SIOP PNET 5 MB NECESSARY DOCUMENTATION€¦ · SIOP PNET 5 MB Final Version 11 – 2014, Nov 17 CRF...

SIOP PNET 5 MB Final Version 11 – 2014, Nov 17 CRF Appendix I

SIOP PNET 5 MB NECESSARY DOCUMENTATION

Timing Form Number

Form Name Form Return Date Form Sent

Diagnosis Form 1 2 pages

Screening for eligibility As soon as possible

Form 2A Form 2B

To neuroradiology review Neuroradiology review form

As soon as possible Central reference evaluation has to be completed by day 22 after surgery

Form 3A Form 3B

To pathology review Pathology review form

Form 4A Form 4B 2 pages each

To biology stratification Biology stratification

Form 5A Form 5B 2 pages each

Registration PNET 5 MB-LR Registration and randomisation PNET 5 MB-SR

As soon as possible Before day 28

Before RT Form 6 5 pages

Status after surgery and before radiotherapy

Within 3 months after surgery

Form 7A 1 page Form 7B 4 pages

Central prospective review of RT Radiotherapy quality control

As soon as possible. RT quality control to be completed no later than first week of RT

Radiotherapy to be started within 28 days after surgery

During treatment

Form 8 6 pages

Radiotherapy

Within 1 month after the end of radiotherapy

Form 9 Carboplatin concomitant to RT (only for PNET 5 MB- SR patients randomized for Carboplatin)

Form 10 2 pages

Toxicity between RT and chemotherapy

Within 1 month after assessment

Form 11A 2 pages Form 11B 2 pages

Chemotherapy, Regimen A Chemotherapy, Regimen B

Within 1 month after the end of each course (complete form after every course)

Post treatment

Form 12 End of therapy Within 3 months after end of therapy

Form 13 4 pages

Post treatment - late effects 2 years after diagnosis, 5 years after diagnosis, and at age of 18 years Within 3 months after assessment

Form 14

Follow-up, first Relapse, and death

End of therapy, afterwards annually, at first relapse, second malignancy or death Within 1 month after assessment

Form 15A Form 15B

To follow-up neuroradiology review Follow-up radiology review

Two years after diagnosis, and in case of relapse Within 1 month after assessment

Form 16 Posterior fossa relapse/ progression

Within 1 month after relapse/ progression

SAE Form 17 3 pages

Serious adverse event (SAE) Within 24 hours after knowledge of the event


SIOP PNET 5 MB SCREENING FOR ELIGIBILITY

to be sent as soon as possible (before day 28) after surgery Form 1 page 1/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________

Patients name* Date of birth (DD/MM/YYYY) Centre ID Local patient ID

Male Female * please indicate name only, if this is according to your national policy and laws

INCLUSION CRITERIA several items applicable, please tick

Age ≥ 3 years and < 22 years at surgery Yes No Primary tumour in posterior fossa Yes No

No prior treatment of medulloblastoma other than surgery Yes No CTC grades < 2 for liver, renal, and haematological function Yes No EXCLUSION CRITERIA

Clinical evidence of intra or extra CNS metastasis Yes No Medical contraindication to RT or chemotherapy Yes No DNA breakage syndrome, or identified Turcot or Li Fraumeni Syndrome Yes No Pregnancy or females who are sexually active without reliable contraception Yes No Limitations of regular follow-up or of adherence to toxicity guidelines Yes No Previous brain tumour or malignant disease Yes No Date of first surgery: __ __ / __ __ / __ __ __ __ DD MM YYYY

If applicable

second surgery Yes No, if `yes´ Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Neuroradiology (mandatory) Preop. and early postop. cranial MRIs and spinal MRIs sent for central review (form 2A)

Yes No Histology (mandatory) Formalin fixed paraffin embedded tissue sent for central review (form 3A) Yes No Biological stratification (mandatory) Material sent for biological stratification (form 4A) Yes No CSF (LP) free from tumour cells: Yes No Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Not performed

CSF sent for central review Yes No Audiology: Audiometry (PTA) performed Yes No, if `yes´ Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Hearing loss ≥ 20 dB at 1-3 kHz excluded? Yes No If no PTA: history of hearing deficit excluded? Yes No normal OAE present? Yes No


SIOP PNET 5 MB SCREENING FOR ELIGIBILITY

to be sent as soon as possible (before day 28) after surgery Form 1 page 2/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Investigator

.......................................……………………………. ……………….. ………………………………...

Name of local investigator Date Signature

...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................

Fax Telephone E-mail

Send pages 1+2 for central evaluation of eligibility to the national data center

[email protected]

After results of central evaluations are available and sent to the national data centre,

this form will be returned to the local investigator.

Please note that radiotherapy should start within 28 days (no later than 40 days) after

surgery. Registration is only possible within this time limit.

For registration please send the respective registration FAX (Form 5A or 5B).

For National data centre use National data centre ID: __ __ __

Reference neuroradiology has been performed and results allow inclusion Yes No (according to form 2B)

Reference histology has been performed and results allow inclusion Yes No (according to form 3B)

Biological stratification has been performed and results allow inclusion Yes No (according to form 4B)

Date of receipt of complete information for eligibility screening __ __ / __ __ / __ __ __ __ DD MM YYYY

Timeline for registration within 28 (40) days after surgery is met Yes No

According to biological studies patient is eligible for inclusion in

PNET 5 MB – LR

PNET 5 MB – SR

Documentation of eligibility criteria is complete Yes No

If `no´, please complete the following missing information and send this Fax form again:

__________________________________________________________________________

Send back to local investigator.

mailto:[email protected]


Send to central review urgently. Central review process has to be completed 22 days after surgery.

SIOP PNET 5 MB TO NEURORADIOLOGY REVIEW (S54836) central review for evaluation of eligibility according to national group decision

to be sent as soon as possible after surgery Form 2A page 1/1

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Investigator

.......................................……………………………. ……………….. ………………………………...


...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................


This patient with medulloblastoma will be evaluated for eligibility for PNET 5 MB. These studies involve central review of neuroradiology to confirm non-metastatic disease and the absence of a residual tumour > 1.5 cm2 (on axial plane).

Date of first surgery: __ __ / __ __ / __ __ __ __ DD MM YYYY

If applicable

second surgery No Yes, Date __ __ / __ __ / __ __ __ __ DD MM YYYY

For this patient we send (please tick!)

Cranial MRI before surgery Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Spinal MRI before or after surgery Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Early postoperative cranial MRI* Date __ __ / __ __ / __ __ __ __ DD MM YYYY

*recommended to be performed within 72 h after surgery, preferentially on day 1 or 2 but not on the day of surgery (= day 0)

If applicable

Early postoperative cranial MRI after 2nd surgery Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Please send anonymised images to UZ Leuven through lamp system (or on CD) and send this form to [email protected]

Send to central review neuroradiologist of national group: Name UZ Leuven Prof Demaerel/ Prof Heye Hilde Vandenhout/ Philip Koutsos Adress Herestraat 49 City 3000 Leuven

SIOP PNET 5 MB

NEURORADIOLOGY CENTRAL REVIEW

(within national groups)



Send to national data center ([email protected]) urgently. Central review process has to be completed 22 days after surgery.

SIOP PNET 5 MB NEURORADIOLOGY REVIEW FORM To be completed by central review neuroradiologist for evaluation of eligibility according to national group decision

to be sent as soon as possible after surgery Form 2B page 1/1

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Preoperative status: MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Tumour size ( cm ) craniocaudal __ __ . __, left-right __ __ . __, anterior-posterior __ __ . __ (axial) (coronal) (sagittal)

□ size not assessable

Signs of hydrocephalus □ no □ enlarged ventricles (slight)

□ periventricular edema (moderate) □ compressed sulci at the vertex (severe)

Postoperative status MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Residual tumour □ no □ doubtful residue ≤ 1,5 cm2, not measurable

□ yes, ≤ 1,5 cm2 □ yes, > 1,5 cm2 (not eligible)

size __ __ . __ cm X __ __ . __ cm (sagittal and coronal diameter measured in the axial slice)

Signs of hydrocephalus □ no □ enlarged ventricles (slight)

□ periventricular edema (moderate) □ compressed sulci at the vertex (severe)

Spinal MRI (before or after surgery) MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Meningeal metastases □ no

□ yes, cranial (M2; not eligible) □ yes, spinal (M3; not eligible)

Technical quality in reviewed scans □ appropriate for staging

□ inappropriate for staging (not eligible)

If imaging has been judged inappropriate, please consider additional imaging and re-review!

Comments _______________________________________________________________________________

_________________________________________________________________________________________

......................................................... ............................ .................................................................

Name of reviewing neuroradiologist Date Signature



SIOP PNET 5 MB TO PATHOLOGY REVIEW (S54836) central review for evaluation of eligibility according to national group decision


……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________

Patients name Date of birth (DD/MM/YYYY) Centre ID Local patient ID

............................................... Male Female Patients surname ………………………………………………………………………………………………………………………. Patients address ………………………………………………………… ………………………………… ……./…… Name insurance Member number insurance KG1/KG2

This patient with medulloblastoma will be evaluated for eligibility for PNET 5 MB. These studies

involve mandatory central review of pathology.


If applicable second surgery No Yes, Date __ __ / __ __ / __ __ __ __ DD MM YYYY

The diagnosis from the referring local pathologist is Classic medulloblastoma (CMB) Nodular-desmoplastic medulloblastoma (DMB) Anaplastic medulloblastoma (AMB) Large-cell medulloblastoma Medulloblastoma with extensive nodularity Medulloblastoma not further specified (MBEN) …………………………………………………………. ……………………………………………………. Name of local pathologist Signature

………………………………………………………………………………………………………………………. Hospital, City, Country

…………………………………………………………. ……………………………………………………. E-mail Fax For referring pathologist: Please submit 30 FFPE slides of 5µm and a copy of the pathology report. Please note that submission of unstained slides for either component of the study is not sufficient.

Your submitted slides will be used responsibly for pathological review according to the study protocol. If possible the remaining slides will be returned as soon as possible. Only the required amount of tissue for the biological studies will be sent to researchers, who will not have access to patient identifiers. Number of slides sent:_________________

Please send pathology slides ambient to UZ Leuven and send this form to [email protected]

SIOP PNET 5 MB

PATHOLOGY CENTRAL REVIEW (within national groups)

Send to central review pathologist of national group: Name UZ Leuven Prof Sciot/ Prof Debiec Marleen Franssens/Peter Leemans Adress Herestraat 49 City 3000 Leuven



Send to national data center ([email protected]) urgently. Central review process has to be completed 22 days after surgery. .

SIOP PNET 5 MB PATHOLOGY REVIEW FORM To be completed by central review pathologist for evaluation of eligibility according to national group decision


……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Alternative to this form, a report can be sent to the participating institution / national data centre, if the histological subgroup of medulloblastoma is clearly described. Pathological diagnosis (according to central pathology review):

Classic medulloblastoma (eligible for PNET 5 MB)

Nodular-desmoplastic medulloblastoma (eligible for PNET 5 MB)

Anaplastic medulloblastoma (not eligible)

Large-cell medulloblastoma (not eligible)

Medulloblastoma with extensive nodularity (not eligible)

other diagnosis, specify ____________________________________________________

Number of histopathological report: ______

Comments

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

_________________________________________________________________________________________

......................................................... ............................. .................................................................

Name of reviewing pathologist Date Signature



SIOP PNET 5 MB TO BIOLOGY STRATIFICATION (S54836) central review for evaluation of eligibility according to National Group decision


……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________

Patients name Date of birth (DD/MM/YYYY) Centre ID Local patient ID

............................................... Male Female Patients surname ………………………………………………………………………………………………………………………. Patients address ………………………………………………………… ………………………………… ……./…… Name insurance Member number insurance KG1/KG2

This patient with medulloblastoma will be evaluated for eligibility for PNET 5 MB – LR or PNET 5 MB -

SR. These studies involve mandatory central review of biology for stratification of the patient in the

respective study, and additional biological studies.


If applicable second surgery No Yes, Date __ __ / __ __ / __ __ __ __ DD MM YYYY

For this patient we send (please tick all that apply!) 30 FFPE 5µm slides (mandatory-see pathology review) Number of slides sent: _____ Fresh frozen tumour tissue (mandatory) Whole blood (10ml EDTA) frozen CSF frozen (2aliquots) Consent for biologic screening evaluation has been signed Yes No …………………………………………………………. …………………………………………………… Name of local pathologist / investigator Signature ……………………………………………………………………………………………………………………… Hospital, City, Country …………………………………………………………. ……………………………………………………. E-mail Fax For referring pathologist:

Your submitted tissue will be used responsibly for biological review and biological studies according to the study protocol. Please note that FFPE slides will also be needed for mandatory pathological review (see form 3A). Only the required amount for the biological studies will be sent to researchers, who will not have access to patient identifiers.

Please send pathology material (slides and fresh frozen material), frozen blood and frozen CSF to UZ Leuven and send this form to [email protected]

SIOP PNET 5 MB

BIOLOGICAL STUDIES CENTRAL REVIEW (within National groups)

Send to central review pathologist of national group: Name UZ Leuven Prof Sciot/Prof Debiec Marleen Franssens/ Peter Leemans Adress Herestraat 49. City 3000 Leuven




SIOP PNET 5 MB BIOLOGY STRATIFICATION To be completed by responsible person at central review biology institution for evaluation of eligibility according to national group decision


……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Was the submitted biological material including fresh frozen tumour material of high quality: Yes (eligible for PNET 5 MB) No (not eligible) Estimated tumour cell content (%) of frozen biopsy used for FISH analysis: _______(%) MYC amplification (FISH) (mandatory) Total number of cell nuclei analysed: _____ Percentage of total cell nuclei with amplification: _____ % MYC amplification absent MYC amplification present MYC amplification not evaluable

MYCN amplification (FISH) (mandatory) Total number of cell nuclei analysed: _____ Percentage of total cell nuclei with amplification: _____ % MYCN amplification absent MYCN amplification present MYCN amplification not evaluable

-catenin status (IHC and mutation, mandatory) Percentage of immunopositive nuclei: _____ %

-catenin nuclear immunonegativity by IHC

-catenin nuclear immunopositivity by IHC

-catenin by IHC not evaluable

-catenin mutation absent

-catenin mutation present

-catenin mutation not evaluable

If ß-catenin positive, please give nature of -catenin mutation detected (nucleotide and amino acid alteration): _________________________________________________________________________ Chromosome 6 status (FISH or aCGH) (optional) Total number of cell nuclei analysed (FISH): _____ Percentage of total cell nuclei with monosomy 6 (FISH): _____ Monosomy 6 absent

Monosomy 6 present



Monosomy 6 not evaluable Monosomy 6 not evaluated

SIOP PNET 5 MB BIOLOGY STRATIFICATION To be completed by responsible person at central review biology institution for evaluation of eligibility according to national group decision


……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Conclusion on patient’s biological status:

ß-catenin by IHC

ß-catenin mutation

present

nuclear immunonegative

ß-catenin by IHC

monosomy 6present

monosomy 6absent, not evaluable,

or not evaluated

monosomy 6present, absent, not

evaluable, or not evaluated



High quality material

MYC/ MYCNamplification

no

present ornot evaluable

yes

absent

not eligible

not eligible

PNET 5 MB-LR* PNET 5 MB-LR* PNET 5 MB-SR* PNET 5 MB-SR* not eligible

nuclear immunopositive not evaluable

absent or not evaluable

nuclear immunopositive, immuno-negative or not evaluable



*Decision only according to biology profile; final decision on study-arm to be made by national coordinator, taking all inclusion and exclusion criteria into account (e.g. results of reference histopathology and reference radiology, age of patient, ability to start radiotherapy within 40 days).

Comments _______________________________________________________________________

......................................................... ............................. ............................................................

Name of biology reviewer Date Signature


SIOP PNET 5 MB – LR REGISTRATION

to be sent before day 28 from date of surgery Form 5A page 1/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Registration is only possible after the eligibility screening form has been submitted and eligibility for PNET 5 MB – LR has been confirmed by the national data centre. This is the confirmation form to register the patient into PNET 5 MB – LR.

Investigator

.......................................……………………………. ……………….. ………………………………...


...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................


Informed consent has been signed for: Study participation No Yes, Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Storage of biological samples and No Yes

use for biological studies (no germline analysis)

Use of biological samples for No Yes germline analysis

Parents/ patient requested information about relevant results of biological analyses No Yes Informed consent from child No Yes, Date __ __ / __ __ / __ __ __ __

Not asked DD MM YYYY

Valid protocol version Version 10 – 2013, Feb 21 Version 11 – 2014, Sep 01


SIOP PNET 5 MB – LR REGISTRATION

to be sent before day 28 from date of surgery Form 5A page 2/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Start of RT planned to begin within 40 days after surgery? Yes No Please send RT plan to national RT Quality Control MARVIN ID: GPOH.__ __ __ __ __ (Please use this MARVIN ID for further documentation)

send to NATIONAL DATA CENTRE [email protected]

For national data centre use: National data centre ID: __ __ __

PNET 5 MB – LR Date of registration: __ __ / __ __ / __ __ __ __ DD MM YYYY

...............…………………………………………………. Signature national coordinator

Send back to local investigator and national QoS coordinator



SIOP PNET 5 MB – SR REGISTRATION AND RANDOMISATION

to be sent before day 28 from date of surgery Form 5B page 1/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Registration is only possible after the eligibility screening form has been submitted and eligibility for PNET 5 MB - SR has been confirmed by the national data centre. This is the confirmationform to register the patient into PNET 5 MB – SR.

Investigator

.......................................……………………………. ……………….. ………………………………...


...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................


Informed consent has been signed for: Study participation and No Yes, Date __ __ / __ __ / __ __ __ __

randomisation DD MM YYYY

Storage of biological samples and No Yes

use for biological studies (no germline analysis)

Use of biological samples for No Yes germline analysis

Parents/ patient requested information about relevant results of biological analyses No Yes Informed consent from child No Yes, Date __ __ / __ __ / __ __ __ __

Not asked DD MM YYYY

Valid protocol version Version 10 – 2013, Feb 21 Version 11 – 2014, Sep 01


SIOP PNET 5 MB – SR REGISTRATION AND RANDOMISATION

to be sent before day 28 from date of surgery Form 5B page 2/2

……………………………… __ __ / __ __ / __ __ __ __ __ __ __ ________________



Start of RT planned to begin within 40 days after surgery? Yes No Please send RT plan to national RT Quality Control MARVIN ID: GPOH.__ __ __ __ __ (Please use this MARVIN ID for further documentation)

send to NATIONAL DATA CENTRE [email protected]

For national data centre use: National data centre ID: __ __ __

PNET 5 MB – SR Date of randomisation __ __ / __ __ / __ __ __ __ DD MM YYYY

A Radiotherapy alone B Radiotherapy + Carboplatin

...............…………………………………………………. Signature national coordinator

Send back to local investigator and national QoS coordinator



Complete in Marvin within 3 months after surgery.

SIOP PNET 5 MB STATUS AFTER SURGERY, BEFORE RT

to be completed within 3 months after surgery Form 6 page 1/5

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

1. Surgery Date of first (tumour) surgery __ __ / __ __ / __ __ __ __ DD MM YYYY

First surgery was performed at study participating centre other hospital Category of surgery elective emergency Estimated extent of resection based on surgeon’s judgement (of first surgery)

microscopically complete resection

macroscopically complete resection subtotal resection

less than subtotal resection not determined

Days admitted to an intensive care unit after first (tumour) surgery __ __ days Did the patient receive postoperative blood transfusions Yes No Second (tumour) surgery Yes No, if `yes´ Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Second surgery was performed at study participating centre other hospital

Estimated extent of resection based on surgeon’s judgement (of second surgery) microscopically complete resection

macroscopically complete resection subtotal resection

less than subtotal resection not determined

Days admitted to an intensive care unit after second (tumour) surgery __ __ days Did the patient receive postoperative blood transfusions Yes No 2. History of symptomatic hydrocephalus? Yes No If ‘Yes’ please give further information Use of steroids Yes No Not known Permanent intervention for hydrocephalus Ventriculo-cisternostomy Ventriculo-peritoneal shunt (VP-shunt) Ventriculo-atrial shunt (VA shunt) Ventriculo-cisternostomy + VP shunt Ventriculo-cisternostomy + VA shunt No

Onset of hydrocephalus symptoms:

Before first tumour surgery, days from onset of symptoms to operation __ __ days

After first tumour surgery, days from operation to onset of symptoms __ __ days

......................................................... ............................. .............................................................

Name of investigator Date Signature





__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

3. Does the patient have any restriction or lack of ability to perform an activity due to any motor problem, cranial nerve palsy or poor vision? Yes No Please encircle information for pre-resection and post-resection, and please also give information on change of ability after resection compared to pre-resection:

If you answered ‘Yes’ to limb stiffness / weakness, please specify pattern of weakness (please tick all that apply)

Pre-resection Upper limbs right left Lower limbs right left Post-resection Upper limbs right left Lower limbs right left Date of post-operative assessment __ __ / __ __ / __ __ __ __ DD MM YYYY

......................................................... ............................. .............................................................


a) pre-resection

b) post-resection, before RT start (preferably approx.30 days after surgery)

c) change between pre- and post-resection

encircle the most appropriate response !

consciousness full / impaired / not known

full / impaired / not known

same / better / worse / not known

vision according to age (II)

normal / impaired / not known

normal / impaired / not known

same / better / worse / not known

impairment of extra ocular movements (III, IV, VI)

yes / no / not known

yes / no / not known same / better / worse / not known

facial weakness (VII) yes / no / not known


impairment of swallowing (IX,X,XI)



ataxia of arm(s) yes / no / not known


ataxia of leg(s) yes / no / not known


truncal ataxia



limb stiffness / weakness







__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

4. Posterior fossa syndrome Were symptoms of posterior fossa syndrome present after the initial tumour resection Yes No If ‘Yes’ please specify Time of onset = immediately postoperative = Days 1–2 = Days 3–4 = > Day 4 Mutism / reduced speech = none = mild (mutism < 1 week) = moderate (mutism 1–4 weeks) = severe (mutism > 4 weeks) Please indicate end of symptoms by date: __ __ / __ __ / __ __ __ __ DD MM YYYY

Ataxia = none = mild (persists < 1 week) = moderate (persists 1–4 weeks) = severe (persists > 4 weeks) Please indicate end of symptoms by date: __ __ / __ __ / __ __ __ __ DD MM YYYY

Hypotonia / quadriparesis = none = mild (can’t sit or stand by < 1 week) = moderate (can’t sit or stand 1–4 weeks) = severe (can’t sit or stand > 4 weeks) Please indicate end of symptoms by date: __ __ / __ __ / __ __ __ __ DD MM YYYY

Irritability / behavioural = none disturbances = mild (persists 1 < week) = moderate (persists 1–4 weeks) = severe (persists > 4 weeks) Please indicate end of symptoms by date: __ __ / __ __ / __ __ __ __ DD MM YYYY

......................................................... ............................. .............................................................





to be completed within 3 month after surgery Form 6 page 4/5

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

5. The Brief Ataxia Rating Scale (BARS) To be evaluated by a physician Date of evaluation __ __ / __ __ / __ __ __ __ DD MM YYYY

......................................................... ............................. ............................................................


a) Gait 0 Normal 1 Almost normal naturally, but unable to walk with

feet in tandem position 2 Walking without support, but clearly abnormal and

irregular 3 Walking without support but with considerable

staggering; difficulties in half turn 4 Walking without support not possible; uses support

of the wall for 10-meter test 5 Walking possible only with one cane 6 Walking possible only with two canes or with a

stroller 7 Walking possible only with one accompanying

person 8 Walking impossible with one accompanying person

(2-person assist; wheelchair)

b) Knee tibia test (decomposition of movement and intention tremor) 0 Normal 1 Lowering of heel in continuous axis, but

movement is decomposed in several phases, without real jerks, or abnormally slow

2 Lowering jerkily in the axis 3 Lowering jerkily with lateral movements 4 Lowering jerkily with extremely long

lateral movements, or test impossible

Score:

Score Left: Right:

c) Finger to nose test (decomposition and dysmetria of arm and hand) 0 Normal 1 Oscillating movement of arm and / or hand without

decomposition of the movement 2 Segmented movement in 2 phases and / or

moderate dysmetria in reaching nose 3 Segmented movement in more than 2 phases and /

or considerable dysmetria in reaching nose 4 Dysmetria preventing the patient from reaching

nose

d) Dysarthria 0 Normal 1 Mild impairment of rate / rhythm / clarity 2 Moderate impairment of rate / rhythm /

clarity 3 Severely slow and dysarthric speech 4 Speech absent or unintelligible

Score

Left: Right: Score:

e) Oculomotor abnormalities 0 Normal 1 Slightly slowed pursuit, saccadic intrusions, hypo /

hypermetric saccade, nystagmus 2 Prominently slowed pursuit, saccadic intrusions,

hypo / hypermetric saccade, nystagmus

Score:





__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

6. Growth and puberty Height __ __ __ cm Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Weight __ __ __ . __ kg

Sitting height __ __ __ cm

Gestational age __ __ weeks Birth weight __ __ . __ kg

Maternal height __ __ __ cm Measured Reported Not known

Paternal height __ __ __ cm Measured Reported Not known Pubertal status: If female Breast stage (Tanner): 1 2 3 4 5 (please encircle)

Menarche No

Yes, irregular

Yes, regular menstrual cycle Last menstrual period: __ __ / __ __ / __ __ __ __ (for interpretation of FSH levels) DD MM YYYY

If male Genital stage (Tanner): 1 2 3 4 5 (please encircle) Testicular volumes (ml): (please encircle) Right 0/1 2 3 4 6 8 10 12 15 20 25 30

Left 0/1 2 3 4 6 8 10 12 15 20 25 30 7. Follicle stimulating hormone FSH __ __ __ . __ IU/L Date of evaluation __ __ / __ __ / __ __ __ __ DD MM YYYY

Does the patient receive oral contraception or sex steroid to induce or maintain pubertal development? Yes No 8. QoS questionnaires done? Yes No Don’t know Data retrieval by HealthTracker Booklet ......................................................... ............................. ............................................................



Send to central review urgently. Central review process has to be completed prior to start of RT.

SIOP PNET 5 MB CENTRAL PROSPECTIVE REVIEW OF RT (S54836)

central review of radiotherapy according to national group decision Form 7A page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

This patient with a posterior fossa PNET (medulloblastoma) has been entered into the international study SIOP PNET5 MB which involves: Central review of radiotherapy by the national radiotherapy quality control coordinator and the national radiotherapy quality control panel. According to national group decision this will be performed no later than the first week after start of radiotherapy. Local radiotherapist

.......................................……………………………. ……………….. ………………………………...

Name of local radiotherapist Date Signature

...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................


Please send the RT planning/images through the lamp system (or on CD) to UZ Leuven and email this form to [email protected]

SIOP PNET 5 MB - LR

SIOP PNET 5 MB - SR

RADIOTHERAPY QUALITY

CONTROL

Send to central review radiotherapist of national group: Name: UZ Leuven Prof Menten/ Prof Van Beek Adress: Herestraat 49 City: 3000 Leuven



Send to national data centre [email protected] urgently. Central review process has to be completed prior to start of RT.

SIOP PNET 5 MB RADIOTHERAPY QUALITY CONTROL to be completed by reference radiotherapist Form 7B page 1/4

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Radiotherapy quality control performed: Yes No Radiotherapy quality control completed prior to start of RT: Yes No Date of Quality Control Date __ __ / __ __ / __ __ __ __ DD MM YYYY

A = Sup. part of eye blocks ______ 1 Safety margin < 3 mm 2 Safety margin ≥ 3 mm and < 5 mm 3 Safety margin ≥ 5 mm B = Post part of eye blocks ______ 1 Safety margin < 5 mm 2 Safety margin ≥ 5 mm and < 10 mm 3 Safety margin ≥ 10 mm C = Temporal fossa ______ 1 Safety margin < 5 mm 2 Safety margin ≥ 5 mm and < 10 mm 3 Safety margin ≥ 10 mm D = Margin around the skull ______ 1 Safety margin < 5 mm 2 Safety margin ≥ 5 mm and < 10 mm 3 Safety margin ≥ 10 mm E = Anterior part of cervical spine ______ 1 Safety margin < 5mm 2 Safety margin ≥ 5 mm and < 10 mm 3 Safety margin ≥ 10 mm F = Dorso-lumbar spine ______ 1 Inadequate inferior margin 2 Too large 3 Too narrow 4 Correct G = Energy ______ 1 Energy inadequate 2 Energy adequate

......................................................... ............................. .................................................................

Name of reviewing radiotherapist Date Signature





__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Site(s) of disagreement between local radiotherapist and reference radiotherapist please encircle

major deviation none, A B C D E F not determinable minor deviation none, A B C D E F not determinable

Comments to local radiotherapist:

_________________________________________________________________________________

_________________________________________________________________________________

......................................................... ............................. .................................................................


Whole brain: A = Sup part of eye block to cribriforme plate B = Post part of eye block to temporal lobe C = Temporal fossa to block D = Minimal margin around skull to field





__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Dosimetry for craniospinal axis radiotherapy using complex 3D or IMRT approaches

Dosimetric aim 95% of prescribed dose to 95% of PTV 90% of prescribed dose to 100% of PTV 107% of prescribed dose to ≤ 5% of PTV

Brain 95% isodose to └┴┴┘% of PTV

Correct Minor deviation (95% isodose to ≥ 90% and < 95% of PTV) Major deviation (95% isodose to < 90% of PTV) Deviation site Frontal lobe Cribriforme plate Temporal lobe Other, specify _________________

107 % isodose to └┴┴┘% of PTV

Correct Minor deviation (107% isodose to > 5% but < 10% of PTV) Major deviation (107% isodose to ≥ 10% of PTV) Deviation site Frontal lobe Cribriforme plate Temporal lobe Other, specify _________________

Spine 95% isodose to └┴┴┘% of PTV

Correct Minor deviation (95% isodose to ≥ 90% and < 95% of PTV) Major deviation (95% isodose to < 90% of PTV) Deviation site Cervical spine Thoracic spine Lumbar spine Other, specify _________________


Correct Minor deviation (107% isodose to > 5% but < 10% of PTV) Major deviation (107% isodose to ≥ 10% of PTV) Deviation site Cervical spine Thoracic spine Lumbar spine Other, specify _________________ ......................................................... ............................. ….............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Boost 95% isodose to └┴┴┘% of PTV

Correct Minor deviation (95% isodose to ≥ 90% and < 95% of PTV) Major deviation (95% isodose to < 90% of PTV) Deviation site Frontal lobe Cribriforme plate Temporal lobe Other, specify _________________


Correct Minor deviation (107% isodose to > 5% but < 10% of PTV) Major deviation (107% isodose to ≥ 10% of PTV) Deviation site Frontal lobe Cribriforme plate Temporal lobe Other, specify _________________ ......................................................... ............................. ….............................................................




Complete in Marvin within 1 month after the end of radiotherapy.

SIOP PNET 5 MB RADIOTHERAPY

to be completed by local radiotherapist Form 8 page 1/6

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

1. Dates of treatment Radiotherapy start date __ __ / __ __ / __ __ __ __ DD MM YYYY

Radiotherapy end date __ __ / __ __ / __ __ __ __ DD MM YYYY

For patients receiving carboplatin during radiotherapy, please also complete form 9. 2. Weight Weight at start of radiotherapy __ __ __ . __ kg

Weight at end of radiotherapy __ __ __ . __ kg

3. Carboplatin during radiotherapy Yes No 4. Radiotherapy treatment interruption Yes No If yes, total number of days of interruption __ __ days

Number of interruptions __ __ Causes Toxicity Yes No Disease progression Yes No Bank holidays Yes No Other Yes No 5. Hospitalisation during radiotherapy Yes No

Causes Toxicity Yes No Disease progression Yes No Other Yes No Number of days of hospitalisation __ __ days 6. Was radiotherapy modified after quality assurance review Yes No If yes, please give date of implementation __ __ / __ __ / __ __ __ __ DD MM YYYY

......................................................... ............................. ............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

7. Dose prescription Total Dose / fractionation

Target volume Total dose Gy Dose / fraction Gy

Whole brain ___ ___. ___ Gy ___ ___. ___ Gy

Whole spinal canal ___ ___. ___ Gy ___ ___. ___ Gy

Primary tumour bed boost ___ ___. ___ Gy ___ ___. ___ Gy

8. Dose to organs at risk

Organs Max [Gy] Mean [Gy]

Pituitary gland

Brain stem

Optic chiasm

Left optic nerve

Right optic nerve

Left eye lens

Right eye lens

Left cochlea

Right cochlea

Left hippocampus

Right hippocampus

Left temporal lobe

Right temporal lobe

Left thalamus

Right thalamus

Left hypothalamus

Right hypothalamus

Whole brain

Supratentorial brain

Infratentorial brain

Thyroid gland

Heart

Lungs

Left kidney

Right kidney

9. Boost tumor site

Volume GTV (cm³) ________ Safety margin GTV-CTV (mm) ________ Volume CTV (cm³) ________ Safety margin CTV-PTV (mm) ________ Volume PTV (cm³) ________

......................................................... ............................. ............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

10. Treatment technique Whole brain and spine Start date __ __ / __ __ / __ __ __ __ End date __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY

Linear accelerator (energy) whole brain __ __ MeV

spinal canal __ __ MeV

Electron fields Yes No Energy upper field __ __ MeV Energy lower field __ __ MeV Dose at reference point for upper field (ICRU) __ __ . __ Gy Dose at reference point for lower field (ICRU) __ __ . __ Gy Maximum dose __ __ . __ Gy Minimum dose __ __ . __ Gy Image fusion (MR / CT) for treatment planning Yes No 3-D treatment planning Yes No IMRT Yes No Proton Yes No Tomotherapy Yes No Rapid arc Yes No Positioning Prone Supine Positioning aids / fixation methods Individual face mask Yes No Vacuum pillows Yes No Immobilization cast Yes No Rigid mask / stereotactic equipment Yes No Bite bloc Yes No

Others ……………………………………………………………………………

......................................................... ............................. ............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Primary tumour bed boost Start date __ __ / __ __ / __ __ __ __ End date __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY

Linear accelerator (energy) __ __ MeV

Image fusion (MR/CT) for treatment planning Yes No 3-D treatment planning Yes No IMRT Yes No Proton Yes No Tomotherapy Yes No Rapid arc Yes No Dose mean __ __ . __ [Gy] Dose maximum __ __ . __ [Gy] Positioning Prone Supine Positioning aids / fixation methods Individual face mask Yes No Vacuum pillows Yes No Immobilization cast Yes No Rigid mask / stereotactic equipment Yes No Bite bloc Yes No

Others……………………………………………………………………………

......................................................... ............................. ............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

11. Maximal myelotoxicity during radiotherapy Blood count at start of RT Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Haemoglobin __ __ . __ g/dL or mmol/L

WBC __ __ . __ G/L (= 109/L = 103/µL = /nL) Neutrophils __ __ . __ G/L Platelets __ __ . __ G/L Blood count during RT (nadir values) Date Haemoglobin (nadir) __ __ . __ g/dL or mmol/L __ __ / __ __ / __ __ __ __ DD MM YYYY

WBC (nadir) __ __ . __ G/L __ __ / __ __ / __ __ __ __ DD MM YYYY

Neutrophils (nadir) __ __ . __ G/L __ __ / __ __ / __ __ __ __ DD MM YYYY

Platelets (nadir) __ __ . __ G/L __ __ / __ __ / __ __ __ __ DD MM YYYY

Blood count at end of RT Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Haemoglobin __ __ . __ g/dL or mmol/L WBC __ __ . __ G/Ll Neutrophils __ __ . __ G/L Platelets __ __ . __ G/L Administration of growth factors Yes No Transfusion erythrocytes Yes No, if `yes´ number of transfusions __ __ Transfusion platelets: Yes No, if `yes´ number of transfusions __ __ Life-threatening consequences of haematological toxicity Yes No Haematological toxicity necessitating hospitalisation Yes No ......................................................... ............................. .............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

12. Maximal acute morbidity (CTC4-Criteria) during radiotherapy Neurotoxicity

Headache No Yes, CTC-grade ______ Hospitalisation necessary (1 Mild 2 Moderate 3 Severe)

Seizure No Yes, CTC-grade ______ Hospitalisation necessary (1 Brief partial seizure, no loss of consciousness 2 Brief generalized seizure 3 Multiple seizures despite medical intervention 4 Life-threatening; prolonged repetitive seizures 5 Death)

Gastrointestinal Mucositis oral No Yes, CTC-grade ______ Hospitalisation necessary (1 Asymptomatic or mild symptoms 2 Moderate pain, not interfering with oral intake

3 Severe pain, interfering with oral intake 4 Life threatening 5 Death)

Esophagitis No Yes, CTC-grade ______ Hospitalisation necessary (1 Asymptomatic 2 Symptomatic, altered eating/swallowing 3 Severely altered

eating/swallowing, tube feeding, TPN, or hospitalisation 4 Life-threatening 5 Death)

Nausea No Yes, CTC-grade ______ Hospitalisation necessary (1 Loss of appetite 2 Oral intake decreased, without significant weight loss;

3 inadequate oral intake, tube feeding, TPN, or hospitalisation)

Vomiting No Yes, CTC-grade ______ Hospitalisation necessary: (1 1-2 episodes/24 h 2 3-5 episodes/24 h 3 ≥ 6 episodes/24h, tube feeding, TPN or

hospitalisation 4 Life-threatening 5 Death)

Febrile neutropenia No Yes, CTC-grade ______ Hospitalisation necessary (3 Neutrophils < 1000/mm3 with a single temperature of >38.3°C, or sustained

temperature of ≥ 38 °C for more than 1 hour 4 Life-threatening 5 Death)

Radiation dermatitis No Yes, CTC-grade ______ Hospitalisation necessary (1 Faint erythema, or dry desquamation 2 Moderate to brisk erythema; patchy, moist

desquamation, mostly confined to skin folds 3 Moist desquamation in areas other than skin folds; bleeding induced by minor trauma 4 Life-threatening, skin necrosis or ulceration, spontaneous bleeding 5 Death)

Otitis externa No Yes, CTC-grade ______ Hospitalisation necessary (2 Localized, local intervention indicated (e.g. topical antibiotic) 3 IV medication

indicated, radiologic, or operative intervention indicated 4 Life-threatening 5 Death)

Other ______________CTC-grade ______ Hospitalisation necessary


Note that any severe (CTC Grade ≥ 4) non-haematological toxicity, any death, and any unexpected hospitalisation needs to be immediately documented as SAE on separate form (form 17). See definitions of SAE and exceptions from immediate SAE reporting in chapter 13 of the protocol.

......................................................... ............................. ............................................................




SIOP PNET 5 MB - SR CARBOPLATIN CONCOMITANT TO RT

to be completed after end of Carboplatin treatment Form 9 page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Note: This form needs to be filled out for all PNET 5 MB – SR patients who are randomized to receive carboplatin. Carboplatin First application __ __ / __ __ / __ __ __ __ DD MM YYYY

Last application __ __ / __ __ / __ __ __ __ DD MM YYYY

Height __ __ __ cm Weight __ __ __ . __ kg

Carboplatin dosage (35 mg/m2) Absolute dose administered at first application __ __ . __ mg

Note: The weight of the patient should be measured on a weekly basis to allow carboplatin dose adjustments due to weight changes. Number of applications __ __

Deviations of drug doses will be recognized in Marvin through the calculation of the recommended dosage using the body surface area.

Significant toxicity that led to disruption or abruption of treatment with carboplatin Yes No If ‘Yes’ please indicate the reason for disruption or abruption of treatment Myelotoxicity Non-haematological toxicity, please specify:___________________________________ (please document only non-haematological toxicities, which led to disruption or abruption of carboplatin treatment. Incidence and severity of non-haematological toxicity are to be documented by the radiotherapist on form 8)

Period in which carboplatin was omitted

1. __ __ / __ __ / __ __ __ __ to __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY



4. Other ______________________________________ Note that any severe (CTC Grade 4) non-haematological toxicity, any death, and any unexpected hospitalisation needs to be immediately documented as SAE on separate form (form 17). See definitions of SAE and exceptions from immediate SAE reporting in chapter 13 of the protocol.

......................................................... ............................. .............................................................

Name of local radiotherapist/ Date Signature investigator


Complete in Marvin within 1 month after assessment.

SIOP PNET 5 MB TOXICITY BETWEEN RT AND CHEMOTHERAPY to be completed in case of any toxicity observed between end of radiotherapy and start of maintenance chemotherapy

Form 10 page 1/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

1) Haematologic toxicity Yes No Transfusion of erythrocytes No Yes, number of transfusions: ____ Transfusion of platelets No Yes, number of transfusions: ____ Necessitating delay of therapy Yes No Life–threatening consequences of haematological toxicity Yes No Haematological toxicity necessitating hospitalisation Yes No 2. Non-haematologic toxicity (CTCAE Version 4.0 should be used for determination of severity) Neurotoxicity

Headache No Yes, CTC-grade ______ Hospitalisation necessary (1 Mild 2 Moderate 3 Severe)

Seizure No Yes, CTC-grade ______ Hospitalisation necessary (1 Brief partial seizure, no loss of consciousness 2 Brief generalized seizure; 3 Multiple seizures despite medical intervention 4 Life-threatening; prolonged repetitive seizures 5 Death)

Gastrointestinal Mucositis oral No Yes, CTC-grade ______ Hospitalisation necessary (1 Asymptomatic or mild symptoms 2 Moderate pain, not interfering with oral intake

3 Severe pain, interfering with oral intake 4 Life threatening 5 Death)

Esophagitis No Yes, CTC-grade ______ Hospitalisation necessary (1 Asymptomatic 2 Symptomatic, altered eating/swallowing 3 Severely altered

eating/swallowing, tube feeding, TPN, or hospitalisation 4 Life-threatening 5 Death)

Nausea No Yes, CTC-grade ______ Hospitalisation necessary (1 Loss of appetite 2 Oral intake decreased, without significant weight loss

3 Inadequate oral intake, tube feeding, TPN, or hospitalisation)

Vomiting No Yes, CTC-grade ______ Hospitalisation necessary: (1 1-2 episodes/24 h 2 3-5 episodes/24 h 3 ≥ 6 episodes/24h, tube feeding, TPN or

hospitalisation 4 Life-threatening 5 Death)



Radiation dermatitis No Yes, CTC-grade ______ Hospitalisation necessary (1 Faint erythema, or dry desquamation 2 Moderate to brisk erythema; patchy, moist

desquamation, mostly confined to skin folds 3 Moist desquamation in areas other than skin folds; bleeding induced by minor trauma 4 Life threatening, skin necrosis or ulceration, spontaneous bleeding 5 Death)



SIOP PNET 5 MB TOXICITY BETWEEN RT AND CHEMOTHERAPY to be completed in case of any toxicity observed between end of radiotherapy and start of maintenance chemotherapy

Form 10 page 2/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Otitis externa No Yes, CTC-grade ______ Hospitalisation necessary (2 Localized, local intervention indicated (e.g. topical antibiotic) 3 IV medication

indicated, radiologic, or operative intervention indicated 4 Life-threatening 5 Death)



Note that any severe (CTC Grade ≥ 4) non-haematological toxicity, any death, and any unexpected hospitalisation needs to be immediately documented as SAE on separate form (form 17). See definitions of SAE and exceptions from immediate SAE reporting in chapter 13 of the protocol.

......................................................... ............................. .............................................................



Complete in Marvin within 1 month after the end of each course.

SIOP PNET 5 MB CHEMOTHERAPY REGIMEN A

to be completed after each course A (course 1, 3, 5, 7) Form 11A page 1/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Course 1 3 5 7 (only PNET 5 MB-SR) 1. Drug doses Start of course __ __ / __ __ / __ __ __ __ DD MM YYYY

Height __ __ __ cm Weight __ __ __ . __ kg

VCR (dosage 1.5 mg/m2/day, max. 2 mg/day) Absolute dose administered Day 1 __ . __ __ mg Not administered Absolute dose administered Day 8 __ . __ __ mg Not administered

Absolute dose administered Day 15 __ . __ __ mg Not administered

Cisplatin (dosage 70 mg/m2) Absolute dose administered __ __ __ __ mg Not administered CCNU (dosage 75 mg/m2) Absolute dose administered __ __ __ __ mg Not administered Carboplatin (if used instead of cisplatin, dosage 400 mg/m2): Absolute dose administered __ __ __ __ mg Not administered Deviations of drug doses will be recognized in Marvin through the calculation of the normal dosage using the body surface area. Are the stated absolute drug doses based on intended dose reductions? Yes No Beside supportive therapy, were there any other drugs administered? Yes No If ‘Yes’ please specify (e.g. other anti-neoplastic therapy) ____________________________ 2. Toxicity

Was there any toxicity which led to delay, modification, or abruption of chemotherapy after this course? Yes No If ‘Yes’ please specify ________________________________________________________ Haematologic toxicity: Transfusion of red blood cells No Yes, number of transfusions ____ Transfusion of platelets No Yes, number of transfusions ____ Necessitating delay of therapy Yes No Life –threatening consequences of haematological toxicity Yes No Haematological toxicity necessitating hospitalisation Yes No ......................................................... ............................. .............................................................




SIOP PNET 5 MB CHEMOTHERAPY REGIMEN A

to be completed after each course A (course 1, 3, 5, 7) Form 11A page 2/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Course 1 3 5 7 (only PNET 5 MB-SR)



Non-haematologic toxicity (CTCAE Version 4.0 should be used for determination of severity)

Neurotoxicity

Seizure No Yes, CTC-grade ______ Hospitalisation necessary (1 Brief partial seizure, no loss of consciousness 2 Brief generalized seizure 3 Multiple seizures despite medical intervention 4 Life-threatening; prolonged repetitive seizures 5 Death)

Ileus No Yes, CTC-grade ______ Hospitalisation necessary (2 Symptomatic, altered GI function, bowel rest indicated 3 Severely altered GI function, TPN indicated 4 Life-threatening consequences, urgent intervention indicated 5 Death)

Dysaesthesia/ No Yes, CTC-grade ______ Hospitalisation necessary paresthesia/ (1 Mild sensory alteration or loss of deep tendon reflexes 2 Moderate sensory

neuropathy alteration, limiting instrumental ADL 3 Severe sensory alteration, limiting self care

ADL 4 Life-threatening consequences, urgent intervention indicated 5 Death)

Nephrotoxicity Creatinine increased No Yes, CTC-grade ______ Hospitalisation necessary

(1: >1 - 1.5 x baseline, or >ULN - 1.5 x ULN 2: >1.5 - 3.0 x baseline, or >1.5 - 3.0 x ULN 3: >3.0 baseline, or >3.0 - 6.0 x ULN 4: >6.0 x ULN)

GFR reduced No Yes, CTC-grade ______ Hospitalisation necessary (1 eGFR (estimated glomerular filtration rate) or CrCl (creatinine clearance) < LLN - 60 ml/min/1.73 m2 2 eGFR or CrCl 59 - 30 ml/min/1.73 m2 3 eGFR or CrCl 29 - 15 ml/min/1.73 m2 4 eGFR or CrCl <15 ml/min/1.73 m2, dialysis or renal transplant indicated 5 Death)

Weight loss No Yes, CTC-grade ______ Hospitalisation necessary (1 5 to <10% from baseline; intervention not indicated 2 10 - <20% from baseline; nutritional support indicated 3 >=20% from baseline, tube feeding or TPN indicated)

Ototoxicity Necessitating cisplatin dose modification Yes No

Other toxicity specify _________________________________________________

CTC-grade ______ Hospitalisation necessary


CTC-grade ______ Hospitalisation necessary Note that any severe (CTC Grade 4) non-haematological toxicity, any death, and any unexpected hospitalisation needs to be immediately documented as SAE on separate form (form 17). See definitions of SAE and exceptions from immediate SAE reporting in chapter 13 of the protocol.

......................................................... ............................. .............................................................




SIOP PNET 5 MB CHEMOTHERAPY REGIMEN B

to be completed after each course B (course 2, 4, 6, 8) Form 11B page 1/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Course 2 4 6 8 (only PNET 5 MB-SR) 1. Drug doses Start of course __ __ / __ __ / __ __ __ __ DD MM YYYY

Height __ __ __ cm Weight __ __ __ . __kg

VCR (dosage 1.5 mg/m2, max. 2 mg) Absolute dose administered __ . __ __ mg Not administered Cyclophosphamide (dosage 1000 mg/m2/day) Absolute dose administered day 1 __ __ __ __ mg Not administered Absolute dose administered day 2 __ __ __ __ mg Not administered

Deviations of drug doses will be recognized in Marvin through the calculation of the normal dosage using the body surface area. Are the stated absolute drug doses based on intended dose reductions? Yes No Beside supportive therapy, were there any other drugs administered? Yes No If ‘Yes’ please specify (e.g. other anti-neoplastic therapy) ____________________________ 2. Toxicity

Was there any toxicity which led to delay, modification, or abruption of chemotherapy after this course? Yes No If ‘Yes’ please specify ________________________________________________________ Haematological toxicity: Transfusion of erythrocytes No Yes, number of transfusions ____ Transfusion of platelets No Yes, number of transfusions ____ Necessitating delay of therapy Yes No Life –threatening consequences of haematological toxicity Yes No Haematological toxicity necessitating hospitalisation Yes No

Febrile neutropenia: No Yes, CTC-grade ______ Hospitalisation necessary (3 Neutrophils < 1000/mm3 with a single temperature of >38.3°C, or

sustained temperature of ≥ 38 °C for more than 1 hour 4 Life-threatening 5 Death)

......................................................... ............................. .............................................................




SIOP PNET 5 MB CHEMOTHERAPY REGIMEN B

to be completed after each course B (course 2, 4, 6, 8) Form 11B page 2/2

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Course 2 4 6 8 (only PNET 5 MB-SR)

Non-haematological toxicity (CTCAE Version 4.0 should be used for determination of severity)

Neurotoxicity

Seizure No Yes, CTC-grade ______ Hospitalisation necessary (1 Brief partial seizure, no loss of consciousness 2 Brief generalized seizure; 3 Multiple seizures despite medical intervention 4 Life-threatening; prolonged repetitive seizures 5 Death)

Ileus No Yes, CTC-grade ______ Hospitalisation necessary (2 Symptomatic, altered GI function, bowel rest indicated 3 Severely altered GI function, TPN indicated 4 Life-threatening consequences, urgent intervention indicated 5 Death)

Dysaesthesia/ No Yes, CTC-grade ______ Hospitalisation necessary paresthesia/ (1 Mild sensory alteration or loss of deep tendon reflexes 2 Moderate sensory

neuropathy alteration, limiting instrumental ADL 3 Severe sensory alteration, limiting self care

ADL 4 Life-threatening consequences, urgent intervention indicated 5 Death)

Nephrotoxicity Creatinine increased No Yes, CTC-grade ______ Hospitalisation necessary

(1 >1 - 1.5 x baseline, or >ULN - 1.5 x ULN 2 >1.5 - 3.0 x baseline, or >1.5 - 3.0 x ULN 3: >3.0 baseline, or >3.0 - 6.0 x ULN 4: >6.0 x ULN)

GFR reduced No Yes, CTC-grade ______ Hospitalisation necessary (1 eGFR (estimated Glomerular Filtration Rate) or CrCl (creatinine clearance) <LLN - 60 ml/min/1.73 m2 2 eGFR or CrCl 59 - 30 ml/min/1.73 m2 3 eGFR or CrCl 29 - 15 ml/min/1.73 m2 4 eGFR or CrCl <15 ml/min/1.73 m2, dialysis or renal transplant indicated 5 Death)

Haematuria No Yes, CTC-grade ______ Hospitalisation necessary (1 Asymptomatic, clinical or diagnostic observations only, intervention not indicated 2 Symptomatic; urinary catheter or bladder irrigation indicated, limiting instrumental ADL 3 transfusion, IV medications or hospitalization indicated, elective intervention indicated 4 life-threatening consequences; urgent radiologic or operative intervention indicated 5 Death)


CTC-grade ______ Hospitalisation necessary


CTC-grade ______ Hospitalisation necessary Note that any severe (CTC Grade 4) non-haematological toxicity, any death, and any unexpected hospitalisation needs to be immediately documented as SAE on separate form (form 17). See definitions of SAE and exceptions from immediate SAE reporting in chapter 13 of the protocol.

Comments ______________________________________________________________

......................................................... ............................. .............................................................



Complete in Marvin within 3 months after end of protocol treatment.

SIOP PNET 5 MB END OF THERAPY

to be completed within 3 month after end of protocol treatment Form 12 page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Reason for end of treatment Due to completion of protocol treatment

Premature termination of treatment, due to Toxicity (please complete corresponding form) Relapse / Progression (please complete forms 14 and 15)

Death (please complete form 14 and SAE form 17) Parents decision other, please specify _________________________________ Last application of protocol therapy Date __ __ / __ __ / __ __ __ __ DD MM YYYY

MRI after last application of protocol therapy Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Disease status at end of therapy Complete remission Persistent residual lesion Relapse / Progression First complete remission (First CR) (In case of initial residual tumour: please give a date of the first complete remission) Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Additional anti-neoplastic treatment after end of protocol therapy: Yes No If ‘Yes’ please specify:

__________________________________________________________________ __________________________________________________________________ __________________________________________________________________ ......................................................... ............................. .............................................................



Complete in Marvin within 3 months after assessment.

SIOP PNET 5 MB POST TREATMENT – Late effects

to be completed 2 and 5 years after diagnosis and at age of 18 years Form 13 page 1/4

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Time point of assessment 2 years 5 years age of 18 years

If assessment after 2 years: Please send MRI to neuroradiology review (form 14A) Date of assessment __ __ / __ __ / __ __ __ __ DD MM YYYY

1. Measurements Height __ __ __ cm Sitting height __ __ __ cm Weight __ __ __ . __ kg

2. Does the patient have any restriction or lack of ability to perform an activity due to any motor problem, cranial nerve palsy or poor vision postoperatively? Vision according to age (II): Impaired Normal Not known Impairment of extra ocular movements: (III, IV, VI)

Yes No Not known

Facial weakness (VII): Yes No Not known Impairment of swallowing (IX, X, XI): Yes No Not known Limb stiffness / weakness: Yes, upper right

Yes, lower right No

Yes, upper left Yes, lower left Not known

3. Audiology Ototoxicity according to Chang grading (based on pure tone audiometry) Please send one original audiogram performed 2 years after diagnosis to the national data centre. Grade 0 ≤ 20 dB at 1,2, and 4 kHz Grade 1a ≥ 40 dB at any frequency 6 to 12 kHz Grade 1b > 20 and < 40 dB at 4 kHz Grade 2a ≥ 40 dB at 4 kHz and above Grade 2b > 20 and < 40 dB at any frequency below 4 kHz Grade 3 ≥ 40 dB at 2 or 3 kHz and above Grade 4 ≥ 40 dB at 1 kHz and above Note: the grading is based on the lowest grading i.e. the ‘BEST ear’ 4. Dysphagia Normal swallowing Difficulties eating solid food Difficulties eating soft food Can take liquids only Totally unable to swallow 5. QoS questionnaires distributed? Yes No Not known Data retrieval by HealthTracker Booklet ......................................................... ............................. ............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Time point of assessment 2 years 5 years age of 18 years

6. Puberty If female Breast stage (Tanner) 1 2 3 4 5 (please encircle) Menarche No Yes, irregular Yes, regular menstrual cycle

Last menstrual period: __ __ / __ __ / __ __ __ __ (for interpretation of FSH levels) DD MM YYYY

If male Genital stage (Tanner) 1 2 3 4 5 (please encircle) Testicular volumes (ml) (please encircle) Right 0/1 2 3 4 6 8 10 12 15 20 25 30

Left 0/1 2 3 4 6 8 10 12 15 20 25 30

7. Follicle stimulating hormone

FSH __ __ __ . __ IU/L Date of evaluation __ __ / __ __ / __ __ __ __ DD MM YYYY

Did or does the patient receive oral contraception or sex steroid to induce or maintain pubertal development? Yes No

8. Did or does patient receive hormone supplementation Yes, see below No

a) Thyroxine Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY

Continuing No Not known

b) Growth hormone Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY


c) Hydrocortisone Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY


d) GnRH analogues Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ (to suppress puberty) DD MM YYYY DD MM YYYY


e) Sex steroid Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ Specify:__________ DD MM YYYY DD MM YYYY


f) Other Yes, from __ __ / __ __ / __ __ __ __ until __ __ / __ __ / __ __ __ __ Specify:__________ DD MM YYYY DD MM YYYY


......................................................... ............................. .............................................................






__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Time point of assessment 2 years 5 years age of 18 years 9. The Brief Ataxia Rating Scale (BARS) To be evaluated by a physician Date of evaluation __ __ / __ __ / __ __ __ __ DD MM YYYY

......................................................... ............................. .............................................................


a) Gait 0 Normal 1 Almost normal naturally, but unable to walk with

feet in tandem position 2 Walking without support, but clearly abnormal and

irregular 3 Walking without support but with considerable

staggering; difficulties in half turn 4 Walking without support not possible; uses support

of the wall for 10-meter test. 5 Walking possible only with one cane 6 Walking possible only with two canes or with a

stroller 7 Walking possible only with one accompanying

person 8 Walking impossible with one accompanying person

(2-person assist; wheelchair)

b) Knee tibia test (decomposition of movement and intention tremor) 0 Normal 1 Lowering of heel in continuous axis, but

movement is decomposed in several phases, without real jerks, or abnormally slow

2 Lowering jerkily in the axis 3 Lowering jerkily with lateral movements 4 Lowering jerkily with extremely long

lateral movements, or test impossible

Score:

Score Left: Right:

c) Finger to nose test (decomposition and dysmetria of arm and hand) 0 Normal 1 Oscillating movement of arm and/or hand without

decomposition of the movement 2 Segmented movement in 2 phases and / or

moderate dysmetria in reaching nose 3 Segmented movement in more than 2 phases and /

or considerable dysmetria in reaching nose 4 Dysmetria preventing the patient from reaching

nose

d) Dysarthria 0 Normal 1 Mild impairment of rate / rhythm / clarity 2 Moderate impairment of rate / rhythm /

clarity 3 Severely slow and dysarthric speech 4 Speech absent or unintelligible

Score

Left: Right: Score:

e) Oculomotor abnormalities 0 Normal 1 Slightly slowed pursuit, saccadic intrusions, hypo /

hypermetric saccade, nystagmus 2 Prominently slowed pursuit, saccadic intrusions,

hypo / hypermetric saccade, nystagmus

Score:





__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Time point of assessment 2 years 5 years age of 18 years 10. SAE, which do not require immediate reporting on the SAE form: Definition (see also chapter 13 of the protocol): Any AE, which

- results in death - is life–threatening - requires hospitalisation, or prolongation of hospitalisation - results in persistent or significant disability or incapacity - is a congenital anomaly or birth defect - is another medically important condition

AND which occurs later than 30 days after end of protocol treatment, within the follow-up period AND for which the investigator does not suspect a causal relationship to the protocol defined treatment Any SAE, corresponding to the above mentioned criteria: Yes No If ‘Yes’, please describe: Diagnosis _________________________________________________________________ If possible give CTC Grade _______, or severity Mild Moderate Severe Date of onset __ __ / __ __ / __ __ __ __ DD MM YYYY

Comments ________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ (to report more than 1 SAE, please copy page and use for multiple reporting) Note: All SAE which are not excepted from immediate reporting (as described above) have to be immediately documented on the SAE form (form 17) until the end of the follow-up period. ......................................................... ............................. ............................................................




SIOP PNET 5 MB FOLLOW-UP, FIRST RELAPSE AND DEATH To be completed at 1 year after treatment, afterwards annually,

at first relapse, and death Form 14 page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Time point of assessment Year after treatment:___ Relapse Death

1. Status at follow up of surviving patients Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Alive - CR Alive with post op residual tumour Alive after relapse / progression

2. Lost to follow up?

No Yes, address unknown Yes, no further contact wanted

Yes, other reasons

3. First relapse / progression Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Please send the MRI to neuroradiology review (form 15A)

Posterior fossa (local relapse) please send form 16 to central review

Metastasis please tick all that apply:

CNS, solid /nodular supratentorial (M2b) infratentorial (M2b) spinal (M3b)

CNS, diffuse, meningeal supratentorial (M2a) infratentorial (M2a) spinal (M3a)

CNS, CSF

CSF lumbar CSF ventricular

Extra CNS, location _____________________________

Histologic evaluation Yes No, if yes, Date: __ __ / __ __ / __ __ __ __ DD MM YYYY

Histologic confirmation of medulloblastoma relapse? Yes, posterior fossa Yes, metastasis No Please send the paraffin block to the pathological reference centre for review and further biological research

4. Second Malignancy Yes No, if yes, Date: __ __ / __ __ / __ __ __ __ DD MM YYYY

If ’yes’, please specify __________________________ 5. Death Yes No, if yes, Date: __ __ / __ __ / __ __ __ __ DD MM YYYY

Cause of death : Primary tumour disease Cannot differentiate if tumour or treatment Relapse/ progression Second malignancy Treatment related mortality Other cause, specify_____________________

Comments ________________________________________________________________

......................................................... ............................. .............................................................



Send to central review within 1 month after assessment.

SIOP PNET 5 MB TO FU NEURORADIOLOGY REVIEW (S54836) to be sent two years after diagnosis to central review according to national group decision for

leukencephalopathy (LEP)-grading or in case of relapse Form 15A page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Local neuroradiologist / investigator

.......................................……………………………. ……………….. ………………………………...

Name of local neuroradiologist / investigator Date Signature

...............……………………………………………… .…........................................................................

Hospital Country

.................................... ...................………… .. ……………..........................................................


This patient with medulloblastoma has been included and received therapy within the PNET 5 MB studies. These studies involve central review of neuroradiology. 2 years after diagnosis in case of relapse

(please tick appropriate box)

For this patient we send (please tick!)

Cranial MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Spinal MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY

Comments _______________________________________________________________________

__________________________________________________________________________________

_________________________________________________________________________________________

Please send anonymised images to UZ Leuven through lamp system (or on CD) and send this form to [email protected]

Send to central review neuroradiologist of national group: Name: UZ Leuven Prof Demaerel/ Prof Heye Hilde Vandenhout /Philip Koutsos Adress: Herestraat 49 City: 3000 Leuven

SIOP PNET 5 MB

NEURORADIOLOGY CENTRAL REVIEW

(within national groups)



Send to national data centre [email protected] within 1 month after assessment.

SIOP PNET 5 MB FOLLOW-UP RADIOLOGY REVIEW to be completed by central review neuroradiologist according to national group decision two

years after diagnosis for LEP-Grading or in case of relapse Form 15B page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Please tick appropriate tick box for indication of central review of MRI

1. MRI for central review two years after diagnosis

Leukencephalopathy grading Grade 0: no pathology Grade 1: punctated or small T2-hyperintensities max up to 25% of the frontoparietal white matter Grade 2: confluating T2-hyperintensities between 25 and max 50% of the area of the frontoparietal white matter Grade 3: more than 50% of the frontoparietal white matter

White matter cysts Yes No White matter lesion enhancement Yes No

OR

2. MRI of restaging for central review in case of relapse

Cranial MRI Date __ __ / __ __ / __ __ __ __ Spinal MRI Date __ __ / __ __ / __ __ __ __ DD MM YYYY DD MM YYYY

Tumour size (cm) Craniocaudal __ __ . __, left-right __ __ . __, anterior-posterior __ __ . __

□ Size not assessable

Location Posterior fossa (local relapse)

Metastasis please tick all that apply:

CNS, solid / nodular Supratentorial Infratentorial Spinal

CNS, diffuse, meningeal Supratentorial Infratentorial Spinal

Extra CNS, location:_____________________________

Technical quality in reviewed assessable scans Appropriate Inappropriate for staging

Technical problems in reviewing:

Movement artefacts No Yes, cranial yes, spinal

Incomplete scanning cranial No Yes, cranial yes, spinal

Incomplete scanning spinal No Yes, cranial yes, spinal

Contrast medium No Yes, cranial yes, spinal

Only post contrast exam No Yes, cranial yes, spinal

Other problems No Yes, cranial yes, spinal

Comments ________________________________________________________________________ ............................................................... ....................... ….............................................................

Name of reviewing neuroradiologist Date Signature



Send to national data centre [email protected] within 1 month after relapse/ progression.

SIOP PNET 5 MB POSTERIOR FOSSA RELAPSE/ PROGRESSION

completed by local radiotherapist Form 16 page 1/1

__ __ __ GPOH. __ __ __ __ __

Centre ID MARVIN ID

Local relapse / progression location The relapse/ progression is within the posterior fossa Yes No

If ‘yes’ Within the posterior fossa but outside the boost field Yes No

Within the boost field Yes No Relapse outside posterior fossa Yes No Relapse cribriforme plate Yes No Relapse temporal lobe Yes No

…………………………………………………………. …………………………………………………… Name of local radiotherapist Signature ……………………………………………………………………………………………………………………… Hospital, City, Country

…………………………………………………………. …………………………………………………….

E-mail Fax

Please send RT planning/images through the lamp system (or on CD) to UZ Leuven and send this form to [email protected]

To be completed by national radiotherapy quality control: If boost Isodose = __ __ % Cumulative total dose at relapse: __ __ . __ Gy ......................................................... ............................. ….............................................................


SIOP PNET 5 MB - LR

SIOP PNET 5 MB - SR

RADIOTHERAPY QUALITY

CONTROL

Send to central review radiotherapist of national group: Name: UZ Leuven Prof Menten/ Prof Van Beek Adress: Herestraat 49 City: 3000 Leuven




Send to pharmacovigilance centre Münster within 24 h after knowledge of the event.

SIOP PNET 5 MB SERIOUS ADVERSE EVENT (SAE) to be documented within 24 hours Form 17 page 1/3

SIOP PNET 5 MB NECESSARY DOCUMENTATION€¦ · SIOP PNET 5 MB Final Version 11 – 2014, Nov 17 CRF...

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