PAEDIATRIC SOLID TUMOURS
Alan Davidson
Haematology - Oncology
Red Cross Children’s Hospital
CANCER IN CHILDHOOD
•
US figures show total of 146 cancers per million children
aged 0-14 per year
11.3
34.6 ALL
32.4 BRAIN TUMOURS
NEUROBLASTOMA
8.7 NHL
8.6 WILMS TUMOUR
7.1 AML
5.3 HODGKIN’S DISEASE
5 RHABDOMYOSARCOMA
4.6 RETINOBLASTOMA
3.7 OSTEOSARCOMA
EWING’S TUMOUR
2.1
23.2
OTHERS
CHILDHOOD CANCER AT RCCH
• Approximately 130 new cases per year
• Many present with advanced disease
• Many have presented to the health service
several times over the preceding weeks or
months !
• These delays make treatment more difficult …
and adversely effects prognosis.
SPECTRUM AT RCCH
Numbers represent actual number of tumours for 2003 / 2004 / 2005
17
17
16
14
11
9
5
5
5
4
6
5
3
3
7
6
4
5
0 4
6
1
3
4
2 1
AML
8
WILMS TUMOUR
7
7
NHL
12
16
BRAIN TUMOURS
15
13
8
ALL
15
NEUROBLASTOMA
RHABDOMYOSARCOMA
GERM CELL TUMOUR
HODGKIN’S DISEASE
HEPATOBLASTOMA
BONE TUMOURS
RETINOBLASTOMA
3
16
16
10
OTHER
ONCOLOGY FOR THE PAEDIATRICAN:
What’s the central message ?
• EARLY DIAGNOSIS
• MEANS …
– Improved prognosis
– Less treatment related morbidity
• NEEDS …
– Working knowledge of common tumours
– High index of suspicion
IMPROVED PROGNOSIS
“WHAT A DIFFERENCE A DAY (OR TWO) MAKES”
1.0
0.9
0.8
FAVOURABLE HISTOLOGY
WILMS’ TUMOUR
0.7
0.6
0.5
0.4
Complete
Chi-square = 22.898
0.3
Censored
df = 3 p = 0.00004
Cumulative Proportion Surviving
Stage I
Stage II
Stage III
Stage IV
0.2
0.1
94.4%
96.2%
84.9%
54.2%
0.0
0
50
100
150
200
Time - months
250
300
350
Overall 5-year Survival
LMB Chemotherapy
1988-2004
[Log Rank p value 0.06]
Complete
Censored
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
BURKITT’S LYMPHOMA
Cumulative Proportion Surviving
0.2
Stage II and III
[88.2%]
0.1
0.0
0
20
40
60
80
100
120
Time - months
140
160
180
200
220
Stage IV
[66.0%]
EWING’S SARCOMA
LESS TOXICITY
“SMALLER OMELETTE … LESS EGGS”
WILMS’ TUMOUR TREATMENT…
– Surgery (primary or delayed) for all
– Chemotherapy
• Stage I or II:
• Stage III or IV:
Vincristine + Dactinomycin
Add DOXORUBICIN
– RENAL BED RADIOTHERAPY for local Stage III
– PULMONARY RADIOTHERAPY for lung metastases
CLASSIFYING CHILDHOOD
MALIGNANCY
• LEUKAEMIAS
– ALL / AML / CML
• BRAIN TUMOURS
– Seperate textbook !
• BONE TUMOURS
– Osteogenic Sarcoma
– Ewing’s Sarcoma
• EMBRYONAL TUMOURS
–
–
–
–
–
–
–
Neuroblastoma
Nephroblastoma
Rhabdomyosarcoma
Hepatoblastoma
Retinoblastoma
PNET
Germ Cell Tumour
• RARE TUMOURS
– Thyroid Ca / Melanoma
NEPHROBLASTOMA
• Named for MAX WILMS
• Derived from the metanephros = hence the classic
triphasic nature = epithelial / blastemal / stromal
• Associations
– Overgrowth = BWS / Hemihypertrophy
– Non-overgrowth = Aniridia / WAGR / Denys-Drash
•
•
•
•
Age 0-5yrs (median 3yrs)
Presents with Mass / Pain / Haematuria / Paraneoplasias
Renal mass … L>R (not across midline) 10% bilateral
Metastasis … lungs / liver / brain / (bone)
STAGING
WILMS’ TUMOUR
• Stage I ... confined to kidney
• Stage II ... through capsule
• Stage III ... residual tumour
» Local spread
» Nodes
» IVC Thrombus
• Stage IV
• Stage V
... metastatic disease
... bilateral disease
DIAGNOSIS AND MANAGEMENT
• DIAGNOSIS and STAGING
–
–
–
–
–
FBC / Urea & Creatinine / LDH
Urine
Ultrasound and CT Abdomen
CXR and CT Chest
Biopsy if deemed inoperable or protocol calls for pre-op chemo
• MANAGEMENT
– Two schools (NWTS and SIOP)
– Surgery + Chemo +/- XRT
– Same results !
In fact …
So good that we’re deintensifying treatment !!
1.0
0.9
0.8
FAVOURABLE HISTOLOGY
WILMS’ TUMOUR
0.7
0.6
0.5
0.4
Complete
Chi-square = 22.898
0.3
Censored
df = 3 p = 0.00004
Cumulative Proportion Surviving
Stage I
Stage II
Stage III
Stage IV
0.2
0.1
94.4%
96.2%
84.9%
54.2%
0.0
0
50
100
150
200
Time - months
250
300
350
NEUROBLASTOMA
• Derived from primitive neural crest cells of the sympathetic
nervous system
– Hence they are found along the sympathetic chain
– 1/3 adrenal 1/3 abdominopelvic 1/3 thoracic or cervical
• Age 0-3yrs [median of 17m] [40% are infants]
– Prognosis inversely related to age … Younger kids usually have lower
grade tumours (some of which regress spontaneously) in more
favourable sites (cervicothoracic) and are much less likely to
metastasize
• Staging:
–
–
–
–
–
I: confined to organ
II: extends outside organ (+/- nodes) NOT across midline
III: across midline … involving contralateral nodes
IV: Metastasis to Liver / Bone and BM / Skin
IVS: I/II with remote disease in liver, skin, bone marrow (<10%)
CLINICAL PRESENTATION
• Abdominal mass > 50% … usually smooth and hard (crosses midline)
• Pelvic Mass
• Mediastinal or cervical mass
• Mass effect … proptosis / superior mediastinal syndrome / UAO /
spinal cord compression
• Bone marrow … anaemia / thrombocytopaenia / bone pain with limp
• Metabolic (catecholamines and vasoactive intestinal peptides) …
sweating / diarrhoea & vomiting / hypertension
• Bluish skin marks (typically blanch)
• Opsoclonus-myoclonus / Cerebellar ataxia
DIAGNOSIS AND MANAGEMENT
• DIAGNOSIS and STAGING
–
–
–
–
–
FBC / Urea & Creatinine / LDH
Urinary catecholamines (HVAs and VMAs)
Calcified mass on plain AXR
Imaging of abdomen, chest and possibly spine
Bone Marrow / MIBG / Bone Scan
– Biopsy can be avoided if BM involved !
• MANAGEMENT
– Surgery +/- Chemotherapy
RHABDOMYOSARCOMA
• Commonest soft tissue sarcoma of childhood
• Derived from primitive muscle
• Age 2-15yrs
• Prognosis varies with
– Histology: Embryonal > Alveolar
– Site:
Orbit > Paratesticular > Vaginal > Bladder / Prostate >
Retroperitoneal > Extremity > Parameningeal
– Stage
• Staging:
– I to IV based on complex system using TNM and Site
– IRS Grouping now generally followed …
Group I completely excised
Group II microscopic residua
Group III macroscopic residua Group IV metastases
DIAGNOSIS AND MANAGEMENT
• DIAGNOSIS and STAGING
– FBC / Urea & Creatinine / LDH
– Local imaging …
CT for abdomen / MRI for parameningeal tumours
– CXR and CT chest
– Bone Marrow
• MANAGEMENT
– Chemotherapy with Surgery +/- XRT
HEPATOBLASTOMA
•
•
•
•
Commonest paediatric liver tumour
Age usually under 18 months
Presents as hepatomegaly with elevated FP
Metastasizes locally and to lungs
• DIAGNOSIS
– FBC / Renal and liver functions / FP
– CT abdmen and chest
• MANAGEMENT
– Chemotherapy
– Surgery
CLINICAL SCENARIOS IN
SOLID PAEDIATRIC TUMOURS
AN APPROACH FOR THE GENERAL
PAEDIATRICIAN
1. PANCYTOPAENIA
 LEUKAEMIA
 LYMPHOMA or NEUROBLASTOMA
• ASK ABOUT …
– bone pain
• WATCH OUT FOR …
–
–
–
–
swollen gums
lymph nodes
abdominal masses
proptosis
1. PANCYTOPAENIA
 MUST exclude HIV infection …
 LEUKAEMIA (or LYMPHOMA)
– FBC: Hb Plt  WCC / … look for blasts
– Chemistry: LDH  (with a normal ALT) and Urate 
– CXR: mediastinal mass in T-cell lymphoma
 NEUROBLASTOMA
–
–
–
–
Look for an Abdominal Mass !
FBC: typically anaemic with preserved platelets
Chemistry: LDH  (with a normal ALT) and urinary HVAs
Xrays: lytic bone lesions or calcified abdominal mass
1. PANCYTOPAENIA
WHO SHOULD DO THE BONE MARROW ?
 Generally the receiving hospital but this matter
should always be discussed!
 LEUKAEMIA (or ANY SUSPECTED MALIGNANCY)
– Aspirates and trephines  Flow cytometry  Cytogenetics
 Ig gene rearrangements by PCR  FISH for translocations
– Complicated set of investigations: leave for referral centre !
 OTHER INDICATIONS
– Disseminated TB / ITP / Storage disorders.
– Probably fine to do.
2. BONE PAIN
• NOT localised
• Wakes the child
• Limp or Reluctance to bear
weight
• A toddler who stops
walking
• Backache!!
2. BONE PAIN
• Again, malignancies involving the bone marrow…
 LEUKAEMIA or LYMPHOMA
 NEUROBLASTOMA
• Remember … if local pain and swelling (especially
around the knee joint)…
 BONE TUMOURS eg. OSTEOGENIC SARCOMA
3. ABDOMINAL MASS
• from 6m to 6y …
ABDOMINAL MASS
is a tumour until
proven otherwise
ALWAYS CONSIDER SEDATING
THE PATIENT IF YOU CAN”T
PALPATE THE ABDOMEN !
3. ABDOMINAL MASS
 WILMS TUMOUR
•
flank mass / typical imaging /  LDH
No need for
BIOPSY !!
 HEPATOBLASTOMA
•
hepatomegaly / typical imaging /  Feto-protein
 NEUROBLASTOMA
•
•
adrenal mass / typical imaging /  LDH and HVAs
? signs of metastatic involvement
 BURKITT LYMPHOMA
•
central abdominal mass / nodes on imaging /  LDH
REFER
(3. PELVIC MASS)
 GERM CELL TUMOUR
 Feto-protein
 BURKITT LYMPHOMA
 LDH and urate
No need for
BIOPSY !!
 RHABDOMYOSARCOMA
 LDH
 NEUROBLASTOMA
 LDH
REFER
4. AN UNEXPLAINED MASS
• SITES
– Head and Neck
– Limbs
– Testis
5. UNEXPLAINED NEUROLOGY
•
•
•
•
Headache > 2 weeks
Early morning vomiting
Ataxia / unsteady gait
Cranial Nerve Palsy
 BRAIN TUMOURS
•
•
(watch out for neurocutaneous syndromes)
Posterior fossa … ataxia and cranial nerve palsies
Supratentorial … headache and vomiting  hemiplegia
 RHABDOMYOSARCOMA (often occult in the sinuses)
•
Lower cranial nerve palsies eg. VI, VII, IX, XII
 NEUROBLASTOMA (secondary to skull infiltration)
•
Commonly VI nerve palsy
7. EYE CHANGES
• White Reflex
• Recent Onset Squint
• Loss of Vision
 RETINOBLASTOMA
• Proptosis
 LEUKAEMIA especially Acute Myeloid Leukaemia
 NEUROBLASTOMA
 RHABDOMYOSARCOMA
7. EYE CHANGES
• Leukocoria
• REFER to an Ophthalmologist urgently
for slit lamp examination
7. EYE CHANGES
• Proptosis
• CONSIDER Leukaemia / Neuroblastoma / Rhabdomyosarcoma …
abnormal FBC means diagnosis might be made on BM
examination … REFER
• OTHERWISE REFER to an Ophthalmologist for urgent biopsy
IN SUMMARY …
REMEMBER THE WARNING SIGNS
•
•
•
•
•
•
•
Pallor plus Bleeding
Persistent Fever / Apathy / Weight Loss
Bone Pain
Adenopathy
Unexplained Neurological Signs
Unexplained Mass
Eye Changes
THE BOTTOM LINE
• Be aware of the clinical spectrum of childhood
cancer
• Don’t waste time with special investigations …
Seek expert advice
• Refer cases early … and URGENTLY !