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Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

EANO/EURACAN

2019: Franceschi et al. EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma PubMed

NCCN

NCCN Guidelines - Pediatric Central Nervous System Cancers

Upfront therapy, older children

COG ACNS0331 Standard Dose CSRT with Reduced Volume Boost to Tumor Bed

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Michalski et al. 2021 (COG ACNS0331)	2004-04-30 to 2014-01-06	Phase 3 (E-de-esc)	COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost	Non-inferior EFS (primary endpoint) EFS60: 82.5% vs 80.5% (HR 0.97, 94% CI 1.32)

Note: this protocol is given in two parts, induction (chemoradiation) followed by maintenance. The induction portion lasts 6 weeks, followed by 4 weeks of rest (weeks 7-10), followed by the maintenance portion which lasts for 58 weeks, consisting of alternating A cycles and B cycles (AAB-AAB-AAB). The non-inferiority comparison was one-sided, with the upper bound reported here.

Ages 3+
All patients must begin therapy within 31 days of surgery.

Induction

Radiotherapy

Craniospinal External beam radiotherapy 2340 cGy in 13 daily fractions
Tumor Bed Boost External beam radiotherapy 3060 cGy in 17 daily fractions

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
- Round vincristine down to the nearest 0.1 mg

6-week course, followed by 4-weeks rest, followed by:

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Lomustine (CCNU) 75 mg/m² PO once on day 1, taken on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- - Pediatric Lomustine Dosing Chart
  - Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- - Dose rounded down to the nearest 0.1 mg
  - Can be given IV push over 1-minute or by infusion via minibag as per institution policy

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day on days 1 & 2
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1 & 8
- - Dose rounded down to the nearest 0.1 mg
  - Can be given IV push over 1-minute or by infusion via minibag as per institution policy

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes once per day on days 1 & 2
- - Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
  - Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion

42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)

References

COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. Epub 2021 Jun 10. link to original article link to PMC article PubMed NCT00085735

COG ACNS0331 Standard Dose CSRT with Standard Volume Boost

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Michalski et al. 2021 (COG ACNS0331)	2004-04-30 to 2014-01-06	Phase 3 (C)	COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost to Tumor Bed	Non-inferior EFS

Ages 3+
All patients must begin therapy within 31 days of surgery.

Induction

Radiotherapy

Craniospinal External beam radiotherapy 2340 cGy in 13 daily fractions
Posterior Fossa Boost External beam radiotherapy 3060 cGy in 17 daily fractions

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
- Round vincristine down to the nearest 0.1 mg

6-week course, followed by 4-weeks rest, followed by:

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Lomustine (CCNU) 75 mg/m² PO once on day 1, taken on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
- - Pediatric Lomustine Dosing Chart
  - Give Lomustine (CCNU) with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1, 8, 15
- - Dose rounded down to the nearest 0.1 mg
  - Can be given IV push over 1-minute or by infusion via minibag as per institution policy

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day on days 1 & 2
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1 & 8
- - Dose rounded down to the nearest 0.1 mg
  - Can be given IV push over 1-minute or by infusion via minibag as per institution policy

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

Mesna (Mesnex) 360 mg/m² IV over 15 to 30 minutes once per day on days 1 & 2
- - Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
  - Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion

42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)

References

COG ACNS0331: Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. Epub 2021 Jun 10. link to original article link to PMC article PubMed NCT00085735

COG ACNS0332 Protocol A

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Leary et al. 2021 (COG ACNS0332)	2007-03 to 2018-09	Phase 3 (C)	COG ACNS0332 Protocol B (with carboplatin)	Did not meet primary endpoint of EFS

Induction

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
- Round vincristine down to the nearest 0.1 mg

Radiotherapy

Craniospinal External beam radiotherapy 1.8000 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26 (3600 cGy in 20 daily fractions)
Posterior Fossa Boost External beam radiotherapy 1.8000 cGy per day on days 29 to 33, 36 to 40, 43 (1980 cGy in 11 daily fractions; cumulative dose of 5580 cGy)
- For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage

6-week course, followed by:

Maintenance

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 60 minutes once on day 1
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
- Round vincristine down to the nearest 0.1 mg
Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day on days 2 & 3, given at least 24 hours after cisplatin on day 2

28-day cycle for 6 cycles; begin each cycle on day 29 and when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours

References

COG ACNS0332: Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol. 2021 Sep 1;7(9):1313-1321. link to original article link to PMC article PubMed NCT00392327

COG ACNS0332 Protocol B

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Leary et al. 2021 (COG ACNS0332)	2007-03 to 2018-09	Phase 3 (E-esc)	COG ACNS0332 Protocol A (no carboplatin)	Did not meet primary endpoint of EFS

Induction

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
- Round vincristine down to the nearest 0.1 mg
- Administer prior to Carboplatin
Carboplatin (Paraplatin) 35 mg/m² IV over 15 minutes once per day, given 1 to 4 hours prior to radiation therapy (Total of 30 doses)
- First dose administered on the first day of radiation therapy
- Should be HELD if radiation treatment is not given
- Since there are 31 fractions of radiation, No carboplatin should be given prior to the final radiation fraction

Radiotherapy

Craniospinal External beam radiotherapy 1.8000 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26 (3600 cGy in 20 daily fractions)
Posterior Fossa Boost External beam radiotherapy 1.8000 cGy per day on days 29 to 33, 36 to 40, 43 (1980 cGy in 11 daily fractions; cumulative dose of 5580 cGy)
- For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage

6-week course, followed by:

Maintenance

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 60 minutes once on day 1
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
- Round vincristine down to the nearest 0.1 mg
Cyclophosphamide (Cytoxan) 1000 mg/m² IV over 60 minutes once per day on days 2 & 3, given at least 24 hours after cisplatin on day 2

28-day cycle for 6 cycles; begin each cycle on day 29 and when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours

References

COG ACNS0332: Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol. 2021 Sep 1;7(9):1313-1321. link to original article link to PMC article PubMed NCT00392327

Upfront therapy, younger children

COG ACNS0334 Protocol A

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (COG ACNS0334)	2007-NR	Phase 3 (C)	COG ACNS0334 Protocol B (HD-MTX)	TBD if different primary endpoint of CR rate

Induction

Chemotherapy

Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15
Etoposide (Vepesid) 2.5 mg/kg (maximum concentration is 0.4 mg/ml) IV over 60 minutes once per day on days 1, 2, 3
- Begin Etoposide (Vepesid) infusion 1 hour before the Cyclophosphamide (Cytoxan) or Cisplatin (Platinol) infusions
Cyclophosphamide (Cytoxan) 60 mg/kg IV over 60 minutes once per day on days 1 & 2, given with hyperhydration and mesna
- Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
Cisplatin (Platinol) 3.5 mg/kg IV over 6 hours once on day 3
- Cisplatin (Platinol) doses may require the use of mannitol to augment hydration and diuresis
- Must reduce urine specific gravity to less than or equal to1.010 prior to starting cisplatin

Supportive therapy

Mesna (Mesnex) 12 mg/kg IV five times per day on days 1 & 2
- Dose 1: Initial bolus dose of may be administered before or at the same time as the cyclophosphamide
- Dose 2: A 3-hour infusion immediately after the cyclophosphamide infusion (Hours 2 - 5)
- Doses 3 to 5: 3 subsequent bolus doses are given at hours 6, 9, 12, or by institutional protocol
- Mesna (Mesnex) may also be given as a 24-hour continuous infusion starting 30 minutes before cyclophosphamide and finishing no sooner than 12 hours after the end of the cyclophosphamide infusion, or by institutional protocol
Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day, starting 24-36 hours after Cisplatin infusion and continue until ANC greater than 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC greater than 2000/μL.

21-day cycle for 3 cycles

Consolidation, autologous HSCT

Chemotherapy

Carboplatin (Paraplatin) 17 mg/kg IV over 2 hours once per day on days 1 & 2
- If corrected GFR is < 100 ml/min/1.73m², the Carboplatin (Paraplatin) dose should be calculated using the modified Calvert formula
Thiotepa (Thioplex) 10 mg/kg IV over 2 hours once per day on days 1 & 2, given immediately after carboplatin administration
- Skincare, frequent bathing, and linen changes during Thiotepa (Thioplex) administration are important and required to avoid chemical skin burns
PBSC on day 4

Supportive therapy

Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day, starting on day 5 (24 hours after infusion of PBSC) and continue until ANC greater than 2000/μL
- If Filgrastim (Neupogen) is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion

28-day cycle for 3 cycles

References

COG ACNS0334: NCT00336024

COG ACNS0334 Protocol B

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (COG ACNS0334)	2007-NR	Phase 3 (E-esc)	COG ACNS0334 Protocol A (no HD-MTX)	TBD if different primary endpoint of CR rate

Induction

Chemotherapy

Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15
High Dose Methotrexate (MTX) 400 mg/kg (maximum dose of 20,000 mg) IV over 4 hours once on day 1
Etoposide (Vepesid) 2.5 mg/kg (maximum concentration is 0.4 mg/ml) IV over 60 minutes once per day on days A, B, C
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Begin Etoposide (Vepesid) infusion 1 hour before the Cyclophosphamide or CIS platin infusions
Cyclophosphamide (Cytoxan) 60 mg/kg IV over 60 minutes once per day on days A & B
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
Cisplatin (Platinol) 3.5 mg/kg IV over 6 hours once on day C
- Day A of chemotherapy begins when the serum Methotrexate (MTX) level is less than 0.1 micromolar
- Cisplatin (Platinol) doses may require use of mannitol to augment hydration and diuresis
- Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour

Supportive therapy

Leucovorin (Folinic acid) 10 mg/m² PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
- Leucovorin (Folinic acid) must be started 24 hours from the beginning of the methotrexate infusion
Mesna (Mesnex) 12 mg/kg IV five times per day on days A & B
- Dose 1: Initial bolus dose may be administered before or at the same time as cyclophosphamide
- Dose 2: A 3 hour infusion immediately after cyclophosphamide infusion
- Dose 3 to 5: 3 subsequent bolus doses given at hours 6, 9, 12 or by institutional protocol
- Mesna (Mesnex) 60 mg/kg/day may also be given as a 24 hour continuous infusion by institutional protocol
- Day A of chemotherapy begins when the serum MTX level is less than 0.1 micromolar
Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC greater than 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC greater than 2000/μL.

21-day cycle for 3 cycles, followed by:

Consolidation, Autologous HSCT

Chemotherapy

Carboplatin (Paraplatin) 17 mg/kg IV over 2 hours given once per day on days 1 & 2
- If corrected GFR is < 100 ml/min/1.73m², the Carboplatin (Paraplatin) dose should be calculated using the modified Calvert formula
Thiotepa (Thioplex) 10 mg/kg IV over 2 hours once per day on days 1 & 2 immediately after carboplatin administration
- Skincare, frequent bathing, and linen changes during Thiotepa (Thioplex) administration are important and required to avoid chemical skin burns
PBSC on day 4

Supportive therapy

Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day starting on day 5 (24 hours after infusion of PBSC) and continued until ANC greater than 2000/μL
- If Filgrastim (Neupogen) is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion

28-day cycle for 3 cycles

References

COG ACNS0334: NCT00336024

Head Start III Protocol D2

Study	Dates of enrollment	Evidence
Dhall et al. 2020 (Head Start III)	2003-05 to 2009-12	Non-randomized

Induction

Chemotherapy, A portion (cycles 1 & 3)

Cisplatin (Platinol) 3.5 mg/kg IV once on day 1
Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Cyclophosphamide (Cytoxan) 55 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 4 mg/kg IV once per day on days 2 & 3
High Dose Methotrexate (MTX) 270 mg/kg IV over 4 hours once on day 3

Supportive therapy, A portion (cycles 1 & 3)

Leucovorin (Folinic acid) 10 mg/m² PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
- Leucovorin (Folinic acid) must be started 24 hours from the beginning of the methotrexate infusion

Chemotherapy, B portion (cycles 2 & 4)

Vincristine (Oncovin) 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
Cyclophosphamide (Cytoxan) 55 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 1.65 mg/kg PO once per day on days 1 to 10
Temozolomide (Temodar) 6.5 mg/kg PO once per day on days 1 to 5

Chemotherapy, C portion (cycle 5)

Cisplatin (Platinol) 3.5 mg/kg IV once on day 1
Cyclophosphamide (Cytoxan) 5 mg/kg IV once per day on days 2 & 3
Etoposide (Vepesid) 4 mg/kg IV once per day on days 2 & 3
High Dose Methotrexate (MTX) 270 mg/kg IV over 4 hours once on day 3

Supportive therapy, C portion (cycle 5)

Leucovorin (Folinic acid) 10 mg/m² PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
- Leucovorin (Folinic acid) must be started 24 hours from the beginning of the methotrexate infusion

15-day cycle for 5 cycles; patients with no evidence of disease (NED) after induction or second look surgery proceed to:

Consolidation

Chemotherapy, myeloablative with autologous stem cell rescue

Carboplatin (Paraplatin) AUC 7 IV once per day on days 1 to 3
Thiotepa (Thioplex) 300 mg/m² IV once per day on days 1 to 3, given immediately after carboplatin administration
Etoposide (Vepesid) 250 mg/m² IV once per day on days 1 to 3

Supportive therapy

Autologous stem cells re-infused on unspecified day

One course

References

Head Start III: Dhall G, O'Neil SH, Ji L, Haley K, Whitaker AM, Nelson MD, Gilles F, Gardner SL, Allen JC, Cornelius AS, Pradhan K, Garvin JH, Olshefski RS, Hukin J, Comito M, Goldman S, Atlas MP, Walter AW, Sands S, Sposto R, Finlay JL. Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Neuro Oncol. 2020 Dec 18;22(12):1862-1872. link to original article link to PMC article PubMed NCT00392327

SJMB-96 Protocol High Risk

Study	Dates of enrollment	Evidence
Gajjar et al. 2006 (SJMB-96)	1996-10 to 2003-05	Non-randomized

Induction

Chemotherapy

Topotecan (Hycamtin) 5.5 mg/m² IV over 4 hours once per day on days 1 to 5
- Day 1 Topotecan (Hycamtin) plasma concentration will be used to adjust the dose (see full protocol?)

Supportive therapy

Filgrastim (Neupogen) 10 mcg/kg SC or IV (per institutional policy) mobilization prior to PBSC harvest
- PBSC harvest after first cycle, or second cycle if first PBSC is inadequate

14-day cycle for 2 cycles

Definitive therapy

Radiotherapy

Craniospinal axis External beam radiotherapy by the following stage-based criteria:
- M₀ or M₁: 3600 cGy in 18 daily fractions
- M₂ or M₃: 36 to 3960 cGy in 18 to 22 daily fractions
  - See protocol for additional details on dose
Posterior fossa External beam radiotherapy 5580 cGy in 31 daily fractions
- Local boost External beam radiotherapy to 5940 cGy in 33 daily fractions at investigator's option for residual tumor measuring > 1.5 cm²

~ 6 week duration, followed in 6 weeks by:

Consolidation

Chemotherapy, High Dose with PBSC support

Cisplatin (Platinol) 75 mg/m² IV over 6 hours once on day -4
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push once per day on days -4 & +6
Cyclophosphamide (Cytoxan) 2000 mg/m² IV over 60 minutes once per day on days -3 & -2

Supportive therapy

Amifostine (Ethyol) 600 mg/m² IV push over 1 minute given 5 minutes prior to cisplatin infusion and 3 hours into cisplatin infusion once on day -4
Mesna (Mesnex) 500 mg/m² IV push 15 minutes prior to cyclophosphamide infusion once per day on days -3 & -2
Mesna (Mesnex) 1500 mg/m² IV continuous infusion on days -3, -2
PBSC Infusion on day 0
Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC greater than 2000/μL for 2 consecutive days.

28-day cycle for 4 cycles

References

SJMB-96: Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820. link to original article PubMed NCT00003211
1. Toxicity analysis: Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118. link to original article PubMed

SJMB-96 Protocol Average Risk

Study	Dates of enrollment	Evidence
Gajjar et al. 2006 (SJMB-96)	1996-10 to 2003-05	Non-randomized

Mobilization

Growth factor therapy

Filgrastim (Neupogen) 10 mcg/kg SC or IV (per institutional policy) mobilization prior to PBSC harvest

Definitive therapy

Radiotherapy

External beam radiotherapy to the craniospinal axis: 2340 cGy in 13 daily fractions
External beam radiotherapy to the posterior fossa: 5580 cGy in 31 daily fractions

~ 6 week duration, followed in 6 weeks by:

Consolidation

Chemotherapy, High Dose with PBSC support

Cisplatin (Platinol) 75 mg/m² IV over 6 hours once on day -4
Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push once per day on days -4 & +6
Cyclophosphamide (Cytoxan) 2000 mg/m² IV over 60 minutes once per day on days -3 & -2

Supportive medications

Amifostine (Ethyol) 600 mg/m² IV push over 1 minute given 5 minutes prior to cisplatin infusion and 3 hours into cisplatin infusion once on day -4
Mesna (Mesnex) 500 mg/m² IV push 15 minutes prior to cyclophosphamide infusion once per day on days -3 & -2
Mesna (Mesnex) 1500 mg/m² IV continuous infusion on days -3 & -2
PBSC Infusion on day 0
Filgrastim (Neupogen) 5 mcg/kg SC or IV (per institutional policy) once per day beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC greater than 2000/μL for 2 consecutive days.

28-day cycle for 4 cycles

References

SJMB-96: Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820. link to original article PubMed NCT00003211
1. Toxicity analysis: Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118. link to original article PubMed

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+[[#top|Back to Top]]
+</div>
+{{#lst:Editorial board transclusions|peds-neuro}}
 ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Medulloblastoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 {| class="wikitable" style="float:right; margin-right: 5px;"
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 {{TOC limit|limit=4}}
 =Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 ==EANO/EURACAN==
-*'''2019:''' Franceschi et al. [https://doi.org/10.1016/S1470-2045(19)30669-2 EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma]
+*'''2019:''' Franceschi et al. [https://doi.org/10.1016/S1470-2045(19)30669-2 EANO–EURACAN clinical practice guideline for diagnosis, treatment, and follow-up of post-pubertal and adult patients with medulloblastoma] [https://www.ncbi.nlm.nih.gov/pubmed/31797797 PubMed]
-=Upfront Therapy Older Children=
-==COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed==
+==NCCN==
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1509 NCCN Guidelines - Pediatric Central Nervous System Cancers]
+=Upfront therapy, older children=
+==COG ACNS0331 Standard Dose CSRT with Reduced Volume Boost to Tumor Bed==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)]
+|2004-04-30 to 2014-01-06
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#COG_ACNS0331_Protocol_for_Standard_Dose_CSRT_with_Standard_Volume_Boost|COG ACNS0331 Protocol for Standard Dose CSRT with Standard Volume Boost]]
+| style="background-color:#eeee01" |Non-inferior EFS (primary endpoint)<br>EFS60: 82.5% vs 80.5%<br>(HR 0.97, 94% CI 1.32)
+|-
+|}
+''Note: this protocol is given in two parts, induction (chemoradiation) followed by maintenance. The induction portion lasts 6 weeks, followed by 4 weeks of rest (weeks 7-10), followed by the maintenance portion which lasts for 58 weeks, consisting of alternating A cycles and B cycles (AAB-AAB-AAB). The non-inferiority comparison was one-sided, with the upper bound reported here.''
 *Ages 3+
 *All patients must begin therapy within 31 days of surgery.
-===Chemoradiotherapy===
+<div class="toccolours" style="background-color:#eeeeee">
-====XRT====
+===Induction===
-*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions
+<div class="toccolours" style="background-color:#b3e2cd">
-*Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions
+====Radiotherapy====
+*Craniospinal [[External beam radiotherapy]] 2340 cGy in 13 daily fractions
+*'''Tumor Bed Boost''' [[External beam radiotherapy]] 3060 cGy in 17 daily fractions
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
 **Round vincristine '''down''' to the nearest 0.1 mg
-'''7-week course'''
+'''6-week course, followed by 4-weeks rest, followed by:'''
-===Maintenance Regimen A===
+</div></div><br>
- Cycles 1, 2, 4, 5, 7, 8
+<div class="toccolours" style="background-color:#eeeeee">
-====Chemotherapy====
+===Maintenance===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
+*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1, taken on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
-**[[Pediatric Lomustine Dosing Chart]]
+***[[Pediatric Lomustine Dosing Chart]]
-**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
+***Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
 *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15
-**Dose rounded '''down''' to the nearest 0.1 mg
+***Dose rounded '''down''' to the nearest 0.1 mg
-**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
+***Can be given IV push over 1-minute or by infusion via minibag as per institution policy
-'''6-week cycle'''
+====Chemotherapy, second portion (cycles 3, 6, 9; "Part B")====
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+***Dose rounded '''down''' to the nearest 0.1 mg
+***Can be given IV push over 1-minute or by infusion via minibag as per institution policy
+====Supportive therapy, second portion (cycles 3, 6, 9; "Part B")====
+*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 1 & 2
+***Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
+***Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion
+'''42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)'''
+</div></div></div>
+===References===
+#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. Epub 2021 Jun 10. [https://doi.org/10.1200/JCO.20.02730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] [https://clinicaltrials.gov/study/NCT00085735 NCT00085735]
-===Maintenance Regimen B===
+==COG ACNS0331 Standard Dose CSRT with Standard Volume Boost==
- Cycles 3, 6, and 9
+<div class="toccolours" style="background-color:#c8a2c8">
-====Chemotherapy====
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2
+!style="width: 20%"|Study
-*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes on Days 1, 2
+!style="width: 20%"|Dates of enrollment
-**Dose is given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
+!style="width: 20%"|Comparator
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-**Dose rounded '''down''' to the nearest 0.1 mg
+|-
-**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ Michalski et al. 2021 (COG ACNS0331)]
-'''6-week course'''
+|2004-04-30 to 2014-01-06
-=====References=====
+| style="background-color:#1a9851" |Phase 3 (C)
-#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735
+|[[#COG_ACNS0331_Protocol_for_Standard_Dose_CSRT_with_Reduced_Volume_Boost_to_Tumor_Bed|COG ACNS0331 Protocol for Standard Dose CSRT with Reduced Volume Boost to Tumor Bed]]
-==COG ACNS0331 Standard Dose CSRT/Standard Volume Boost==
+| style="background-color:#eeee01" |Non-inferior EFS
+|-
+|}
 *Ages 3+
 *All patients must begin therapy within 31 days of surgery.
-===Chemoradiotherapy===
+<div class="toccolours" style="background-color:#eeeeee">
-====XRT====
+===Induction===
-*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions
+<div class="toccolours" style="background-color:#b3e2cd">
-*Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions
+====Radiotherapy====
+*Craniospinal [[External beam radiotherapy]] 2340 cGy in 13 daily fractions
+*'''Posterior Fossa Boost''' [[External beam radiotherapy]] 3060 cGy in 17 daily fractions
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)
 **Round vincristine '''down''' to the nearest 0.1 mg
-'''7-week course'''
+'''6-week course, followed by 4-weeks rest, followed by:'''
-===Maintenance Regimen A===
+</div></div><br>
- Cycles 1, 2, 4, 5, 7, 8
+<div class="toccolours" style="background-color:#eeeeee">
-====Chemotherapy====
+===Maintenance===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
+*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1, taken on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)
-**[[Pediatric Lomustine Dosing Chart]]
+***[[Pediatric Lomustine Dosing Chart]]
-**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
+***Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age
 *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15
-**Dose rounded '''down''' to the nearest 0.1 mg
+***Dose rounded '''down''' to the nearest 0.1 mg
-**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
+***Can be given IV push over 1-minute or by infusion via minibag as per institution policy
-'''6-week cycle'''
+====Chemotherapy, second portion (cycles 3, 6, 9; "Part B")====
-===Maintenance Regimen B===
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 2
- Cycles 3, 6, and 9
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+***Dose rounded '''down''' to the nearest 0.1 mg
+***Can be given IV push over 1-minute or by infusion via minibag as per institution policy
+====Supportive therapy, second portion (cycles 3, 6, 9; "Part B")====
+*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes once per day on days 1 & 2
+***Dose is given at least 15 minutes prior to or at the same time as cyclophosphamide and repeated at 4 and 8 hours post cyclophosphamide
+***Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as cyclophosphamide and finished no sooner than 8 hours after the end of the cyclophosphamide infusion
+'''42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course, then 42-day cycle for 2 cycles, then 28-day course (9 cycles total; AAB-AAB-AAB)'''
+</div></div></div>
+===References===
+#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol. 2021 Aug 20;39(24):2685-2697. Epub 2021 Jun 10. [https://doi.org/10.1200/JCO.20.02730 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8376317/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34110925/ PubMed] [https://clinicaltrials.gov/study/NCT00085735 NCT00085735]
+==COG ACNS0332 Protocol A==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)]
+|2007-03 to 2018-09
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#COG_ACNS0332_Protocol_B|COG ACNS0332 Protocol B (with carboplatin)]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
-*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes on Days 1, 2
-**Dose given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]]
-**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8
-**Dose rounded '''down''' to the nearest 0.1 mg
-**Can be given IV push over 1-minute or by infusion via minibag as per institution policy
-'''6-week course'''
-====References====
-#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735
-==COG ACNS0332 Regimen A==
-===Chemoradiotherapy===
-====XRT====
-*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)
-*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
- For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
-====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
 **Round vincristine '''down''' to the nearest 0.1 mg
-'''6-Week Course'''
+====Radiotherapy====
-===Maintenance Cycle===
+*Craniospinal [[External beam radiotherapy]] 1.8000 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26 (3600 cGy in 20 daily fractions)
-Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles.
+*Posterior Fossa Boost [[External beam radiotherapy]] 1.8000 cGy per day on days 29 to 33, 36 to 40, 43 (1980 cGy in 11 daily fractions; cumulative dose of 5580 cGy)
+**For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
+'''6-week course, followed by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Maintenance===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
 **Round vincristine '''down''' to the nearest 0.1 mg
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2, 3
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 & 3, '''given at least 24 hours after cisplatin on day 2'''
-**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2
+'''28-day cycle for 6 cycles; begin each cycle on day 29 and when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours'''
-'''28-Day Course'''
+</div></div></div>
-=====References=====
+===References===
-#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327
+#'''COG ACNS0332:''' Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol. 2021 Sep 1;7(9):1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 NCT00392327]
-#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327
+==COG ACNS0332 Protocol B==
-==COG ACNS0332 Regimen B==
+<div class="toccolours" style="background-color:#c8a2c8">
-===Chemoradiotherapy===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-====XRT====
+!style="width: 20%"|Study
-*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)
+!style="width: 20%"|Dates of enrollment
-*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
- For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ Leary et al. 2021 (COG ACNS0332)]
+|2007-03 to 2018-09
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#COG_ACNS0332_Protocol_A|COG ACNS0332 Protocol A (no carboplatin)]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15, 22, 29, 36, starting within one week of the start of CSRT
 **Round vincristine '''down''' to the nearest 0.1 mg
 **Administer prior to Carboplatin
-*[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes given daily 1 to 4 hours prior to radiation therapy (Total of 30 doses)
+*[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes once per day, given 1 to 4 hours prior to radiation therapy (Total of 30 doses)
-**[[Carboplatin (Paraplatin)]] first dose administered on the first day of radiation therapy
+**First dose administered on the first day of radiation therapy
-**[[Carboplatin (Paraplatin)]] should be '''HELD''' if radiation treatment is not given
+**Should be '''HELD''' if radiation treatment is not given
-**Since there are 31 fractions of radiation, No [[Carboplatin (Paraplatin)]] should be given prior to the final radiation fraction
+**Since there are 31 fractions of radiation, No carboplatin should be given prior to the final radiation fraction
-'''6-Week Course'''
+====Radiotherapy====
-===Maintenance Cycle===
+*Craniospinal [[External beam radiotherapy]] 1.8000 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26 (3600 cGy in 20 daily fractions)
-Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles.
+*Posterior Fossa Boost [[External beam radiotherapy]] 1.8000 cGy per day on days 29 to 33, 36 to 40, 43 (1980 cGy in 11 daily fractions; cumulative dose of 5580 cGy)
+**For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage
+'''6-week course, followed by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Maintenance===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1 & 8
 **Round vincristine '''down''' to the nearest 0.1 mg
-*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2, 3
+*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 & 3, '''given at least 24 hours after cisplatin on day 2'''
-**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2
+'''28-day cycle for 6 cycles; begin each cycle on day 29 and when ANC at least 750/μL, platelets at least 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours'''
-'''28-Day Course'''
+</div></div></div>
 ===References===
-#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327
+#'''COG ACNS0332:''' Leary SES, Packer RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol. 2021 Sep 1;7(9):1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8299367/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34292305/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 NCT00392327]
-#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327
-=Upfront Therapy Younger Children=
+=Upfront therapy, younger children=
-==COG ACNS0334 Regimen A==
+==COG ACNS0334 Protocol A==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://clinicaltrials.gov/study/NCT00336024 Awaiting publication (COG ACNS0334)]
+|2007-NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#COG_ACNS0334_Protocol_B|COG ACNS0334 Protocol B (HD-MTX)]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of CR rate
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
 ===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-'''3 Cycles'''
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15
-*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum single dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on Day 1, 8, 15
+*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration is 0.4 mg/ml) IV over 60 minutes once per day on days 1, 2, 3
-*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 1 hour once daily on Day 1, 2, 3
 **Begin [[Etoposide (Vepesid)]] infusion 1 hour before the [[Cyclophosphamide (Cytoxan)]] or [[Cisplatin (Platinol)]] infusions
+*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV over 60 minutes once per day on days 1 & 2, given with hyperhydration and mesna
-*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV over 1 hour (Hour 1-2) on Days 1, 2 with hyperhydration and [[Mesna (Mesnex)]]
+**Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
-**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
+*[[Cisplatin (Platinol)]] 3.5 mg/kg IV over 6 hours once on day 3
+**[[Cisplatin (Platinol)]] doses may require the use of mannitol to augment hydration and diuresis
-*[[Mesna (Mesnex)]] 60 mg/kg IV on Days 1, 2, of which the total daily [[Mesna (Mesnex)]] dose is administered in 5 equally divided doses of 12 mg/kg:
+**Must reduce urine specific gravity to less than or equal to1.010 prior to starting cisplatin
-**Dose 1: Initial bolus dose of mesna may be administered before or at the same time as the [[Cyclophosphamide (Cytoxan)]]
+====Supportive therapy====
-**Dose 2: A 3-hour infusion of [[Mesna (Mesnex)]] immediately following the [[Cyclophosphamide (Cytoxan)]] infusion (Hours 2 - 5)
+*[[Mesna (Mesnex)]] 12 mg/kg IV five times per day on days 1 & 2
-**Dose 3-5: 3 subsequent [[Mesna (Mesnex)]] bolus doses are given at hours 6, 9, 12, or by institutional protocol
+**Dose 1: Initial bolus dose of may be administered before or at the same time as the cyclophosphamide
+**Dose 2: A 3-hour infusion immediately after the cyclophosphamide infusion (Hours 2 - 5)
+**Doses 3 to 5: 3 subsequent bolus doses are given at hours 6, 9, 12, or by institutional protocol
 **[[Mesna (Mesnex)]] may also be given as a 24-hour continuous infusion starting 30 minutes before cyclophosphamide and finishing no sooner than 12 hours after the end of the cyclophosphamide infusion, or by institutional protocol
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day, starting 24-36 hours after Cisplatin infusion and continue until ANC greater than 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC greater than 2000/μL.
+'''21-day cycle for 3 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Cisplatin (Platinol)]] 3.5 mg/kg IV infusion over 6 hours on Day 3
+===Consolidation, autologous HSCT===
-**[[Cisplatin (Platinol)]] doses may require the use of mannitol to augment hydration and diuresis
+<div class="toccolours" style="background-color:#b3e2cd">
-**Must reduce urine specific gravity to ≤1.010 prior to starting of [[Cisplatin (Platinol)]
-*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting 24-36 hours after Cisplatin infusion and continue until ANC > 1000/μL then increase to 10 μg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL.
-'''21 Day Course'''
-===Consolidation===
 ====Chemotherapy====
-'''3 Cycles'''
+*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours once per day on days 1 & 2
-*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given daily on Days 1 & 2
 ** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, the [[Carboplatin (Paraplatin)]] dose should be calculated using the modified Calvert formula
+*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once per day on days 1 & 2, given immediately after carboplatin administration
-*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once daily on Days 1 & 2 immediately following [[Carboplatin (Paraplatin)]] administration
 ** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns
+*PBSC on day 4
+====Supportive therapy====
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day, starting on day 5 (24 hours after infusion of PBSC) and continue until ANC greater than 2000/μL
+**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
+'''28-day cycle for 3 cycles'''
+</div></div></div>
+===References===
+#'''COG ACNS0334:''' [https://clinicaltrials.gov/study/NCT00336024 NCT00336024]
-*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL
+==COG ACNS0334 Protocol B==
-**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
+<div class="toccolours" style="background-color:#c8a2c8">
-'''28-Day Course'''
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-=====References=====
+!style="width: 20%"|Study
-#'''COG ACNS0334:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024
+!style="width: 20%"|Dates of enrollment
-==COG ACNS0334 Regimen B==
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://clinicaltrials.gov/study/NCT00336024 Awaiting publication (COG ACNS0334)]
+|2007-NR
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#COG_ACNS0334_Protocol_A|COG ACNS0334 Protocol A (no HD-MTX)]]
+| style="background-color:#d3d3d3" |TBD if different primary endpoint of CR rate
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
 ===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-'''3 Cycles'''
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute or IV infusion once per day on days 1, 8, 15
-*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum single dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15
+*High Dose [[Methotrexate (MTX)]] 400 mg/kg (maximum dose of 20,000 mg) IV over 4 hours once on day 1
-*High Dose [[Methotrexate (MTX)]] 400 mg/kg (20 gram maximum) IV over 4 hours on day 1
+*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration is 0.4 mg/ml) IV over 60 minutes once per day on days A, B, C
-*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum [[Methotrexate (MTX)]] levels are less than 0.1 micromolar
-**[[Folinic acid (Leucovorin)]] must be started 24 hours from the beginning of the [[Methotrexate (MTX)]] infusion
-*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 1 hour once daily on days A, B, C
 **Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar
 **Begin [[Etoposide (Vepesid)]] infusion 1 hour before the Cyclophosphamide or CIS platin infusions
-*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day over 1 hour on days A, B
+*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV over 60 minutes once per day on days A & B
 **Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar
-**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
+**Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
-*[[Mesna (Mesnex)]] 12 mg/kg IV on days A, B as described below:
+*[[Cisplatin (Platinol)]] 3.5 mg/kg IV over 6 hours once on day C
-**Dose 1:Initial bolus dose of [[Mesna (Mesnex)]] may be administered before or at the same time as the [[Cyclophosphamide (Cytoxan)]]
-**Dose 2:A 3 hour infusion of [[Mesna (Mesnex)]] immediately following the [[Cyclophosphamide (Cytoxan)]] infusion
-**Dose 3 to 5: 3 Subsequent [[Mesna (Mesnex)]] bolus doses given at hours 6, 9, 12 or by institutional protocol
-**[[Mesna (Mesnex)]] 60 mg/kg/day may also be given as a 24 hour continuous infusion by institutional protocol
-**Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar
-*[[Cisplatin (Platinol)]] 3.5 mg/kg IV infusion over 6 hours on day C
 **Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar
 **[[Cisplatin (Platinol)]] doses may require use of mannitol to augment hydration and diuresis
-**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
+**Must reduce urine specific gravity to less than or equal to 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour
-*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC > 1000/μL then increase to 10 μg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC > 2000/μL.
+====Supportive therapy====
-'''21 Day Course'''
+*[[Leucovorin (Folinic acid)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
-===Consolidation===
+**[[Leucovorin (Folinic acid)]] must be started 24 hours from the beginning of the methotrexate infusion
+*[[Mesna (Mesnex)]] 12 mg/kg IV five times per day on days A & B
+**Dose 1: Initial bolus dose may be administered before or at the same time as cyclophosphamide
+**Dose 2: A 3 hour infusion immediately after cyclophosphamide infusion
+**Dose 3 to 5: 3 subsequent bolus doses given at hours 6, 9, 12 or by institutional protocol
+**[[Mesna (Mesnex)]] 60 mg/kg/day may also be given as a 24 hour continuous infusion by institutional protocol
+**Day A of chemotherapy begins when the serum MTX level is less than 0.1 micromolar
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day starting on day D (24-36 hours after Cisplatin infusion) and continue until ANC greater than 1000/μL then increase to 10 mcg/kg and plan for harvest 2 days later. If PBSC harvest after the first cycle is insufficient, then harvests may occur after the second (and third if required) cycle. If PBSC harvest is not planned, continue until ANC greater than 2000/μL.
+'''21-day cycle for 3 cycles, followed by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Consolidation, Autologous HSCT===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-'''3 Cycles'''
+*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given once per day on days 1 & 2
-*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given daily on Days 1 & 2
 ** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, the [[Carboplatin (Paraplatin)]] dose should be calculated using the modified Calvert formula
+*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once per day on days 1 & 2 immediately after carboplatin administration
-*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once daily on Days 1 & 2 immediately following [[Carboplatin (Paraplatin)]] administration
 ** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns
+*PBSC on day 4
+====Supportive therapy====
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day starting on day 5 (24 hours after infusion of PBSC) and continued until ANC greater than 2000/μL
+**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
+'''28-day cycle for 3 cycles'''
+</div></div></div>
+===References===
+#'''COG ACNS0334:''' [https://clinicaltrials.gov/study/NCT00336024 NCT00336024]
-*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL
+==Head Start III Protocol D2==
-**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion
+<div class="toccolours" style="background-color:#c8a2c8">
-'''28-Day Cycle'''
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-=====References=====
+!style="width: 33%"|Study
-#'''COG ACNS0334:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024
+!style="width: 33%"|Dates of enrollment
-==Head Start III Regimen D2==
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-===Induction Cycles 1 & 3===
+|-
-====Chemotherapy====
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ Dhall et al. 2020 (Head Start III)]
+|2003-05 to 2009-12
+| style="background-color:#91cf61" |Non-randomized
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, A portion (cycles 1 & 3)====
 *[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1
-*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once on days 1, 8, & 15
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
-*[[Cyclophosphamide (Cytoxan)]] 55 mg/kg IV once on days 2 & 3
+*[[Cyclophosphamide (Cytoxan)]] 55 mg/kg IV once per day on days 2 & 3
-*[[Etoposide (Vepesid)]] 4 mg/kg IV once daily on days 2 & 3
+*[[Etoposide (Vepesid)]] 4 mg/kg IV once per day on days 2 & 3
 *High Dose [[Methotrexate (MTX)]] 270 mg/kg IV over 4 hours once on day 3
-*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum [[Methotrexate (MTX)]] levels are less than 0.1 micromolar
+====Supportive therapy, A portion (cycles 1 & 3)====
-**[[Folinic acid (Leucovorin)]] must be started 24 hours from the beginning of the [[Methotrexate (MTX)]] infusion
+*[[Leucovorin (Folinic acid)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
-'''15 day course'''
+**[[Leucovorin (Folinic acid)]] must be started 24 hours from the beginning of the methotrexate infusion
-===Induction Cycles 2 & 4===
+====Chemotherapy, B portion (cycles 2 & 4)====
-====Chemotherapy====
+*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once per day on days 1, 8, 15
-*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum dose of 2 mg) IV once on days 1, 8, & 15
+*[[Cyclophosphamide (Cytoxan)]] 55 mg/kg IV once per day on days 2 & 3
-*[[Cyclophosphamide (Cytoxan)]] 55 mg/kg IV once on days 2 & 3
+*[[Etoposide (Vepesid)]] 1.65 mg/kg PO once per day on days 1 to 10
-*[[Etoposide (Vepesid)]] 1.65 mg/kg PO once daily on Day 1 to 10
 *[[Temozolomide (Temodar)]] 6.5 mg/kg PO once per day on days 1 to 5
-'''15 day course'''
+====Chemotherapy, C portion (cycle 5)====
-===Induction Cycle 5===
-====Chemotherapy====
 *[[Cisplatin (Platinol)]] 3.5 mg/kg IV once on day 1
-*[[Cyclophosphamide (Cytoxan)]] 55 mg/kg IV once on days 2 & 3
+*[[Cyclophosphamide (Cytoxan)]] 5 mg/kg IV once per day on days 2 & 3
-*[[Etoposide (Vepesid)]] 4 mg/kg IV once daily on days 2 & 3
+*[[Etoposide (Vepesid)]] 4 mg/kg IV once per day on days 2 & 3
 *High Dose [[Methotrexate (MTX)]] 270 mg/kg IV over 4 hours once on day 3
-*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum [[Methotrexate (MTX)]] levels are less than 0.1 micromolar
+====Supportive therapy, C portion (cycle 5)====
-**[[Folinic acid (Leucovorin)]] must be started 24 hours from the beginning of the [[Methotrexate (MTX)]] infusion
+*[[Leucovorin (Folinic acid)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum methotrexate levels are less than 0.1 micromolar
-'''15 day course'''
+**[[Leucovorin (Folinic acid)]] must be started 24 hours from the beginning of the methotrexate infusion
-===Myeloablative Chemotherapy with AuHCR===
+'''15-day cycle for 5 cycles; patients with no evidence of disease (NED) after induction or second look surgery proceed to:'''
-*Patients with no evidence of disease (NED) after induction or second look surgery.
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Consolidation===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, myeloablative with autologous stem cell rescue====
+*[[Carboplatin (Paraplatin)]] AUC 7 IV once per day on days 1 to 3
+*[[Thiotepa (Thioplex)]] 300 mg/m<sup>2</sup> IV once per day on days 1 to 3, given immediately after carboplatin administration
+*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 3
+====Supportive therapy====
+*[[Autologous stem cells]] re-infused on unspecified day
+'''One course'''
+</div></div></div>
+===References===
+#'''Head Start III:''' Dhall G, O'Neil SH, Ji L, Haley K, Whitaker AM, Nelson MD, Gilles F, Gardner SL, Allen JC, Cornelius AS, Pradhan K, Garvin JH, Olshefski RS, Hukin J, Comito M, Goldman S, Atlas MP, Walter AW, Sands S, Sposto R, Finlay JL. Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Neuro Oncol. 2020 Dec 18;22(12):1862-1872. [https://doi.org/10.1093/neuonc/noaa102 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32304218/ PubMed] [https://clinicaltrials.gov/study/NCT00392327 NCT00392327]
+==SJMB-96 Protocol High Risk==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(06)70867-1 Gajjar et al. 2006 (SJMB-96)]
+|1996-10 to 2003-05
+| style="background-color:#91cf61" |Non-randomized
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Induction===
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC of 7/day once daily on days 1 to 3
+*[[Topotecan (Hycamtin)]] 5.5 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 5
-*[[Thiotepa (Thioplex)]] 300 mg/m<sup>2</sup> IV once daily on Days 1 to 3 immediately following [[Carboplatin (Paraplatin)]] administration
+**Day 1 [[Topotecan (Hycamtin)]] plasma concentration will be used to adjust the dose (see full protocol?)
-*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV once daily on Day 1 to 3
+====Supportive therapy====
-'''3 Day Course'''
+*[[Filgrastim (Neupogen)]] 10 mcg/kg SC or IV (per institutional policy) mobilization prior to PBSC harvest
-=====References=====
+**PBSC harvest after first cycle, or second cycle if first PBSC is inadequate
-#'''Head Start III:''' Dhall G, O'Neil SH, Ji L, Haley K, Whitaker AM, Nelson MD, Gilles F, Gardner SL, Allen JC, Cornelius AS, Pradhan K, Garvin JH, Olshefski RS, Hukin J, Comito M, Goldman S, Atlas MP, Walter AW, Sands S, Sposto R, Finlay JL. Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial. Neuro-Oncology 2020 Apr 18: 22(12);1862-1872 [https://doi.org/10.1093/neuonc/noaa102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32304218/ link to PubMed] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746930/ link to PMC article] NCT00392327
+'''14-day cycle for 2 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Definitive therapy===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*Craniospinal axis [[External beam radiotherapy]] by the following stage-based criteria:
+**M<sub>0</sub> or M<sub>1</sub>: 3600 cGy in 18 daily fractions
+**M<sub>2</sub> or M<sub>3</sub>: 36 to 3960 cGy in 18 to 22 daily fractions
+***See protocol for additional details on dose
+*Posterior fossa [[External beam radiotherapy]] 5580 cGy in 31 daily fractions
+**Local boost [[External beam radiotherapy]] to 5940 cGy in 33 daily fractions at investigator's option for residual tumor measuring > 1.5 cm<sup>2</sup>
+'''~ 6 week duration, followed in 6 weeks by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Consolidation===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, High Dose with PBSC support====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 6 hours once on day -4
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once per day on days -4 & +6
+*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV over 60 minutes once per day on days -3 & -2
+====Supportive therapy====
+*[[Amifostine (Ethyol)]] 600 mg/m<sup>2</sup> IV push over 1 minute given 5 minutes prior to cisplatin infusion and 3 hours into cisplatin infusion once on day -4
+*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV push 15 minutes prior to cyclophosphamide infusion once per day on days -3 & -2
+*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion on days -3, -2
+*PBSC Infusion on day 0
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC greater than 2000/μL for 2 consecutive days.
+'''28-day cycle for 4 cycles'''
+</div></div></div>
+===References===
+#'''SJMB-96:''' Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820. [https://doi.org/10.1016/S1470-2045(06)70867-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17012043/ PubMed] [https://clinicaltrials.gov/study/NCT00003211 NCT00003211]
+##'''Toxicity analysis:''' Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118. [https://doi.org/10.1200/JCO.2008.13.5293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18309946/ PubMed]
+==SJMB-96 Protocol Average Risk==
+<div class="toccolours" style="background-color:#c8a2c8">
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(06)70867-1 Gajjar et al. 2006 (SJMB-96)]
+|1996-10 to 2003-05
+| style="background-color:#91cf61" |Non-randomized
+|-
+|}
+<div class="toccolours" style="background-color:#eeeeee">
+===Mobilization===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Growth factor therapy====
+*[[Filgrastim (Neupogen)]] 10 mcg/kg SC or IV (per institutional policy) mobilization prior to PBSC harvest
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Definitive therapy===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*[[External beam radiotherapy]] to the craniospinal axis: 2340 cGy in 13 daily fractions
+*[[External beam radiotherapy]] to the posterior fossa: 5580 cGy in 31 daily fractions
+'''~ 6 week duration, followed in 6 weeks by:'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Consolidation===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, High Dose with PBSC support====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 6 hours once on day -4
+*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once per day on days -4 & +6
+*[[Cyclophosphamide (Cytoxan)]] 2000 mg/m<sup>2</sup> IV over 60 minutes once per day on days -3 & -2
+====Supportive medications====
+*[[Amifostine (Ethyol)]] 600 mg/m<sup>2</sup> IV push over 1 minute given 5 minutes prior to cisplatin infusion and 3 hours into cisplatin infusion once on day -4
+*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV push 15 minutes prior to cyclophosphamide infusion once per day on days -3 & -2
+*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion on days -3 & -2
+*PBSC Infusion on day 0
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC or IV (per institutional policy) once per day beginning on day 1 (24-36 hours after PBSC reinfusion) and continue for at least 7 days or continue until ANC greater than 2000/μL for 2 consecutive days.
+'''28-day cycle for 4 cycles'''
+</div></div></div>
+===References===
+#'''SJMB-96:''' Gajjar A, Chintagumpala M, Ashley D, Kellie S, Kun LE, Merchant TE, Woo S, Wheeler G, Ahern V, Krasin MJ, Fouladi M, Broniscer A, Krance R, Hale GA, Stewart CF, Dauser R, Sanford RA, Fuller C, Lau C, Boyett JM, Wallace D, Gilbertson RJ. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006 Oct;7(10):813-820. [https://doi.org/10.1016/S1470-2045(06)70867-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17012043/ PubMed] [https://clinicaltrials.gov/study/NCT00003211 NCT00003211]
+##'''Toxicity analysis:''' Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008 Mar;26(7):1112-1118. [https://doi.org/10.1200/JCO.2008.13.5293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18309946/ PubMed]
 [[Category:Medulloblastoma regimens]]
 [[Category:Disease-specific pages]]
 [[Category:Pediatric neurologic neoplasms]]

Difference between revisions of "Medulloblastoma"

Latest revision as of 12:10, 23 June 2024

Guidelines

EANO/EURACAN

NCCN

Upfront therapy, older children

COG ACNS0331 Standard Dose CSRT with Reduced Volume Boost to Tumor Bed

Induction

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

References

COG ACNS0331 Standard Dose CSRT with Standard Volume Boost

Induction

Radiotherapy

Chemotherapy

Maintenance

Chemotherapy, first portion (cycles 1, 2, 4, 5, 7, 8; "Part A")

Chemotherapy, second portion (cycles 3, 6, 9; "Part B")

Supportive therapy, second portion (cycles 3, 6, 9; "Part B")

References

COG ACNS0332 Protocol A

Induction

Chemotherapy

Radiotherapy

Maintenance

Chemotherapy

References

COG ACNS0332 Protocol B

Induction

Chemotherapy

Radiotherapy

Maintenance

Chemotherapy

References

Upfront therapy, younger children

COG ACNS0334 Protocol A

Induction

Chemotherapy

Supportive therapy

Consolidation, autologous HSCT

Chemotherapy

Supportive therapy

References

COG ACNS0334 Protocol B

Induction

Chemotherapy

Supportive therapy

Consolidation, Autologous HSCT

Chemotherapy

Supportive therapy

References

Head Start III Protocol D2

Induction

Chemotherapy, A portion (cycles 1 & 3)

Supportive therapy, A portion (cycles 1 & 3)

Chemotherapy, B portion (cycles 2 & 4)

Chemotherapy, C portion (cycle 5)

Supportive therapy, C portion (cycle 5)

Consolidation

Chemotherapy, myeloablative with autologous stem cell rescue

Supportive therapy

References

SJMB-96 Protocol High Risk

Induction

Chemotherapy

Supportive therapy

Definitive therapy

Radiotherapy

Consolidation

Chemotherapy, High Dose with PBSC support

Supportive therapy

References

SJMB-96 Protocol Average Risk

Mobilization

Growth factor therapy

Definitive therapy