropharyngeal Squamous Cell
Carcinoma: A Case Report
Conor McKenna (The University of Manchester Medical School), Dr.
Beng Yap (The Christie Hospital)
Introduction: Oropharyngeal squamous cell carcinoma (SCC)
is one subtype of the family of head and neck cancers. It is a
relatively uncommon malignancy, however it is associated with
high levels of morbidity and mortality due to the frequency of late
stage presentation. This case report aims to show the journey of a
patient from initial presentation, to diagnostic workup and the selection
of treatment.
Aetiology and Presentation: Oropharyngeal SCC is most commonly
found in men aged 65-75 with a history of smoking and alcohol abuse,
however in recent years, infection with human papillomavirus (HPV)
has been identified as a separate aetiological factor for oropharyngeal
SCC. Presentation is often with the sensation of a sore throat however
in their early stages these cancers can be asymptomatic and
patients can present initially with a painless neck mass indicative of
nodal metastasis.
Treatment Discussion: Due to the importance of the pharynx and
adjacent structures, treatment method for advanced oropharyngeal
SCC must be carefully selected using a multi-disciplinary team
in order to avoid unacceptable morbidity. Current treatment
modalities include varying combinations of surgery, radiotherapy
and chemoradiotherapy depending on the stage of the disease. The
advancement of radiotherapy techniques culminating in Intensity
Modulated Radiotherapy (IMRT) has resulted in significantly reduced
morbidity for patients especially in terms of xerostomia. Further to
this, it has been shown that the use of chemotherapy in addition
to radiotherapy yields successful results over radiotherapy alone.
In the case described induction chemotherapy was used followed
by concurrent chemoradiotherapy. This is an intensive treatment
regimen and this case report also aims to indicate the importance of
careful organisation of treatment, management of side effects and
maintenance of nutrition during treatment.
Poster Presentation 41:
Audit of Non Small Cell Lung Cancer (NSCLC) patients with Epidermal
Growth Factor Receptor (EGFR) activating mutations
Dr Elizabeth Connolly, Dr Fiona Blackhall, Dr Paul Taylor & Dr Yvonne
Summers (The Christie NHS Foundation Trust)
The presence of EGFR activating mutations in patients with NSCLC
was first described in 2005. Patients who exhibit these mutations show
sensitivity to treatment with an oral Tyrosine Kinase Inhibitor (TKI).
Response rates to these drugs are typically high (70-80% compared
to 25-35% response rate for unselected patients to standard
chemotherapy). Testing for the presence of EGFR mutations in patients
with non squamous NSCLC began in the Greater Manchester in the last
quarter of 2009.
Results: 62 patients were identified up to March 2011; notes were
available for 49. The median age of patients with EGFR mutations
was 67 years (range 50-86) with the mutation being more common
in females (67% female: 33% males). 69% of patients had been
diagnosed with adenocarcinomas, 4% NSCLC NOS, 2% large cell and
the rest unknown. 90% of patients had stage IV disease. Analysis of
smoking history showed that 35% of patients were never smokers, 43%
ex-smokers, 8% current smokers and in 14 % status was unknown. 38
patients (77%) had received treatment with a TKI (Gefitinib or Erlotinib),
8 (16%) received no treatment at all and 3 (6%) had already received
radical treatment and had not yet been started on a TKI. 30 of the 38
(79%) had received Gefitinib 1st line therapy as per NICE guidelines
and the other 8 (21%) received Erlotinib at some point in the treatment
pathway. 32 (84%) patients showed response to TKI treatment, 1 (3%)
had a complete response 3 (8%) had stable disease and 2 (5%) had
disease progression. 74% of patients treated had some degree of
diarrhoea and 71% had some degree of rash. Rates were similar with
either drug.
Results confirm that treatment with a TKI is effective for patients with
EGFR activating mutations and that the side-effect profile is consistent
with published data.
Poster Presentation 42:
An audit of two-week-wait referrals for head and neck cancer.
T. Dessouki (University of Bristol), J. Morgan, M.S. Noormohamed (North
Bristol NHS Trust)
The NHS Cancer Plan was introduced in the year 2000, setting out a 10year programme of investment and reform with the aim of improving the
management of cancer in the UK. One of the commitments of
the Cancer Plan was to ensure that all patients with suspected cancer
would be seen by a specialist in an outpatients’ clinic within two weeks
of referral by their General Practitioner. An audit into the two-week-wait
system for head and neck cancer at Southmead Hospital was carried
out in 2001-2002, and recommended that changes needed to be
made in order to make the initiative an efficient means of seeing
and diagnosing patients with suspected cancer. Ten years on, we reaudited all fast-track referrals for suspected head and neck cancer at
Southmead between January and March 2011, and all new patients
diagnosed with cancer who were not referred via the two-week-wait
system. We found that only 8.1% of patients referred via the two-weekwait system were subsequently found to have a malignancy, and that
78.1% of patients diagnosed with head and neck cancer were not
referred via the fast-track system. Our results show that although 97.6%
of fast-track patients were offered an outpatients appointment within
two weeks of referral, the low yield of cancer diagnosis and the fact
that only 21.9% of cancers were found via the two-week-wait system
suggest that the initiative is currently not fulfilling its key purpose of
reducing cancer morbidity and mortality. What is more, it seems that
despite the changes recommended by the previous audit, very little
has changed in the last decade at Southmead. We conclude that
there is a great need for further reform in the fast-track system, and
propose some changes which could help to reduce inappropriate
referrals and improve the initial management of patients with
suspected cancer.
Poster Presentation 43:
Correlation of Dose-Volume Histograms with Rectal and Bowel Toxicity in
Prostate Cancer Patients Treated with Radical Radiotherapy
EJ Maile (School of Medicine, The University of Manchester), GJ
Webster, R Swindell, A Choudhury (The Christie Hospital, Manchester)
Introduction: Radical radiotherapy is a potentially curative treatment
for organ-confined prostate cancer. However, the radiation dose
delivered to the prostate is limited by organs in close proximity such as
the rectum. This is because high doses of radiation to normal tissue can
result in tissue damage and late toxicity, affecting the patient’s quality
of life. This study aims to determine the relationship between rectal
radiation dose and the level of late toxicity experienced by patients.
Methods: One hundred and forty patients who had received radical
radiotherapy for organ-confined prostate cancer were asked to
complete the LENT/SOMA questionnaire to determine the level of late
toxicity experienced. To calculate the radiation dose delivered to the
rectum, four rectal outlines were produced: 1) Anatomical rectum,
including rectal contents. 2) Rectal wall, only including normal tissue
forming the wall. 3) Full (extending from the anal sphincter to the
sigmoid flexure) and 4) Truncated (only extending to 0.5cm above
and below the Planning Target Volume) versions of these outlines were
produced, giving four outlines in total. Statistical analysis was used to
determine the relationship between rectal radiation dose and
late toxicity.
Results: There was no correlation between the radiation dose
delivered to the rectum and the level of late toxicity. Neither the full
outlines nor the rectal wall outline provided additional predictive data
for late toxicity.
Discussion & Conclusions: Radiation to normal tissue causes late
toxicity. However, the lack of correlation between rectal radiation
dose and late toxicity is likely to be due to a number of factors, not
least the variation in radiosensitivity between individual patients.
There is little need to outline the rectal wall or the full rectum as this
provides no additional predictive information for late toxicity. Therefore,
these results have the potential to save time during the planning of
radical radiotherapy.
Poster Presentation 44:
An Audit of the use of Intravesical BCG for Bladder Cancer at Stepping
Hill Hospital
Maeve Kilrane (Manchester University), Mr A Adeyoju (Stepping Hill
Hospital)
Introduction: Bacillus Calmette Guérin (BCG) is a live attenuated form of
Mycobacterium Bovis. It was 35 years ago that BCG was found to be a
treatment for non-muscle invasive bladder cancer. The treatment evokes
an immune response in the bladder, however the exact
mechanism of action is unknown. Intravesical BCG has been shown to
be more effective than chemotherapy in reducing a patient’s risk of
progression to muscle invasive disease, however it is associated with
significant side effects.
Objectives: The aim of this audit was to determine if both procedures
and outcomes at the Department of Urology, Stepping Hill Hospital
relating to this treatment followed European guidelines.
Patient and methods: Seventy-seven patients who commenced BCG
therapy over a 5 and a half year period were included. Data regarding
the treatment procedures and outcomes from these patients was
collected retrospectively using a proforma designed for this audit. Data
collected included patient demographics, histology results from first
and second TURBT, schedule and duration of BCG treatment, details of
side effects and missed doses, details of any recurrences and current
disease status.
Results: Of 77 patients commencing the treatment, 2 had muscleinvasive disease, for which BCG treatment is unsuitable. Almost half
of 67 maintenance patients (48%) have missed one or more doses
due to side effects. 16.4% of 67 patients commencing maintenance
treatment stopped treatment due to side effects. 18.18% of patients had
recurrence in 12 months following starting BCG. In total 86% of all 77
patients are now alive and free of disease.
Conclusions: The procedures employed and outcomes of BCG therapy at
the Urology department corroborate well with European guidelines. The
work of the nurse specialists within the department is important to ensure
patients are supported through this often tough treatment, this may mean
tailoring schedules for individual patients.
Poster Presentation 45:
The Resources Available for the Psychosocial Needs of Adult Survivors of
Childhood CNS Tumours in the North West
Min-young Kim, Jennifer Newton (Department of Undergraduate
Medicine, University of Manchester), Dr Rao Gattamaneni (The Christie
NHS Foundation Trust), Professor Jillian Birch (School of Cancer and
Enabling Sciences, Manchester Academic Health Science Centre,
University of Manchester), Professor Eddy Estlin (Royal Manchester
Children’s Hospital)
Adult survivors of childhood central nervous system (CNS) tumours are
vulnerable to poor psychosocial outcomes in their life. Many suffer from
unemployment, discrimination at work, physical and mental handicaps
that prevent them from leading a fully independent life.
In order to tackle this growing problem, local districts and counties
within the North West were investigated to find useful psychosocial
services that offered help to meet the identified needs of the adult
survivors. This led to a compilation of a comprehensive, user-friendly
directory that contained contact details of 459 psychosocial services
found in the North West. The districts and counties covered were
Greater Manchester, Lancashire, Cumbria, Macclesfield, Blackburn and
Darwen, Blackpool.
Results showed that Blackburn and Darwen had the largest number of
services per 100,000 population (25/100,000), whilst Greater
Manchester had one of the lowest number of services per 100,000
population (8.7/100,000).
Moreover, the provision of social and leisure activities (17%),
housing and domiciliary help (18%) and other miscellaneous supports
such as advocacy groups, counselling and legal advice (21%) were
found to be the most frequent resources. Conversely, help with transition
into adulthood (3%), advice and information on benefits and finance
(5%), treatments and complementary therapies such as physiotherapy
and acupuncture (5%) were found to be the least prevalent.
In conclusion, the psychosocial aspects of every adult survivor of
childhood CNS tumours must be carefully evaluated and a continuous
psychosocial support must be provided throughout their adult lives.
This directory will help to facilitate this process for adult patients
undergoing follow up in The Survivorship Clinics at The Christie hospital in
Manchester. Further studies will focus on the distribution of different types
of services across individual districts investigated in the North West so as
to optimise this resource for our patients.
Poster Presentation 46:
Is there a role for L-asparaginase in the treatment of relapsed
childhood acute lymphoblastic leukaemia (ALL)?
Caroline YK Fong, Ashish Masurekar, Adiba Hussain, Catriona Parker,
JiZhong Liu, Vaskar Saha (Children’s Cancer Group , School of Cancer
and Enabling Sciences, Manchester Academic Health Science Centre,
University of Manchester)
Introduction: The key anti-leukaemic agent, L-asparaginase (ASNase), is
a bacterial enzyme used worldwide to treat both de novo and relapsed
childhood ALL. As it is a protein, serial use can lead to the development
of inactivating antibodies, questioning its utility in relapsed patients.
In this study, the adequacy of intramuscular polyethylene glycol
(PEG)-asparaginase at 1000U/m2 given every 2 weeks for 12 weeks in
patients with relapsed ALL was analysed.
Methods: Trough plasma asparaginase activity (7 : 14 days post PEGASNase) of patients enrolled in the ALLR3 trial1 was measured using the
indooxine method.2 Adequate asparaginase activity was defined
as >100U/L. The overall and progression-free survivals (OS and PFS) at
maximum follow-up (8 years) of patients who did not receive Oncospar
due to previous toxicity on frontline protocols was compared with that of
patients who had received the drug whilst enrolled on the trial using the
Kaplan-Meier method and log-rank test.
Results: From July 2008 to July 2011, 39 samples from 16 patients who
participated in the ALLR3 asparaginase study were assayed. Eighty-two
percent (n=32) of samples had adequate activity, with 66% (n=26)
achieving activity >2 times the therapeutic threshold. Survival analysis
of patients who had not received Oncospar (n=16) against patients
who received the drug (n=214) showed non-significant differences
in OS [8-year survival rate: 38.1% vs. 60.4%; 95% confidence interval
(95% CI): 27.1-49.1 vs. 48.2-70.5 months] (p=0.128) and PFS (8-year
survival rate: 28.6% vs. 51.7%; 95% CI: 18.1-40.0 vs. 40.0-62.2 months)
(p=0.145).
Conclusion: Intramuscular PEG-ASNase at 1000U/m2 achieves
adequate asparaginase activity in patients but does not contribute
towards the outcome of patients with relapsed ALL. This suggests the
development of intrinsic resistance in leukaemic blasts in relapsed
disease and warrants further investigation and revision of the use of
PEG-ASNase in this setting.
Notes
Brochure Abstracts
Acute Lymphoblastic Leukaemia in Children: A Case Report
Stefano Prisco Penna (The Medical School, University of Manchester)
Case Report: Vocalisation after clival chordoma resection causes
bilateral hypoglossal nerve palsy
Joanna White (The Medical School, University of Manchester)
Chordomas are rare cancers originating from remnants of embryonic
notochord in the skull or spine. Clival chordomas are often the most
difficult to treat of the three main categories of chordoma, due to their
complex anatomical relations which often include the internal carotid
artery and cavernous sinus. This can make surgical resection more
complicated, and often complete resection of the chordoma is not
safely possible. For this reason patients may be referred to Switzerland
for proton particle therapy after surgery to help treat patients with a
curative intent.
This case report describes a patient who suffered bilateral hypoglossal
nerve palsy secondary to surgical debulking of his clival chordoma.
Bilateral hypoglossal nerve palsy is an unusual rare clinical finding.
As the hypoglossal nerve innervates all of the muscles of the tongue,
bilateral palsy patients usually lose any function of their tongue
and therefore are not able to speak or swallow, unless the bilateral
hypoglossal nerve palsy subsides. Remarkably the patient is now able
to speak despite still having bilateral hypoglossal nerve palsy. As far as I
am aware, this is the first time that this has been reported. There is very
little research into this unusual disorder, but it is thought that the patient
has learnt to adapt the way he speaks through compensatory muscle
movements, specifically by shortening his genioglossus muscle.
A study into the factors which influence breast cancer patients’
decision to accept chemotherapy treatment
Sophie Hancock, (The Medical School, University of Manchester), Dr
Elaine Young (Lancashire Teaching Hospitals Foundation Trust)
Background/Aims: Ideas about acceptability of cancer treatment
differ greatly between patients and healthcare professionals and the
concept of shared decision making which has grown in popularity over
recent years is something which may remedy this. I have undertaken
a questionnaire-based study about decision making in adjuvant
chemotherapy for breast cancer in order to examine treatment
decisions in cancer and the ways in which this is facilitated by the
multi-disciplinary team.
Method: Patients recommended for adjuvant chemotherapy
were identified in clinics and in the chemotherapy suite to fill in
questionnaires regarding their support network, previous healthcare
experiences, mental wellbeing, their decision making process and
the information they received to supplement their decision. The
responses were then coded and put into a spreadsheet to allow
statistical analyses.
Results: The results show that the majority of women have a good
family support network and consider their family when making
treatment decisions. The majority of women were active decision
makers but over a quarter preferred to play a passive role in the
process. The types of information preferred by women varied and the
healthcare professional considered most useful by the majority of
women was their Oncologist. Prior to commencing chemotherapy,
women were most concerned about feeling physically ill, losing their
hair and that it may not cure their cancer.
Conclusions: By making specialists more aware of decision making roles
and information preferences, discussion between patient and doctor
regarding these points can be encouraged. This will improve the
physician’s understanding of the patient’s needs and improve overall
patient satisfaction and potentially reduce future distress levels.
Acute lymphoblastic leukaemia (ALL) is the most common childhood
cancer and has, therefore, been subject to years of research. It
commonly occurs in children around the ages of 2-5 years and
often has varying prognoses, depending on the genetic alterations
involved. TEL-AML1 and hyperdiploidy are the two most common
genetic alterations that are associated with a very good prognosis and
occur typically in precursor B-cells. Typical presentation is due to bone
marrow failure and comprises pallor and fatigue due to anaemia,
pyrexia due to neutropenia and bruising due to thrombocytopenia.
Diagnosis is based on morphological testing, immunophenotyping
and cytogenetic analysis. Treatment is generally chemotherapy over
2-3 years based on UKALL 2003 guidelines. Minimal residual disease is
tested early on to assess treatment effectiveness and outcomes. Much
of our understanding of the causes and natural history of ALL comes
from studies using twins, which have shown there to be a foetal origin
of a pre-leukaemic clone cell. This can spread to the other twin via
anastomoses in the placenta, meaning they have an increased risk of
developing ALL. A two-hit hypothesis has been suggested to account
for the still considerably high discordance rate, which may be to do
with abnormal immune responses to everyday infections later in life.
This report will discuss the above issues, in particular the use of twin
studies, using the case of a 4-year-old boy who is one of triplets and
developed ALL.
The prognostic value of KLF5 in locally advanced cervical cancer
Dimple Jain (The Medical School, University of Manchester), Professor
Catharine West, Dr John Hall (Translational Radiobiology Group, The
Christie Hospital)
Background: For successful cancer treatment, predicting the response to
radiotherapy is important. Identifying genes differentially expressed
between radiosensitive and radioresistant tumours will increase our
understanding of how patients respond to radiotherapy. Expression
of the gene KLF5 promotes cell proliferation, progression through the
cell cycle, and cell survival. The pro-proliferative effect of KLF5 has
been associated with carcinoma of the colon, breast, bladder, and
oesophagus. KLF5 is also known to be affected by hypoxia, another
important factor influencing outcome following radiotherapy. The aim
of this study was to determine the prognostic value of KLF5 in patients
with locally advanced cervical cancer, who received radiation therapy
with curative intent.
Method: Immunohistochemistry was performed on tumour sections
from a retrospective cohort of 65 patients with carcinoma of the cervix
(stage IB-IVA). The fidelity of the antibody used for KLF5 was tested. A
reproducible semi-quantitative image analysis scoring system was used
to analyse the percentage staining and intensity of KLF5 expression.
Results: Univariate Cox Regression analysis showed an insignificant
association between KLF5 expression and cancer-specific survival
(p=0.17), local failure (p=0.39), and metastatic failure (p=0.42).
Conclusion and Implications: Although the association was statistically
insignificant, a trend for poorer survival in patients with high levels of
KLF5 protein was seen. A power calculation showed that looking at
KLF5 protein levels in a larger cohort may allow the study to reach
significance. Therefore, further analysis of KLF5 as a prognostic marker
for outcome following radiotherapy is essential as it could alter how
cervical cancer patients are treated.
Diffuse Large B-cell Lymphoma Case Report
Katie Smith, (The Medical School, University of Manchester), Dr Adam
Gibb (The Christie Hospital, Manchester)
Here we report on a 74 year old female with Diffuse Large B cell
Lymphoma (DLBCL.) She presented in April 2011 acutely to the
emergency department with hemi-body oedema up to the sacrum
and shortness of breath at rest. A CT angiogram was performed. In
addition to a pulmonary embolism a large intra-abdominal mass was
also identified. A cutting needle biopsy was then performed which
demonstrated DLBCL. Further staging was performed with positron
emission tomography (PET) and bone marrow trephine (BMT). She was
staged as IVxB on the Ann Arbor system (IV = multi focal extra-nodal
disease, X = bulk, B = night sweats and weight loss.)
She was commenced on treatment with the internationally
accepted R-CHOP immunochemotherapy regimen (rituximab,
cyclofosfamide, doxorubicin, vincristine, prednisolone). Cycle one
was received with full tumour lysis prophylaxis in view of the aggressive
histology and bulky presentation. Interval re-staging CT following three
of a planned six chemotherapy cycles has demonstrated a good
quality partial response, and this has been accompanied by dramatic
clinical improvement.
DLBCL is the commonest sub-type of type of aggressive nonHodgkin lymphoma with approximately 3000 new cases per year in the
UK. Prognosis can be estimated with the revised International Prognostic
Index (R-IPI). Staging investigations include lymph node biopsy, BMT, CT
and PET scans.
The recent introduction of rituximab (MabThera, Roche) to
CHOP chemotherapy has significantly improved patient outcomes across
all stages and R-IPI scores. This patient was also eligible and consented to
a National Cancer Research Institute (NCRI) phase three study looking at
the prognostic value of interim PET/CT after 2 cycles of chemotherapy.
Future research and trials in this area are aiming to move towards
individualization of care, tailoring therapy to histology, tumour and host
genetics, and early treatment response, with the dual aims of improved
survival and reduced toxicity.
with underlying illness, characterized by loss of muscle with or without
loss of fat mass.” It has been shown that cancer patients who develop
cachexia have increased risk of infection, prolonged convalescence,
impaired muscle work capacity and death. The purpose of this study
is to review the current potential therapeutic role of anabolic steroids
(AAS) in human cachexia and muscle wasting in cancer patients.
Methods: Seventeen electronic resources, including MEDLINE, EMBASE
and Cochrane, were searched from inception to June 2011 to identify all
interventional, observational and review studies that have reported the
effects of AAS on cachexia and muscle strength and/or function in
patients with a diagnosis of cancer.
Results: A total of 70 articles were identified and the title and abstract
of each paper was assessed. Eighteen papers were found to address
our research question but only five reported outcomes in terms of
muscle strength or return of function.
Discussion: AAS represent a broad category of chemically-related
structures derived from the male sex hormone testosterone.
Testosterone, oxandrolone and nandrolone decanoate have been
approved in medicinal forms for conditions such as male
hypogonadism and renal failure and have undergone clinical trials
looking at efficacy in cachexia and muscle wasting.
Generally, AAS have demonstrated favourable effects in their ability to
enhance body weight and muscle strength. Relatively robust data has
shown the efficacy of AAS in chronic states that induce cachexia but
only a small number of clinical trials have investigated their effects on
cachexia in cancer. Stimulation of muscle anabolism could represent
a promising and valid therapeutic alternative for cancer-related
muscle wasting, however further research into this field is required.
The role of DNA damage response in mediating tumour response to
chemotherapy in ovarian cancer
Yong LY, Kay C, Um I, Langdon SP, Faratian D. (Division of Pathology &
Edinburgh Breakthrough Research Unit, Institute of Genetics and
Molecular Medicine, University of Edinburgh)
Background: Treatment resistance to the standard chemotherapy
regime is a phenomenon that is known to occur in a subgroup of
patients with ovarian cancer. We hypothesized that DNA damage
response is involved in modulating tumour sensitivity to chemotherapy.
Methods: Protein expression was measured using quantitative
immunofluorescence in 2 ovarian cancer cell line xenografts, OV1002
which was sensitive to chemotherapy and HOX424 which was resistant.
Both xenografts were treated with two different chemotherapy
regimens: carboplatin and carboplatin+paclitaxel. Targeted proteins were
known to be involved in nuclear excision repair, mismatch repair,
homologous recombination, apoptosis and proliferation (ERCC1, PMS2,
MSH6, MLH1, MSH2, BRCA1, phospho BRCA1, phospho p53, phospho
Histone 2A.X, pHH3, Ki67, BCL2 and cleaved caspase 3).
Results: Growth curves showed a clear difference between sensitive
and resistant xenografts. There was an appropriate DNA damage
response seen in OV1002 with increased protein expression in the
treated groups, with carboplatin+paclitaxel eliciting a greater
response. In contrast, there was a lack of DNA damage response in the
HOX424 group.
Conclusion: Further studies using replicate staining would be needed to
validate the significance of the result in this study. Comparison with gene
expression profiling would also help to verify the change at the
molecular level.
Anabolic Steroids in Cancer Cachexia and Muscle Wasting
Evan Watts, Charlotte Philippson, Adam Maguire (Institute of Clinical
Education, University of Warwick)
Introduction: From the 2006 Cachexia Consensus Conference,
cachexia was defined as “a complex metabolic syndrome associated
Gastrointestinal stromal tumours; a review over the past 10 years at the
University Hospital of South Manchester
Tom Fleming, (The Medical School, University of Manchester), Mr Simon
Galloway (University Hospital of South Manchester)
Background: Gastrointestinal (GI) stromal tumours (GISTs) are lesions
of the interstitial cells of Cajal and are defined by c-kit positive staining.
They are the most common mesenchymal tumour of the GI tract
and the prognosis is variable, dependent on their size, mitiotic rate
and location
Aim: To review the clinical and pathological features of all identified
GISTs at UHSM over a 10 year period, identifying any trends and
comparing them to the current literature.
Methods: 44 patients were identified from pathology reports, discharge
summaries and GI multi-disciplinary team records between May 2001 and
April 2011 inclusive. Clinical and pathological features were
collated from each patient’s medical notes and analysed.
Results: The mean age at diagnosis was 65.4 in males and 63.4 in
females, with a male to female ratio of 1 to 0.69. 37 of 44 (84.5%)
GISTs were gastric in origin, with 6 jejunal (13.6%) and 1 rectal (2.2%).
GI bleeding was the most common presenting symptom, present
in 45.5% of cases. Jejunal GISTs had a mean diameter of 71.3mm and
mean mitotic rate of 23.3/50 HPF, compared with 59.7mm and 3.2/50
HPF in gastric GISTs. There were 2 recorded deaths as a result of
metastatic lesions and 1 un-related death.
Conclusion: Jejunal GISTs were found to have a worse prognosis than
gastric GISTs as they presented with a greater mean diameter and
mitotic rate. Clinical presentation was shown to correlate to tumour
location, with GI bleeding more commonly seen in gastric GISTs and
bowel perforation in jejunal GISTs.
Arterial embolisation in the management of connective tissue
tumours
Oisin J F Keenan, (The Medical School, University of Manchester)
Aims: To examine the use of selective arterial catheterisation and
embolisation (SACE) in the management of patients with connective
tissue tumours.
Methods: Clinical case notes and angiographic imaging were
reviewed retrospectively for all patients who had undergone SACE
for tumours involving connective tissue in the last three years at our
institution. Data collected included age, sex, tumour type, indication
for embolisation, angiographic outcome, functional outcome and
complications.
Results: Four patients underwent SACE, including two individuals with
malignant connective tissue tumours of the gluteus and two individuals
with hypervascular metastatic lesions of the humerus, tibia and femur. In
the former two cases, SACE was successfully performed for palliation and
clinical improvement in symptoms. In the latter two cases, SACE led to
angiographic stasis or significant reduction in tumour vascularity, and
permitted uncomplicated surgical excision, open reduction and internal
fixation or intramedullary nail insertion. No peri-embolisation or
post-embolisation complications were encountered.
Conclusion: Arterial embolisation may be used effectively in the
management of both primary and metastatic tumours involving
connective tissue. It has a definite role in palliative tumour reduction
where surgery is inappropriate, and should also be considered
before surgical excision to reduce the risk of severe bleeding in
vascularised tumours.
Audit of Patient Care in admission with Neutropenic Sepsis
Dr. Sarah Lord, Jolene Brown, Dr. Annette Nicolle (Queen Elizabeth
Hospital, Gateshead).
‘Neutropenic sepsis is the term used to describe a significant
inflammatory response to a bacterial infection in a person with
neutropenia this can be with or without fever.’ (1) There is little national
data on the morbidity and mortality associated with this although it is
thought that adopting a policy of IV antibiotic therapy has dramatically
reduced mortality rates. (1)
Therefore Gateshead Health Foundation Trust have a neutropenic
sepsis protocol which aims to guide staff in efficient recognition and
treatment of patients admitted with suspected neutropenic sepsis
An audit was conducted between December 2010 and March
2011 to look at the adherence to this protocol in patients who were
diagnosed with neutropenic sepsis on admission to the Haematology
ward at Queen Elizabeth Hospital, Gateshead. The main objective
of the audit was to assess adherence to local protocol with respect
to administration of antibiotic therapy to patients admitted with
neutropenic sepsis. Data was collected on 10 patients, (9 female
and 1 male). They ranged in age from 47 to 83 years. The audit
demonstrated that only 4 patients received antibiotics within the 1 hour
recommended time frame. Two patients received antibiotic therapy
between 1 and 2 hours, two patients between 2 and 3 hours and two
patients in over 3 hours. This outlines a need to address improvement
in the service to ensure more patients receive recommended therapy
within the directed timeframe of within 1 hour. Overall there was a
low level of morbidity found in this patient group associated with
neutropenic sepsis, though continuation of the audit would provide
further statistical strength to the data.
(1) NICE guidelines-http://www.nice.org.uk/nicemedia/
live/12349/49068/49068.pdf
Establishing tobacco smoking as a major cause of lung cancer A
Davies (The Medical School, University of Manchester)
An Audit of Risk Reducing Surgery for Women at High risk of Breast
Cancer
Carcinoma of the lung is the leading cause of death from cancer
worldwide and has an annual mortality of approximately 1.4 million;
smoking accounts for the majority of cases.
During the 19th century cancer of the lip was noted to be more
prevalent in pipe smokers. The evidence to support a link between
smoking and lung cancer grew over the first half of the 20th century
and in 1939 Muller published the first case-control study. Initially the
scientific community was sceptical. Two larger case-control studies
published in the United Kingdom and the United States in 1950 were
of pivotal importance, however many continued to disagree with
their conclusions.
Robust evidence was supplied by the later cohort studies
of Doll and Hill along with Hammond and Horn. The decision to
recruit registered British doctors by Hill in 1951 led to a reliable study
population of 34,439 which was successfully followed up for 50 years.
Subsequent studies have established, in part, the carcinogens present
in tobacco smoke.
In 1950 approximately 80% of men and 40% of women in the
U.K. smoked. By 2009 this had fallen to 21% and 20% respectively.
Death rates from lung cancer in men have fallen from the 1980s with the
peak in mortality dependant on age. Mortality rates continue to
rise in women over 75 years of age due to an initial increase in the
prevalence of smoking in women up until 1970. During the 20th century
smoking was shown to cause other diseases including cardiovascular
disease, cerebrovascular disease and multiple cancers which provide
further incentives to stop smoking.
The quality of the epidemiological evidence has encouraged the
large scale cessation of a well established yet harmful practice and is an
outstanding achievement for the prevention of cancer.
Huw Garrod (Liverpool University), Lynn Greenhalgh (Royal Liverpool
Children’s Hospital)
Introduction: A familial element is present in up to 20% of breast
cancers and mutations in the BRCA genes confer a high risk of breast,
ovarian and other cancers. This audit focuses on a multidisciplinary riskreducing surgery (RRS) clinic at the Liverpool Womens’ Hospital offering
bilateral risk-reducing mastectomy to women at high risk of breast
cancer.
Methods: Patients records were analysed and audited against local
and NICE guidelines.
Results: 38 patients attended the RRS clinic. 9 incorrect referrals were
excluded. Patients had an average age of 38.5. 15 patients chose risk
reducing surgery, 12 of which were seen by the psychologist. Several
patients chose only bilateral salpingoophorectomy or combined it with
bilateral risk-reducing mastectomy.
Discussion: The clinic operates to an excellent standard and nearly all
standards were met. Several standards were removed due to a lack
of patient information. A greater proportion of younger patients chose
surgery.
Conclusion: Risk reducing mastectomy is a difficult decision for women
who are at high risk of developing breast cancer. A multidisciplinary clinic
is run at the Liverpool Womens Hospital to help high risk women
understand and decide upon treatment. The clinic is well run and national
and local protocols are adhered to.
Cerebrovascular Accident during Cisplatin Chemotherapy:
A Case Study
Rebecca Katherine Marchmont (The Medical School, University of
Manchester), Dr Elaine A Young, Dr Natalie Charnley (Lancashire
Teaching Hospitals NHS Foundation Trust)
Cisplatin is a highly effective anti-neoplastic agent, used in the
treatment of ovarian, testicular, lung, oesophageal, stomach, and
bladder malignancies.(1) There are several well known toxicities are
associated with its use. However, there have been several case reports
that implicate the use of Cisplatin with severe vascular events, for
example cerebrovascular accidents.(2,3,4,5,6) The cause of this toxicity
is unknown, and the implications of this could affect the course of a
patient’s treatment, particularly if the event occurs before the end of
chemotherapy treatment.
This report looks at the case of Mrs A, a 67 year old woman who
developed a left cerebellar infarct after her third cycle of Cisplatin
chemotherapy. It considers the potential causes for this event, and what
the implications may be if further evidence shows a connection between
Cisplatin and cerebrovascular accidents.
1.
2.
3.
4.
5.
6.
Fuertes M.A.; Castilla J.; Alonso C.; Prez J.M. Cisplatin Biochemical
Mechanism of Action: From Cytotoxicity to Induction of Cell
Death Through Interconnections Between Apoptotic and Necrotic
Pathways. Current Medicinal Chemistry, Volume 10, Number 3,
February 2003 , pp. 257-266(10)
El Amrani, M. MD; Heinzlef, O. MD; Debrouker, T. MD; Roullet, E.
MD; Bousser, M. G. MD; Amarenco, P. MD. Brain infarction following
5-fluorouracil and cisplatin therapy. Neurology. 51(3):899-901,
September 1998.
Fikri αçli M.D., Handan Karaoαuz M.D., Dilek Dinçol M.D., Ahmet
Demirkazik M.D., Nazan Günel M.D., Remzi Karaoαuz M.D., Aytu
Üner M.D. Severe vascular toxicity associated with cisplatin-based
chemotherapy. Cancer Volume 72, Issue 2, pages 587-593, 15
July 1993.
Provencio, M., Bonilla, F., Lacasta, A. Cerebral infarction after
Cisplatin-based chemotherapy. Postgrad Med J 1994;70:525-52
Gamble, G.E., Tyrrell, P. Acute Stroke following Cisplatin Therapy.
Clinical Oncology (1998) 10:274-275
Samuels, B.L., Vogelxang, N.J., Kennedy, B.J. Severe vascular
toxicity associated with Vinblastine, Bleomycin and Cisplatin
chemotherapy. Cancer Chemotherapy Pharmacology (1987)
19:253-256
An Audit into the use of Prophylactic Antibiotics in Lung Cancer
Patients on Chemotherapy
Christopher Doyle (The Medical School, University of Manchester), Dr.
Margaret Harris (The Christie Hospital, Manchester)
Lung cancer is the second most commonly diagnosed cancer in
the UK and there were 33,000 deaths from it in 2004. Treatment of
lung cancer with chemotherapy can lead to complications such as
infections, neutropaenic sepsis and even death. With this in mind, the
Christie hospital put in guidelines to give prophylactic antibiotics to
certain high risk groups of lung cancer chemotherapy patients with a
view to preventing infections in this group.
This audit looked at a patient group who received their first cycle
of chemotherapy, within a six month period, and how well the
guidelines are being followed in this group of patients.
There were 85 patients in total. 53% of the patients who should
have received prophylaxis did. The results from this sample also show
that there was as much risk of getting an infection if you had received
prophylactic antibiotics as if you had not.
This calls into question the usefulness of these guidelines but I
decided that they should remain unchanged as if they are preventing
some infections then they are useful. There is however a need to look
at implementation of the guidelines amongst the practitioners. I’ve
suggested future audits to have larger samples and to also look at
issues with communication to other hospitals over causes of death.
I would hope that with these changes, future audit cycles will see
better use of the guidelines and with this a reduction in infection rates
in these patients.
The Psychosocial Impact of Cancer on Young Adult Patients
Megan Alice Steward (The Medical School, University of Manchester) Dr
Smith (The Christie Hospital, Manchester)
The management of Young Adults with cancer is extremely different to
the management of any other age group. The unique psychosocial
needs of those aged between 16-24 years old requires a smooth
working and wide based multidisciplinary team. Their psychosocial
needs are well documented and their specific requirements whilst
going through cancer treatment have developed since 1959 when
their needs were first recognized.
The ‘YOU’ at the Christie and their patients have provided a base for
this report. This unit works extremely well and provides excellent
psychosocial support whilst maintaining patient independence. This is
aided by upholding peer support and offering a wide range of
behavioural techniques in an age-appropriate environment with
correctly trained staff. I feel areas for development could include
access to the psycho-oncology service for all patients, developing a
bereaved sibling support group, and the use of scrapbooks for patients to
document their progress throughout treatment.
A comparison of the management of paediatric cancer care in the
developing country of Belize to the UK: Is Belize a candidate for a
twinning approach?
Lisa Milverton (Birmingham University)
Introduction: Rates in paediatric cancer in the developing world
is thought to be increasing due to advancements in the control of
infectious diseases. This is resulting in inadequate treatment and severe
suffering. In contrast, developed countries achieve high survival rates.
It may not be limited resources in developing countries leading to lack
of treatment, it may be absence of care pathways and protocols.
Twinning programmes show the potential of increasing survival in a
developing country when aided by a developed country. Belize is
a developing country undergoing similar transitions in disease
burden thus the aim was to investigate if standardised care exists
for paediatric cancer.
Aims: To describe disease burden in the paediatric population of Belize
using national data, compare the management pathway of paediatric
cancer in Belize to the UK and determine the potential of Belize for a
twinning approach.
Methods: National data was obtained from the ministry of health
(MOH) for the paediatric population. Standardised questionnaires
and interviews were used at Western Regional hospital and Belize
cancer centre to obtain qualitative information about the standard of
care. Government set care pathways in the UK will be used as a gold
standard to compare paediatric cancer care and determine the
potential of Belize for a twinning approach.
Results: Only available data provided by the MOH was cancer
mortality. Only 38 cases were recorded from 2004-2010 thus it was not
possible to perform statistics. Haematological malignancies were the
most frequent malignancy recorded. Questionnaire results revealed
that no standards exist for paediatric cancer care in Belize. The Belize
cancer centre was the only unit in Belize to provide cancer care for
children, specifically chemotherapy. Acute lymphoid leukaemia (ALL)
was estimated to be the most frequently treated malignancy.
Conclusion: The standard of cancer care for children in Belize is poor.
However there may be potential for a twinning approach focusing
on chemotherapeutic treatment of haematological malignancies
specifically ALL.
A patient with synchronous stage IIIC poorly differentiated ovarian
carcinoma and stage IA moderately differentiated endometrioid
endomentrial cancer; A case report indicating the first-line
management of Ovarian Cancer
Minimally Invasive Oesophagectomy: Is it better than the traditional
Open Oesophagectomy?
Divyan Sankaran, (The Medical School, University of Manchester),
Mr Kish Pursnani
Sophie Brotherton (The Medical School, University of Manchester)
Introduction: Ovarian cancer is a devastating disease which leads to
nearly 7000 diagnoses and over 4600 deaths each year in the UK. The
overall-5 year survival rate in ovarian cancer patients is currently less
than 50%. Due to the insidious nature of the disease, often patients
do not present until the cancer has become advanced. Advanced
ovarian cancer is associated with more complications and worse
prognosis. There is currently no validated screening program me.
Case Presentation: A 51 year -old Endocrine nurse is diagnosed
with probable stage IIIC poorly differentiated ovarian carcinoma
and synchronous stage 1A moderately differentiated endometrioid
endometrial cancer. It was difficult to determine whether the
tumours were synchronous or just metastasis of the other. The ovarian
carcinoma was the more aggressive tumour and therefore the patient
underwent standard first-line management for ovarian cancer. There will
be an evidence-based discussion regarding standard first-line
management for ovarian cancer and future developments.
Conclusion: Despite extensive research into management strategies in
ovarian cancer, the overall survival rate has failed to increase
significantly for women with advanced disease since the 1970s. The
insidious course of disease and absence of a validated screening
protocol are huge obstacles in improving the management and
survival rates in these patients.
Minimally invasive oesophagectomy (MIO) was introduced in the 1990s
to provide an answer to the high morbidity and mortality rates
associated with the traditional open oesophagectomy (OE), used to
treat oesophageal cancers.
OEs can be split into transthoracic and transhiatal surgeries. MIO is
classified in the same manner, where the thoracotomy is replaced with
thoracoscopy and laparotomy with laparoscopy. There are many
combinations in which laparoscopy and thoracoscopy techniques are
used, giving rise to several MIO procedures. Greater experience and
better medical technology has led to many modifications such as hand
assisted and robotic surgery.
The benefits and drawbacks of MIO over OE have been
studied in many case series studies. Reduced morbidity, mortality
rates and shortened hospital stay were recorded with MIO. However,
complications which occur from MIO often result in the conversion of MIO
to OE. No formal study comparing the cost effectiveness of MIO and OE
has been done so far. Only one randomised controlled trial has been
performed. This trial showed that despite the obvious benefits MIO offers,
there is still a role for the OE procedure. However, more such trials need to
be performed to ascertain this.
Quality of life (QOL) assessments done following MIO showed
that patient regain their original QOL faster than with OE. Furthermore,
faster recovery was observed with most aspects of health except reflux
and diarrhoea. The care of patients following surgery plays a key role
in determining the overall QOL. Implementing the enhanced recovery
programme will further enhance the successful, prompt recovery of
these patients.
The use of dye infused anti-bacterial soaps in the reduction of
Health Care Associated Infections
Case Report: Soft Tissue Sarcoma of the Thigh
Radhika Khanna (Barts and The London)
Miss Dilanka Jayawardena Ratnayake, (The Medical School, University of
Manchester)
Introduction: Health care associated infections (HCAI) are the most
frequent adverse event post the delivery of health care, with between
5-12% of hospitalised patients in the developed world acquiring at
least one HCAI in their lifetime. Patients with cancer are at increased risk of
HCAI due to impaired immune defences, arising from the disease itself
and anti-cancer therapy.
Objective: I propose the use of a dye infused anti-bacterial soap as
a means to reducing hand related infection transmission, in a
clinical environment.
Methods: Disclosing tablets are used to make dental plaque visible,
relying upon the dye erythrosine to stain the bacteria in plaque. The
technology behind disclosing tablets can be combined with that
of pre-existing anti-bacterial soaps to create ‘disclosing soaps’.
Results: ‘Disclosing soaps’ have the ability to expose areas where
bacteria, including C.difficile, have colonized. With more precise
and effective handwashing in place HCAIs can be reduced helping to
shorten hospital stay and absolve, what is often avoidable, HCAIrelated mortality.
Conclusion: Preliminary research has supported the implementation of
this innovation, with health professionals in agreement that this
technology is: feasible, much required and having the ability to be
adapted for many applications.
Introduction: This case examines how errors made earlier on in
managing a case of a soft tissue sarcoma of the thigh may have
affected the outcome for the patient. Soft tissue sarcomas can affect
muscles, tendons, fat, blood vessels, nerves and synovial structures.
Leiomyosarcoma is the sub-type of soft tissue sarcoma implicated in
this case.
Clinical Case: Prior to the diagnosis of the lesion on the patient’s left thigh
as cancerous, it was treated as an abscess and surgically drained. After
drainage there were some tumour cells left behind which metastasized to
distant organs such as the lungs. Hence, the patient was deemed
inoperable and referred to palliative care.
Conclusion: The case high-lights the importance of referral to a
specialist centre when a soft tissue sarcoma is suspected. Had the
patient been referred to a specialist sarcoma unit, they may not
have reached the stage where the cancer had metastasized into the
lung parenchyma. There is also the need to publicise and audit, the
guidelines and patient pathway for the management of soft tissue
sarcomas, as suspected cancers should be referred promptly to a
specialist clinician.
Skin Sparing Mastectomy and Immediate Breast Reconstruction - A
Case Report of a CDH1 mutation and Review of the Literature.
Christopher Roberts, (The Medical School, University of Manchester)
A Cdh1 mutation affects the E-cadherin glycoproteins and results in
a faulty protein being produced, which reduces the aggregation of
cells in a tissue. This results in an increased risk of developing breast
cancer and a risk reducing mastectomy may be offered in an attempt to
prevent the development of breast cancer. Despite the high risk
of developing cancer with a genetic mutation, the risk reducing
mastectomy is a controversial procedure and the mastectomy
technique even more so. Skin Sparing Mastectomy (SSM) has fallen
out of favour since its peak in popularity at the end of the 90s, due to
concerns about its safety and increased risk of local recurrence. Post
mastectomy, patients can undergo reconstruction either immediately or
waiting for a period of time. Immediate reconstruction of the breast
following a mastectomy has a number of different options. Patients can
either have prosthetic implants, or tissue flaps, which can be from the back
(latissimus dorsi flap), abdomen (TRAM or DIEP flap), gluteal region or the
inner thigh (TUG flap). The choice of reconstruction depends
upon not only patient preference, but also the patient’s level of activity and
their body shape (to allow harvesting of the flap).
adenocarcinoma. PET-CT incidentally revealed a large endoluminal
mass in the right colon, diagnosed as a malignant semipedunculated
polyp following a colonoscopy. After careful staging, treatments for both
primary tumours were assessed according to hospital protocol in Spain.
The patient was considered suitable for surgery, and due to local invasion
of the oesophageal cancer, neoadjuvant chemotherapy was commenced
with three cycles of cisplatin and capecitabine over two months.
Revaluation in response of the tumour to chemotherapy treatment would
take place prior to surgery.
Result: A positive response was seen to neoadjuvant chemotherapy, with
a reduction in size and partial devitalisation of both oesophageal tumour
and polyp in the colon. Surgery was carried out with successful removal of
both tumours.
Conclusion: Neoadjuvant chemotherapy proved successful in both
palliative and surgical management of multiple cancers in this case.
An Evaluation of the current state of Palliative and Supportive Care
Research in the UK
C.D Jacobs, (The Medical School, University of Manchester) A.
Molassiotis (School of Cancer and Supportive Care,
The University of Manchester)
Small Cell Carcinoma of the Oesophagus: A Case Report
The aim of this study was to establish the current state of the research
environment in the UK in supportive care and palliative care. Three
approaches were used to evaluate the current research environment in
supportive and palliative care. A) A bibliometric analysis was
conducted on published research output over the past 5 years. B) An
analysis of the UKCRN portfolio of trials was undertaken to establish the
current research environment. C) A questionnaire survey was
distributed to research groups in the field with the purpose of mapping
the workforce, exploring funding/funding sources and gauging opinions
about challenges in supportive and palliative care research. 586
papers met inclusion criteria for the bibliometric analysis, 76 studies
were included in the UKCRN portfolio analysis and 36 questionnaires
(overall response rate 74.5%) were received from UK research groups.
An expansion in research activity is reflected by an increased trend
in research output (57% over 5 years) and an increased proportion
of studies registered with the NCRN portfolio of trials. Study designs
were dominated by observational methods, however a trend towards
increased interventional methods was identified. In the workforce, an
aging researcher population was identified and an increased tendency to
work in few but large research groups was evident. Group opinions
included increased collaboration in the field over the past 5 years,
however the withdrawal of a major funding partner from the field is
currently a major challenge for the majority.
Small cell carcinoma (SCC) of the oesophagus is a rare type of cancer
that is commonly found in the lung and has yet to beget sufficient
information on optimal treatment therapies. It presents as an aggressive
disease with a poor prognosis, early dissemination and frequent
reoccurrences and due to similarities with small cell carcinoma of the
lung, the treatment plan is often the same; however management
does rely heavily on the extent of the disease at diagnosis. Since this
type of cancer is difficult to control, it demonstrates high mortality
rates especially since many patients present at an advanced stage
at diagnosis. The success of treatment is poor with most patients
relapsing and a complete cure presenting as an incredibly rare
outcome. A case of a primary oesophageal small cell carcinoma in
a 66 year old male patient in whom the only presenting symptoms
were left hypochondiral pain and some degree of dysphagia is herein
presented. On investigation of the patient, an endoscopy revealed
a longitudinal ulcerating lesion in the mid oesophageal region and
the biopsy specimen demonstrated substantial crush artefact, poorly
formed glands with a high mitotic rate and many apoptoses, thus
identifying SCC. A CT classified the tumour as T3 N1 MX and the patient
underwent treatment, which entailed six cycles of chemotherapy with
cisplatin and etoposide, 15 fractions of consolidation radiotherapy to
the oesophagus and prophylactic cranial irradiation. He responded
well to therapy but did not demonstrate complete remission. His case is
described and discussed.
Case report on the use of neoadjuvant chemotherapy in the
treatment of multiple primary cancers within the Spanish Healthcare
System
Amna Sadiq (The Medical School, University of Manchester)
Case Study on a Patient Suffering from Graves’ Ophthalmopathy
Elizabeth Banks (The Medical School, University of Manchester)
Savana Shakir (The Medical School, University of Manchester), Professor
Antonio José Torres García, Dr Esteban Martin Antona (Department of
Surgery, Hospital Clinico San Carlos, Madrid, Spain)
Background: The best prognosis for malignant neoplasms remains in
early detection through adequate screening methods that are sensitive
and specific. Appropriate management options for cancer patients
should be discussed as part of a multidisciplinary team. Subsequent
treatment is delivered based on the clinical staging of tumour(s) at
the time of presentation, patient’s physical and psychological status,
probability of survival, and their personal wishes. In most cases, surgical,
multimodal and palliative approaches are used in management
of cancers, providing individualised and responsive oncological
treatment. Depending on each case, these therapies can be used
in combination or individually, to increase overall patient survival and
quality of life.
Case Presentation: A 75 year old male presented with dysphagia
and rapid weight loss over 2 months. His medical history includes
Barrett’s oesophagus and duodenal ulcers. Investigation using PETCT and endoscopic ultrasound showed a non-stenosing, malignant
lesion in the distal third of the oesophagus classed as T3 N0 M1a
(stage IIIA), histologically diagnosed as a moderately differentiated
Graves’ ophthalmopathy is the most common extrathyroidal
manifestation of Graves’ disease. This is a case study and discussion on a
54 year old woman with an extensive history of thyroid disease and
Graves’ ophthalmopathy which was increasing in severity.
There are many interesting factors related to Graves’
ophthalmopathy which have been discussed within this case study.
These include; the pathogenesis and clinical features of this condition;
the profound effect of Graves’ ophthalmopathy on not only the
patient’s sight but also on their quality of life and the increased risk
associated with smoking and the use of radioiodine therapy for
thyrotoxicosis. The European Group on Graves’ Orbitopathy ’s newly
developed activity score is also discussed in detail within the case
study, along with management options available and new treatments
which are still undergoing research.
Despite extensive investigation Graves’ ophthalmopathy is still
not completely understood. However, with the developing knowledge
of associated risk factors and the new treatment options which are
becoming available we a coming closer to being able to manage this
complex condition.
The effect of multidisciplinary team care on cancer management
Ganiy Opeyemi Abdulrahman, Jnr, (Cardiff University School
of Medicine)
Mr EE was an 86 year old man who was diagnosed with metastatic
renal cancer in 2009. Although he went through series of treatment,
he was most appreciative of the multidisciplinary team management
of his illness. In the course of his treatment, he was managed by the
surgeons, medical oncologists, nurses, palliative care specialists and
social service workers, all of whom ensured that he received the best
care. Over the past 15 years, the multidisciplinary team management
of many medical conditions especially cancers has increasingly
taken a prominent role in patient management in many hospitals and
medical centres in the developed countries. In the United Kingdom, it
began to gain prominence following the Calman-Heine report in 1995
which suggested that each Cancer Unit in a hospital should have in
place arrangements for non-surgical oncological input into services,
with a role for a non-surgical oncologist. The report further suggested
that a lead clinician with a well established interest in cancer care
should be appointed to organise and coordinate the whole range of
cancer services provided within the Cancer Unit. Many people have
argued that the multidisciplinary team management of patients has
resulted in better care and improved survival. However, there are
barriers to the optimal effectiveness of the multidisciplinary team. This
presentation will discuss how the multidisciplinary team managed
Mr EE and also examine various studies on the effectiveness of the
multidisciplinary team in the management of cancer patients. Some
of the barriers to multidisciplinary team management of patients would
also be discussed.
Notes
Notes
Thank you
Up-coming events
The tremendously positive attitude of The Christie Hospital towards
teaching and education has made this event possible. The Manchester
Oncology Society would like to thank the following members of staff for
their limitless support and enthusiasm.
Gynaecology Study Day - Ovarian Cancer
Tuesday 20th September 2011
Dr Richard Berman
Dr Richard Cowan
Robert Boyle
Shirley Crook
Rachel Rosenhead
Diane Byrne
Steve Glover
Jon Burton
All members of the judging panel
Still Confused about Feeding Tubes?
Monday 26th September 2011
Teenage and Young Adult Cancer - Patient Perspectives
Wednesday 12th October 2011
Metastatic Spinal Cord Compression
Thursday 27th October 2011
Nursing Issues in Stem Cell Transplantation
Monday 21st November 2011
Prostate Cancer: Current Treatments & Challenges
Thursday 1st December 2011
Psychological Wellbeing in Cancer Care
Thursday 8th December 2011
Rehabilitation in Cancer Care
Thursday 23rd - Friday 24th February 2012
Palliative Care
Monday 30th April 2012