แนวทางการรักษาโรคมะเร็งในเด็ก-2557 (1)

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Irradiation guideline*Start radiation after finished chemotherapy*1. For embryonal CNS tumors and choroid plexus carcinoma*Dose of radiation depends on the patient’s age on the day of starting radiation*-If age above 12 months but less than 18 months, M0; posterior fossa or tumor bed 54-60 Gy M+; CSI 12 Gy with boost at posterior fossa or tumor bed 54-60 Gy-If age above 18 months but less than 24 months, M0; CSI 12 Gy with boost at posterior fossa or tumor bed 54-60 Gy M+; CSI 18 Gy with boost at posterior fossa or tumor bed 54-60 Gy-If age above 24 months but less than 36 months, M0; CSI 18 Gy with boost at posterior fossa or tumor bed 54-60 Gy M+; CSI 24 Gy with boost at posterior fossa or tumor bed 54-60 Gy-If age above 36 months, M0; CSI 24 Gy with boost at posterior fossa or tumor bed 54-60 Gy M+; CSI 36 Gy with boost at posterior fossa or tumor bed 54-60 Gy2. For ependymoma-Focal irradiation 54-60 Gy3. For high grade gliomas-Focal irradiation 54-60 GyInfant Brain Tumors (Age < 3 years old): Irradiation guideline 187

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ High dose methotrexate infusion guidelineHD MTX administration  Hold bactrim, NSAID, penicillins, PPI or aspirin containing medication on the day of IV MTX infusion and for at least 72 hours after start MTX infusion.  Hours -6 to 0: D5W+40-60 mEq NaHCO3/L+ 10 mEq KCL/L at 200 ml/m2/H to achieve urine pH 7-8  Hours 0 to 4: Methotrexate 5 g/m2 in 500 ml/m2 D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h IV over 4 hours. All doses should be round up to the next highest full gram value.  Hours 4 to 54: Post-hydration with D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h.  Hour 24: Begin leucovorin 15 mg/m2 PO/IV Q 6 hours. Beginning at T=24h (from the beginning of MTX infusion) and continue until serum MTX is < 0.1 uM or until delayed excretion criteria is reached.Laboratory monitoring  MTX level and serum Cr should be obtained at T= 24 H, 48H, 72H then Q 24H if delayed excreationMTX toxicity- recommendation for management For elevated MTX level or delayed excretion monitor serum creatinine q 12-24 hours and MTX level q 24 hours. Doses of leucovorin > 25 mg PO should be given IV due to saturation of absorption. Leucovorin contain calcium and should not be given at the rate faster than 160 mg per minute. During MTX administration maintain urine pH 7-8 at all times. Mucositis grading systemSeverity Stomatitis Gastritis ColitisGrade I Painless ulcers, erythema - - or mild soreness in the absence of lesionGrade II Painful erythema, edema Requiring medical management Abdominal pain with mucus and/or or ulcers but can eat or or non-surgical treatment blood in stool swallowGrade III Painful erythema, edema Bleeding without perforation, Abdominal pain, fever, change inGrade IV or ulcers requiring IV uncontrolled by outpatient bowel habits with ileus or peritoneal hydration medical management, requiring signs and radiographic or biopsy hospitalization or surgery documentation Severe ulceration or Perforation or bleeding requiring Perforation or requiring surgery or requires parenteral or emergency surgery toxic megacolon enteral nutrition support or prophylactic intubationInfant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline 188

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Leucovorin rescue guidelineExcretion 24 H MTX level 48 H MTX level 72 H MTX level Leucovorin rescue/ToxicityExpected =< 10 uM < 1 uM < 0.1 uM Maintain hydration at 125 ml/m2/hexcretion 15 mg/m2 q 6 H PO/IV until MTX levelGrade I 11-49 uM 1-4.9 uM 0.1-0.49 uM < 0.1 uMMild-Delayed and/or and/or Maintain hydration at 125 ml/m2/hexcretion 25-50% increase 25-50% increase 0.5-4.9 uM 15 mg/m2 q 6 H PO/IV until MTX level Cr Cr and/or < 0.1 uMGrade I and/or and/or 25-50% increase Recheck MTX level/Cr q 24 H;Mild toxicity Grade I-II Grade I-II Cr discontinue leucovorin when MTX level stomatitis stomatitis and/or < 0.1 uMGrade II 11-49 uM 1-4.9 uM Grade I-II Increase hydration to 200 ml/m2/hModerate toxicity and/or and/or stomatitis 15 mg/m2 q 6 H PO/IV until MTX level < 50-100% increase 50-100% increase 0.5-4.9 uM 0.1 uMGrade III Cr Cr and/or Recheck MTX level/ Cr q 24 H;Severe Toxicity and/or and/or 50-100% increase discontinue leucovorin when MTX level On previous or On previous or Cr < 0.1 uM or normalized Cr or resolvedGrade IV current course of current course of and/or mucositisLife threatening HD MTX: Grade HD MTX: Grade On previous or Increase hydration to 200 ml/m2/h III-IV stomatitis, III-IV stomatitis, current course of 15 mg/m2 q 3 H IV until MTX level < 0.1 myelosupression myelosupression HD MTX: Grade uM 50-499 uM 5-99 uM III-IV stomatitis, Recheck MTX level/ Cr q 24 H; and/or and/or myelosupression discontinue leucovorin when MTX level >100% increase >100% increase 5-49 uM < 0.1 uM or normalized Cr or resolved Cr Cr and/or mucositis >100% increase >= 500 uM >= 100 uM Cr Increase hydration to 200 ml/m2/h 150 mg/m2 q 3 H IV until MTX level >= 50 uM < 0.1 uM Recheck MTX level/ Cr q 24 H; discontinue leucovorin when MTX level < 0.1 uM or normalized Cr or resolved mucositis Nephrology consultation Increase hydration to 200 ml/m2/h 1,500 mg/m2 q 3 H IV until MTX level < 0.1 uM Recheck MTX level/ Cr q 24 H; discontinue leucovorin when MTX level < 0.1 uM Nephrology consultationInfant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline 189

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Neuroblastoma International neuroblastoma risk group (INRG) staging systemStage DescriptionL1 Localized tumor not involving vital structures as defined by the list of image-defined risk factors and confined to one body compartmentL2 Locoregional tumor with presence of one or more image-defined risk factorsM Distant metastatic disease (except stage MS)MS Metastatic disease in children younger than 18 months with metastases confined to skin. Liver, and/or bone marrowImage-Defined Risk Factors in Neuroblastic Tumors Ipsilateral tumor extension within two body compartments - Neck-chest, chest-abdomen, abdomen-pelvis Neck - Tumor encasing carotid and/or vertebral artery and/or internal jugular vein - Tumor extending to base of skull - Tumor compressing the trachea Cervico-thoracic junction - Tumor encasing brachial plexus roots - Tumor encasing subclavian vessels and/or vertebral and/or carotid artery - Tumor compressing the trachea Thorax - Tumor encasing the aorta and/or major branches - Tumor compressing the trachea and/or principal bronchi - Lower mediastinal tumor, infiltrating the costo-vertebral junction between T9 and T12 Thoraco-abdominal - Tumor encasing the aorta and/or vena cava Abdomen/pelvis - Tumor infiltrating the porta hepatis and/or the hepatoduodenal ligament - Tumor encasing branches of the superior mesenteric artery at the mesenteric root - Tumor encasing the origin of the coeliac axis, and/or of the superior mesenteric artery - Tumor invading one or both renal pedicles - Tumor encasing the aorta and/or vena cava - Tumor encasing the iliac vessels - Pelvic tumor crossing the sciatic notch Intraspinal tumor extension whatever the location provided that: - More than one third of the spinal canal in the axial plane is invaded and/or the perimedullary leptomeningeal spaces are not visible and/or the spinal cord signal is abnormal Infiltration of adjacent organs/structures - Pericardium, diaphragm, kidney, liver, duodeno-pancreatic block, and mesentery Conditions to be recorded, but not considered imaged-defined risk factors - Multifocal primary tumors - Pleural effusion, with or without malignant cells - Ascites, with or without malignant cellsNeuroblastoma: International neuroblastoma risk group (INRG) staging system 190

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Pre-treatment risk classification modified by ThaiPOGINRG Age Tumor histology Tumor differentiation MYCN Shimada Pre-treatmentStage (months) histology risk group GN maturingL1/L2 Any GNB intermixed Any Any Any Very lowL1 Any Any, except GN Any Non-Amp Very low maturing or Amp Any GNB intermixed High Any, except GN Favorable Low <18 maturing or Any Non-Amp Unfavorable Intermediate GNB intermixed Favorable LowL2  18 GNB nodular; Differentiating Non-Amp Unfavorable Intermediate Neuroblastoma Poorly differentiated Intermediate or undifferentiated Any Any Any Any Amp High Non-Amp IntermediateM <18 Any Any Amp Any High  18 Any High Favorable Very lowMS <18 Any Any Non-Amp Unfavorable High Amp Any HighAbbreviation: GN= Ganglioneuroma; GNB= Ganglioneuroblastoma; Non-Amp = MYCN non-amplified;Amp=MYCN amplified.Neuroblastoma: Pre-treatment risk classification modified by ThaiPOG 191

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Schematic treatment Protocol for very low/ low risk neuroblastoma (ThaiPOG-NB-13-LR) Very Low/ Low risk Neuroblastoma* Stage MS Non-stage MSNo complication Respiratory compromise Surgical removal of 1st tumor Severe liver dysfunctionClose observe  Chemotherapy (low-risk >50% resection <50% resection protocol) Close observe Chemotherapy  150 cGy 2-3 times to the (low-risk protocol) anterior 2/3 of the liver through lateral oblique ports*Gangioneuroma maturing and Gangliomeuroblastoma intermixed – complete resection and observationChemotherapy doses are adjusted for children < 365 days of age or who are ≤ 12 kg in weight and aregiven as mg/kg.Cycle 1 2 3 4Days 1 2 3 22 43 44 45 64 65 66Carboplatin   Etoposide   Cyclophosphamide  Doxorubicin Drug DosageCarboplatin 560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4Etoposide 120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4Cyclophosphamide 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3Doxorubicin 30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle 2,4• Note: After each cycle administer G-CSF 5 mcg/kg SQ starting 24- 36 hours after last dose ofchemotherapy. Continue until the absolute neutrophil count (ANC) is > 1,000/mm3 for two consecutivedays following the nadir for myelosuppression.• Start chemotherapy when ANC > 1,000/mm3, platelets > 75,000/mm3.• Hold doxorubicin if bilirubin > 3.0 mg/dl. Hold doxorubicin if ECHO SF <29%Neuroblastoma: Schematic treatment 192

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Protocol for standard risk neuroblastoma (ThaiPOG-NB-13-SR)Chemotherapy doses are adjusted for children < 365 days of age or who are ≤ 12 kg in weight and aregiven as mg/kg.Cycle 1 2 3 4 65 66Days 1 2 3 22 43 44 45 64 Carboplatin    8 148Etoposide    Cyclophosphamide  Doxorubicin  Assess treatment response, and perform surgery if feasibleCycle 5 6 7Days 85 86 87 106 127 128 129 Carboplatin  Etoposide Cyclophosphamide  Doxorubicin Assess treatment response, and perform surgery if residual primary tumor detectedDrug Dosage 560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4,6,7Carboplatin 120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4,5,7EtoposideCyclophosphamide 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3,5,6,8 30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle 2,4,6,8Doxorubicin Note: After each cycle administer G-CSF 5 mcg/kg SQ starting 24- 36 hours after last dose of chemotherapy. Continue until the absolute neutrophil count (ANC) is > 1,000/mm3 for two consecutive days following the nadir for myelosuppression. Start chemotherapy when ANC > 1,000/mm3, platelets > 75,000/mm3. Hold doxorubicin if bilirubin > 3.0 mg/dl. Hold doxorubicin if ECHO SF < 29%. After four cycles, assess treatment response, and perform surgery if feasible. After eight cycles, assess treatment response, and perform surgery if residual primary tumor detected. At the end of 4 cycles and again post-cycle #8: CT or MRI of primary site, bone scan, MIBG scan (if positive at diagnosis) and bone marrow aspirates and biopsies.Neuroblastoma: Schematic treatment 193

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Protocol for high risk neuroblastoma (ThaiPOG-NB-13-HR)Induction ChemotherapyInduction Agent (s) Dose (s) 1.2 mg/m2 IV on daily Day 1-5Cycle 1,2 Topotecan Cyclophosphamide >12 kg 400 mg/m2 IV once daily Day 1-5  12 kg 13.3 mg/kg IV once daily Day 1-5 >12 kg 50 mg/m2 IV once daily Day 1-4Cycle 3,5 Cisplatin  12 kg 1.66 mg/kg IV once daily Day 1-4 >12 kg 200 mg/m2 IV once daily Day 1-3 Etoposide  12 kg 6.67 mg/kg IV once daily Day 1-3Cycle 4,6 Cyclophoshamide >12 kg 2,100 mg/m2 IV once daily Day 1,2  12 kg 70 mg/kg IV once daily Day 1,2 >12 kg 25 mg/m2 IV once daily Day 1-3 Doxorubicin  12 kg 0.83 mg/kg IV once daily Day 1-3 >12 kg & ≥ 12 mo 0.67 mg/m2 IV once daily Day 1-3 Vincristine  12 kg & ≥ 12 mo 0.022 mg/kg IV once daily Day 1-3 <12 mo 0.017 mg/kg IV once daily Day 1-3Subsequent cycle begin 21 days after the previous cycle when the ANC > 1,000 /mm3 and platelets > 75,000/μL, following nadir.Neuroblastoma: Schematic treatment 194

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Recommended MIBG treatmentHD-MIBG in HSCT patients  Aim to eradicate tumor cells  18 mCi/kg in single visit - Since only 150-200 mCi/week can be obtained, the plan is to give weekly dose until achieving the goal - eg. 30 kg patient needs 18 x 30 = 540 mCi  to give weekly dose x 3 weeksLD-MIBG in non-HSCT patients  Maintenance low dose (30 mCi) given every 3 months and to continue during maintenance therapy until the completion of 13 Cis-retinoic acid except for the duration of local XRT (LD-MIBG should be held during the local XRT treatment)  To give as outpatient setting with 2-3 hours of observation post MIBGNeuroblastoma: Recommended MIBG treatment 195

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก 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) ..................................... BSA...................m2Age ............. yr...............m. BW…...........kg Ht...............cm.สทิ ธิการรักษา บตั รประกนั สขุ ภาพ จ่ายตรง อื่นๆ (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 …………………………..…… Serum NSE ………………………..… Urine VMA …………………………….…GFR (………/………/………)  calculated /  measured) …………………………………ml/min/1.73m2B. Imaging studiesCT Neck (………/………/………) ……………..……….……………………..……………………………………………CT chest (………/………/………) ……………..……….……………………..……………………………………………CT abdomen/ pelvis (………/………/………) ……………..………………..……………………………………………Chest X-Ray (………/………/………) ..……………..……….……………………..……………………………………..Bone scan (………/………/………) ..……………..……….……………………..………………………………………..MIBG scan (………/………/………) ……………..……….……………………..…………………………………………C. Bone marrow for metastatic work upBone marrow aspiration/biopsy (………/………/………)  1.positive  1.1 minimal  1.2 extensive  2. negativeBone marrow result..……………..……….……………………..…………………………………………………………..D. OthersAudiogram (………/………/………)…………………...…………………………………………..….....…………………EKG (………/………/………) ………………………………………………………………………………………………Echo (………/………/………) ………………………………………………………………………………………………Other (………/………/………) ……………………………………………………………………………………………...Neuroblastoma: Data entry form 196

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR]Protocol name ThaiPOG- NB-13-LRProtocol for Low Risk NeuroblastomaReference Adapted from Baker DL, et al., N Engl J Med. 2010 Sep 30;363(14):1313-23Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Given dose/day Drug Dosage.....................mg Carboplatin 560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4.....................mg Etoposide 120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4.....................mg Cyclophosphamide* 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3.....................mg Doxorubicin 30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle.....................mg Mesna* 2,4...................mcg GCSF 200 mg/m2 (or 6.5 mg/kg) IV immediately before and then every 3 hours x 4 doses post cyclophosphamide (total 5 doses) 5 mcg/kg/day SC starting 24 hours after completion of each cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2 daysCycle 1 23 4Days 1 2 3 22 43 44 45 64 65 66Carboplatin  Etoposide   Cyclophosphamide* Doxorubicin Cycle Cycle day Treatment Date given Remarks1 Carboplatin/ Etoposide NSE/VMA12 Etoposide3 Etoposide21 Carboplatin/Cyclophos*/ Doxorubicin NSE/VMA1 Cyclophos*/Etoposide NSE/VMA32 Etoposide3 Etoposide1 Carboplatin/Etoposide/Doxorubicin NSE/VMA42 Etoposide 3 EtoposideRequirements to begin chemotherapy: ANC > 1,000/mm3 and platelet count > 75,000/mm3* Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide dosePost-treatment evaluationsCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination, if initial BM involvement (………/………/………)…………………...…………………...………………………………………………………………………………………………………………………………….MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR] 197

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR]Protocol name ThaiPOG- NB-13-SRProtocol for Standard Risk NeuroblastomaReference Adapted from Baker DL, et al., N Engl J Med. 2010 Sep 30;363(14):1313-23Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Given dose/day Drug Dosage..........................mg Carboplatin 560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4,6,7..........................mg Etoposide 120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4,5,7..........................mg Cyclophosphamide* 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3,5,6,8..........................mg Doxorubicin 30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle 2,4,6,8..........................mg Mesna* 200 mg/m2 (or 6.5mg/kg) IV immediately before and then every 3 hours x 4 doses post cyclophosphamide (total 5 doses)........................mcg GCSF 5 mcg/kg/day SC starting 24 hours after completion of each cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2 daysCycle 1 23 4Days 1 2 3 22 43 44 45 64 65 66Carboplatin  Etoposide   Cyclophosphamide*  DoxorubicinCycle Cycle day Treatment Date given Remarks1 Carboplatin/ Etoposide NSE/VMA12 Etoposide3 Etoposide21 Carboplatin/Cyclophos*/ Doxorubicin NSE/VMA1 Cyclophos*/Etoposide NSE/VMA32 Etoposide3 Etoposide1 Carboplatin/Etoposide/Doxorubicin NSE/VMA42 Etoposide 3 EtoposideRequirements to begin chemotherapy: ANC > 1,000/mm3 and platelet count > 75,000/mm3* Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide doseNeuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR] 198

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Assess treatment response, and perform surgery if feasibleCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Cycle 5 6 7 8Days 85 86 87 106 127 128 129 148Carboplatin Etoposide  Cyclophosphamide*   Doxorubicin  Cycle Cycle day Treatment Date given Remarks1 Cyclophos*/ Etoposide NSE/VMA52 Etoposide3 Etoposide61 Carboplatin/Cyclophos*/ Doxorubicin NSE/VMA1 Carboplatin/Etoposide NSE/VMA72 Etoposide3 Etoposide81 Cyclophos*/ Doxorubicin NSE/VMARequirements to begin chemotherapy: ANC > 1,000/mm3 and platelet count > 75,000/mm3* Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide doseAssess treatment response, and perform surgery if residual primary tumor detectedCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR] 199

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR]Protocol name ThaiPOG- NB-13-HRProtocol for High Risk NeuroblastomaOpen Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Induction I Dosage Given dose/day Drug 1.2 mg/m2 IV once daily Day 1-5 ..........................mg Topotecan >12 kg 400 mg/m2 IV once daily Day 1-5 ..........................mg Cyclophosphamide  12 kg 13.3 mg/kg IV once daily Day 1-5 5 mcg/kg/day SC starting 24 hours after completion of ........................mcg GCSF* each cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2 daysCycle 1 2*Days 1 2 3 4 5 12345 Topotecan  Cyclophosphamide     Cycle Cycle day Treatment Date given Remarks 1 Cyclophosphamide/ Topotecan NSE/VMA 2 Cyclophosphamide / Topotecan1 3 Cyclophosphamide / Topotecan 4 Cyclophosphamide / Topotecan 5 Cyclophosphamide / Topotecan 1 Cyclophosphamide / Topotecan NSE/VMA 2 Cyclophosphamide / Topotecan2* 3 Cyclophosphamide / Topotecan 4 Cyclophosphamide / Topotecan 5 Cyclophosphamide / Topotecan*To give GCSF at 10 mcg/kg/day after cycle 2 if plan to collect stem cells (frozen)Requirements to begin chemotherapy  ANC > 1,000/mm3 and platelet count > 75,000/mm3  Serum creatinine < 1.5 mg/dL, bilirubin < 1.2 mg/dL.  Urinalysis < 25 RBC/hpf and Specific Gravity ≤ 1.010Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 200

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Induction II Drug DosageGiven dose/day Cisplatin >12 kg 50 mg/m2 IV once daily Day 1-4...................................mg Etoposide  12 kg 1.66 mg/kg IV once daily Day 1-4...................................mg Cyclophoshamide** >12 kg 200 mg/m2 IV once daily Day 1-3...................................mg Doxorubicin  12 kg 6.67 mg/kg IV once daily Day 1-3...................................mg Vincristine >12 kg 2,100 mg/m2 IV once daily Day 1-2...................................mg  12 kg 70 mg/kg IV once daily Day 1-2 Mesna** >12 kg 25 mg/m2 IV once daily Day 1-3...................................mg  12 kg 0.83 mg/kg IV once daily Day 1-3 GCSF* >12 kg &  12 mo 0.67 mg/m2 IV once daily Day 1-3...................................mcg  12 kg &  12 mo 0.022 mg/kg IV once daily Day 1-3 < 12 mo 0.017 mg/kg IV once daily Day 1-3 420 mg/m2 (or 14 mg/kg) IV immediately before and then every 3 hours x 4 doses post cyclophosphamide (total 5 doses) 5 mcg/kg/day SC starting 24 hours after completion of each cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2 daysCycle 3 4 4 5 6*Day 1 23  123 1234 123Cisplatin        Etoposide  Cyclophoshamide  DoxorubicinVincristineNeuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 201

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Induction II (continue)Cycle Cycle day Treatment Date Remarks given 1 Cisplatin/Etoposide NSE/VMA3 2 Cisplatin/Etoposide 3 Cisplatin/Etoposide 4 Cisplatin 1 Cyclophosphamide**/ Doxorubicin/ Vincristine NSE/VMA4 2 Cyclophosphamide**/ Doxorubicin/ Vincristine 3 Doxorubicin/ Vincristine 1 Cisplatin/Etoposide NSE/VMA5 2 Cisplatin/Etoposide 3 Cisplatin/Etoposide 4 Cisplatin 1 Cyclophosphamide**/ Doxorubicin/ Vincristine NSE/VMA6* 2 Cyclophosphamide**/ Doxorubicin/ Vincristine 3 Doxorubicin/ Vincristine* To give GCSF 10 mcg/kg/day after cycle 6 if plan to collect stem cells (fresh) in case of no HD-MIBGplanned** Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide doseRequirements to begin chemotherapy  ANC > 1,000/mm3 and platelet count > 75,000/mm3  Serum creatinine < 1.5 mg/dL, bilirubin < 1.2 mg/dL.  Urinalysis < 25 RBC/hpf and Specific Gravity ≤ 1.010Evaluation treatment responseCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 202

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk Neuroblastoma Treatment Plan (ThaiPOG-NB-13-HR) – ICEGiven dose/day Drug Dosage........................mg Carboplatin 635 mg/m2 IV Day 1........................mg Etoposide 100 mg/m2/day IV Day 2, 3, 4........................mg Ifosfamide 2,000 mg/m2/day IV Day 2, 3, 4........................mg Mesna 650 mg/m2 IV immediately before and then 3 and 6 hours after ifosfamide (total 3 doses)......................mcg GCSF 5 mcg/kg/day SC starting 24 hours after completion of each cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2 days Day 1234 Carboplatin  Etoposide Ifosfamide  Mesna  Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 203

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2High Risk Neuroblastoma Treatment Plan (ThaiPOG-NB-13-HR) – ICE (continue)Cycle Cycle day Treatment Date given Remarks NSE/VMA 1 Carboplatin NSE/VMA1 2 Ifosfamide /Etoposide 3 Ifosfamide /Etoposide NSE/VMA 4 Ifosfamide /Etoposide NSE/VMA 1 Carboplatin2 2 Ifosfamide /Etoposide 3 Ifosfamide /Etoposide 4 Ifosfamide /Etoposide3 1 Carboplatin 2 Ifosfamide /Etoposide 3 Ifosfamide /Etoposide 4 Ifosfamide /Etoposide4 1 Carboplatin 2 Ifosfamide /Etoposide 3 Ifosfamide /Etoposide 4 Ifosfamide /EtoposideRequirements to begin chemotherapy  ANC > 1,000/mm3 and platelet count > 75,000/mm3  Serum creatinine < 1.5 mg/dL, bilirubin < 1.2 mg/dL.  Urinalysis < 25 RBC/hpf and Specific Gravity ≤ 1.010Evaluation treatment responseCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 204

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Maintenance with Cyclo/Topo Dosage 0.75 mg/m2 IV once daily Day 1-5 Given dose/day Drug 250 mg/m2/day IV once daily Day 1-5 ........................mg Topotecan ........................mg Cyclophosphamide Day 1 2 3 4 5 Topotecan  Cyclophosphamide     Cycle Cycle Treatment Date given Remarks day 1 Cyclophosphamide/Topotecan NSE/VMA 2 Cyclophosphamide/Topotecan1 3 Cyclophosphamide/Topotecan 4 Cyclophosphamide/Topotecan 5 Cyclophosphamide/Topotecan 1 Cyclophosphamide/Topotecan NSE/VMA 2 Cyclophosphamide/Topotecan2 3 Cyclophosphamide/Topotecan 4 Cyclophosphamide/Topotecan 5 Cyclophosphamide/Topotecan 1 Cyclophosphamide/Topotecan NSE/VMA 2 Cyclophosphamide/Topotecan3 3 Cyclophosphamide/Topotecan 4 Cyclophosphamide/Topotecan 5 Cyclophosphamide/TopotecanEvaluation treatment responseCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 205

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Maintenance with 13 Cis-retinoic acidGiven dose/day Drug Dosage........................mg 13-cis-retinoic acid 80 mg/m2/dose PO BID (total 160 mg/m2/day)Cycle Cycle Treatment Date given Remarks week NSE/VMA1 1-2 13-cis-retinoic acid 3-4 Off2 5-6 13-cis-retinoic acid 7-8 Off3 9-10 13-cis-retinoic acid NSE/VMA 11-12 Off4 13-14 13-cis-retinoic acid 15-16 Off5 17-18 13-cis-retinoic acid NSE/VMA 19-20 Off6 21-22 13-cis-retinoic acidEvaluation treatment responseCT /MRI (………/………/………) ……………..……….……………………..……………………………………………Bone scan (………/………/………) ..……………..……….……………………..………………………………………..Bone marrow examination (………/………/………)…………………...…………………………….....……………......MIBG (………/………/………) ……………………..………………………………………………………………..……..NSE/VMA (………/………/………)…………………………………………………………………………………………Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 206

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Haploidentical donor HSCT (following HD-MIBG) – recommended regimenDay Treatment Date given Remarks-9 Fludarabine 40 mg/m2/day IV-8 Fludarabine 40 mg/m2/day IV-7 Fludarabine 40 mg/m2/day IV-6 Fludarabine 40 mg/m2/day IV-5 Fludarabine 40 mg/m2/day IV-4 Busulfan 37.5 mg/m2/dose IV every 6 hr-3 Busulfan 37.5 mg/m2/dose IV every 6 hr-2 Melphalan 50 mg/m2/day IV-1 Melphalan 50 mg/m2/day IV0 HSC Infusion+4 Cyclophosphamide* 50 mg/kg IV one dose+5 Tacrolimus§ 0.03 mg/kg/day continuous IV MMF§ 600 mg/m2 PO twice a day+7 GCSF 5 mcg/kg/day until ANC > 2,000/mm3 x 2 SQ* On day +4, Mesna 10 mg/kg/dose will be given pre-cyclophosphamide and then every 3 hours x 4 dosespost cyclophosphamide (total 5 doses).§ Tacrolimus and MMF started from day +5Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 207

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Matched-related donor HSCT (following HD-MIBG) – recommended regimenDay Treatment Date given Remarks-6 Busulfan 37.5 mg/m2/dose IV every 6 hr-5 Busulfan 37.5 mg/m2/dose IV every 6 hr-4 Busulfan 37.5 mg/m2/dose IV every 6 hr-3 Busulfan 37.5 mg/m2/dose IV every 6 hr Melphalan 70 mg/m2/day IV-2 Cyclosporine§ 2.5 mg/kg IV every 12 hr-1 Melphalan 70 mg/m2/day IV0 HSC Infusion MMF* 600 mg/m2 PO twice a day+5 GCSF 5 mcg/kg/day until ANC > 2,000/mm3 x 2 SQ* MMF started from day 0§ Cyclosporine started from day -2Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 208

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Autologous HSCT (following HD-MIBG) – recommended regimenDay Treatment Date given Remarks-6 Busulfan 37.5 mg/m2/dose IV every 6 hr-5 Busulfan 37.5 mg/m2/dose IV every 6 hr-4 Busulfan 37.5 mg/m2/dose IV every 6 hr-3 Busulfan 37.5 mg/m2/dose IV every 6 hr-2 Melphalan 70 mg/m2/day IV-1 Melphalan 70 mg/m2/day IV0 HSC Infusion+5 GCSF 5 mcg/kg/day until ANC > 2,000/mm3 x 2 SQNeuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 209

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Retinoblastoma Staging systemInternational Classification System for Intraocular Retinoblastoma(Murphree AL: Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin NorthAm 2005; 18:41-53.)Group A: Small intraretinal tumors away from foveola and disc  All tumors are 3 mm or smaller in greatest dimension, confined to the retina and  All tumors are located further than 3 mm from the foveola and 1.5 mm from the optic diskGroup B: All remaining discrete tumors confined to the retina  All other tumors confined to the retina not in Group A  Tumor associated with subretinal fluid less than 3 mm form the tumor with no subretinal seedingGroup C: Discrete local disease with minimal subretinal or vitreous seeding  Tumors are discrete  Subretinal fluid, present or past, without seeding involving one fourth of the retina  Local fine vitreous seeding may be present close to discrete tumor  Local subretinal seeding less than 3 mm (2 disk diameters) from the tumorGroup D: Diffuse disease with significant vitreous or subretinal seeding  Tumors may be massive or diffuse  Subretinal fluid present or past without seeding, involving up to total retinal detachment  Diffuse or massive vitreous disease may include “greasy” seeds or avascular tumor masses  Diffuse subretinal seeding may include plaques or tumor nodulesGroup E: Presence of any one or more of these poor prognostic features  Tumor touching the lens  Tumor anterior to the anterior vitreous face involving ciliary body or anterior segment  Diffuse infiltrating retinoblastoma  Neovascular glaucoma  Opaque media from hemorrhage  Tumor necrosis with aseptic orbital cellulites  Phthisis bulbiRetinoblastoma: Staging system 210

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Pathologic classification (pTNM)(From American Joint Committee on Cancer Retinoblastoma. Manual for staging of cancer. 7th ed, 2010)Primary Tumour (pT) pTX: Primary Tumour cannot be assessed. pT0: No evidence of primary tumour pT1: Tumour confined to the eye with no optic nerve or choroidal invasion. pT2: Tumour with minimal optic nerve and / or choroidal invasion: pT2a: Tumour superficially invades optic nerve head but does not extend past lamina cribrosa, or tumour exhibits focal choroidal invasion. pT2b: Tumour superficially invades optic nerve head but does not extend past lamina cribrosa and tumour exhibits focal choroidal invasion. pT3: Tumour with significant optic nerve and / or choroidal invasion: pT3a: Tumour invades optic nerve past lamina cribrosa but not to surgical resection line, or tumour exhibits massive choroidal invasion. pT3b: Tumour invades optic nerve past lamina cribrosa but not to surgical resection line and exhibits massive choroidal invasion. pT4: Tumour invades optic nerve to surgical resection line or exhibits extra-ocular extension elsewhere. pT4a: Tumour invades optic nerve to resection line, but no extra-ocular extension identified. pT4b: Tumour invades optic nerve to resection line, and extra-ocular extension identified.Regional Lymph Nodes (pN) pNX: Regional lymph nodes cannot be assessed. pN0: No regional lymph node metastasis pN1: Regional lymph node involvement (preauricular, cervical) pN2: Distant lymph node involvementMetastasis (pM) pMX: Presence of metastasis cannot be assessed. pM0: No distant metastasis pM1: Metastasis to sites other than Central Nervous System pM1a: Single lesion pM1b: Multiple lesions pM1c: CNS metastasis pM1d: Discrete masses without leptomeningeal and / or CSF involvement pM1e: Leptomeningeal and / or CSF involvementFinal Staging ___________________________________________Retinoblastoma: Pathologic classification (pTNM) 211

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ InvestigationsExamination -Examination under anesthesia by ophthalmologist -Audiology evaluation (hearing test) if systemic carboplatin is consideredImaging studies -CT or MRI scan of brain and orbit should include the pineal gland to exclude trilateral retinoblastoma ( prefer MRI to avoid radiation exposure)Laboratory evaluations -CBC -BUN, Cr, electrolytes, Ca, Mg, P, LFT -Calculated creatinine clearance -Urine analysisDiagnostic studies -Lumbar puncture only when there is radiographic or clinical suspicion of CNS disease ie. optic nerve involvement or ≥ stage pT2 -Bone scan only with bone pain or other extraocular disease -Bone marrow aspiration and biopsy only when there is abnormal blood counts (without alternative explanation) or other extraocular disease -Pathologic evaluation if enucleation is performed.Indications of enucleation1. Large tumor >50% of globe volume (ICRB group E, + D)2. No potential for visions3. Painful eyes4. Optic nerve involvementLaser photocoagulation and cryotherapyFor ICRB Group A: repeat every 3-4 weeks until evidence of tumor regression and inactivity (indirectfundoscopy showing flat scar (or type IV regression pattern) along with the absence of new tumor foci,evidence of tumor recurrence, or evidence of subretinal fluid, subretinal seeds, or vitreous seeds).External beam radiation therapy (EBRT: lens sparing EBRT vs whole eye EBRT)Standard dose is 40-45 Gy, preferably conformal, stereotactic, proton-beam or intensity-modulatedradiotherapy, and delayed to after 1 year of age with use of systemic adjuvant chemotherapy to avoid risk ofsecondary malignancyFamily screeningEvaluation ScheduleEye examination for -Parents and siblings of patients should have screening ophthalmicparents and siblings examinations to exclude an unknown familial disease. -Siblings should be under close surveillance until age 3 to 5 years (every 1-2 months during the first year, then every 2 months during the second year, then every 4-6 months during the third year, then once or twice a year until age 5, after that follow as general population ) or until confirmed not to have a genetic mutation.Retinoblastoma: Investigations 212

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Summary treatment strategy based on laterality and retinoblastoma groupingInternationalClassification Unilateral Bilateral* ofRetinoblastomaA Laser or cryotherapy Laser or cryotherapyB/C CEV or plaque + Laser or cryotherapy CEV + Laser or cryotherapyD Enucleation or CEV + SCC + Laser or CEV + SCC + Laser or cryotherapy cryotherapyE Enucleation Enucleation but if both eyes equally advanced then CEC + SCC + Laser or cryotherapy + low – dose EBRT* Treatment in bilateral cases is usually based on the most advanced eye, Laser, laser photocoagulation; EBRT, external beamradiotherapy; plaque, plaque radiotherapy; SCC, subconjuctival carboplatin; CV, vincristine, carboplatin plus thermotherapy orcryotherapy; CEV, vincristine, etoposide, carboplatin plus thermotherapy or cryotherapy.Note: May consider ICEV instead of CEV+SCC Chemotherapy should be perform within 24 hours of local treatment by ophthalmologistOn the basis of the International Classification of Retinoblastoma, chemoreduction success is achieved in eyesurvival rate 100% of group A, 93% of group B, 90% of group C, 47% of group D eyes, and 0% of group E.Reference  Adapted from Carol L, Shields and Jerry A. Shields. Basic understanding of current classification and management of retinoblastoma. Current Opinion in Ophthalmology 2006; 17: 228 – 234.  ARET0331 progress report 22/01/2010 closure of trial of systemic neoadjuvant chemotherapy for group B intraocular retinoblastomaThe regression pattern (examined by EUA) after treatment:  Type I is calcification.  Type II is fish flesh lesion.  Type III is mixed type I and II.  Type IV is flat scar.Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 213

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็ก Schematic treatment for intraocular retinoblastoma Unilateral retinoblastoma -ICRB group E ie.Large tumor > 50% of globe volume -No potential for visions -Painful eyes -Optic nerve involvement No YesICRB Group A ICRB Group B, C ICRB Group D Enucleation Cryotherapy Chemotherapy Protocol Chemotherapy Protocol High risk features: assessed by pathologist and/or ThaiPOG-RB-I3-01 ThaiPOG-RB-13-02 -Anterior chamber seeding (Carbo/Eto/VCR) (Ifos/Carbo/Eto/VCR) -Optic nerve tumor beyond lamina cribosa, but not to surgical marginLaser therapy X 6 cycles X 6-8 cycles -Choroidal involvement -Intraocular hemorrhage -Posterior uveal involvement with any optic nerve disease (optic nerve head, pre or postlaminar cribosa) No Yes Enucleation or EBRT Low risk High risk if not fully responded Schedule regular Chemotherapy Protocol fundoscopic ThaiPOG-RB-13-01 examination (Carbo/VCR/Eto) X 6 cyclesRetinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 214

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเดก็ Schematic treatment for extraocular retinoblastoma Extraocular retinoblastomaRegional disease Metastatic diasese: CNS, bone, bone- Disease at the surgical margin marrow involvement- Orbital recurrence (orbital mass)- Tumor in an emissary canal - Isolated meningeal disease (intrascleral involvement) - Ectopic intracranial retinoblastoma- Episcleral disease- Positive pre-auricular lymph nodes Chemotherapy ThaiPOG-RB-13-04 (ICE protocol every 4 weeks x 6-8 cycles) Enucleation plus IT chemotherapy (ThaiPOG-RB-13-05) if positive CSF cytologyEBRT at orbit at week 6 + Chemotherapy Myeloablative chemotherapy and Protocol ThaiPOG-RB-13-03 autologous stem cell rescue (VCR/Ida/CTX alternate Eto/carbo EBRT for bulky disease at week 6 of SCT every 3 weeks x 4 cycles)Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 215

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Post-treatment evaluationFor patients with preserved eyeEvaluation Schedule NoteEye examination under - Every 3-4 weeks until no active tumor on minimum 3 Patients should be examined withoutanesthesia (EUA) EUAs anesthesia when old enough to cooperate. -Then every 6-8 weeks until 3 years of age -Then every 4-6 months until 10 years of age -Then yearlyMRI brain and orbit -Every 6-12 months until 5 years of ageFor patients after enucleation and/or received EBRTEvaluation Schedule NoteEye examination under -At 4-6 weeks post treatment Patients should be examined withoutanesthesia (EUA) -Then every 2-3 months in year 1 anesthesia when old enough to cooperate. -Then every 3-4 months in year 2 -Then every 6 months until 5 years of age -Then yearlyFor patients with extraocular diseaseEvaluation Schedule NoteCT or MRI of the brain and Every 6 months in first 3 years then every year until 5 - prefer MRI to avoidorbits years after off treatment radiation exposureCSF profiles and cytology Every 6 months in first 3 years then every year until 5 years after off treatmentBone marrow aspiration and If unexplained cytopenia or bone scan positivebiopsyBone scan -Every 1 year for first 3 yearsFor patients with bilateral retinoblastoma, esp. whom diagnosed before 1 year of age or positive familyhistoryEvaluation Schedule NoteCT or MRI of the brain and Every 6 months from the end of treatment until 5 years - Screen for trilateralorbits of age retinoblastoma - prefer MRI to avoid radiation exposureFor patients who received chemotherapy and/or radiation therapyEvaluation Schedule NoteHistory and physical -Every 3 months until 2 years off treatment - Late effects of treatmentexamination -Then every 6 months until 5 years off - Growth and developmentVisual acuity assessment treatment - Surveillance for second malignantCBC -Then yearly neoplasms (osteosarcoma, soft tissue -Yearly sarcomas, skin cancers, breast -Yearly for 10-15 years from exposure of cancers) chemotherapy -Surveillance for secondary leukemiaRetinoblastoma: Post-treatment evaluation 216

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment Protocol for Retinoblastoma 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) ..................................... BSA...................m2Age ............. yr...............m. BW…...........kg Ht...............cm.สิทธิการรกั ษา บตั รประกันสุขภาพ จา่ ยตรง อืน่ ๆ (ระบ)ุ ...................................History eye painPresenting S&S leukocoria orbital mass Others……………………………………………………………..……….............…..Prenatal History X-ray exposure Medication……………………..………………..……………………………………… Illness…..……………………chemical exposure…..………………..……..…… Others………………………………………………………………………..……….…Cancer in family None Retinoblastoma other cancers…..………..………Physical examination PedigreePre- treatment investigations.A. Blood date (………/………/………)CBC ………………………….…………………………..…………………………………………………………….*start each course of chemotherapy when ANC > 1,000/mm3BUN …………Creatinine ………… LDH ………… SGOT …………SGPT …………… Alk Phos …………Na …………… K ………………….. Cl …………… HCO3 …………… Ca …………..… Mg…….…………B. Imaging studyCT/ MRI orbit and brain with contrast (………/………/………) ……………..……….……………..………….…………………………………………………………………………………………………………………………Chest X-Ray (……/……/…..…) Result positive………………………………………………negativeLumbar Puncture : CSF cell count and cytospin (…../…../…..) Result positive…………………. negativeBone scan (……/……/…..…) Result positive………………………………………………negative* For patient with bone pain or extraocular disease onlyC. Bone marrow for metastatic work upBone marrow aspiration* : Wright stain smear and clotted marrow sent for pathological review(………/………/………) Result positive negative*For patient with unexplained cytopenia or extraocular disease onlyBMA/ biopsy (………/………/………) ……………………..…………………………………………………….….Retinoblastoma: Data entry form 217

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01]Protocol name ThaiPOG-RB-13-01Protocol for Retinoblastoma ICRB group B, C or Post enucleation with high risk featuresReference Orkin SH,et al. Oncology of Infancy and Childhood, 1st ed, 2009. P 576-601. Lanzkowsky P. Manual of Ped Hematology and Oncology, 5th ed, 2011. P.759-775Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteriaRetinoblastoma ICRB group B Retinoblastoma ICRB group CRetinoblastoma post enucleation with high risk featuresAnterior chamber seeding Optic nerve tumor, but not to surgical marginChoroidal involvement Intraocular hemorrhagePosterior uveal involvement with any optic nerve diseaseGiven dose Drug Dosage Day_______mg Vincristine 0.05 mg/kg or 1.5 mg/m2/day in NSS IV slowly push 1 (max 2 mg) 1_______mg Carboplatin 18.6 mg/kg or 560 mg/m2/day in D5W IV in 15-30 min 1, 2_______mg Etoposide 5 mg/kg or 150 mg/m2/day IV in D5W IV in 60 min*In patient BW < 12 kg, use doses per kg Give chemotherapy every 28 days for total 6 courses Give G-CSF 5 mcg/kg SC daily in subsequent course of chemotherapy that results in neutropenia (to be started on day 3, at least 24 hours from last dose of chemotherapy, until ANC > 1,000/mm3) Criteria for starting chemotherapy: o Absolute neutrophil count >1,000/ mm3 o Platelet count >100,000/ mm3o ALT <10 × the upper limit of normalo Normal glomerular filtration rate Record BP q 15 min during etoposide infusion Fundoscopic examination by ophthalmologist before each cycle Hearing exam before starting chemotherapy, at cycle 3 or 4 and end of treatment (Optional) Consider enucleation or EBRT if patient does not fully respond to chemotherapyRetinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01] 218

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 Schedule of chemotherapy Protocol ThaiPOG-RB-13-01Course Date BW / BSA Dose adjusted Note123456Retinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01] 219

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็ก Treatment protocol for retinoblastoma [ThaiPOG-RB-13-02]Protocol name ThaiPOG-RB-13-02Protocol for Retinoblastoma ICRB group D/ EReference SH Lee. et.al, Bone Marrow Transplantation 2008; 42: 385-391Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Retinoblastoma ICRB group D Retinoblastoma ICRB group EGiven dose Drug Dosage Day_______mg Ifosfamide 60 mg/kg or 1,800 mg/m2/day in NSS IV drip in 30-60 min 0, 1, 2_______mg Etoposide 5 mg/kg or 150 mg/m2/day in D5W IV drip in 60 min 0, 1, 2_______mg Mesna 20 mg/kg or 600 mg/m2/dose IV drip in 15 min before 0, 1, 2 Ifosfamide then at 3, 6 hr after Ifosfamide (total 3 doses) 0_______mg Carboplatin 18.6 mg/kg or 560 mg/m2/day in D5W IV drip in 15-30 min 0_______mg Vincristine 0.05 mg/kg or 1.5 mg/m2 in NSS IV slowly push (max 2 mg)***I*nsHtpaayrtidternGat t-BiCoWnS<Ffo152llokmwg,cinugsg/ekhgdiog_she_s_dp_oe_sr_ek_gc_y_c_lomphcogsOphDamafitdeer/cIofomspfalemtiiodne ogfucidheelmineotherapy 24 hr Give chemotherapy every 4 weeks until the tumor disappear, or until local therapy can control the tumor Record water intake/ output and give diuretic if necessary Check CBC, BUN, Cr, Electrolyte, Ca2+, Mg2+, PO4 and LFT before start each course Criteria for starting chemotherapy: o Absolute neutrophil count >1,000/ mm3 o Platelet count >100,000/ mm3 o ALT <10 × the upper limit of normal o Normal glomerular filtration rate Record BP q 15 min during etoposide infusion Fundoscopic examination by ophthalmologist before each cycle Consider hearing exam peroidically Consider enucleation or EBRT if patient does not fully respond to chemotherapyRetinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-02] 220

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 Schedule of chemotherapy Protocol ThaiPOG-RB-13-02Course Date BW / BSA Dose adjusted Note123456789101112Retinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-02] 221

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for retinoblastoma [ThaiPOG-RB-13-03]Protocol name ThaiPOG-RB-13-03Protocol for Extraocular Retinoblastoma: Regional diseaseReference Chantada G, et.al. Cancer 2004;100(4): 834-842.Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Disease at the surgical margin  Orbital recurrence (orbital mass) Tumor in an emissary canal (intrascleral involvement)  Episcleral disease Positive pre-auricular lymph nodesEvaluation extent of disease before treatmentImaging studies .............................................................................................................................................Bone scan .....................................................................................................................................................CSF studies ……...........................................................................................................................................BMA ..............................................................................................................................................................Chemotherapy schedule 18 21 A4 B4 Week 0 3 6 9 12 15 Course A1 B1 A2 B2 A3 B3 Date***** Start G-CSF at 24 -48 hr after completion each course of chemotherapy *****Course AGiven dose Drug Dosage Day__________mg Vincristine 0.05 mg/kg or 1.5 mg/m2 IV slowly push 1__________mg Idarubicin 0.33 mg/kg or 10 mg/m2 IV infusion in 60 min 1__________mg Cyclophosphamide* 65 mg/kg or 2,000 mg/m2 IV drip in 30-60 min 1__________mg Mesna 30 mg/kg or 1,000 mg/m2 IV drip in in15 min 1 at 0,3 hr after CTX (total 2 doses) Day 1-3I*nhpyadtiernattiBoWn <fo1ll2okwgi,nugseHdiogshesdpoesrekgCTX guideline 1-2Course B Dosage 3.3 mg/kg or 100 mg/m2 IV drip in 60 min Given dose Drug 18.6 mg/kg or 560 mg/m2 IV drip in 15-30 min __________mg Etoposide __________mg CarboplatinIn patient BW < 12 kg, use doses per kgRetinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-03] 222

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2  Check CBC, BUN, Cr, Electrolyte, Ca2+, Mg2+, PO4 and LFT before start each course  Record water intake/ output and give diuretic if necessary.  Criteria for starting chemotherapy: o Absolute neutrophil count >1,000/ mm3 o Platelet count >100,000/ mm3 o ALT <10 × the upper limit of normal o Normal glomerular filtration rate  Record BP q 15 min during etoposide infusion  Fundoscopic examination by ophthalmologist before each cycle  Consider hearing exam periodically  Consider enucleation or EBRT if patient does not fully respond to chemotherapy Schedule of chemotherapy Protocol ThaiPOG-RB-13-03Course Date BW / BSA Dose adjusted NoteA1B1A2B2A3B3A4B4Retinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-03] 223

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for retinoblastoma [ThaiPOG-RB-13-04]Protocol name ThaiPOG-RB-13-04Protocol for Metastasis retinoblastomaOpen Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Retinoblastoma with CNS/ bone/ bone marrow involvement Retinoblastoma with isolated meningeal disease Ectopic intracranial retinoblastomaGiven dose Drug Dosage Day___________mg Carboplatin 18.6 mg/kg or 560 mg/m2/day in D5W IV drip in 15-30 min 1___________mg Ifosfamide 60 mg/kg or 1,800 mg/m2/day in NSS IV drip in 30-60 min 1-5___________mg Mesna 15 mg/kg or 450 mg/ m2/dose IV drip in 15 min before 1-5 Ifosfamide, then at 3, 6, 9 hours post Ifosfamide (total 4 1-5 doses)___________mg Etoposide 3.3 mg/kg or 100 mg/m2/day in D5W IV drip in 60 min***I*nsHtpaayrtditernGat t-BiCoWnS<Ffo152llokmwg,cinugsg/ekhgdiog_she_s_dp_oe_sr_ek_gC__y_clompchgosOpDhaamftiedre/coIfmospflaemtioidneogfucihdeemlinoetherapy 24 hr Give chemotherapy every 4 weeks Record water intake/output and give diuretic if necessary Record BP q 15 min during etoposide infusion Check CBC, BUN, Cr, Electrolyte, Ca2+, Mg2+, PO4 and LFT before start each course Criteria for starting chemotherapy: o Absolute neutrophil count >1,000/ mm3 o Platelet count >100,000/ mm3 o ALT <10 × the upper limit of normal o Normal glomerular filtration rate Fundoscopic examination by ophthalmologist before each cycle Consider myeloablative chemotherapy and autologous stem cell rescue EBRT for bulky disease at week 6 of SCTRetinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-04] 224

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 Schedule of chemotherapy Protocol Thai-POG-13-04Course Date BW / BSA Dose adjusted Note12345678Retinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-04] 225

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for intrathecal in retinoblastoma [ThaiPOG-RB-13-05]Protocol name ThaiPOG-RB-13-05Protocol for Retinoblastoma with CNS involvementReference Adapted from Orkin's Oncology of Infancy and Childhood 1st ed, 2009 p.576-601Open Date January 2014Patient’s name..................................................................... Sex.................. HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2* age adjusted dose intrathecal < 4mo 4– 11 mo 12-23 mo 24-36 mo >36 mochemotherapyMethotrexate 3 6 8 10 12Ara-C 10 20 30 50 70 Give IT chemotherapy until CSF is negative 2 times consecutively with minimum 4 dosesCycle week/ date given CSF result1 week 0/week 1/week 2/week 3/2 week 4/week 5/week 6/week 7/3 week 8/week 9/week 10/week 11/4 week 12/week 13/week 14/week 15/Retinoblastoma: Treatment protocol for intrathecal in retinoblastoma [ThaiPOG-RB-13-05] 226

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Renal tumor Staging system for renal tumorsStage NWTSG (before chemotherapy) SIOP (after chemotherapy)I (a) Tumor is limited to the kidney and (a) Tumor is limited to kidney or surroundedcompletely excised with fibrous pseudocapsule if outside of the(b) The tumor was not ruptured before or during normal contours of the kidney, the renal capsuleremoval or pseudocapsule may be infiltrated with the(c) The vessels of the renal sinus are not tumor, but it does not reach the outer surface,involved beyond 2 mm and is completely resected (resection margins(d) There is no residual tumor apparent beyond “clear”)the margins of excision (b) The tumor may be protruding into the pelvic system and “dipping” into the ureter (but it is not infiltrating their walls) (c) The vessels of the renal sinus are not involved (d) Intrarenal vessel involvement may be presentII (a) Tumor extends beyond the kidney but is (a) The tumor extends beyond kidney orcompletely excised penetrates through the renal capsule and/or(b) No residual tumor is apparent at or beyond fibrous pseudocapsule into perirenal fat but isthe margins of excision completely resected (resection margins “clear”)(c) Tumor thrombus in vessels outside the (b) The tumor infiltrates the renal sinus and/orkidney is stage II if the thrombus is removed en invades blood and lymphatic vessels outside thebloc with the tumor renal parenchyma but is completely resected (c) The tumor infiltrates adjacent organs or vena cava but is completely resectedIII Residual tumor confined to the abdomen: (a) Incomplete excision of the tumor, which(a) Lymph nodes in the renal hilum, the extends beyond resection margins (gross orperiaortic chains, or beyond are found to microscopical tumor remains postoperatively)contain tumor (b) Any abdominal lymph nodes are involved(b) Diffuse peritoneal contamination by the (c) Tumor rupture before or intraoperativelytumor (irrespective of other criteria for staging)(c) Implants are found on the peritoneal (d) The tumor has penetrated through thesurfaces peritoneal surface(d) Tumor extends beyond the surgical margins (e) Tumor thrombi present at resection marginseither microscopically or grossly of vessels or ureter, transsected or removed(e) Tumor is not completely resectable piecemeal by surgeonbecause of local infiltration into vital structures (f) The tumor has been surgically biopsied (wedge biopsy) prior to preoperative chemotherapy or surgeryIV Presence of hematogenous metastases or Hematogenous metastases (lung, liver, bone,metastases to distant lymph nodes brain, etc.) or lymph node metastases outside the abdomino-pelvic regionV (a) Tumor extends beyond the kidney but is Bilateral renal tumors at diagnosiscompletely excisedNote: ThaiPOG ใช้ NWTSG stagingRenal tumor: Staging system for renal tumors 227

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Protocol assignment Histology Stage I Stage II Stage III Stage IV Regimen E Regimen E Regimen D Regimen DFavorable histology (FH) Regimen D Regimen D Regimen D Regimen D Regimen D Regimen I Regimen I Regimen I Focal anaplasia Regimen I Regimen I Regimen I Regimen IDiffuse anaplasiaClear cell sarcoma (CCSK) Radiation therapy dosing guidelines (within 10-14 days after surgery)Tumor Characteristics Radiation Dose/FieldStage I and II FH Wilm’s tumor NoneStage I-II FA or DA or CCSK 10.5 Gy flankStage III FH or CCSK of FA 10.5 Gy flankCytology-positive ascites or preoperative rupture or 10.5 Gy WAIdiffuse operative tumor spillageResidual gross disease >3 cm 10.8 Gy boost to residual diseaseStage III DA 20 Gy flank or WAI, as for ascites or rupture aboveStage I-III RTKRecurrent abdominal Wilms’ tumor 12.6-18 Gy (<12 months of age), or 21.6 Gy (older children) if previous rediation dose is <10.8 Gy. Boost dose of up to 9 Gy to gross residual tumor after surgeryLung metastases 12 Gy whole lung in 8 fractions (1,050 cGY if <12 months age)Brain metastases 30.6 Gy whole brain in 17 fractions, or 20 Gy whole brain + 10-15 Gy IMRT or stereotactic boostLiver metastases 19.8 Gy whole liver in 11 fractionsBone metastases 25-30 Gy to the lesion plus 3-cm marginLymph node metastases 19.8 Gy to lymph nodes in 17 fractionsFH, Favorable histology; FA, focal anaplasia; DA, diffuse anaplasia; CCSK, clear cell sarcoma of the kidney;WAI, whole abdomen irradiation; RTK, rhabdoid tumor of kidney; IMRT, intensity-modulated radiotherapy.Note: 1. Actinomycin-D and doxorubicin doses should be decreased 50% if given withn 6 weeks followingwhole- lung or whole-abdomen RT.2. Pneumocystie jiroveci prophylaxis with cotrimoxazole or pentamidine should be instituted in patientsreceiving lung RT.Renal tumor: Protocol assignment 228

Thai Pediatric Oncology Group female ชมรมโรคมะเร็งเดก็ Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-01] Data entry formPatient’s name......................................................... HN............................ Sex  maleAddress.....................................................................................................................................................................................................................................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 บัตรประกนั สุขภาพ จ่ายตรง อน่ื ๆ (ระบุ) ...................................History Physical examination Histology Stage I Stage II Favorable histology (FH) Regimen E  Regimen EPre- treatment investigations.A. Blood date (………/………/………)CBC …………………..…………….………..…………..…………………………………………………………….BUN …………Creatinine ………… Electrolyte…….………………………………………………………………LFT…………………..…………………………………….……………………………………………………………B. Imaging studyCT chest (………/………/………) ……………..………………………………………………………..………….………………………………………………………………………………………………………………………….Chest X-Ray (………/………/………) …………………...………………………………………………..……….CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..……….* Use the same imaging modality – CT or MRI – for all disease evaluations.Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-01] 229

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment Protocol for Wilms’ tumorProtocol name ThaiPOG-WT-13-01Protocol for Favorable histologyReference NWTS-5, Regimen EOpen Date January 2014Patient’s name.................................................................... Sex................... HN...........................................Age (yy/mm).............................. BW...........................kg HT...............................cm BSA.........................m2Drug Dose Information Drug Age < 12 months Dosage BW ≥ 30 kgAMD = Actinomycin-D X 1day 0.023 mg/kg IV Age ≥ 12 months 1.35 mg/M2 IV 0.045 mg/kg IV (Maximum dose 2.3 mg)VCR1 = Vincristine X 1day 0.025 mg/kg IV 1.5 mg/M2 IV 0.05 mg/kg IV (Maximum dose 2 mg)VCR2 = Vincrintine X 1day 0.034 mg/kg IV 2 mg/M2 IV 0.067 mg/kg IV (Maximum dose 2 mg)Week Date BSA AMD VCR1 VCR2 Note012Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………345Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………678Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-01] 230

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กWeek Date BSA AMD VCR1 VCR2 NoteEvaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………910Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..………………………………………………………………………………………………………Chest X-Ray (………/………/………) …………………...……………………………………………………..…………12Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..……………………………………………………………………………………………………..…1518Post- treatment investigations.A. Blood date (………/………/………) CBC …………………..…………….……….………………….……….BUN …………Creatinine ………… Electrolyte………………………………………………………….…………LFT…………………..……………………………………………………………………………………….…………B. Imaging studyCT chest (………/………/………) ……………..………………………………………………………….……..…………………………………………………………………………………………………………………………….Chest X-Ray (………/………/………) …………………...……………………………………………………..….CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..……….*Use the same imaging modality – CT or MRI – for all disease evaluations.Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-01] 231

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-02] 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) ..................................... BSA...................m2Age ............. yr...............m. BW…...........kg Ht...............cm.สิทธิการรักษา บตั รประกนั สุขภาพ จา่ ยตรง อืน่ ๆ (ระบุ) ...................................History Physical examinationHistology Stage I Stage II StageIII StageIVFavorable histology (FH)Focal anaplasia Regimen D Regimen D Regimen DDiffuse anaplasia  Regimen D Regimen D Regimen D Regimen DPre- treatment investigations.A. Blood date (………/………/………)CBC ………………….…….…………………………..…………..………………………………………………….BUN …………Creatinine ………… Electrolyte……………………………………………………………………LFT…………………..…………………………………………………………………………………………………B. Imaging studyCT chest (………/………/………) ……………..………………………………………………………….……….………………………………………………………………………………………………………………………….Chest X-Ray (………/………/………) …………………...…………………………………………………………CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..………* Use the same imaging modality – CT or MRI – for all disease evaluations.Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-02] 232

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment Protocol for Wilms’ tumorProtocol name ThaiPOG-WT-13-02Protocol for Favorable histology and anaplasiaReference NWTS-5, Regimen DOpen Date January 2014Patient’s name..................................................................... Sex.................. HN...........................................Age (yy/mm).............................. BW...........................kg HT...............................cm BSA.........................m2Drug Dose Information Drug Age < 12 months Dosage BW ≥ 30 kgAMD = Actinomycin-D X 1day 0.023 mg/kg IV Age ≥ 12 months 1.35 mg/M2 IV 0.045 mg/kg IV (Maximum dose 2.3 mg)VCR1 = Vincristine X 1day 0.025 mg/kg IV 1.5 mg/M2 IV 0.05 mg/kg IV (Maximum dose 2 mg)VCR2 = Vincrintine X 1day 0.034 mg/kg IV 2 mg/M2 IV 0.067 mg/kg IV (Maximum dose 2 mg)DOX1 = Doxorubicin X 1day 0.75 mg/kg IV 45 mg/M2 IVDOX2 = Doxorubicin X 1day 0.5 mg/kg IV 1.5 mg/kg IV 30 mg/M2 IV 1 mg/kg IVWeek Date BSA AMD VCR1 VCR2 DOX1 DOX2 Note 0 *XRT 1 2Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………** XRT start by Day 10 post-nephrectomy (no later than Day 14) 3 4 5Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….………………… 6 7 8Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-02] 233

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Week Date BSA AMD VCR1 VCR2 DOX1 DOX2 NoteEvaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….………………… 9 10 11Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………CT chest$ (………/………/………) ……………..………………………………………………………………..………..$for patients with pulmonary metastases at diagnosis only.………………………………………………………………………………………………………………………………..………………………………………………………………………………………………………………………………..………………………………………………………………………………………………………………………………..Chest X-Ray (………/………/………) …………………...……………………………………………………..………..CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..…………….EKG/ECHO (………/………/………) …………………...…………………...………………………………..…………. 12 13 14Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….………………… 15 16 17Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….………………… 18 19 20Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….…………………Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-02] 234

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กWeek Date BSA AMD VCR1 VCR2 DOX1 DOX2 Note 21 22 23Evaluate: date (………/…....../……..) CBC …………………..…………….………………………………..………...BUN …………Creatinine ………… Electrolyte………………………………………………………………………….LFT…………………..…………………………………………………………………………………….………………… 24 25 26Post- treatment investigations.A. Blood date (………/………/………)CBC …………………..…………….…………………..……………………………………….…………………….BUN …………Creatinine ………… Electrolyte……………………………………………………………………LFT…………………..…………………………………………………………………………………………………B. Imaging studyCT chest (………/………/………) ……..……..………………………………………………………………..………………………………………………………………………………………………………………………………..Chest X-Ray (………/………/………) …………………...……………………………………………………..…..Abdominal Ultra Sound (………/………/………) ……………..………………...…………………………………CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..………..EKG/ECHO (………/………/………) …………………...…………………...………………………………..…….* Use the same imaging modality – CT or MRI – for all disease evaluations.#at baseline abdominal US and Doppler recommended but not require excluding IVC tumor thrombusRenal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-02] 235

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-03] Data entry formPatient’s name..................................................................... Sex.................. HN...........................................Date of Birth........................................ Date of Diagnosis................................... สทิ ธิการรักษา....................Address.........................................................................................................................................................................................................................................Contact person....................................Tel........................Age (yy/mm/dd)................................ BW................................ HT................................ BSA.........................Father............................................................................ Age........................... Occupation...........................Mother............................................................................ Age........................... Occupation...........................History Physical examinationHistology Stage I Stage II StageIII StageIVDiffuse anaplasia Regimen I Regimen I Regimen I Regimen IClear cell sarcoma (CCSK) Regimen I Regimen I Regimen IPre- treatment investigations.A. Blood date (………/………/………)CBC …………………..…………….…………………..…………………………………………………………….BUN …………Creatinine ………… Electrolyte……………………………………………………………………LFT…………………..…………………………………………………………………………………………………B. Imaging studyCT chest (………/………/………) ……………..………………………………………………………………..….………………………………………………………………………………………………………………………….Chest X-Ray (………/………/………) …………………...……………………………………………………..…CT/ MRI abdomen* (………/………/………) …………………...…..……..……………………………..………* Use the same imaging modality – CT or MRI – for all disease evaluations.Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-03] 236