แนวทางการรักษาโรคมะเร็งในเด็ก-2557 (1)

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment Protocol for Wilms’ tumorProtocol name ThaiPOG-WT-13-03Protocol for Diffuse anaplasia and Clear cell sarcomaReference NWTS-5, Regimen IOpen 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 kg 0.75 mg/kg IV Age ≥ 12 months 45 mg/M2 IVDOX = Doxorubicin X 1day 0.025 mg/kg IV 1.5 mg/kg IV 1.5 mg/M2 IVVCR1 = Vincristine X 1day 0.05 mg/kg IV (Maximum dose 2 mg) 2 mg/M2 IVVCR2 = Vincrintine X 1day 0.034 mg/kg IV 0.067 mg/kg IV (Maximum dose 2 mg) 440 mg/M2/dayCTX5 = Cyclophophamide X 5 days 7.35 mg/kg/day 14.7 mg/kg/dayCTX3 = Cyclophophamide X 3 days 3.3 mg/kg/day 100 mg/M2/dayETOP = Etoposide X 5 days 1.65 mg/kg/dayWeek Date BSA DOX VCR1 VCR2 CTX5 CTX3 ETOP 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…………………..…………………………………………………………………………………….………………Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-03] 237

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กWeek Date BSA DOX VCR1 VCR2 CTX5 CTX3 ETOP Note 6 7 8Evaluate: 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 20Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-03] 238

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กWeek Date BSA DOX VCR1 VCR2 CTX5 CTX3 ETOP NoteEvaluate: date (………/…....../……..) CBC …………………..…………….………………………………..……….BUN …………Creatinine ………… Electrolyte………………………………………………………………………..LFT…………………..…………………………………………………………………………………….……………… 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-13-03] 239

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-04] 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 ธิการรกั ษา บัตรประกนั สุขภาพ จา่ ยตรง อืน่ ๆ (ระบ)ุ ...................................History Physical examinationHistology FH Focal anaplasia  Diffuse anaplasia Clear cell SarcomaStage I II V III IVPre- 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-13-04] 240

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment Protocol for Wilms’ tumorProtocol name ThaiPOG-WT-13-VHRProtocol for Bilateral Wilms’ tumorReference NWTS-5, Bilateral Wilm tumorOpen Date January 2014Patient’s name..................................................................... Sex.................. HN...........................................Age (yy/mm).............................. BW...........................kg HT...............................cm BSA.........................m2Inclusion criteriaInitial treatment with VAD 6 weeks then reevaluate 1. If bilateral partial nephrectomy feasible  Definite surgery at week 6 2. If bilateral partial nephrectomy NOT feasible a. ≥ partial response in both kidney  continue VAD for 6 weeks i. Definite surgery at Week 12 ii. Complete response  Start regimen D b. < partial response in either kidney i. Bilateral open biopsy at week 6 3. If complete response in both kidney  start regimen EDrug Dose Information Age < 12 months Dosage Age ≥ 3 years Drug 0.023 mg/kg IV Age ≥ 12 months 0.045 mg/kg IV 1.5 mg/M2 IVAMD = Actinomycin-D X 1day 0.025 mg/kg IV (Maximum 2.3 mg) (Maximum dose 2 mg)VCR = Vincristine X 1day 0.05 mg/kg IVDOX = Doxorubicin X 1day 1.2 mg/kg IV 35 mg/M2 IVWeek Date BSA AMD VCR DOX Note012345Renal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-04] 241

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็กRenal tumor: Treatment protocol for Wilms’ tumor [ThaiPOG-WT-13-04] 242

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Post- treatment investigationsA. 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-13-04] 243

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก การติดตามการรกั ษา (Recommended imaging studies for follow-up)Favorable-histology Wilms' without metastatic disease, 1. CXR + abdominal U/S alternate with CXR + abdominal/pelvic CT q 3 months during first 3 years. 2. CXR + U/S q 6 months for 2 years (in 4th + 5th year)Wilms' with metastatic or anaplastic disease; 1. CXR + abdomen/pelvic CT q 3 months x 2 years 2. CXR + U/S q 6 months in 3rd to 5th yearBilateral Wilms' tumor or nephrogenic rest;Abdominal ultrasound examinations should be performed every 3 months until age 8.Renal tumor: การติดตามการรักษา (Recommended imaging studies for follow-up) 244

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กHepatoblastomaName Data entry form for hepatoblastoma HNAddress Age Sex DOBFatherMother Age OccupationBirth weight Age OccupationDate Registered Gestational ageHistory Physical examinationPre-treatment InvestigationsA. Imaging study CT scan liver (___/___/___)CXR PA/lateral (___/___/___)CT chest (___/___/___)Bone scan (Optional) (___/___/___)B. CBC (___/___/___)C. Tumor Markers (___/___/___) AFP β-HCG LDH KCD. Blood chemistry (___/___/___) BUN Cr uric acid Na AP GGTHCO3 Ca P Mg AST ALT DB TB ml/min/1.73m2E. GFR ( □ calculated / □ measured)F. Coagulogram (___/___/___) PT aPTT fibrinogenG. Hepatitis profile (___/___/___)H. EKG (___/___/___)I. Audiogram (___/___/___)J. Other (___/___/___)Hepatoblastoma: Data entry form for hepatoblastoma 245

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเดก็ PRETEXT (Pre-treatment extent of disease) staging system PRETEXT is based upon division of the liver into four sections. Section 1 (left lateral) : Couinaud 2 and 3 Section 2 (left medial) : Couinaud 4 Section 3 (right anterior) : Couinaud 5 and 8 Section 4 (right posterior) : Couinaud 6 and 7 In addition any group may have: „„V‟‟ : invasion vena cava or all 3 major hepatic veins „„P‟‟ : invasion main portal vein or bifurcation „„E‟‟ : intra-abdominal extrahepatic extension „„M‟‟ : distant metastasis „„C‟‟ : caudate lobe involvement□ PRETEXT I = One section is involved, three contiguous sections free of tumor□ PRETEXT II = Two sections involved, two contiguous sections free of tumor□ PRETEXT III = Two or three sections involved, no two adjoining sectors free of tumor□ PRETEXT IV = All four sections involved, no section free of tumor Pretreatment diagnosis : Hepatoblastoma PRETEXT __________Indication for biopsy 1. Age <6 months, or >3 years  Biopsy is mandatory because of the wide differential diagnosis of hepatic masses and the possible confounding effect of an “elevated” serum AFP level if age <6 months, and because of the risk of misdiagnosing hepatocellular carcinoma if age >3 years 2. Age 6 months - 3 years  Biopsy is not required if typical radiological finding of hepatoblastoma and elevated AFP (>100 ng/ml) are presentHepatoblastoma: PRETEXT (Pre-treatment extent of disease) staging system 246

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก High dose cisplatinum (CDDP) administration protocol1. ก่อนให้ CDDP ต้องตรวจ electrolytes, Ca, Mg, BUN creatinine, U/A คานวณ GFR จาก Schwartz formula GFR (ml /min /1.73 m2) = k x Height cm Serum cr mg / dLk = 0.33 (infant with Hx LBW), 0.45 (infant), 0.55 (child or adolescent girl), 0.7 (adolescent boy) ให้ยาเมื่อ GFR > 60 ml /min /1.73 m22. 4 ชม. กอ่ นเร่มิ ยา Hydration ด้วย 5%D NSS/_____ (Vol ______ml/bottle) + KCl (10 mEq/L) _____ ml + MgSO4 (8 mEq/L) _____ml IV drip at rate _____ /hr (125 ml /m2 /hr) x 4 hr Hour 0 วดั ความดนั ชง่ั น้าหนัก record I/O ให้ยาแก้อาเจยี น ตามความเหมาะสม ซ้าไดท้ ุก 4-6 ชม. เรม่ิ ให้ยา : 5%D NSS/_____ , Vol ________ ml mg (80 mg /m2) + CDDP + mannitol gm (500 mg /kg) + KCl ml (1 mEq /kg) ml /hr (125 ml /m2 /hr) x 24 hr IV at rate(ระหวา่ งการให้ CDDP ต้องมปี ัสสาวะออก 3-4 ml /kg /hr ถ้านอ้ ยกวา่ นใ้ี ห้ mannitol ไดอ้ กี 200 mg /kg in 25 mlNSS IV over 15 min ถา้ ไมด่ ขี ึ้นใน 1 ชม. ใหฉ้ ีด lasix 0.5 mg /kg ได้) Hour 24 หยุด CDDP และเปลยี่ น IV fluid เป็น 5%D NSS/_____ (Vol ________ml/bottle) + KCl (10 mEq/L) _____ ml + MgSO4 (8 mEq/L) _____ml IV drip at rate _____ /hr (125 ml /m2 /hr) x 12 hr หลงั จากนัน้ ลด rate IV เปน็ ml /hr ( 65 ml /m2 /h )3. Oral Mg supplement : Minimal daily requirement = 0.3 mEq /kg /d (12 mg Mg = 1 mEq) Mag oral tab = 7 mEq Mg / tab Milk of Magnesia = 13 mEq Mg / 5 ml Mg sulfate solution 50% = 20 mEq / 5 mlHepatoblastoma: High dose cisplatinum (CDDP) administration protocol 247

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Post-treatment evaluation1. Monitor AFP level - Every 2 months in the 1st year - Every 3 months in the 2nd year - Every 4 months in the 3rd year - Every 6 months in the 4th year2. Hearing test - Pretreatment - Before delayed surgery - At the end of treatment - At 1 year after treatment3. Echocardiogram/ MUGA scan - Yearly for 4 years in patient who received Doxorubicin4. Imaging - CT chest/abdomen is not necessary if AFP > 100 ng/ml at the time of diagnosis - In patient with low AFP (< 100 ng/ml) at diagnosis, CT chest/abdomen should be performed - Every 3 months for 2 year - Every 4 months in the 3rd year - Every 6 months in the 4th year - CT abdomen can be used in alternate sequence with U/S abdomen only if high resolution U/Sabdomen is availableHepatoblastoma: Post-treatment evaluation 248

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR]1. Patient of PRETEXT I, II, III without any high risk features (+V, P, E, M or AFP <100 ng/ml) will beproceed to upfront surgery if gross total tumor removal can be achieved. Patient who found to have V/P/Minvolvement in the operative field will be shifted to high risk group (HR) irrespective of the PRETEXT staging.2. Classify tumor into 4 groups (VLR, LR, IR, HR) according to PRETEXT, AFP, surgery and pathologyresult.3. Very low risk patient does not require chemotherapy.Hepatoblastoma: Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR] 249

Protocol name Thai Pediatric Oncology GroupProtocol for ชมรมโรคมะเร็งเด็กOpen dateModified from ThaiPOG-HB-13-VLR Very low risk hepatoblastoma January 2014 N Engl J Med 2009;361:1662-70Patient eligibility Exclusion criteria PRETEXT I, II, III with total tumor removal, and pure fetal histology (PFH)  AFP < 100 ng/ml  tumor with high risk features (+V/P/E/M)Patient’s name Age Sex HNBW BSA HtInitial surgery ( Date _____/_____/_____ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other_________________________section # ______________ result _______________________________________________________________Hepatoblastoma: Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR] 250

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็กTreatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR]1. Patient of PRETEXT I, II, III without any high risk features (+V, P, E, M or AFP <100 ng/ml) will beproceed to upfront surgery if gross total tumor removal can be achieved. Patient who found to have V/P/Minvolvement in the operative field will be shifted to high risk group (HR) irrespective of the PRETEXT staging.2. Classify tumor into 4 groups (VLR, LR, IR, HR) according to PRETEXT, AFP, surgery and pathologyresult.3. First course of chemotherapy should be started within 7-14 days after the diagnosis4. If CT chest is not available before the treatment, it MUST be done no later than 14 days after starting ofthe first course of chemotherapy5. Chemotherapy will be given every 2 weeks for 4 courses6. Hearing test should be performed at pre-treatment, before surgery, end of treatment and 1 year post offtreatment Anti-emetic guideline1. Ondansetron 5 mg/m2/dose IV pre-chemo and then q 8 hr PLUS2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) IV drip in 10 min pre-chemo, then q 12 hrNote Aprepitant 125 mg po on day 1, then 80 mg po daily on day 2,3 may be given as an additional anti-emetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.Hepatoblastoma: Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR] 251

Protocol name Thai Pediatric Oncology GroupProtocol for ชมรมโรคมะเร็งเดก็Open dateModified from ThaiPOG-HB-13-LR Low risk hepatoblastoma January 2014 N Engl J Med 2009;361:1662-70Patient eligibility Exclusion criteria PRETEXT I, II, III with total tumor removal  tumor with AFP < 100 ng/ml  tumor with high risk features (V, P, E, M)(non PFH & non SCU histology) Sex HNPatient’s name AgeBW Ht BSA Given dose Drug Desired dose Route Day___________ mg Cisplatin (CDDP) 80 mg/m2/dose IV drip in 24 hr 1 Give chemotherapy q 2 weeks, ANC > 1,000 and platelet > 100,000 before start chemotherapy Blood for LFT, AFP before each course and record liver size every course If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) xBW] G-CSF is not necessary, unless the patient has febrile neutropenia from the previous courseInitial surgery  yes ( Date _____/_____/_____ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other________________________section # ______________ result ______________________________________________________________Course Date AFP Dose adjusted liver size Hearing test I ___/___/___ * II ___/___/___ III ___/___/___ * IV ___/___/___Hepatoblastoma: Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR] 252

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กTreatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR]1. Patient of PRETEXT I, II, III without any high risk features (+V, P, E, M or AFP <100 ng/ml) will beproceed to upfront surgery if gross total tumor removal can be achieved. Patient who found to have V/P/Minvolvement in the operative field will be shifted to high risk group (HR) irrespective of the PRETEXT staging.2. Classify tumor into 4 groups (VLR, LR, IR, HR) according to PRETEXT, AFP, surgery and pathologyresult.3. First course of chemotherapy should be started within 7-14 days after the diagnosis4. If CT chest is not available before the treatment, it MUST be done no later than 14 days after starting ofthe first course of chemotherapy5. Chemotherapy will be given every 2 weeks for 4 courses, then re-evaluate with imaging* - Resectable tumor  surgery plus 2 additional courses of CMT - Unresectable tumor  2 more courses of CMT, follow with surgery, no post-op CMT*Imaging is not necessary at this time point for patients with SCU cell type or residual disease from initialsurgery; they will receive chemotherapy for the total of 6 courses6. Maximum CMT is 6 courses for intermediate risk patient7. Hearing test should be performed at pre-treatment, before surgery, end of treatment and 1 year post offtreatment Anti-emetic guideline1. Ondansetron 5 mg/m2/dose iv pre-chemo and then q 8 hr PLUS2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) iv drip in 10 min pre-chemo, then q 12 hrNote Aprepitant 125 mg po on day 1, then 80 mg po daily on day 2,3 may be given as an additional anti-emetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.Hepatoblastoma: Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR] 253

Protocol name Thai Pediatric Oncology GroupProtocol for ชมรมโรคมะเร็งเดก็Open dateModified from ThaiPOG-HB-13-IR Intermediate risk hepatoblastoma January 2014 N Engl J Med 2009;361:1662-70Patient eligibility Exclusion criteria PRETEXT I, II, III without upfront surgery  tumor with high risk features (+V, P, E, M) PRETEXT I, II, III with SCU cell type  AFP < 100 ng/ml PRETEXT I, II, III with residual disease from upfront surgeryPatient’s name Age Sex HNBW BSA Ht Given dose Drug Desired dose Route Day___________ mg Cisplatin (CDDP) 80 mg/m2/dose IV drip in 24 hr 1 Give chemotherapy q 2 weeks, ANC > 1,000 and platelet > 100,000 before start chemotherapy Blood for LFT, AFP before each course and record liver size every course If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) x BW] G-CSF is not necessary, unless the patient has febrile neutropenia from the previous courseInitial surgery  no  yes ( Date _____/_____/_____ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other___________________section # ______________ result ______________________________________________________________Course Date AFP Dose adjusted liver size Hearing testI ___/___/___ *II ___/___/___III ___/___/___IV ___/___/___ * Re-evaluate after 4 courses of CMT (Date ________________)  Resectable : Surgery plus 2 more courses of CMT  Unresectable : 2 additional courses of CMT, then surgery, no post-op CMT  PRETEXT I, II, III with residual disease or SCU cell type: No imaging needed, continue CMT untilfinish cycle 6 V ___/___/___VI ___/___/___ *Delayed surgery ( Date _____/_____/_____ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other_________________________section # ______________ result ____________________________________________________________________Hepatoblastoma: Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR] 254

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กTreatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR]1. First course of chemotherapy should be started within 7-14 days after the diagnosis2. If CT chest is not available before the treatment, it SHOULD be done no later than 14 days after startingof the first course of chemotherapy3. Chemotherapy will be given every 2 weeks for 7 courses, then re-evaluate - Resectable tumor  will proceed to surgery, then receive 3 additional courses of CMT - Unresectable tumor  will receive 3 more courses of CMT, follow with surgery, no post-op CMT4. Maximum CMT is 10 courses for high risk patient5. Hearing test should be performed at pre-treatment, before surgery, end of treatment and 1 year post offtreatment Anti-emetic guideline1. Ondansetron 5 mg/m2/dose iv pre-chemo and then q 8 hr PLUS2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) iv drip in 10 min pre-chemo, then q 12 hrNote Aprepitant 125 mg po on day 1, then 80 mg po daily on day 2,3 may be given as an additional anti-emetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.Hepatoblastoma: Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR] 255

Protocol name Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กProtocol forOpen date ThaiPOG-HB-13-HRReference High risk hepatoblastoma January 2014 J Clin Oncol 2010;28:2584-2590Patient eligibility Exclusion criteria PRETEXT IV tumor  Low AFP (< 100 ng/ml) Tumor with high risk features (+V, P, E, M) Sex HNPatient’s name Age BSABW HtGiven dose Drug Desired dose Day___________ mg Cisplatin (CDDP) 80 mg/m2 IV drip in 24 hr Day 1 of course 1, 3, 5, 7, 9___________ mg Carboplatin 500 mg/m2 IV drip in 1 hr Day 1 of course 2, 4, 6, 8, 10___________ mg Doxorubicin 60 mg/m2 IV drip in 48 hr Day 1-2 of course 2, 4, 6, 8, 10 Give chemotherapy q 2 weeks, ANC > 1,000 and platelet > 100,000 before start chemotherapy Blood for LFT, AFP before each course and record liver size every course If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) xBW] G-CSF is not necessary, unless the patient has febrile neutropenia from the previous courseInitial Biopsy  no  yes ( Date ___/___/___ ) section # ______________ result _________________Course Date AFP Dose adjusted liver size Hearing test I ___/___/___ *II ___/___/___ *III ___/___/___ *IV ___/___/___V ___/___/___VI ___/___/___VII ___/___/___Re-evaluate after 7 courses of CMT (Date ________________)  Resectable : Surgery plus 3 more courses of chemotherapy  Unresectable : Give 3 additional courses of CMT, then surgery, no post-op CMTVIII ___/___/___IX ___/___/___X ___/___/___Delayed surgery ( Date ___/___/___ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other_________________section # ______________ result ____________________________________________________________Hepatoblastoma: Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR] 256

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR]1. Patients with low AFP (AFP <100 ng/ml) will need biopsy to confirm the diagnosis of hepatoblastoma,these patients will be classified as a very high risk group2. First course of chemotherapy should be started within 7-14 days after the diagnosis3. If CT chest is not available before the treatment, it SHOULD be done no later than 14 days after startingof the first course of chemotherapy4. All patients will receive upfront chemotherapy with 2 courses of VI regimen, then re-evaluate - Responder will then receive another 9 courses of chemotherapy (C5VD-C5VD-VI x 3 cycles) : 6 courses of neo-adjuvant CMT followed with Surgery, and 3 course of adjuvant CMT - Non-responder will receive another 6 course of chemotherapy (C5VD x 6 cycles) : 4 courses of neo-adjuvant CMT followed with Surgery, and 2 course of adjuvant CMT5. Surgery will be performed after the 4th course of C5VD regimen of each protocol6. Hearing test should be performed at pre-treatment, before surgery, end of treatment and 1 year post offtreatmentHepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 257

Protocol name Thai Pediatric Oncology GroupProtocol for ชมรมโรคมะเร็งเดก็Open dateReference ThaiPOG-HB-13-VHR Very High risk hepatoblastoma January 2014 COG AHEP0731 protocol, treatment regimen WPatient eligibility Patient with low AFP (< 100 ng/ml)Patient’s name Age Sex HNBW Ht BSARegimen Given Dose Drug Desired dose DayVI regimen ____________ mg Vincristine (VCR) 1.5 mg/m2 IV push 1, 8 ____________ mg Irinotecan 50 mg/m2 IV drip in 90 min 1-5C5VD regimen ____________ mg Cisplatin (CDDP) 100 mg/m2 IV drip in 6 hr 1 ____________ mg 5-Flouracil (5-FU) 600 mg/m2 IV push slowly 2 ____________ mg Vincristine (VCR) 1.5 mg/m2 IV push 2, 9, 16 ____________ mg Doxorubicin 30 mg/m2 IV drip in 15 min 1, 2Anti-emetic guideline 5 mg/m2 IV pre-chemo, then q 8 hr during CMT___________ mg Ondansetron___________ mg Dexamethasone* 8 mg/m2 IV drip in 10 min pre-chemo, then q 12 hr during CMT___________ mg Aprepitant** 125 mg PO on day 1, then 80 mg PO daily on day 2,3 * Reduce Dexamethasone by half, if Aprepitant was given **May be given as an additional anti-emetic in patient >12 year Give chemotherapy q 3 weeks, ANC > 1,000 and platelet > 100,000 before start chemotherapy Blood for LFT, AFP before each course and record liver size every course If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) xBW] Start G-CSF 5 ug/kg daily at 24-36 hours after completion of each cycle of chemotherapy Surgery will be performed after the 4th course of C5VD regimen of each protocolHepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 258

Patient’s name Thai Pediatric Oncology Group Sex HNBW ชมรมโรคมะเร็งเด็ก Age Ht BSAThaiPOG-HB-13-VHR protocolInitial Biopsy  no  yes ( Date ___/___/___ ) section # ______________result__________________________Course Date Regimen AFP Dose adjusted liver Hearing test size *I ___/___/___ VIII ___/___/___ VIRe-evaluate after 2 upfront VI regimen (Date ________________)  Responder : will receive VI regimen after each 2 cycles of C5VD regimen  Non-responder : will receive 6 additional courses of C5VD (no more VI regimen)III ___/___/___ C5VDIV ___/___/___ C5VDV* ___/___/___ VI*VI ___/___/___ C5VDVII ___/___/___ C5VDVIII* ___/___/___ VI* *Re-evaluate after the 4th course of C5VD regimen (Date ________________)  Resectable : Surgery plus 2-3 more courses of chemotherapy  Unresectable : 2-3 additional courses of CMT then surgery, no post-op CMTIX ___/___/___ C5VDX ___/___/___ C5VDXI* ___/___/___ VI* *Delayed surgery ( Date ___/___/___ surgeon________________________ )Operation  biopsy  partial removal  total removal  wide excision  other___________________section # ______________ result ____________________________________________________________*For those who response to upfront VI regimen only (responder)Hepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 259

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Osteosarcoma 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 บัตรประกันสุขภาพ จ่ายตรง อืน่ ๆ (ระบ)ุ .............................................History Physical examinationPrimary site  Femur  Humerus  Tibia  Fibula  Other bones………………...…Side  Left  RightMetastasis site at diagnosis  yes  No If yes, specify  Bone  Chest  Other………Status at first visit (Tumor size …………………… cm):  Resectable, non-metastasis  Resectable, metastasis  Non-resectableHistology  Osteoblastic  Chondroblastic  FibroblasticSurgery  Telangiectatic  Small cell  Large cell  Epithelioid  Not-classified  Other…………………….…………….Surgery date (………/………/………) Surgeon ……………………………………………………………….….Type of surgery:  Amputation  Limb salvage  Rotationplasty………………………………………………………………………………………………………………………………….Tumor necrosis ……………………… % Pathology ………………………………………………………….………….Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.) not knownInvestigations.serum ALP (………/………/………) ……………………… iu/mL  Normal  ElevatedCT/ MRI primary lesion (………/………/………) ………………………..……..……………………………..………….………………………………………………………………………………………………………………………………….Work up metastasis CXR…………………………………………………………………  Normal  Abnormal CT chest…………………………………………………………….  Normal  Abnormal Bone scan…………………………………………………………..  Normal  Abnormal Other ………………………………………………………………  Normal  AbnormalOsteosarcoma: Data entry form 260

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD]Protocol name ThaiPOG-OS-13-CDProtocol for High grade localized-osteosarcoma, chondrosarcoma, fibrosarcomaReference SJCRH-OS-99 (launched December 2009)Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteriaLocalized osteosarcomaCycle 1 2 3 4 5 6 7 8 9 10 11 12Week 0 3 6 9 12 14 17 20 23 26 29 32 35 38DateInduction I I I A* I I A I I A I A** Cb Cb Cb A Cb Cb A Cb Cb A** CbEvaluation (1) (1) Surgery Sx Hearing test (audiogram) should be evaluated before starting chemotherapy with cisplatin G-CSF 5 mcg/kg/day is administered for 8 – 10 days after completion of every cycle except for week 9 Keep ANC ≥ 1,500/uL and Platelet count ≥ 100,000 /uL before starting chemotherapy Give chemotherapy every 21 days (1) Evaluation by CT/MRI lesion, CT chest and CXR PA, lateralDrug Dose Route 2.65 gm/m2/dayI: Ifosfamide IV drip in 30 min OD x 3 days 660 mg/m2/dose IV at 0, 3rd, 6th, 9th hour after IfosfamideMesna 450 mg/m2Cb: Carboplatin 25 mg/m2 IV drip 1 hour OD x 1 dayA*: Doxorubicin 50 mg/m2/day IV drip in 1 hour OD x 3 daysA: Doxorubicin IV drip in 2 hour OD x 1 day A**: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%) (Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m2 or when > 200 mg/m2 in infantOsteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD] 261

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Phase I: Neoadjuvant phaseCycle Date BSA Ifosfamide Carboplatin Doxorubicin Note 2.65 gm/m2/day 450 mg/m2 25 mg/m21234SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery:  Amputation  Limb salvage  Rotationplasty………………………………………………………………………………………………………………………………….Tumor necrosis ……………………… % Patho no. …………………………………………………….……………….Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.) not knownEvaluation 1. CT/ MRI …………………………….(………/………/………) ……………..……………………………..……. 2. Bone scan (………/………/………) ………………………………...…………….…………………………….. 3. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Phase I: Adjuvant phase Ifosfamide Carboplatin Doxorubicin Note 2.65 gm/m2/day 450 mg/m2 50 mg/m2Cycle Date BSA 5 6 7 8 9 10 11 12Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD] 262

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Drug administrationA. High dose Ifosfamide (>1,000 mg/m2) 1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/hour at least 2 hours before start the drug, to keep urine output > 3 ml/kg/hour 2. Check urine specific gravity and start chemotherapy when urine specific gravity < 1.010 3. Dilute ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and infuse in 1 hour 4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3rd, 6th, 9th hour of Ifosfamide; dilute mesna with 5%D/W to 20 ml iv drip in 15 minute 5. Keep urine output > 2 ml/kg/hour at least 24 hour after high dose Ifosfamide 6. Furosemide 0.5 mg/kg/dose can be used to increase urine volumeB. Carboplatin 1. Dilute carboplatin in 100 mL of 5%D/W infuse intravenously over 1 hour prior to ifosfamide ordoxorubicin on Day 1 of each courseOsteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD] 263

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX]Protocol name ThaiPOG-OS-13- MTXProtocol for High grade localized-osteosarcoma, chondrosarcoma, fibrosarcomaReference Adapted from AOST0331 and SSG-XIV (Smeland S. Acta Orthop 2011; 82(2):211-6)Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria: Localized osteosarcomaCycle 1 2 3 4567Week 0 3 4 5 8 9 10 13 14 15 18 19 20 23 24 25 28 29 30DateInduction A M M A MM A* M M P P PEvaluation (1) (1) (1)Surgery SxAdjuvant I A M M A* M M A* M M (2) PAdjuvant II A MM I MM I MM I P (3) Hearing test (audiogram) should be evaluated before starting chemotherapy with cisplatin G-CSF 5 mcg/kg/day is administered for 8 – 10 days after completion of every AP or I cycle Keep ANC ≥ 1,500/uL and Platelet count ≥ 100,000 /uL before starting chemotherapy (1) Evaluation by CT/MRI lesion, CT chest and CXR PA, lateral (2) If tumor necrosis > 90%, continue chemotherapy with Adjuvant I (3) If tumor necrosis < 90 %, continue chemotherapy with Adjuvant IIDrug Dose Route 37.5 mg/m2/day IV x 2 days (IV slowly push)A: Doxorubicin 60 mg/m2/day IV over 6 hours x 2 daysP: Cisplatin 12 gm/m2/day IV over 4 hour (max 20 gm)M: HD MTX 15 mg/m2/dose IV every 6 h, starting at 24 h after MTX infusion x 11 doses 2.4 gm/m2/day IV drip in 1 hour OD x 5 days Leucovorin 600 mg/m2/dose IV at 0, 3rd, 6th, 9th hour of IfosfamideI: Ifosfamide Mesna A*: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%) (Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m2 or when > 200 mg/m2 in infantOsteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 264

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Phase I: Induction phaseCycle Week Date BSA Cisplatin Doxorubicin HD MTX Note 10 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day 3 425 8 93 10 (**) 13 14Cumulative dose (mg/m2)SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery:  Amputation  Limb salvage  Rotationplasty………………………………………………………………………………………………………………………………….Tumor necrosis ……………………… %Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.)Evaluation4. CT/ MRI …………………………….(………/………/………) ……………..……………………………..…….5. Bone scan (………/………/………) ………………………………...…………….……………………………..6. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 265

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m22nd Audiogram (postoperative)  Normal  Sensorineural hearing loss*Echocardiogram (postoperative)  Normal  Impaired ejection fraction ………………. % Phase II: Adjuvant I (If tumor necrosis ≥ 90%)Cycle week Date BSA Cisplatin Doxorubicin MTX Note 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day4 15 (***)1819Cumulative dose (mg/m2)5 20 (**)23246 25 (**)2829 Phase II: Adjuvant II (tumor necrosis < 90%)Cycle Week Date BSA Cisplatin Doxorubicin MTX Ifosfamide Note 4 15 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day 2.4 gm/m2/day (***)18195 2023246 252829 7 30*Cardiology consultation for 2nd echocardiogram when cumulative dose of doxorubicin was exceeding 325mg/m2 or 200 mg/m2 in infants** Doxorubicin can be omitted or reduced when cumulative dose of doxorubicin was exceeding 375 mg/m2 orimpaired cardiac function (ejection fraction < 60%)*** Cisplatin can be omitted when cumulative dose of cisplatin was exceeding 480 mg/m2 or evidence ofsensorineural hearing lossOsteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 266

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Drug administrationA. High dose methotrexatePre- and post-hydration is recommended for high dose methotrexate as follows:1. Pre Hydration: Start hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20mL/L at least 24 hours before starting methotrexate infusion, to obtain urine output > 2 ml/kg/h and urinarypH 7 – 7.5 (suggested volume 125 ml/m2/hour, could be adjusted as appropriate) Ensure urine pH is maintained pH 7 – 7.5 by adjusting sodium bicarbonate if required Other strengths of dextrose/ saline are acceptable2. Leucovorin (Calcium folinate) rescue must be commenced exactly 24 hours after the start of themethotrexate infusion at 15 mg/m2 every 6 hours for 11 doses either intravenously or orally (Folinic acid isavailable orally as 15 mg tablets so a dose of 15 mg or 30 mg should be prescribed) *If serum methotrexate level can be measured, treatment must be continued until methotrexate levelis < 0.1 micromol/L *Methotrexate levels should be checked every 24 hours commencing at 48 hours from the start ofthe methotrexate infusion and continuing until methotrexate level is < 0.1 micromol/L3. Post hydration: Hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20 mL/L(alternative strengths accepted) at a rate suitable to obtain urine output > 2 ml/kg/h and urinary pH 7 – 7.5(suggested volume 125 ml/m2/h,could be adjusted as appropriate) until methotrexate level < 0.1 micromol/L If serum methotrexate level is not available, o Liver function test and serum creatinine must be measured at 72nd and 120th hours after completion of methotrexate infusion o If AST / ALT > 5 times of upper normal limits or elevated serum creatinine (>1.5 times of baseline serum creatinine), folinic acid must be continued up to 7 days o Hydration (at a rate of 125 ml/m2/hour) should be maintained for at least 7 days*If MTX level > toxicity alert, increase dose of calcium folinate to (40 x actual MTX conc.) ÷ normal MTX conc(mg/dose)Time MTX toxicity alert Normal MTX conc Calcium folinate dose24 h 20 mmol/L 9 mmol/L As above48 h 2 mmol/L 0.9 mmol/L As above72 h 0.1-0.9 mmol/L < 0.1 mmol/L 10-30 mg IV every 6hIf MTX level at > 72 h is less than 0.1 mol/L, this patient is allowed to discharge.B. High dose Ifosfamide (>1,000 mg/m2)1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/hour at least 2 hours before start the drug, tokeep urine output > 3 ml/kg/h2. Check urine specific gravity and start chemotherapy when urine specific gravity < 1.0103. Dilute ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and infuse in 1 hour4. Mesna Uroprotection (total dose = 80% of Ifosfamide) at 0, 3rd, 6th, 9th hour of Ifosfamide; dilute mesnawith 5%D/W to 20 ml iv drip in 15 minute5. Keep urine output > 2 ml/kg/hour at least 24 hour after high dose cyclophosphamide6. Furosemide 0.5 mg/kg/dose can be used to increase urine volumeOsteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 267

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET]Protocol name ThaiPOG-OS-13-METProtocol for High grade metastatic osteosarcomaReference AOST0331 (EURAMOS01)Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteriaMetastatic osteosarcomaWeek 1 4 5 6 9 10 11 12 15 16 19 20 23 24 27 28 31 32 35 36 39 40DateInduction A MM A MM A M I M A M I M A** M I M A** M M PP P E I* E P E I*Evaluation (1) (1) (1) Surgery Sx Hearing test (audiogram) should be evaluated before starting chemotherapy with cisplatin G-CSF 5 mcg/kg/day is administered for 8 – 10 days after completion of every cycle except for week 9 Keep ANC ≥ 1,500/uL and Platelet count ≥ 100,000 /uL before starting chemotherapy Give chemotherapy every 21 days (1) Evaluation by CT/MRI lesion, CT chest and CXR PA, lateralDrug Dose RouteA: Doxorubicin 37.5 mg/m2/day IV x 2 days (IV slowly push)P: Cisplatin 60 mg/m2/day IV over 6 hours x 2 daysM: HD MTX 12 gm/m2/day IV over 4 hour (max 20 gm) Leucovorin 15 mg/m2/dose IV every 6 h, starting at 24 h after MTX infusion x 11 dosesI: Ifosfamide 2.4 gm/m2/day IV drip in 1 hour OD x 5 days 600 mg/m2/dose IV at 0, 3rd, 6th, 9th hour after Ifosfamide MesnaI*: Ifosfamide 2.4 gm/m2/day IV drip in 1 hour OD x 3 daysE: Etoposide 100 mg/m2/day IV drip in 1 hour OD x 5 days A**: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%) (Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m2 or when > 200 mg/m2 in infantOsteosarcoma: Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET] 268

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Phase I: Neoadjuvant phaseWeek Date BSA Cisplatin Doxorubicin HD MTX Note 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day1456910SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery:  Amputation  Limb salvage  Rotationplasty………………………………………………………………………………………………………………………………….Tumor necrosis ……………………… %Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.)Evaluation 7. CT/ MRI …………………………….(………/………/………) ……………..……………………………..……. 8. Bone scan (………/………/………) ………………………………...…………….…………………………….. 9. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Phase I: Adjuvant phaseCycle Date BSA Cisplatin Doxorubicin HD MTX Ifosfamide Etoposide Note 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day 2.4 gm/m2/day 100mg/m2/day12 (*)15 300  Normal16  Normal19202324Cumulative dose 360 (mg/m2)2nd Audiogram (postoperative)  Sensorineural hearing loss  Impaired ejection fraction ………………. %*Echocardiogram (postoperative)Osteosarcoma: Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET] 269

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Evaluation 1. CT/ MRI …………………………….(………/………/………) ……………..……………………………..……. 2. Bone scan (………/………/………) ………………………………...…………….…………………………….. 3. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Cycle Date BSA Cisplatin Doxorubicin HD MTX Ifosfamide Etoposide Note 60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day 2.4 gm/m2/day 100mg/m2/day272831323536 (*)39 40  Normal  Sensorineural hearing loss3nd Audiogram (end of treatment)  Normal  Impaired ejection fraction ………………. %* Echocardiogram (end of treatment)*Cardiology consultation for 2nd echocardiogram when cumulative dose of doxorubicin was exceeding 325mg/m2 or 200 mg/m2 in infants** Doxorubicin can be omitted or reduced when cumulative dose of doxorubicin was exceeding 375 mg/m2 orimpaired cardiac function (ejection fraction < 60%)*** Cisplatin can be omitted when cumulative dose of cisplatin was exceeding 480 mg/m2 or evidence ofsensorineural hearing lossOsteosarcoma: Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET] 270

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Drug administrationA. High dose methotrexatePre- and post-hydration is recommended for high dose methotrexate as follows:1. Pre Hydration: Start hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20mL/L at least 24 hours before starting methotrexate infusion, to obtain urine output > 2 ml/kg/hr and urinarypH 7 – 7.5 (suggested volume 125 ml/m2/hour, could be adjusted as appropriate) Ensure urine pH is maintained pH 7 – 7.5 by adjusting sodium bicarbonate if required Other strengths of dextrose/ saline are acceptable2. Leucovorin (Calcium folinate) rescue must be commenced exactly 24 hours after the start of themethotrexate infusion at 15 mg/m2 every 6 hours for 11 doses either intravenously or orally (Folinic acid isavailable orally as 15 mg tablets so a dose of 15 mg or 30 mg should be prescribed) *If serum methotrexate level can be measured, treatment must be continued until methotrexate levelis < 0.1 micromol/L *Methotrexate levels should be checked every 24 hours commencing at 48 hours from the start ofthe methotrexate infusion and continuing until methotrexate level is < 0.1 micromol/L3. Post hydration: Hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20 mL/L(alternative strengths accepted) at a rate suitable to obtain urine output > 2 ml/kg/hr and urinary pH 7 – 7.5(suggested volume 125 ml/m2/h,could be adjusted as appropriate) until methotrexate level < 0.1 micromol/L If serum methotrexate level is not available, o Liver function test and serum creatinine must be measured at 72nd and 120th hours after completion of methotrexate infusion o If AST / ALT > 5 times of upper normal limits or elevated serum creatinine (>1.5 times of baseline serum creatinine), folinic acid must be continued up to 7 days o Hydration (at a rate of 125 ml/m2/) should be maintained for at least 7 days*If MTX level > toxicity alert, increase dose of calcium folinate to (40 x actual MTX conc.) ÷ normal MTX conc(mg/dose)Time MTX toxicity alert Normal MTX conc Calcium folinate dose24 h 20 mmol/L 9 mmol/L As above48 h 2 mmol/L 0.9 mmol/L As above72 h 0.1-0.9 mmol/L < 0.1 mmol/L 10-30 mg IV every 6hIf MTX level at > 72 h is less than 0.1 mol/L, this patient is allowed to discharge.B. High dose Ifosfamide (>1,000 mg/m2)1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/hour at least 2 hours before start the drug,to keep urine output > 3 ml/kg/h2. Check urine specific gravity and start chemotherapy when urine specific gravity < 1.0103. Dilute ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and infuse in 1 hour4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3rd, 6th, 9th hour of Ifosfamide; dilute mesnawith 5%D/W to 20 ml IV drip in 15 minute5. Keep urine output > 2 ml/kg/h at least 24 hour after high dose IfosfamideFurosemide 0.5 mg/kg/dose can be used to increase urine volumeOsteosarcoma: Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET] 271

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Ewing Sarcoma Family of Tumors 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 บัตรประกันสุขภาพ จ่ายตรง อน่ื ๆ (ระบ)ุ .............................................Diagnosis: ……………………………………………………... Staging ………………………….………………………History………………………………………………………………………………………...………………………………………………………………………………………………………………………………………………………………….…………………………………………………...…………………………………………………………………………….Physical examination of affected part (specific site eg. Pelvis, scapula; size of tumor)............................................................................................................................. ........................................................................................................................................................................................................................ ................................................................................................................................... ..........................................................Primary site of tumor……………………………………………………………………………………………….…………................................Pre- treatment investigations.A. Blood date (………/………/………)CBC …………………..…………….…………………………..…………………………………………………………….BUN/Cr …………… Electrolyte……………………………………………………………………………….…….………LFT…………………..…………………………………………………………………………………………………………LDH…………………ALP………………… Ca……………..….…PO4……………….….Uric acid………….…………B. Imaging studyPlain film of primary site: date (………/………/………) …..…………………………………………………………….………………………………………………………………………………………………………………………………….CXR (………/………/………) ……………………….………………………….............................................………….CT/ MRI of primary site (………/………/………) ……………..………………………………………………………….………………………………………………………………………………………………………………………………….CT chest (………/………/………) …….……..…………………………………………….....................…....................………………………………………………………………………………………………………………………………….Whole body bone scan (99 m)Tc-MDP (………/………/………) ….……………….………………………………….EKG (………/………/………) …………….…………………………..…………………………………………………….C. Bone marrow for metastatic work upBMA smear (………/………/………) …………………...………………………………………………………………….BM Biopsy (………/………/………) ……………………..………………………………………………………….…….Ewing Sarcoma Family of Tumors: Data entry form 272

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR]Protocol name ThaiPOG-EWS-13-SRProtocol for localized and metastasis EWSReference Womer RB, West DC, Krailo MD, et al. J Clin Oncol 2012;30:4148-54.Open Date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2 localized EWS  metastatic EWSWk Cycle date BW HT BSA Drug Calculated Dose with BSA VCR 2 mg/ m2 = ............................................................mg CTX 1,200 mg/ m2 = ………...…………… mg with Mesna VDC Doxo 37.5 mg/ m2 /day (x2day) = .................................mg0 1 ...../....../........ day1..................................................................................... day2 …................................................................................ Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….2 2 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........ VCR 2 mg/ m2 = ............................................................mg CTX 1,200 mg/ m2 = ………...…………… mg with Mesna VDC Doxo 37.5 mg/ m2 /day (x2day) = .................................mg4 3 ...../....../........ day1..................................................................................... day2 …................................................................................ Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….6 4 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........ VCR 2 mg/ m2 = ............................................................mg CTX 1,200 mg/ m2 = ………...…………… mg with Mesna VDC Doxo 37.5 mg/ m2 /day (x2day) = .................................mg8 5 ...../....../........ day1..................................................................................... day2 …................................................................................ Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….10 6 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 273

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Wk Cycle date BW HT BSA Drug Calculated Dose with BSA12 Surgery (tumor removal) date of...../....../....... ………………………………………………………………………………………………….  Adequate margin ( no need for radiation)  Inadequate margin (need radiation at primary site)* VCR 2 mg/ m2 = ............................................................mg14 7 ...../....../........ VDC CTX 1,200 mg/ m2 = ………...…………… mg with Mesna With Doxo 37.5 mg/ m2 /day (x2day) = .................................mg *start day1..................................................................................... radiation day2 …................................................................................ Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….16 8 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........ VCR 2 mg/ m2 = ............................................................mg18 9 ...../....../........ CTX 1,200 mg/ m2 = ………...…………… mg with Mesna VDC Doxo 37.5 mg/ m2 /day (x2day) = .................................mg day1..................................................................................... day2 …................................................................................ Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….20 10 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........ VCR 2 mg/ m2 = ............................................................mg22 11 ...../....../........ VC CTX 1,200 mg/ m2 = ……...……………… mg with Mesna Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….24 12 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........ VCR 2 mg/ m2 = ............................................................mg26 13 ...../....../........ VC CTX 1,200 mg/ m2 = ……...……………… mg with Mesna Ifosphamide 1,800mg/ m2 /day Etoposide 100 mg/ m2/day (x5day) =…………….….mg (x5day) =…………….….mg day1……………………...…. day1……………………..….28 14 ...../....../........ IE day2………………………… day2………………………... day3………………………… day3……………………....... day4………………………… day4………………………… day5……………………....... day5……………………........Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 274

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Start chemotherapy every 2 wks when ANC> 750 and platelet > 75000 and after 24 hours of G-CSF doseTotal cumulative dose of Doxorubicin is 375 mg/ m2, consult cardiologist at END of protocol for evaluation cardiacfunctionI: Ifosphamide 1,800 mg a day for 5 days each cycle with Mesna (attached guideline for Mesna andrehydration)E: Etoposide 100 mg/ m2 a day for 5 days each cycleV: Vincristine 2 mg/ m2 (maximum dose 2 mg)D: doxorubicin 37.5 mg/ m2 a day for 2 days each cycleC: Cyclophosphamide 1,200 mg/ m2 with Mesna (attached guideline for Mesna and rehydration)Radiation*: Start at week 14 of protocolLocalized disease: No need for localized and adequate surgical margin (more than 2 cm but recommended 5 cm) BUT Consult radiation oncologist for localized disease WITH inadequate surgical margin (usually 45-55 Gy with conventional fractionation)Metastatic disease: Consult radiation for metastatic site Primary site depend on surgical margin (adequate or inadequate margin)G-CSF 5 microgram per Kg was given after 12 hours of each course of cycle and was to stop whenANC> 750 and Platelet > 75,000Give appropriate anti-emetics drugsEwing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 275

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเดก็ Follow up schedule after complete treatmentPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Date of start of treatment (………/………/………)Date of end of treatment (………/………/………)1. Primary site : AP and lateral plain radiographsEvery 3 months x 2 years,Every 6 months x 3 years,Every 12 months x 5 yearsMRI with gadolinium and/or CT with contrast If abnormal imaging or symptoms2. Chest: CT non-contrastEvery 3-6 months x 2 years,Every 6-12 months x 3 years,Every 12 months x 5 yearsAP and lateral radiographs Every 12 months x 5 years after last CT3. Bone metastases site: AP and lateral radiographsEvery 3 months x 2 years,Every 6 months x 3 years,Every 12 months x 5 yearsMRI with gadolinium and/or CT with contrast If abnormal imaging or symptomsWhole body (99 m) Tc-MDP Bone Scan If abnormal imaging or symptomsAP-anterior posterior; MRI-magnetic resonance imaging; CT-computerized tomography;99 mTc-MDP-99 m technetium methylene disphosphonateEwing Sarcoma Family of Tumors: Follow up schedule after complete treatment 276

Thai Pediatric Oncology Groupชมรมโรคมะเร็งเด็ก Anthracycline record sheetPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Diagnosis........................................................ Treatment protocol.......................................................................... Consult cardiologist for 2D-Echocardiogram when accumulative dose of doxorubicin > 300 mg / m2 or when > 200 mg / m2 in infantDate of Anthracycline used Dose Cumulative dose EKG/Echo mg mg/m2 mg mg/m2Ewing Sarcoma Family of Tumors: Anthracycline record sheet 277

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Guideline for administration of high dose cyclophosphamide/ ifosfamideHigh dose Cyclophosphamide (>1,000 mg/m2) 1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/hr at least 2 hours before start the drug to keep urine output > 3 ml/kg/h 2. Check urine specific gravity and start chemotherapy when urine Sp.Gr. < 1.010 3. Dilute CTX in 5%D/NSS/2 to the final concentration of 10 mg/ml and IV infusion in 1 hr 4. Mesna Uroprotection (total dose = 100% of CTX) at 0, 3, 6, 9 hr of CTX  First dose (25% of CTX): IV drip 15 min before start CTX or drip together with CTX at hr 0  2nd, 3rd dose and 4th dose (25 % of CTX) at hour 3, 6, 9 5. Keep the rate of IV fluid at least 2 x maintenance and urine output > 2 ml/kg/h at least 24 hr after high dose CTX 6. Furosemide 0.5 mg/kg/dose can be used to increase urine volume.High dose Ifosfamide (>1,000 mg/m2) 1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/h at least 2 hours before start the drug to keep urine output > 3 ml/kg/h 2. Check urine specific gravity and start chemotherapy when urine Sp.Gr. < 1.010 3. Dilute Ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and IV infusion in 1 hr 4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3, 6, 9 hr of Ifosfamide  First dose IV drip 15 min before start Ifosfamide or drip together with Ifos at hour 0  2nd, 3rd and 4th dose (25% of Ifosfamide) at hour 3, 6, and 9 5. Keep the rate of IV fluid at least 2 x maintenance and urine output > 2 ml/kg/h at least 24 hr after high dose Ifosfamide 6. Furosemide 0.5 mg/kg/dose can be used to increase urine volumeEwing Sarcoma Family of Tumors: Guideline for administration of high dose cyclophosphamide/ 278ifosfamide

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Rhabdomyosarcoma 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 บัตรประกนั สุขภาพ จ่ายตรง อนื่ ๆ (ระบ)ุ .............................................History Physical examinationPrimary site:  Favorable site  Orbit  Head and neck (excluding parameningeal)  Genitourinary (non-bladder/non-prostate)  Unfavorable  Bladder/Prostate  Extremities  Cranial, parameningeal  Others, please specify……………..…………………………………………..…Size of primary tumor  ≤ 5 cm in diameter  > 5 cm in diameterRegional nodes involvement  N0 (Not clinically involved)  N1 (Clinically involved)  NX (Clinical status unknown)Metastasis  M0 (no metastasis)  M1 (Distant metastasis), please specify …………………………...………….Treatment  Upfront surgery  Upfront chemotherapySurgery: date (………/………/………) ……………………………………………………………………………………………………………………………………………………………………………………………………………………….Histology:  Embryonal RMS  Alveolar RMS  Others, specifyPre- treatment investigationsA. CBC (………/………/………)……..……………………………….…………………………..…………………………………………………………..….B. Imaging studyCT scan (………/………/………) ……………..………………………………………………………………..…….…….CXR PA/lateral (………/………/………) ……………..………………………………………………………………..…..CT chest (………/………/………) ……………………………….....………………………………………………………Bone scan (………/………/………) Result positive……………………………………………. negativeC. Bone marrow for metastatic work upBone marrow (optional) (………/………/………)…………………………………………………………………………Rhabdomyosarcoma: Data entry form 279

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็Pre-treatment staging (STS-COG) 1 2 3 4 Stage Site Size Regional node involvement Metastasis1F Any Any M02U ≤ 5 cm N0 or NX M03U ≤ 5 cm N1 M0 > 5 cm Any M04 Any Any Any M1F: Favorable sites-ตา (orbit) ทางเดินปัสสาวะ (genitourinary tract; ยกเว้นกระเพาะปัสสาวะและตอ่ มลกู หมาก)ศรี ษะและคอ (head and neck; ยกเวน้ parameningeal);U: Unfavorable sites-กระเพาะปสั สาวะ (bladder) ตอ่ มลกู หมาก (prostate) แขนขา (extremities) cranialparameningeal และบรเิ วณอ่ืนๆParamenigeal: base of skull, nesopharynx, paranasal sinus, infratemporal และ pterygopalatine fossaN0: Not clinically involved; N1: Clinically involved; NX: Clinical status unknownM0: No metastasis; M1: Distant metastasisPostoperative Clinical Grouping System (IRS)  I  II  III  IVGroup Extent of disease I A. Localized, completely resected, confined to site of origin B. Localized, completely resected, infiltrated beyond site of origin A. Localized, grossly resected, microscopic residual B. Regional disease, involved lymph nodes, completely resected II C. Regional disease, involved lymph nodes, grossly resected with microscopic residual A. Local or regional grossly visible disease after biopsy only: III B. Grossly visible disease after ≥50% resection of primary tumor IV Distant metastasis present at diagnosisLN: lymph nodes, ดดั แปลงมาจาก Maurer HM 1975Rhabdomyosarcoma Prognostic Risk Group and Treatment Schema LOW, SUBSET 1  LOW, SUBSET 2  INTERMEDIATE  HIGH Risk Group Stage* Group** Histology ProtocolLow, subset 1 1 I-II Embryonal RMS LOW1 1 Embryonal RMS VAC 4 cycles, then VA 4 cycles 2 III (Orbit) Embryonal RMS I-IILow, subset 2 1 III (non-orbit) Embryonal RMS LOW2 3 I-II Embryonal RMS VAC for 45 weeksIntermediate 2-3 III Embryonal RMS INTERMEDIATE 1-3 I-III Alveolar RMS VAC for 39 weeksHigh 4 IV Embryonal RMS HIGH 4 IV Alveolar RMS IVA/CbEV/IVE/VACA: Dactinomycin; C: Cyclophosphamide; Cb: Carboplatin; E: Etoposide; I: Ifosfamide; V: Vincristine ดัดแปลงจาก Malempati S 2012, Breneman JC 2003Rhabdomyosarcoma: Data entry form 280

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Post-treatment evaluationFirst Year after Completion of Therapy1. Physical examination including complete blood count every 3 months.2. Chest radiograph every 3 months.3. Appropriate imaging studies (i.e., CT or MRI of the involved region) every 3-6 months.4. Appropriate studies outlined below.Second and Third Years after Completion of Therapy1. Physical examination including complete blood count every 4 months.2. Chest radiograph every 4 months.3. Appropriate imaging studies every 4-6 months.Fourth Year1. Above studies every 6-12 months.Fifth to Tenth Years after Completion of Therapy1. Annual visit for physical examination and studies outlined below.2. Referral to a survivorship program strongly recommended.Ten Years after Completion of Therapy1. Maintain yearly visit or phone contact.2. Record attainment of puberty and pregnancy.3. Long-term follow-up in a survivorship program strongly recommended.Rhabdomyosarcoma: Post-treatment evaluation 281

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็ก Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1]Protocol name ThaiPOG-RMS-13-LR1Protocol for Low risk, subset 1, rhabdomyosarcomaReference Walterhouse D et al. JCO 2011Open date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Embryonal rhabdomyosarcoma, stage 1 group I/II or III (orbit) M0 Embryonal rhabdomyosarcoma, stage 2 group I/II M0Cycle 1234 Evaluation 5 6 78Week 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22Chemo VVVVVVVVVVVV VVVVVVVVVV AAAA A A AA CCCC - - -- Surgery +Radiotherapy**Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodeswho have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week13**Dactinomycin is omitted during radiotherapyDrug Dosage Total doseV: Vincristine 1.5 mg/m2 /day IV push slowly (maximum dose, 2 mg)A: Dactinomycin* 0.045 mg/kg/day IV push slowly (maximum dose, 2 mg)C: Cyclophosphamide 1.2 gm/m2/dose IV drip in 1 hr x 1 dayRhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1] 282

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Cycle Date BSA Vincristine Dactinomycin Cyclophosphamide Note (1.5 mg/m2/dose) (0.045 mg/kg/day) (1.2 gm/m2)1234SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery: ……….…………………………………………………………………………………………………….Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.)RadiotherapyRadiotherapy date (………/………/………) Total dose (Gy): ……………………………………………….Technique: ………………………………….. Involved field: …………………………………………………. - Embryonal rhabdomyosarcoma group I: ไมต่ อ้ งให้รังสรี กั ษา - Embryonal rhabdomyosarcoma group II, node negative: รงั สีรกั ษาขนาด 36 Gy - Embryonal rhabdomyosarcoma group II, node positive: รงั สีรกั ษาขนาด 41.4 Gy - Embryonal rhabdomyosarcoma group III (orbit only): รงั สีรกั ษาขนาด 45 Gyกลมุ่ ทสี่ ามารถตัดออกได้สมบูรณ์ และ RMS group III ท่บี รเิ วณมดลูกหรอื รังไข่ท่ีไม่มกี ารลุกลามมายงั ตอ่ มน้าเหลอื ง(node negative) ท่สี ามารถผ่าตัดได้สมบูรณท์ ีส่ ัปดาห์ท่ี 13 ไม่มีความจาเปน็ ที่ตอ้ งไดร้ ับรงั สรี กั ษาท่ีสัปดาห์ท่ี 13 ส่วนในกลุ่มทีต่ ้องได้รบั รงั สรี ักษา แนะนาใหเ้ ริม่ ในสัปดาห์ท่ี 13 ของการไดร้ บั ยาเคมีบาบดั โดยตอ้ งงด dactinomycinระหว่างที่ไดร้ ับรังสีรักษาEvaluation 1. CT/ MRI …………………………….(………/………/………) ……………..……………………………..……. 2. Bone scan (………/………/………) ………………………………...…………….…………………………….. 3. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Cycle Date BSA Vincristine Dactinomycin Cyclophosphamide Note (1.5 mg/m2/dose) (0.045 mg/kg/day) (1.2 gm/m2) 5 6 7 8Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1] 283

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเดก็ Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2]Protocol name ThaiPOG-RMS-13-LR2Protocol for Low risk, subset 2, rhabdomyosarcomaReference Raney RB et al. JCO 2011;29:1312-8Open date January 2014Patient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Inclusion criteria Embryonal rhabdomyosarcoma, stage 1 group III (non-orbit) M0 Embryonal rhabdomyosarcoma, stage 3 group I/II M0Cycle 12345678 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23Week VVVVVVVVV - - - VVVVVVVVV - - -Chemo A A A* A A A* A* A CCCCCCC - Radiotherapy Radiotherapy (group II or III) (if indicated)‡Cycle 9 10 11 12 13 14 15 16Week 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45Chemo VVVVVVVVV - - - VVVVVVVVV - A A A* A* A A A A CCC - CCC - Radiotherapy (if indicated)‡*Omit dactinomycin at week 6 in patients beginning RT at week 3, weeks 15 and 18 in patients beginning RT atweek 12, and weeks 30 and 33 in patients beginning RT at week 28‡Patients with vaginal primaries and tumor-involved regional lymph nodes or with non-orbital, stage 1, group IIItumors start RT at week 12. Patients with vaginal primaries and negative nodes start RT at week 28, if repeatbiopsies show persistent viable tumor cells.Drug Age(yrs) Dosage Total doseV: Vincristine < 1 0.025 mg/kg IV push slowly (maximum dose, 2 mg) x 1 day 1-3 0.05 mg/kg IV push slowly (maximum dose, 2 mg) x 1 day > 3 1.5 mg/m2/day IV push slowly (maximum dose, 2.5 mg) x 1 dayA: Dactinomycin* < 1 0.025 mg/kg x 1 day ≥ 1 0.045 mg/kg x 1 dayC: < 1 36 mg/kg IV drip in 1 hr x 1 dayCyclophosphamide 1-3 73 mg/kg IV drip in 1 hr x 1 day(given with mesna) >3 2.2 gm/m2/dose IV drip in 1 hr x 1 dayMesna 550 mg/m2/dose IV slowly push slowly at 0, 3, 6, 9 hr after cyclophosphamide infusionRhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2] 284

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Cycle Date BSA Vincristine Dactinomycin Cyclophosphamide Note123* Radiotherapy or Delayed surgery45 Radiotherapy‡ or Delayed surgery6 **7 **8*Omit dactinomycin at week 6 in patients beginning RT at week 3,**Omit dactinomycin at weeks 15 and 18 in patients beginning RT at week 12‡Patients with vaginal primaries and tumor-involved regional lymph nodes or with non-orbital, stage 1, group IIItumors start RT at week 12.SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery: ……………………………………………………………………………………………………………..Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.)RadiotherapyRadiotherapy date (………/………/………) Total dose (Gy): ……………………………………………….Technique: ………………………………….. Involved field: ………………………………………………….Evaluation 4. CT/ MRI …………………………….(………/………/………) ……………..……………………………..……. 5. Bone scan (………/………/………) ………………………………...…………….…………………………….. 6. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2] 285

Thai Pediatric Oncology Group ชมรมโรคมะเร็งเด็กPatient’s name..................................................................... Sex........................... HN...........................................Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2Cycle Date BSA Vincristine Dactinomycin Cyclophosphamide Note910 Radiotherapy‡ or Delayed surgery11 *12 *13141516*Omit dactinomycin at weeks 30 and 33 in patients beginning RT at week 28‡ Patients with vaginal primaries and negative nodes start RT at week 28, if repeat biopsies show persistentviable tumor cells.SurgerySurgery date (………/………/………) Surgeon ……………..……………………………………….…………Type of surgery: ……………………………………………………………………………………………………………..Surgical margin  Adequate (> 5 cm)  Inadequate (not free margin, margin < 5 cm.)RadiotherapyRadiotherapy date (………/………/………) Total dose (Gy): ……………………………………………….Technique: ………………………………….. Involved field: …………………………………………………. - Embryonal RMS group I: ไมต่ อ้ งให้รังสีรกั ษา - Embryonal RMS group II, node negative: รงั สรี กั ษาขนาด 36 Gy - Embryonal RMS group II, node positive: รังสรี ักษาขนาด 41.4 Gy - Embryonal RMS group III (non-orbit): รงั สีรักษาขนาด 50.4 Gy ในกลุม่ ทีม่ ี residual microscopic/gross residual (group II หรือ III) embryonal RMS ควรไดส้ ปั ดาห์ที่ 3 ยกเวน้ - ผู้ปว่ ย RMS ทต่ี าแหนง่ vulva, uterus, biliary tract และ superficial non-parameningeal head/neck (non- orbital stage 1, group III) ที่สามารถผ่าตดั ในสัปดาห์ที่ 12 ได้ (delayed primary excision) รงั สรี ักษาเรมิ่ หลังผา่ ตัด - ผปู้ ว่ ย RMS ตาแหนง่ ชอ่ งคลอดทม่ี กี ารลุกลามไปตอ่ มน้าเหลือง เรมิ่ รงั สรี ักษาสัปดาห์ที่ 12 - ผู้ปว่ ย RMS ตาแหนง่ ชอ่ งคลอดท่ไี มม่ กี ารลกุ ลามไปตอ่ มน้าเหลอื ง เร่ิมรงั สรี ักษาสัปดาหท์ ่ี 28 ยกเวน้ รายท่ี ได้รบั การตัดชิ้นเน้ือแล้วไม่พบมะเร็งก่อนหรือท่ีสัปดาห์ที่ 28 ไมจ่ าเป็นต้องรบั รังสรี ักษาEvaluation 1. CT/ MRI ……………………………. (………/………/………) ……………..……………………………..…… 2. Bone scan (………/………/………) ………………………………...…………….…………………………….. 3. CXR/CT scan chest (………/………/………) ………………………..……………………………..………….Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2] 286