Appendix 1: List of host organisations where individual cryotherapists received
approval by quality assurance review to participate in the CROP study.
Cryotherapy Centre
Date of QA approval
Beatson West of Scotland Cancer Centre
16/06/2011
Bristol Royal Infirmary Hospital
09/11/2012
Darent Valley Hospital
10/04/2012
Maidstone Hospital
29/10/2012
Norfolk and Norwich University Hospital
13/02/2012
Southampton General Hospital
14/10/2011
St Barts Hospital London
14/10/2011
Sunderland Royal Hospital
28/06/2011
Wirral University Teaching Hospital
15/07/2011
Appendix 2: Definition of distant metastasis progression statement for CROP study.
The appearance of new distant metastases will constitute a primary event in this
study. They are defined as below.
Lymph node metastases must fulfil the following criteria on cross sectional imaging:
· Be non-regional to the prostate
· Not present on baseline scan or present with short axis measurement <10mm
· Minimum short axis measurement ≥ 5mm (must be at least 5mm larger than
baseline scan if pre-existing node)
In cases where a lymph node lesion meets these criteria but, in the opinion of the
investigator, an alternative explanation exists for the appearance of the lesion, then
the lesion must be demonstrated to have disappeared or reduced to <15mm short
axis measurement on a confirmatory scan performed ≥ 6 weeks after the index scan.
If the lesion still meets these criteria on a confirmatory scan, then the date of distant
metastasis will be recorded as the date of the index scan (the one which first shows
the lesion to have met the above criteria).
Soft tissue, non-lymph node metastases must fulfil the following criteria on cross
sectional imaging:
· Not present on baseline scan or present with long axis measurement <10mm.
· Minimum long axis measurement of ≥ 10mm (must be at least 5mm larger than
baseline scan if pre-existing lesion)
Bone lesions demonstrated by bone scintigraphy must meet the following criteria:
· Not present on baseline scan (regardless of any change in size or intensity)
· ≥2 new lesions. Where a single new lesion is seen, then the malignant nature must
be confirmed using an alternative imaging modality (e.g. MRI, plain radiology or CT).
· No other explanation (for example trauma). In cases where an alternative
explanation is suspected, then the malignant nature of at least one lesion must be
confirmed using an alternative imaging modality (for example MRI, plain radiology or
CT). Bones lesions detected by other modalities (eg. MRI or CT)
Unequivocal bone metastases will be considered to be new metastatic disease even
if that part of the body has not previously been imaged by this modality. Where the
findings are equivocal then they must be confirmed by another modality (eg. bone
scintigraphy).
In some situations metastatic disease will be discovered between study-protocolled
investigations (for example during investigation for new symptoms). In this situation
the findings may be considered unequivocally metastatic by the investigator. In all
cases, however, every effort should be made to demonstrate malignant nature of the
disease using appropriate radiological investigation.
The date of onset of the symptoms which prompted the investigations will be
considered the date of the first finding of the metastasis.
Appendix 3: The CROP study inclusion and exclusion criteria
Inclusion Criteria:
1. Histologically confirmed relapsed prostate cancer following previous
treatment with
a. radiation therapy (either external beam or brachytherapy) for either
organ confined or
b. non-metastatic locally advanced prostate cancer, namely T1-3aN0M0
disease
2. Life expectancy of at least 5 years
3. Clinical/radiological T1c-T3a
4. PSA level ≤ 20 ng/ml
5. Aged 18 years or over
6. ECOG PS = 0 or 1 or 2
7. Ability to provide informed consent
8. Adequate haematological function as defined by Hb ≥ 100g/L; platelets ≥ 100
x 109/L; neutrophils ≥1.5 x109/L
9. Adequate biochemical function as defined by bilirubin ≤ 1.5 ULN; ALT, AST ≤
2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN and adequate renal function
defined as EITHER serum creatinine ≤ 1.5x ULN OR calculated/measured
creatinine clearance ≥ 60mls/min (as defined by Cockcroft and Gault formula)
Exclusion Criteria:
1. Lymph node >10mm short axis on MRI abdomen and pelvis
2. Previous transurethral resection of prostate gland with evidence of a
significant defect (>10mm in width) on transrectal ultrasound scan
3. Significant lower urinary tract symptoms, including bladder outflow obstructive
symptoms
4. History of abdomino-perineal resection of rectum
5. Known coagulation disorder
6. Complex perianal fistula
7. Previous combined external beam radiotherapy and brachytherapy to the
prostate
8. Significant symptoms/toxicity related to the rectum following radiotherapy
(NCI CTCAE grade 3 or above)
9. Previous androgen deprivation therapy as second line therapy for radiation
recurrent prostate cancer
10. Prior cryotherapy to the prostate
11. Any evidence of severe or uncontrolled systemic conditions (e.g. severe
hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal
lung disease]) or current unstable or uncompensated respiratory or cardiac
conditions which make it undesirable for the patient to participate in the study
or which could jeopardise compliance with the protocol
12. Other prior malignancy with estimated ≥30% chance of relapse within 5 years
Appendix 4: The CROP study Quality Assurance Questionnaire for cryo-therapists.
Page 1 of 6
U171 - CROP
CQA Process Proforma
CROP – CRyOtherapy in Prostate cancer
A randomised controlled trial of deferred androgen deprivation therapy ± upfront cryotherapy in
men with localised radiation recurrent prostate cancer (RRPC) to evaluate efficacy and tolerability
INITIALS: Forename
Surname
DATE OF BIRTH (dd/mon/yyyy):
REFERRING CLINICIAN:
/
/
REFERRING HOSPITAL (name, city):
CRYOTHERAPY QUALITY ASSURANCE PROCESS
PLEASE USE THIS PROFORMA TO SUBMIT DETAILS FOR 3 CONSECUTIVE SOLO CASES
ONE PROFORMA TO BE SUBMITTED PER CASE
PATIENT CHARACTERISTICS
Ethnic
origin
1 = White
2 = Asian(Indian/Bangladeshi/Pakistani etc)
3 = South East Asian(Chinese/Japanese/Korean)
4 = Afro/Caribbean
5 = Other, specify:
__________________________
__________________________
TUMOUR CHARACTERISTICS
(at diagnosis)
Date of first histological confirmation of prostate
cancer:
____/____/______
dd/mon/yyyy
TNM Stage at diagnosis:
T=
(0, 1, 2, 3)
(a, b, c)
N=
(X, 0, 1)
M=
(X, 0, 1)
Gleason score at diagnosis (please add values to boxes):
+
=
Tick if not known
TUMOUR CHARACTERISTICS
(at relapse)
Date of histological confirmation of prostate cancer postradiotherapy:
____/____/______
dd/mon/yyyy
TNM Stage at relapse:
Note ‘N’ and ‘M’ stage must be ‘0’ for patient to be eligible
T=
N=
(0, 1, 2, 3)
Type of biopsy performed for histological confirmation
post-radiotherapy (please tick) :
TRUS
Template biopsy
Other, specify
____________
(a, b, c)
M=
(X, 0, 1)
(X, 0, 1)
Gleason score (please add values to boxes):
+
=
Tick if not known
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Page 2 of 6
Patient's initials (f, s) __ / __
U171 – CROP Patient’s date of birth
/
/
CQA Process Proforma
Hormone assessment (at relapse):
Testosterone (nmol/l) _______ FSH (iu/L) _______ LH (iu/L) _______
Tick if not done
Date of hormone assessment at relapse : ____/____/______
DETAILS OF PRIOR RADIOTHERAPY FOR PROSTATE CANCER
Start date
(dd/mon/yyyy)
End date
(dd/mon/yyyy)
Type of
Radiotherapy
1 = External beam
2 = Brachytherapy
External Beam Treatment
details
Brachytherapy:
Rectal DVH Data
V74 = _____
/
/
/
______
Total dose (Gy)
_______
No fractions
/
Tick if not known
V70 = _____
Tick if not known
V60 = _____
Tick if not known
V50 = _____
Tick if not known
V74 = _____
/
/
/
______
Total dose (Gy)
_______
No fractions
/
Tick if not known
V70 = _____
Tick if not known
V60 = _____
Tick if not known
V50 = _____
Tick if not known
V74 = _____
/
/
/
______
Total dose (Gy)
_______
No fractions
/
Tick if not known
V70 = _____
Tick if not known
V60 = _____
Tick if not known
V50 = _____
Tick if not known
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Page 3 of 6
Patient's initials (f, s) __ / __
U171 - CROP Patient’s date of birth
/
/
CQA Process Proforma
DETAILS OF PRIOR HORMONE THERAPY FOR PROSTATE CANCER
Has the patient received hormone
therapy for prostate cancer prior to
study entry?
Specify treatment:
1 = Yes, please give details below
2 = No, no further details required
Start date
(dd/mon/yyyy)
Tick box if
continuing
If not continuing
provide stop date
(dd/mon/yyyy)
___/___/_____
___/___/_____
___/___/_____
___/___/_____
___/___/_____
___/___/_____
___/___/_____
___/___/_____
Dose and
Units
(e.g , mg)
Schedule
(e.g. od,
mthly, 3mthly)
DIMENSION OF PROSTATE GLAND PRIOR TO CRYOTHERAPY
Length of Prostate:
_____________ mm
(parallel to rectum/typically perpendicular to perineum)
Width of Prostate:
_____________ mm
Volume of Prostate (if available):
_____________ cm 3
POSITION OF THE ICERODS (OR ICESEEDS) AND TEMPERATURE SENSORS
Submission of ultrasound images:
Freehand markup:
Please attach ultrasound images and submit to CRUK CTU,
Glasgow along with this completed and signed form. Patient
identifiable data should not be visible on the images (e.g. patient full
name and hospital number). Please clearly mark the patient initials
and trial number on all images.
The position of the freezing needles and temperature sensors are to be
marked on the prostate cartoon to the left. The position of the urethra
and anterior rectal wall are outlined. If using warming needles and/or
temperature sensor in the rectal wall these should be clearly marked.
(If the Investigator prefers to mark directly on a second print out of a
transverse view of the prostate on ultrasound scan, it is acceptable as
long as the markers are easily visible and made with permanent
marker pen and the image is clearly marked with the patient initials
and trial number).
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Page 4 of 6
Patient's initials (f, s) __ / __
U171 – CROP Patient’s date of birth
/
/
CQA Process Proforma
Please use this space to provide comments. Information on the relative positioning of the temperature sensor particularly in
relation to the rectal wall may be useful:
TEMPERATURE AND FREEZING INTENSITY PROFILE FROM THE CRYOTHERAPY
WORKSTATION
Please tick to confirm that you you are also submitting the temperature and freezing intensity profile print outs from the
computerized workstation within the cryotherapy system
Please include:
-
temperature profile of each sensor
-
Information on the relative ‘freezing’ power during the treatment period
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Page 5 of 6
Patient's initials (f, s) __ / __
U171 - CROP Patient’s date of birth
/
/
CQA Process Proforma
REPRESENTATIVE DIMENSION OF THE ICEBALL AT THE END OF FREEZING CYCLES
Length of iceball
______________mm
Transverse diameter of iceball
______________mm
Or tick to confirm ultrasound images have been submitted to show this
DATE (dd/mon/yyyy)
INVESTIGATOR'S SIGNATURE
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Page 6 of 6
Patient's initials (f, s) __ / __
U171 – CROP Patient’s date of birth
/
/
CQA Process Proforma
For Office Use only:
POSITION OF THE ICERODS (OR ICESEEDS) AND TEMPERATURE SENSORS
Assessment:
Yes/No to the following fields:
Appropriate prostate size for treatment
Y/N
Appropriate choice of ice needle/rod
Y/N
Appropriate positioning of ice needles/rods
Y/N
Appropriate positioning of temperature sensors
Y/N
Freehand comments from reviewers
TEMPERATURE AND FREEZING INTENSITY PROFILE THE COMPUTERISED
WORKSTATION
Assessment:
Yes/No to the following fields:
Satisfactory minimum temperature measured (~-30oC or lower)
Y/N
Satisfactory temperature for surrounding structure
Y/N
Freehand comments from reviewers
DIMENSION OF THE ICEBALL.
Assessment:
Satisfactory treatment to the prostate
Satisfactory relationship to surrounding structures
Y/N
Y/N
Freehand comments from reviewers:
Version 1, 23rd May 2011
Please return completed form to: CRUK Clinical Trials Unit, Level 0, The Beatson West of Scotland Cancer Centre, 1053 Great Western Road, Glasgow,
G12 0YN.
Appendix 5: The CROP study patient acceptance questionnaire. The selected
numbered statement at the bottom of the form signifies the most important factor in
patient decision.
Appendix 6: The CROP study patient declined questionnaire. The selected
numbered statement at the bottom of the form signifies the most important factor in
patient decision.