แนวทางการรักษาโรคมะเร็งในเด็ก-2557 (1)

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name Age SexHospital HN BW kg Ht cm BSA m2Phase IV: HR-INTENSIFICATION-II (3 weeks) Date Start:__________Last day of G-CSF: _________Start Consolidation-II on Day 22 of Intensification-I and ANC ≥ 750/ul (at least 2 days after stop G-CSF)and PLT ≥ 75,000/ul whichever occurs later.Week 1 23 4Day 1 2 3 4 5 6 7 8 15 21 22 Date due Start next phase (Consolidation-I Date given or Salvage) on day 22 or whenMedication: blood countHD-MTX _______ mg IV M parameters areLCV _______ mg IV/PO LLLLLLLLLLL met. ETOP _______ mg IV L EEE IFOS _______ mg IV IIIMESNA _______ mg IV SSS SSS SSS DEX _______ mg IV DDD DDD DDDG-CSF _______ mcg SQ/IV GInvestigation: + ++ + ++CBC/diffESR, E’Lyte, BUN, Cr, AST, ALT, TB,DB +CT C/A/P or PET CT (+)BM aspiration and biopsy Drug Route Dosage DaysHigh-dose Methotrexate IV drip in 4 hours 8,000 mg/m2/day Day 1(HD-MTX)Leucovorin (LCV) IV/PO 15 mg/m2/dose q 6 hours Day 2, 3, 4Etoposide (ETOP) IV over 60-120 minutes 200 mg/m2/day Day 2, 3, 4Ifosfamide (IFOS) IV over 4 hours 2,000 mg/m2/day Day 2, 3, 4Mesna IV 500 mg/m2/dose Day 2, 3, 4Dexamethasone (DEX) IV At hour 0, 3, 6 of IFOS 40mg/m2day divided in 3 Day 1, 2, 3 dose q 8 hoursG-CSF SubQ or IV 5 mcg/kg/day Day 4 then dailyNote: Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ulpost nadir. CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Intensification-II BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement at diagnosisPost Induction treatment assignment: Post Intensification Management Treatment response □ Consolidation I and II □ Salvage protocol□ Complete Response/ Partial Response/ Stable disease□ Progressive diseaseLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 137

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name HN Age Sex m2Hospital BW kg Ht cm BSAPhase V: INVOLVED FIELD RADIATION THERAPY (IFRT):For all IR and HR Hodgkin lymphoma patientsRadiation field :( ) )Total radiation dose : ( )Number of fractions : ( )Date start :( )Last day of radiation :( ) CT date: (Note IFRT should be done within 6 weeks after start consolidation-II with ANC > 1,000/µl and CPlTatcehleetsst>ab1d0o0m,0e0n0/aµnld pelvis should be done 6-8 weeks after complete radiationPost IFRT treatment assignment: Post IFRTmanagement Post radiation treatment response Complete response □ End off therapy evaluation Partial response, Stable disease □ Disease reassessment: repeat biopsy or PET scan to evaluate Progression residual disease □ Salvage protocolLymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 138

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Data entry form for non-Hodgkin lymphomaPatient’s name......................................................... HN............................ Sex  male femaleAddress.......................................................................................................................... ...........................................................................................................Contact person....................................Tel............................Father’s name........................................................ Age...........yr Occupation…………….............................Mother’s name........................................................ Age...........yr Occupation…………….............................Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) ..................................... BSA...................m2Age ............. yr...............m. BW…...........kg Ht...............cm.สิทธิการรกั ษา บตั รประกันสุขภาพ จา่ ยตรง อืน่ ๆ (ระบุ) ...................................History Physical examinationPre- treatment investigations.A. Blood date (………/………/………)CBC ……………………………….…………………………..…………………………………………………………….BUN …………Creatinine ………… Na …………… K ………………….. Cl ……………...…… HCO3 ………….…Ca …………………..… P ………… Mg…….……… AST …………………… ALT ………… TB …………………..DB………………..……. ALP…………………….…… GGT ………………….… LDH …………………………..……CSF (………/………/………) WBC ………………………………..…….…RBC…………………………………..….…Cytospin  positive  negative for malignancyGFR (………/………/………)  calculated /  measured) …………………………………ml/min/1.73m2Coagulogram (………/………/………) aPTT………….…PT………….…INR………….…fibrinogen……………..…B. Imaging studiesCT neck (………/………/………) ……………..……….……………………..……………………………………………CT chest (………/………/………) ……………..……….……………………..……………………………………………CT abdomen/ pelvis (………/………/………) ……………..………………..……………………………………………Chest X-Ray (………/………/………) ..……………..……….……………………..……………………………………..Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Gallium scan (optional, ………/………/………) ..……………..……….……………………..………………………….PET scan (optional, ………/………/………)…..…………..……….……………………..………..……………………..C. Bone marrow for metastatic work upBone marrow aspiration (………/………/………)…………………...…………………………….....…………………..BM biopsy (………/………/………) ……………………..………………………………………………………….……..D. OthersAudiogram (………/………/………)…………………...…………………………………………..….....…………………EKG (………/………/………) ………………………………………………………………………………………………Echo (………/………/………) ………………………………………………………………………………………………Other (………/………/………) ……………………………………………………………………………………………..Lymphoma: Data entry form for non-Hodgkin lymphoma 139

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็กStage I Non-Hodgkin lymphoma (NHL) – Murphy stageStage II A single tumor (extranodal) or single anatomic area (nodal) with the exclusion ofStage III mediastinum or abdomenStage IV A single tumor (extranodal) with regional lymph node involvement Two or more nodal areas on the same side of the diaphragm Two single (extranodal) tumors with or without regional LN involvement on the same side of the diaphragm A primary GI tract tumor, usually in the ileocecal area, with or without involvement of associated mesenteric nodes only, grossly completely resected Two single tumors (extranodal) on the opposite sides of (above and below) the diaphragm All primary intrathoracic (mediastinal, pleural, thymic) tumors All extensive primary intra-abdominal disease, unresectable All paraspinal or epidural tumors, regardless of other tumor site(s) Any of the above with initial involvement of CNS or BM (<25% replacement of marrow elements without circulating blast cells) Treatment plan for patients with NHLLymphoma: Non-Hodgkin lymphoma (NHL) – Murphy stage 140

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment plan for patiants with mature B-cell lymphoma Burkitt lymphoma/leukemia Atypical Burkitt lymphoma Diffuse large B-cell lymphoma Mediastinal large B-cell lymphoma Mature B-cell lymphoma NOSRisk stratificationLow Risk Completely resected stage I or completely resected abdominal stage II lesions.Standard Risk All cases not eligible for low or high risk. (Murphy Stage III and non- CNS Stage IV)High Risk Any CNS involvement and/or bone marrow involvement. For CNS involvement one or more of the following applies: (1) Any L3 blasts in CSF (2) Cranial nerve palsy (if not explained by extracranial tumor) (3) Clinical spinal cord compression (4) Isolated intracerebral mass (5) Parameningeal extension: cranial and/or spinalTreatment planRisk group Pre-Phase Induction X2 Consolidation X2 ContinuationLow risk COPADStandard risk COP COPAD-M3 CYMHigh risk COP COPAD-M8 CYVE Seq. No 1,2,3,4Intrathecal treatment Methotrexate Hydrocortisone Ara-C 8 mg 8 mg 16 mg Age 10 mg 10 mg 20 mg <1 12 mg 12 mg 24 mg 1-2 15 mg 15 mg 30 mg 2-3 >3Lymphoma: Treatment plan for patiants with mature B-cell lymphoma 141

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment plan for patients with anaplastic large cell lymphomaRisk stratificationLow Risk Stage I disease completely resectedStandard Risk  No skin involvement  No mediastinal involvementHigh Risk  No liver, spleen or lung involvement Includes patients with any of the following features:  Presence of biopsy proven skin lesions (except skin lesions overlying an involved node or isolated skin disease*)  Presence of mediastinal involvement  Presence of liver (liver enlargement ≥ 5 cm and / or nodular liver), spleen (spleen enlargement and / or nodular spleen) or lung involvement (biopsy is not necessary for obvious lesions)*Isolated skin lesions is not considered a high risk factor. ALCL confined to skin is extremely rare in childhoodand may represent a distinct form of the disease. Currently it is not clear whether patients with isolated skindisease and no extracutaneous manifestations need chemotherapy at all. Such patients should have carefulstaging, central pathology review of histology and discussed with the study coordinator before adopting a “waitand see” approach.Treatment plan Pre-Phase Intensive phaseRisk group COP A1  B1  A2Low risk COP A1  B1  A2  B2  A2  B3 COP AM1  BM1  AM2  BM2  AM2  BM3Standard riskHigh riskIntrathecal Treatment Methotrexate Hydrocortisone Ara-CAge 6 mg 4 mg 16 mg<1 8 mg 6 mg 20 mg1-2 10 mg 8 mg 24 mg2-3 12 mg 10 mg 30 mg>3Lymphoma: Treatment plan for patients with anaplastic large cell lymphoma 142

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเดก็Appendix I: Supportive care guidelines for high dose methotrexate administration for ThaiPOG-NHL13-BL protocol1) Hydration  Pre-hydrate with 250 ml/m2/h with alkalinization for a minimum of 2 hours in order to achieve a pH of> 6.5.  Methotrexate is administered in dextrose (piggyback into IVF with bicarb) at a dose of 3,000 mg/m2over 3 hours in standard risk and a dose of 8,000 mg/m2 over 4 hours in high risk participants.  After methotrexate infusion, continue hydration at a rate of 3,000 mLs/m2/day with dextrose 5% withadded NaHCO3 (40 mEq/l) and KCL (20 mEq/l) to maintain urinary pH > 7 for a further 48 hours in standardrisk patients (with normal rate of hydration the following 24 hours) or 72 hours after infusion in high riskpatients.2) Drug interactions Drugs which compromise renal function (e.g. aminoglycosides) can decrease clearance ofmethotrexate and lead to systemic toxicity. Avoid concurrent use of NSAIDs, omeprazole, azole antifungals,salicylates and sulphonamides. Large doses of penicillin may interfere with the active renal tubular section ofmethotrexate.3) Leucovorin  Leucovorin (folinic acid) 15 mg/m2 should be given orally or IV every 6 hours. The dose should berounded up to the nearest 5 mg. The rescue begins 24 hours from the start of the methotrexate infusion.Intrathecal drugs should be given before rescue starts. If vomiting occurs within 30 minutes, repeat the dose. Ifpersistent vomiting or diarrhea occurs, give leucovorin by IV injection. Methotrexate levels, urea andelectrolytes should be measured daily for 3 days after methotrexate infusion. Strict attention should be paid tofluid balance. The leucovorin dose should be modified as required based in the methotrexate level. Leucovorin dosage adjustments: Patients will have their leucovorin rescue increased if they meet anyof the following criteria: Dose 3 g/m2MTX Level 8 g/m24 hour > 5 μM > 10 μM48 hour > 1 μM > 1 μM72 hour > 0.1 μM >0.1 μM*If the 48 hour MTX level is < 0.15 μM /l, discontinue leucovorin rescue.  If the patient meets any of these criteria, the leucovorin dosage will be individualized and plasmaconcentrations will be monitored until the plasma level is <0.1 μM. High risk group: Patients who experience Grade IV GI toxicity after COPAD M8 #1 will receiveCOPAD M3 for their subsequent courses. Patients who experience Grade IV GI toxicity after COPAM M3 #1will begin leucovorin at 18 instead of 24 hours with subsequent HDMTXs. A further check on the MTX level should be done at 120 hours in high risk COPADM8 courses toensure that the level does not increase again after IT MTX, and to alter leucovorin rescue as required.Hydration should continue beyond 72 hours in the following situations:(1) If there is still evidence of tumor lysis(2) If cyclophosphamide infusion is still in process(3) If the MTX level is still >0.15 μM.Lymphoma: Appendix I: Supportive care guidelines for high dose methotrexate administration for 143ThaiPOG-NHL13-BL protocol

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Appendix II: Supportive care guidelines for high dose methotrexate administration for ThaiPOG-NHL13-ALCL protocolMethotrexate at 1,000 mg/m2 over 24 hours (course A1, A2, A3, B1, B2 and B3)1) Hydration  Pre- hydrate with 125 ml/m2/h (dextrose saline with NaHCO3 40 mmol/l) for a minimum of 2 hours inorder to achieve a pH of ≥ 7 and a urine output of ≥ 100 ml/m2/h.  During and after MTX infusion, continue hydration at a rate of 3,000 ml/m2 with NaHCO3 40 mmol/land KCL 20 mmol/l added to dextrose saline to maintain urinary pH ≥ 7 for a further 48 hours after the end ofthe methotrexate infusion.  Methotrexate levels, urea and electrolytes should be measured daily for at least 3 days after MTXinfusion.  Strict attention should be paid to fluid balance.2) Methotrexate  Methotrexate 1,000 mg/m2 in 0.9% saline is given on day 1 with 1/10 of the dose as initial IV over 30minutes and 9/10 of the dose as 23.5 hour infusion3) Drug interactions  Drugs which compromise renal function (e.g. aminoglycosides) can decrease clearance ofmethotrexate and lead to systemic toxicity. Avoid concurrent use of NSAIDs, omeprazole, azole antifungals,salicylates and sulphonamides. Large doses of penicillin may interfere with the active renal tubular section ofmethotrexate.  Prophylactic co-trimoxazole (if given) should be stopped one week prior to MTX administration.4) Leucovorin  Leucovorin (folinic acid) 15 mg/m2 should be given IV for an optimal rescue at hrs 42, 48 and 54 fromthe start of MTX infusion.  MTX plasma concentrations are measured at hrs 24 and hr 48 from start of MTX infusion. Theexpected MTX plasma concentrations are as follows.Time from start of MTX Expected MTX level Leucovorin dose24 hrs < 30 μmol/L -42 hrs 15 mg/m2 IV48 hrs < 0.25 μmol/L 15 mg/m2 IV54 hrs 15 mg/m2 IV  If the plasma MTX concentration at 48 hrs from start of MTX infusion is <0.25 μmol/L then leucovorinrescue is stopped after 54 hrs and no more measurements of the plasma MTX concentrations are needed.  If the plasma MTX concentration at 48 hrs from the start of MTX is >0.25 μmol/L, continue theleucovorin rescue beyond 54 hrs according the schedule below, and continue with measurement of the plasmaMTX concentration every 24 hrs.Lymphoma: Appendix II: Supportive care guidelines for high dose methotrexate administration for 144ThaiPOG-NHL13-ALCL protocol

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กMTX level at 48 hrs or later from start of MTX infusion* Leucovorin rescue (mg/m2 IV q6h) (μmol/L)0.25 – 1 151-2 302-3 453-4 604-5 75>5 *** MTX level to be measured every 24 hrs until the level falls below 0.25 μmol/L, then discontinue leucovorin** mg leucovorin IV q6h = MTX level (μmol/L) x body weight (kg)Methotrexate at 3,000mg/m2 over 3 hours (course AM1, AM2, AM3, BM1, BM2 and BM3)1) Hydration  Pre-hydrate with 125 ml/m2/h (dextrose saline with NaHCO3 40 mmol/l) for a minimum of 2 hours inorder to achieve a pH of ≥ 7 and a urine output of ≥ 100 ml/m2/h.  During and after MTX infusion, continue hydration at a rate of 3,000 ml/ m2 with NaHCO3 40 mmol/land KCL 20 mmol/l added to dextrose saline to maintain urinary pH ≥ 7 for a further 48 hours.  Methotrexate levels, urea and electrolytes should be measured daily for 3 days after MTX infusion.  Strict attention should be paid to fluid balance2) Methotrexate  Methotrexate is administered in saline at a dose of 3,000 mg/m2 over 3 hours.3) Drug interactions  Drugs which compromise renal function (e.g. aminoglycosides) can decrease clearance ofmethotrexate and lead to systemic toxicity. Avoid concurrent use of NSAIDs, omeprazole, azole antifungals,salicylates and sulphonamides. Large doses of penicillin may interfere with the active renal tubular section ofmethotrexate.  Prophylactic co-trimoxazole (if given) should be stopped one week prior to MTX administration.4) Leucovorin  Leucovorin (folinic acid) 15 mg/m2 should be given orally or iv every 6 hours. The dose should berounded up to the nearest 5 mg. If leucovorin is given orally, other oral drugs should be avoided within 30minutes of leucovorin administration. If vomiting occurs within 30 minutes, repeat the dose. If persistentvomiting or diarrhoea occurs, then give leucovorin by IV injection.  Methotrexate levels, urea and electrolytes should be measured daily for 3 days after methotrexateinfusion.  Leucovorin doses should be modified according to the MTX level. The level should be measuredevery 24 hours until rescue is complete i.e. plasma MTX level < 0.15 μmol/L.Lymphoma: Appendix II: Supportive care guidelines for high dose methotrexate administration for 145ThaiPOG-NHL13-ALCL protocol

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็  The rescue begins 24 hours from the start of MTX infusion and stops when the MTX level is< 0.15 μmol/L. This may be achieved with fewer than 12 doses. In this situation stop leucovorin after thistime.  If the MTX level does not fall as expected, increase leucovorin as shown below.Time from MTX level (μmol/L) 2-20 20-100start of MTX <0.15 0.15-2 15 mg/m2 IV q6h 10 mg/m2 IV q3h >10048 hrs None 15 mg/m2 IV q6h 10 mg/m2 IV q3h 100 mg/m2 IV q3h 100 mg/m2 IV q3h72 hrs None 15 mg/m2 IV q6h 10 mg/m2 IV q3h 100 mg/m2 IV q3h 1,000 mg/m2 IV q3h96 hrs None 15 mg/m2 IV q6h 10 mg/m2 IV q3h 100 mg/m2 IV q3h 1,000 mg/m2 IV q3h None 15 mg/m2 IV q6h 1,000 mg/m2 IV q3h120 hrsLymphoma: Appendix II: Supportive care guidelines for high dose methotrexate administration for 146ThaiPOG-NHL13-ALCL protocol

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Evaluation for matual B cell lymphomaTests Pre- COP Induction Consolidation Maintenance End of treatment therapyCBC ✔ To do prior to each course of therapyChemistries ✔ To do prior to each course of therapyPT/PTT, INR, ✔ to do prior to each course of therapyfibrinogen, ESR ✔UASurgical Bx of lesion ✔ See CR Eval See CR Eval (LR) (SR and HR)BMA/Bx ✔ See CR Eval See CR Eval ✔ ✔ (LR) (SR and HR) ✔CSF ✔ To do with all IT treatmenrtsImaging study ✔ CT on D7 of See CR Eval See CR Eval(eg. CT neck, chest, COP (LR) (SR and HR)abdomen, pelvis)Bone scan ✔ To follow up as indicatedGallium scan / PET ✔ To follow up as indicated ✔(optional)EKG/Echo ✔ Prior to each course of Doxorubicin if clinically ✔ indicatedCR Evaluation: Includes BM exam (not required if BM negative at diagnosis), surgical biopsy of lesion (ifhaving residual tumor) and imaging studies of primary tumor sites. The time of evaluation varies with riskgroup: - Low risk (LR) – after completion of COPAD#2 - Standard risk (SR) – after completion of CYM#1 - High risk (HR) – after completion of CYVE#2Lymphoma: Evaluation for matual B cell lymphoma 147

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Evaluation for Anaplastic Large Cell Lymphoma Tests Pre-treatment Pre-phase Intensive phase End of therapyCBC ✔ To do prior to each course of therapyChemistries ✔ To do prior to each course of therapyPT/PTT, INR, fibrinogen, ✔ESRUA ✔ To do prior to each course of therapySurgical Bx of lesion ✔BMA/Bx ✔CSF ✔ To do with all IT treatmenrtsImaging study ✔ After the 3rd course in intensive ✔(eg. CT neck, chest,abdomen, pelvis) phaseBone scan ✔ To follow up as indicatedGallium scan / PET ✔ To follow up as indicated(optional)EKG/Echo ✔ Prior to each course of Doxorubicin if clinically ✔ indicatedLymphoma: Evaluation for Anaplastic Large Cell Lymphoma 148

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for low risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-LR]Protocol name ThaiPOG-NHL-13-BL-LRProtocol for Mature B-cell Lymphoma – Low RiskReference: SJBC3 ProtocolOpen Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion Criterla  Completlely stage I  Completely resected abdominal stage II lesionDays 1 2 3 4 5 67Prednisolone       Vincristine    Cyclophosphamide Doxorubicin  G-CSFGiven dose/day Drug Dosage………………….mg Vincristine 2 mg/m2 (max single dose 2 mg) IV bolus on Day 1 and 6………………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7………………….mg Cyclophosphamide inclusive. 250 mg/m2/dose every 12 hours as a 15 minute infusion on………………….mg Doxorubicin Days 1-3 inclusive (500 mg/m2/day). The first dose should be…………….….mcg G-CSF given on day 1 prior to the start of the doxorubicin infusion. Hydration should be maintained at a rate of 3,000 mL/m2/day Low Risk Group (125 mL/m2/hr). Continue hydration until 12 hours after the last COPAD Course 1 dose of cyclophosphamide. Total daily mesna dose to be equal to 60-100% of the daily cyclophosphamide dose 60 mg/m2 as a 6 hour infusion, after the first dose of cyclophosphamide on Day 1 5 mcg/kg/day subcutaneously on Day 7-21 inclusive. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3, even if prior to day 21. Date RemarksCOPAD Course 2Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide doseLymphoma: Treatment protocol for low risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 149LR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-SR]Protocol name ThaiPOG-NHL-13-BL-SRProtocol for Mature B-cell Lymphoma – Standard RiskReference: SJBC3 protocolOpen Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk: Treatment Plan (COP  COPADM3(x2)  CYM(x2))Standard Risk: Pre-phase: COPDays 1 2 3 4 5 6 7   Cyclophosphamide    Vincristine   Prednisolone  IT MTX IT HC IT Ara-C Given dose/day Drug Dosage………………….mg Cyclophosphamide 300 mg/m2 as an infusion over 15 minutes on Day 1………………….mg Vincristine 1 mg/m2 (max single dose 2 mg) IV bolus on Day 1………………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 IT medications See Intrathecal Treatment for dosing (If blasts identified on this LP, patients will be moved to high risk group) Tumor response evaluation should be performed on day 7 before proceeding with COPADM3 course1 Non-responding patients (<20% reduction in size) will be treated with high risk group protocol (start withCOPADM8 course1) Standard Risk Group – Pre-phase Date RemarksCOPLymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 150BL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk : Induction (COPADM3 x 2 courses)The first COPADM3 course starts on Day 8 as long as clinical condition permits. Please note that COPADM3course 1 and 2 are identical.Days 1 2 3 4 5 6 7Vincristine     Prednisolone   Methotrexate  Leucovorin  Cyclophosphamide Doxorubicin   IT MTX    IT HC G-CSF   Rituximab Given dose/day Drug Dosage……………….mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1……………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 inclusive……………….mg Methotrexate 3,000 mg/m2 in dextrose 5% as IV infusion over 3 hours on Day 1.……...…mg/dose Leucovorin 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as required depending on methotrexate levels. This begins at 24……………….mg Cyclophosphamide hours from the start of the methotrexate infusion. 250 mg/m2/dose every 12 hours (500 mg/m2/day) as an infusion……………….mg Doxorubicin over 15 minutes on days 2-4 ( 6 doses). The first dose is given……………….mg IT MTX before start of the doxorubicin infusion. Continue hydration at a rate of 3,000 mls/m2/day until 12 hours after the last dose of……..………mcg G-CSF cyclophosphamide. Total daily mesna dose to be equal to 60- 100% of the daily cyclophosphamide dose……………….mg Rituximab 60 mg/m2 as a 6 hour infusion, after the first dose of cyclophosphamide. Methotrexate and hydrocortisone IT injection on Days 2 and 6 (See Intrathecal Treatment for dosing). Administer Day 2 IT 12-24 hours after HDMTX starts and before leucovorin rescue begins 5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G- CSF should be discontinued when the post nadir ANC reaches 2,000/mm3 even if prior to Day 21. 375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis.Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 151BL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Course #2 of COPADM3 should start when ANC ≥ 1.0 x 109/L and platelets ≥ 100,000 x 109/L. However, thecourse should not be given less than 14-21 days after the start of COPADM3 #1 and should be delayed for 24hours from the last dose of G-CSF. Standard Risk Group – Pre-phase Date RemarksCOPADM3 Course 1COPADM3 Course 2Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 152BL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk: Consolidation (CYM x 2 courses)Each cycle of CYM should start when ANC ≥ 1.0 x 109/L and platelets ≥ 100,000 x 109/L. Please note thatCYM course 1 and 2 are identical.Days 1 23 4 5 6 7Methotrexate   Leucovorin   Cytarabine    IT MTX    IT-Ara-C IT HC  G-CSFRituximab  Given dose/day Drug Dosage…………….mg Methotrexate 3,000 mg/m2 in dextrose 5% as IV infusion over 3 hours on Day 1.……...mg/dose Leucovorin 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as…………….mg required depending on methotrexate levels. This begins at 24 hours from Cytarabine the start of the methotrexate infusion…………..mcg IT 100 mg/m2 in either dextrose or saline as continuous infusion over 24…………….mg medications hours. Repeat daily from Day 2-6 inclusive (total of 5 days). Methotrexate and hydrocortisone IT injection on Day 2. Cytarabine and G-CSF hydrocortisone IT injection on Day 7 (See Intrathecal Treatment for dosing). Administer Day 2 IT methotrexate and hydrocortisone 12-24 Rituximab hours after HDMTX starts and before leucovorin begins. 5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3, even if prior to Day 21. 375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis.-Following recovery from CYM #1, a full assessment of response should be performed. Any residual massesshould be surgically excised, or biopsied if excision is not possible.  If histology negative  Continue with CYM #2  If histology positive (even if completely resected)  Change to high risk protocol by starting with CYVE #1Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 153BL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk Group - Consolidation Date RemarksCYM Course 1CYM Course 2Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 154BL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-HR]Protocol name ThaiPOG-NHL-13-BL-HRProtocol for Mature B-cell Lymphoma – High RiskReference: SJBC3 protocolOpen Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Bone marrow involvement CNS involvement  Any L3 blasts in CSF  Clinical spinal cord compression  Isolated intracerebral mass  Parameningeal extension: cranial and/or spinal  Cranial nerve palsy (if not explained by extracranial tumor)High Risk : Treatment Plan ( COP  COPADM8(x2)  CYVE(x2)  Maintenance 1,2,3,4 )High Risk : Pre-phase: COPDays 1 2 34 56 7 Cyclophosphamide   Vincristine   Prednisolone         IT MTX     IT HC IT Ara-C Leucovorin Given dose/day Drug Dosage………………….mg Cyclophosphamide 300 mg/m2 as an infusion over 15 minutes on Day 1………………….mg Vincristine 1 mg/m2 (max single dose 2 mg) IV bolus on Day 1………………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 IT medications Methotrexate, cytarabine, and hydrocortisone IT injection on………...…mg/dose Days 1, 3, and 5 (See Intrathecal Treatment for dosing) Leucovorin 5 mg/m2/dose (max 5 mg) po given at 24 and 30 hours after IT on Days 2 & 4 High Risk Group – Pre-phase Date RemarksCOPLymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 155HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : Induction (COPADM8 course 1)COPADM8 course 1 should start on day 8 of COP pre-phase therapy, as long as clinical condition permits.Please note that COPADM8 course 1 and 2 are different.Days 1 2 3 4 5 6 7Vincristine          Prednisolone MethotrexateLeucovorin Cyclophosphamide    Doxorubicin  IT MTX    IT HC    IT-Ara-C     G-CSF   RituximabGiven dose/day Drug Dosage……………….mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1……………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7……………….mg Methotrexate inclusive……...…mg/dose Leucovorin 8,000 mg/m2 in dextrose 5% as IV infusion over 4 hours on Day 1……………….mg 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as Cyclophosphamide required depending on methotrexate levels. This begins at 24……………….mg hours from the start of the methotrexate infusion. Doxorubicin 250 mg/m2/dose every 12 hours (500 mg/m2/day) as an infusion………………..mcg IT medications over 15 minutes on days 2-4 ( 6 doses). The first dose is given……………….mg before start of the doxorubicin infusion. Continue hydration until G-CSF 12 hours after the last dose of cyclophosphamide. Total daily mesna dose to be equal to 60-100% of the daily Rituximab cyclophosphamide dose 60 mg/m2 as a 6 hour infusion, after the first dose of cyclophosphamide. Methotrexate, cytarabine, and hydrocortisone IT injection on Days 2, 4, and 6 (See Intrathecal Treatment for dosing). Administer Day 2 IT 12 & 24 hours after HDMTX startsb and before leucovorin rescue begins. 5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3 even if prior to Day 21. 375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis.Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 156HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 High Risk Group - Induction Date RemarksCOPADM8 Course 1Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 157HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : Induction (COPADM8 course 2)OPADM8 course 2 should start when ANC ≥ 1.0 x 109/L and platelets ≥ 100,000 x 109/L. The course shouldnot be given less than 14-21 days after the start of COPADM8 course 1 and should be delayed for 24 hoursfrom the last dose of G-CSF. Please note that cyclophosphamide dose in COPADM8 course 2 is higher thanthe dose in COPADM8 course 1.Days 1 23 4 5 6 7Vincristine     Prednisolone   Methotrexate    Leucovorin    Cyclophosphamide    Doxorubicin    IT MTX IT HC  IT-Ara-C   G-CSF  Rituximab    Given dose/day Drug Dosage……………….mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1……………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7……………….mg Methotrexate inclusive……...…mg/dose Leucovorin 8,000 mg/m2 in dextrose 5% as IV infusion over 4 hours on……………….mg Cyclophosphamide Day 1 (Note: Higher dose than for standard risk group) 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or……………….mg Doxorubicin as required depending on methotrexate levels. This begins at IT medications 24 hours from the start of the methotrexate infusion. 500 mg/m2/dose every 12 hours (1,000 mg/m2/day) as an………….….mcg G-CSF infusion over 15 minutes on days 2-4 (6 doses). The first dose……………….mg Rituximab is given before start of the doxorubicin infusion. Continue hydration until 12 hours after the last dose of cyclophosphamide. Total daily mesna dose to be equal to 60-100% of the daily cyclophosphamide dose 60 mg/m2 as a 6 hour infusion, after the first dose of cyclophosphamide. Methotrexate, cytarabine, and hydrocortisone IT injection on Days 2, 4, and 6 (See Intrathecal Treatment for dosing). Administer Day 2 IT 12 & 24 hours after HDMTX startsb and before leucovorin rescue begins. 5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3 even if prior to Day 21. 375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis.Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 158HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 High Risk Group - Induction Date RemarksCOPADM8 Course 2Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 159HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : Consolidation (CYVE x 2 courses)The first of these two courses should start after COPADM8 cycle 2 when ANC ≥ 1.0 x 109/L and platelets≥ 100,000 x 109/L. G-CSF should have been stopped for 24 hours before the start of this course. Please notethat CYVE course 1 and 2 are identical. Variations in the start/stop times of the agents below are acceptable, as long as the sequence ofadministration of the agents and duration of infusions are as close as possible.Days 1 2 3 4 5 67Cytarabine (continuous)      Runs from 20:00-08:00HD Ara-C     Runs from 08:00-11:00Etoposide      Runs from 14:00-16.00GCSF Rituximab      Given dose/day Drug Dosage…………….mg Cytarabine 50 mg/m2 by continuous infusion over 12 hours. This should start at (continuous) 20:00 hours and run until 08:00 the following day. Repeat daily x 5.…………….mg HD Ara-C 3,000 mg/m2 as IV infusion over 3 hours, to start at the end of the 12…………….mg Etoposide hour infusion of cytarabine for 4 doses (from 08:00 to 11:00 hours). 200 mg/m2 in saline as IV infusion over 2 hours daily x 4 doses. Etoposide starts at 14:00 hours, 3 hours after end of high dose cytarabine.…………...mcg GCSF 5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3,…………….mg Rituximab even if prior to Day 21. 375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of hepatitis B should be closely monitored for clinical and laboratory signs of active HBV infection and for signs of hepatitis. CYVE #2: This course is the same as CYVE #1 and starts once ANC ≥ 1.0 x 109/L and platelets ≥ 100,000 x109/L (usually by day 25-28). Following recovery from CYVE #2, a complete response evaluation should be performed. Residual massesshould be surgically excised, or biopsied if excision is not possible.o If histology negative  Continue on protocolo If histology positive  Autologous hematopoietic stem cell transplantation is recommended aftersalvage therapyHigh Risk Group - Consolidation Date RemarksCYVE Course 1CYVE Course 2Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 160HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : MaintenanceMaintenance therapy includes 4 sequences/blocks of chemotherapy. Each sequence will begin when ANC ≥1.0 x 109/L and platelets ≥ 100,000 x 109/L.High Risk : Maintenance (Sequence No. 1)Days 1 23 4 5 6 7Vincristine     Prednisolone   Cyclophosphamide  Methotrexate     Leucovorin  Doxorubicin  IT MTX  IT HC    IT Ara-C     G-CSF  Given dose/day Drug Dosage…………….mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1…………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 inclusive…………….mg Cyclophospha 500 mg/m2/day given daily as IV infusion over 30 minutes on Days 2 and 3. mide First dose is given before doxorubicin. Total daily mesna dose to be equal…………….mg to 60-100% of the daily cyclophosphamide dose……...mg/dose Methotrexate 8,000 mg/m2 in dextrose 5% IV infusion over 4 hours on Day 1. Leucovorin 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as modified…………….mg depending on methotrexate levels). This begins 24 hours from the start of Doxorubicin the methotrexate infusion.……..…….mcg IT medications 60 mg/m2 as a 6 hour infusion, after first dose of cyclophosphamide Methotrexate, cytarabine, and hydrocortisone IT injection on Day 2 (See GCSF Intrathecal Treatment for dosing). Administer Day 2 IT 12-24 hours after HDMTX starts and before leucovorin rescue begins. 5 mcg/kg/day by subcutaneous injection starting 24 hours aftercompletion of chemotherapy. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3 High Risk Group - Maintenance Date RemarksMaintenance: Sequence No. 1Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 161HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : Maintenance (Sequence No. 2)Days 1 2 3 4 5 6Cytarabine      Etoposide G-CSF    IT MTX IT HC   IT Ara-C Given dose/day Drug Dosage…………….mg Cytarabine 50 mg/m2/dose as subcutaneous injection every 12 hrs (100 mg/m2/day) Days 1-5…………….mg Etoposide 150 mg/m2 IV infusion over 90 minutes Days 1-3………..….mcg G-CSF 5 mcg/kg/day by subcutaneous injection starting 24 hours after completion of chemotherapy. G-CSF should be discontinued when the IT medications post nadir ANC reaches 2,000/mm3. For CNS positive only. Given on day1. (See Intrathecal Treatment for dosing) High Risk Group - Maintenance Date RemarksMaintenance: Sequence No. 2Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 162HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk : Maintenance (Sequence No. 3)Days 1 2 3 4 5 6 7Vincristine     Prednisolone   Cyclophosphamide   Doxorubicin          G-CSF IT MTXIT HC IT Ara-C  Given dose/day Drug Dosage…………….mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1…………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 inclusive…………….mg Cyclophosphamide 500 mg/m2/day given daily as IV infusion over 30 minutes on Days 1 and 2. First dose is given before doxorubicin. Maintain hydration at…………….mg Doxorubicin 3,000 mL/m2/day until 12 hours after 2nd dose. Total daily mesna…………….mcg GCSF dose to be equal to 60-100% of the daily cyclophosphamide dose IT medications 60 mg/m2 as a 6 hour infusion, after first dose of cyclophosphamide 5 mcg/kg/day by subcutaneous injection starting 24 hours aftercompletion of chemotherapy. G-CSF should be discontinued when the post nadir ANC reaches 2,000/mm3 For CNS positive only. Given on day1. (See Intrathecal Treatment for dosing High Risk Group - Maintenance Date RemarksMaintenance: Sequence No. 3Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 163HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk: Maintenance (Sequence No. 4)Days 1 2 3 4 5 6Cytarabine      Etoposide G-CSF    IT MTX IT HC   IT Ara-C Given dose/day Drug Dosage…………….mg Cytarabine 50 mg/m2/dose as subcutaneous injection every 12 hrs (100 mg/m2/day) Days 1-5…………….mg Etoposide 150 mg/m2 IV infusion over 90 minutes Days 1-3…………...mcg G-CSF 5 mcg/kg/day by subcutaneous injection starting 24 hours after completion of chemotherapy. G-CSF should be discontinued when the IT medications post nadir ANC reaches 2,000/mm3. For CNS positive only. Given on day1. (See Intrathecal Treatment for dosing) High Risk Group - Maintenance Date RemarksMaintenance: Sequence No. 4Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 164HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL-LR]Protocol name ThaiPOG- NHL-13-ALCL-LRProtocol for Anaplastic Large Cell Lymphoma – Low RiskReference: AIEOP ALCL99Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Stage I disease completely resectedLow Risk Group Treatment Plan (P  A1  B1  A2 )Low Risk: Pre-phase (COP)Days 1 2 3 4 5 6 7Cyclophosphamide    Vincristine    Prednisolone IT MTX    IT HC IT Ara-C Given dose/day Drug Dosage………………….mg Cyclophosphamide 300 mg/m2 as an infusion over 15 minutes on Day 1………………….mg Vincristine 1 mg/m2 (max single dose 2 mg) IV bolus on Day 1………………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 IT medications See Intrathecal Treatment for dosing Low Risk Group – Pre-phase Date RemarksCOPLymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 165LR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Low Risk: Intensive phase (A1  B1 A2)Low Risk: Intensive phase course A (A1 and A2)The course of A1 begins at day 6 of Pre-phase treatment. Subsequent course, A2, starts as soon as theperipheral counts have recovered with when ANC ≥ 0.5 x 109/L and platelets ≥ 50,000 x 109/L and rising andpatient is clinically well and free of fever for more than 3 days. Please note that course A1 and A2 areidentical.Days 1 2 3 4 5Dexamethasone     Methotrexate IT-MHC     Ifosfamide     Mesna   Cytarabine  Etoposide  Given dose/day Drug Dosage………………….mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV. 1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30………………….mg Methotrexate minutes then 90% as a 23.5h infusion). 15 mg/m2 IV 42, 48 and 54 hours after the beginning of MTX…………..mg/dose Leucovorin infusion. IT medications Day 1 (2 - 4 hours after the beginning of Methotrexate infusion) See Intrathecal Treatment for dosing. 800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before………………….mg Ifosfamide the start of MTX infusion. IV or oral hydration at a rate of 3,000 mls/m2/day should continue until 12 hours after the last dose of………………….mg Mesna Ifosfamide. Given as an IV bolus 330 mg/m2/dose at 0, 4 and 8 hours after………………….mg Cytarabine Ifosfamide. 150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5. (300 mg/m2/day) 100 mg/m2 in 2 hour infusion day 4 and 5 (after the infusion of………………….mg Etoposide Cytarabine).Note: Prophylactic GCSF is not recommendedLymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 166LR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Low Risk: Intensive phase course B (B1)The course of B1 starts as soon as the peripheral counts have recovered with ANC ≥ 0.5 x 109/L andplatelets ≥ 50,000 x 109/L and rising and patient is clinically well and free of fever more than 3 days.Days 1 2 3 4 5Dexamethasone     Methotrexate   IT-MHC     Cyclophosphamide Doxorubicin   Given dose/day Drug Dosage………………….mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV. 1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30………………….mg Methotrexate minutes then 90% as a 23.5h infusion). 15 mg/m2 IV 42, 48 and 54 hours after the beginning of MTX……….…..mg/dose Leucovorin infusion. IT medications Day 1 (2 - 4 hours after the beginning of Methotrexate infusion) See Intrathecal Treatment for dosing.………………….mg Cyclophosphamide 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give before the start of MTX infusion. Hydration IV or PO at a rate of 3,000 mls/m2/day should then continue until 12 hours after the last dose of Cyclophosphamide 25 mg/m2 in 1 hour infusion day 4 and 5.………………….mg DoxorubicinNote: Prophylactic GCSF is not recommended Low Risk Group – Intensive phase Date RemarksCourse A1Course B1Course A2Lymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 167LR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL-SR]Protocol name ThaiPOG- NHL-13-ALCL-SRProtocol for Anaplastic Large Cell Lymphoma – Standard RiskReference: AIEOP ALCL99Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk Group Treatment Plan (P  A1  B1  A2  B2  A3  B3 )Standard Risk : Pre-phase (COP)Days 1 2 3 4 5 6 7Cyclophosphamide     Vincristine  Prednisolone IT-MHC      Given dose/day Drug Dosage………………….mg 300 mg/m2 as an infusion over 15 minutes on Day 1………………….mg Cyclophosphamide 1 mg/m2 (max single dose 2 mg) IV bolus on Day 1………………….mg Vincristine 60 mg/m2/day (divided into bid doses) orally on Days 1-7 Prednisolone See Intrathecal Treatment for dosing IT medications Standard Risk Group – Pre-phase Date RemarksCOPLymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 168NHL-13-ALCL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk : Intensive phase (A1  B1 A2 B2 A3 B3)Standard Risk : Intensive phase course A (A1, A2 and A3)The course of A1 begins at day 6 of Pre-phase treatment. Subsequent courses, A2 and A3, start as soon asthe peripheral counts have recovered with when ANC ≥ 0.5 x 109/L and platelets ≥ 50,000 x 109/L and risingand patient is clinically well and free of fever more than 3 days. Please note that course A1, A2 and A3 areidentical.Days 1 2 3 4 5Dexamethasone     Methotrexate IT-MHC     Ifosfamide   Mesna     Cytarabine    Etoposide Given dose/day Drug Dosage………………mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV.………………mg Methotrexate 1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30 minutes then 90% as a 23.5 h infusion) 15 mg/m2 IV 42, 48 and 54 hours after the beginning of MTX………..mg/dose Leucovorin infusion. IT medications Day 1 (2 - 4 hours after the beginning of Methotrexate infusion) See………………mg Ifosfamide Intrathecal Treatment for dosing. 800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before the start of MTX infusion. IV or oral hydration at a rate of 3,000 mls/m2/day should continue until 12 hours after the last dose of Ifosfamide. Given as an IV bolus 330 mg/m2/dose at 0, 4 and 8 hours after………………mg Mesna Ifosfamide. 150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5. (300………………mg Cytarabine mg/m2/day). 100 mg/m2 in 2 hour infusion day 4 and 5 (after the infusion of………………mg Etoposide Cytarabine).Note: Prophylactic GCSF is not recommendedLymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 169NHL-13-ALCL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Standard Risk : Intensive phase course B (B1, B2 and B3)The courses of B1, B2 and B3 start as soon as the peripheral counts have recovered with ANC ≥ 0.5 x 109/Land platelets ≥ 50,000 x 109/L and rising and patient is clinically well and free of fever for more than 3 days.Please note that course B1, B2 and B3 are identical.Days 1 2 3 4 5Dexamethasone      Methotrexate IT-MHC  Cyclophosphamide       DoxorubicinGiven dose/day Drug Dosage………………….mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV.………………….mg Methotrexate 1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30…………..mg/dose Leucovorin minutes then 90% as a 23.5 h infusion) IT medications 15 mg/m2 IV 42, 48 and 54 hours after the beginning of MTX………………….mg Cyclophosphamide infusion. Day 1 (2 - 4 hours after the beginning of Methotrexate infusion)………………….mg Doxorubicin See Intrathecal Treatment for dosing. 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give before the start of MTX infusion. Hydration IV or PO at a rate of 3,000 mls/m2/day should then continue until 12 hours after the last dose of Cyclophosphamide. 25 mg/m2 in 1 hour infusion day 4 and 5.Note: Prophylactic GCSF is not recommended Standard Risk Group – Intensive phase Date RemarksCourse A1Course B1Course A2Course B2Course A3Course B3Lymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 170NHL-13-ALCL-SR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL-HR]Protocol name ThaiPOG- NHL-13-ALCL-HRProtocol for Anaplastic Large Cell Lymphoma – High RiskReference: AIEOP ALCL99Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Biopsy proven skin lesions (except skin lesions overlying an involved node or isolated skin disease) Presence of mediastinal involvement Presence of liver, spleen or lung involvement (biopsy is not necessary for obvious lesions)High Risk Group Treatment Plan (P  AM1  BM1  AM2  BM2  AM3  BM3)High Risk: Pre-phase (COP)Days 1 2 3 4 5 6 7   Cyclophosphamide    Vincristine    Prednisolone IT MHC Given dose/day Drug Dosage………………….mg Cyclophosphamide 300 mg/m2 as an infusion over 15 minutes on Day 1………………….mg Vincristine 1 mg/m2 (max single dose 2 mg) IV bolus on Day 1………………….mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 IT medications See Intrathecal Treatment for dosing High Risk Group – Pre-phase Date RemarksCOPLymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 17113-ALCL-HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk: Intensive phase (AM1  BM1 AM2BM2 AM3 BM3)High Risk: Intensive phase course AM (AM1, AM2 and AM3)The course of AM1 begins at day 6 of Pre-phase treatment. Subsequent courses, AM2 and AM3, start assoon as the peripheral counts have recovered with when ANC ≥ 0.5 x 109/L and platelets ≥ 50,000 x 109/Land rising and patient is clinically well and free of fever for more than 3 days. Please note that course AM1,AM2 and AM3 are identical.Days 1 2 3 4 5Dexamethasone     Methotrexate Ifosfamide     Mesna     Cytarabine  Etoposide    Given dose/day Drug Dosage………………….mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV. 3,000 mg/m2 over 3 hours day 1………………….mg Methotrexate 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or…………...mg/dose Leucovorin as required depending on Methotrexate levels. This begins 24 hours after start of MTX infusion.………………….mg Ifosfamide 800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before the start of MTX infusion. IV or oral hydration at a rate of 3,000 mls/m2/day should continue until 12 hours after the last dose of………………….mg Mesna Ifosfamide. Given as an IV bolus 330 mg/m2/dose at 0, 4 and 8 hours after………………….mg Cytarabine Ifosfamide. 150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5. (300 mg/m2/day) 100 mg/m2 in 2 hour infusion day 4 and 5 (after the infusion of………………….mg Etoposide Cytarabine).Note: Prophylactic GCSF is not recommendedLymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 17213-ALCL-HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk: Intensive phase course BM (BM1, BM2 and BM3)The courses of BM1, BM2 and BM3 start as soon as the peripheral counts have recovered with ANC ≥ 0.5 x109/L and platelets ≥ 50,000 x 109/L and rising and patient is clinically well and free of fever for more than 3days. Please note that course BM1, BM2 and BM3 are identical.Days 1 2 3 4 5Dexamethasone     Methotrexate Cyclophosphamide     Doxorubicin   Given dose/day Drug Dosage………………….mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV.………………….mg Methotrexate 3,000 mg/m2 over 3 hours day 1…………...mg/dose Leucovorin 15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as required depending on Methotrexate levels. This begins 24………………….mg Cyclophosphamide hours after start of MTX infusion.………………….mg Doxorubicin 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give before the start of MTX infusion. Hydration IV or PO at a rate of 3,000 mls/m2/day should then continue until 12 hours after the last dose of Cyclophosphamide 25 mg/m2 in 1 hour infusion day 4 and 5.Note: Prophylactic GCSF is not recommended High Risk Group – Intensive phase Date RemarksCourse AM1Course BM1Course AM2Course BM2Course AM3Course BM3Lymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 17313-ALCL-HR]

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กCNS Germ Cell Tumor Data entry formPatient’s name......................................................... HN............................ Sex  male femaleAddress.............................................................................................................................. .......................................................................................................Contact person....................................Tel............................Father’s name........................................................ Age...........yr Occupation…………….............................Mother’s name........................................................ Age...........yr Occupation…………….............................Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) ......B...S..A.........................................m...2.Age ............. yr...............m. BW…...........kg Ht...............cm.สทิ ธิการรกั ษา บัตรประกันสุขภาพ จา่ ยตรง อืน่ ๆ (ระบ)ุ .................................HistoryPhysical examinationPre- treatment investigationsTumor marker (Blood) date (………/………/………)β-hCG (serum) ……..……………………….…. AFP(serum)……………..…………………………………..…Imaging studyMRI primary lesion (………/………/………) ..……………………….……………………..…………………….………MRI whole spine (………/………/………) ..……………………….……………………..……………………………*MRI spine should be studied prior to surgery or two weeks after surgeryCerebrospinal fluid study (………/………/………)CSF study from  ventriculostomy VP shunt lumbar punctureCSF cytology positive negative*CSF study should be performed two weeks after surgeryβ-hCG (CSF) ……..……………………….…. AFP(CSF) ……………………………..…………………..…Primary site (location)……………………………………………………………………………………………………Primary tumor size………………………………………………………………………………………………………….Metastasis siteM 1 CSF + M 2 brain metastasis by MRIM 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)OtherOther (………/………/………) ……………………………………………………………………………………………...Initial surgery (………/………/………) surgeon………………………….....…………………………………………...Operation biopsy partial removal total removal wide excision Other…..……………………Histology ……………………………………………………………………………………………………………………...Tumor Histology ClassificationTeratomaImmature teratomaGerminomaNon-germinoma Yolk sac tumor (Endodermal sinus tumor) Embryonal cell carcinoma ChoriocarcinomaMixed germ cell tumorCNS Germ Cell Tumor: Data entry form 174

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for CNS germinoma [ThaiPOG-BT-13-GCT]Protocol name ThaiPOG-BT-13-GCTProtocol for CNS Germinoma (Non-secreting tumor)Open Date January 2014Patient eligibility Exclusion criteria CNS germinomatous germinoma  serum or CSF AFP > 10 ng/dl CNS germinoma with syncytiotrophoblast  serum or CSF β-hCG > 50 U/Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Cycle Agent (s) Dose (s) 560 mg/m2 IV drip in 1 hour once daily Day 11, 2, 3 Carboplatin 150 mg/m2 IV drip in 30 min once daily Day 1-3 Etoposide*start chemotherapy when ANC > 1,000 mcL and platelet > 100,000/mcL*Each course of chemotherapy should be started every 21-28 days apartCycle Date BSA Carboplatin Etoposide123Radiation _______________________________________________________________________________Irradiation should be started after chemotherapy completion for 28 days. 1) Whole ventricle irradiation with a dose of 24 Gy (1.8 – 2 Gy/ fraction) must be applied with a primary tumor boost up to 30 Gy or 36-40 Gy (1.8 – 2 Gy/ fraction) if the tumor response is less than partial response. For the case that basal ganglia is involved, whole brain irradiation or wider than ventricular field 24 Gy (1.8 – 2 Gy/ fraction) should be considered. 2) In case of germinoma with syncytiotrophoblast (serum and CSF AFP < 10 ng/dL and serum or CSF β-hCG positive with the level < 50 U/L), a primary tumor boost up to 50 Gy (1.8 – 2 Gy/ fraction) must be considered. 3) In case of M+, craniospinal irradiation (CSI) 24 Gy (1.8 – 2 Gy/ fraction) must be applied. 4) Intermediate risk disease (elevated β-hCG, extensive or multifocal in brain, mixed type), a primary tumor boost up to 50 Gy (1.8-2 Gy/ fraction) must be considered.Evaluation and follow up MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. LP (………/………/………) …………………………………………………………………………………….. LP (………/………/………) ……………………………………………………………………………………..CNS Germ Cell Tumor: Treatment protocol for CNS germinoma [ThaiPOG-BT-13-GCT] 175

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT]Protocol name ThaiPOG-BT-13-NGCTProtocol for CNS non-germinomaOpen Date January 2014Patient eligibility1. CNS non-germinoma with biopsy proven  Immature teratoma with malignant transformation Yolk sac tumor (endodermal sinus tumor) Embryonal cell carcinoma Choriocarcinoma Mixed germ cell tumor2. Secreting tumor  serum /CSF AFP > 10 ng/dl OR serum/CSF β-hCG > 50 U/LPatient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Cycle Agent (s) Dose (s)1,2,3 Ifosfamide 41,08000mgm/mg/m2 p2rIioVr drip in 1-2 hour daily Day 1-3 Mesna to ifosfamide infusion and then at 3,6,9,12 hr 5af6t0ermifgo/smfa2mIVidedriinpfuinsio1nhour Day 1 Carboplatin 150 mg/m2 IV drip in 2 hour daily Day 1-3 Etoposide 560 mmgg//mm22 IV drip in 1 hour Day 14,5,6,7,8 Carboplatin 150 IV drip in 2 hour daily Day 1-3 Etoposide*start chemotherapy when ANC > 1,000 /mcL and platelet > 100,000 mcL*Each course of chemotherapy should be started every 21-28 days apartCycle Date BSA Ifosafmide Carboplatin Etoposide123 Irradiation4567 8* Second look surgery may be considered before irradiation.*Irradiation should be started after chemotherapy completion for 28 days. 1) Whole ventricle irradiation with a dose of 24 Gy (1.8 – 2 Gy/ fraction) must be applied with a primary tumor boost up to 50 Gy (1.8 – 2 Gy/ fraction). For the case that basal ganglia is involved, whole brain irradiation 24 Gy or wider than ventricular field 24 Gy (1.8 – 2 Gy/ fraction) should be considered. 2) In case of M+, craniospinal irradiation (CSI) 30 Gy (1.8 – 2 Gy/ fraction) must be applied with a boost up dose to 40 Gy (1.8 – 2 Gy/ fraction) for gross residual disease.CNS Germ Cell Tumor: Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT] 176

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Evaluation and follow up MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. LP (………/………/………) …………………………………………………………………………………….. LP (………/………/………) ……………………………………………………………………………………..CNS Germ Cell Tumor: Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT] 177

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กMedulloblastoma Data entry formPatient’s name......................................................... HN............................ Sex  male femaleAddress.....................................................................................................................................................................................................................................Contact person....................................Tel............................Father’s name........................................................ Age...........yr Occupation…………….............................Mother’s name........................................................ Age...........yr Occupation…………….............................Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) ......B...S..A.........................................m...2.Age ............. yr...............m. BW…...........kg Ht...............cm.สทิ ธิการรกั ษา บัตรประกันสขุ ภาพ จ่ายตรง อนื่ ๆ (ระบุ) .................................HistologyEmbryonal CNS tumors Medulloblastoma/supratentorial PNET Atypical/rhabdoid teratoid tumor Pineloblastoma EpendymoblastomaHistoryPhysical examinationPre- treatment investigations.Imaging studyMRI primary lesion (………/………/………) ..……………………….……………………..……………………………MRI whole spine (………/………/………) ..……………………….……………………..…………………………… *MRI spine should be studied prior to surgery or two weeks after surgeryCerebrospinal fluid study (………/………/………)CSF study from ventriculostomy VP shunt lumbar punctureCSF cytology positive negative*CSF study should be performed two weeks after surgery.Primary site (location)……………………………………………………………………………………………………Primary tumor size………………………………………………………………………………………………………….Metastasis site M 2 brain metastasis by MRIM 1 CSF + M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)M 3 spinal cord metastasis by MRIInitial surgery (………/………/………)Operation biopsy partial removal total removal wide excision Other…..……………………Histology (medulloblastoma only)Subtype Classical Desmoplastic Anaplastic/Large cellRisk groupAverage risk (Gross total removal AND M0)High risk (Less than gross total removal AND/OR M+)Less than gross total removal (residual tumor > 1.5 cm2 by MRI)M 1 CSF + M 2 brain metastasis by MRIM 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)Other (………/………/………) ……………………………………………………………………………………………...CNS Germ Cell Tumor: Medulloblastoma 178

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR]Protocol name ThaiPOG-BT-13-MB-AVRProtocol for Average risk medulloblastomaOpen Date January 2014Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Irradiation guideline, CSI (24 Gy with a boost up to 54.6 Gy to the posterior fossa is needed to be appliedwithin 28 days after surgical removal.Chemotherapy during irradiation (Irradiation started within 28 days after surgical removal)Vincristine 1.5 mg/m2 weekly x 6 weeksWeek Vincristine (Actual dose) Date123456CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 179

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Chemotherapy after irradiation (started within 28 days after irradiation completion)Cycle Agent (s) Dose (s)1,3,5,7,9 Cyclophosphamide 800 mg/m2 IV drip 1 hour once daily Day 1-3 1.5 mg/m2 IV push once daily Day 1,8,152,4,6,8,10 Vincristine 200 mg/m2 IV drip in 1 hour once daily Day 1-3 150 mg/m2 IV drip in 30 min once daily Day 1-3 Carboplatin Etoposide*New cycle of chemotherapy should be started within 21-28 days*chemotherapy should be started when ANC > 1,000 /mcL and platelet > 100,000 /mcL*G-CSF should be started at 24-36 hr after completion of each course of chemotherapyCycle Date BSA Cyclophosphamide Vincristine Carboplatin Etoposide12345678910Evaluation and follow up MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. LP (………/………/………) …………………………………………………………………………………….. LP (………/………/………) ……………………………………………………………………………………..CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 180

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR]Protocol name ThaiPOG-BT-13-MB-HRProtocol for High risk medulloblastomaOpen Date January 2014Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2In case of non-complete remission, secondary surgery may be needed to be applied after irradiation.Irradiation guideline, CSI (36 Gy with a boost up to 54.6 Gy to the posterior fossa is needed to be appliedwithin 28 days after surgical removal.Chemotherapy during irradiation (Irradiation started within 28 days after surgical removal)Vincristine 1.5 mg/m2 weekly x 6 weeksWeek Vincristine (Actual dose) Date123456CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR] 181

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Chemotherapy after irradiation (started within 28 days after irradiation completion)Cycle Agent (s) Dose (s)1,3,5,7,9 Cyclophosphamide 800 mg/m2 IV drip 1 hour once daily Day 1-3 1.5 mg/m2 IV push once daily Day 1,8,152,4,6,8,10 Vincristine 200 mg/m2 IV drip in 1 hour once daily Day 1-3 150 mg/m2 IV drip in 30 min once daily Day 1-3 Carboplatin Etoposide*New cycle of chemotherapy should be started within 21-28 days*chemotherapy should be started when ANC > 1,000 /mcL and platelet > 100,000 /mcL*G-CSF should be started at 24-36 hr after completion of each course of chemotherapyCycle Date BSA Cyclophosphamide Vincristine Carboplatin Etoposide12345678910In case of non-complete remission, secondary surgery is needed to be applied.Evaluation and follow up MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. LP (………/………/………) …………………………………………………………………………………….. LP (………/………/………) ……………………………………………………………………………………..CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR] 182

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Infant Brain Tumors (Age < 3 years old) Data entry formPatient’s name......................................................... HN............................ Sex  male femaleAddress.....................................................................................................................................................................................................................................Contact person....................................Tel............................Father’s name........................................................ Age...........yr Occupation…………….............................Mother’s name........................................................ Age...........yr Occupation…………….............................Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) .....................................Age ............. yr...............m. BW…...........kg Ht...............cm. BSA...................m2สิทธิการรกั ษา บตั รประกันสุขภาพ จา่ ยตรง อื่นๆ (ระบุ) .................................HistologyHistory Physical examinationPre- treatment investigations.Imaging studyMRI primary lesion (………/………/………) ..……………………….……………………..……………………………MRI whole spine (………/………/………) ..……………………….……………………..……………………………MRI spine should be studied prior to surgery or two weeks after surgeryCerebrospinal fluid study (………/………/………)CSF study from ventriculostomy VP shunt lumbar punctureCSF cytology positive negativeCSF study should be performed two weeks after surgery.Primary site (location)……………………………………………………………………………………………………Primary tumor size………………………………………………………………………………………………………….Metastasis siteM 1 CSF + M 2 brain metastasis by MRIM 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)Initial surgery (………/………/………)Operation biopsy partial removal total removal wide excision Other…..……………………HistologyEmbryonal CNS tumors Medulloblastoma Supratentorial PNET Pineloblastoma Atypical/rhabdoid teratoid tumor EpendymoblastomaEpendymomaHigh grade gliomasChoroid plexus carcinomaRisk groupAverage risk (Gross total removal AND M0)High risk (Less than gross total removal AND/OR M+) Less than gross total removal (residual tumor > 1.5 cm2 by MRI)M 1 CSF + M 2 brain metastasis by MRIM 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)Other (………/………/………) ……………………………………………………………………………………………...Infant Brain Tumors (Age < 3 years old): Data entry form 183

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB]Protocol name ThaiPOG-BT-13-IFBProtocol for Infant Brain Tumors (Age < 3 year old)Reference Rutkowski S et al N Engl J Med 2005;352:978-86.Open Date January 2014Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm/dd).............................. BW..........................kg Ht..............................cm BSA.........................m2Cycle Agent (s) Dose (s)Week 1,10,19,28,37,46 Cyclophosphamide 800 mg/m2 IV drip 1 hour once daily Day 1-3Week 3,12,21,30,39,48 Vincristine 1.5 mg/m2 IV push once daily Day 1 HDMTX 5 gm/m2 IV drip in 4 hours Day 1 Vincristine 1.5 mg/m2 IV push once daily Day 1Week 5,14,23,32,41,50 HDMTX 5 gm/m2 IV drip in 4 hours Day 1 Vincristine 1.5 mg/m2 IV push once daily Day 1Week 7,16,25,34,43,52 Carboplatin 200 mg/m2 IV drip in 1 hour once daily Day 1-3 Etoposide 150 mg/m2 IV drip in 30 min once daily Day 1-3*start chemotherapy when ANC > 750/mcL and platelet > 80,000 mcLInfant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 184

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Week Date BSA Cyclophosphamide Vincristine HDMTX Carboplatin Etoposide 1 3 5 7 10 12 14 16 19 21 23 25 28 30 32 34 37 39 41 43 46 48 50 52The protocol will be finished at 1 year or the patient reaches 3 years of age, whatever comes first.Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 185

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2Evaluation and follow up MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. MRI (………/………/………) …………………………………………………………………………………….. LP (………/………/………) …………………………………………………………………………………….. LP (………/………/………) ……………………………………………………………………………………..Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 186