Difference between revisions of "Medulloblastoma"
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''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!'' | ''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!'' | ||
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{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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− | + | =COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed= | |
− | = | ||
*Ages 3+ | *Ages 3+ | ||
*All patients must begin therapy within 31 days of surgery. | *All patients must begin therapy within 31 days of surgery. | ||
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*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | *Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions | ||
*Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions. | *Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions. | ||
− | |||
===Chemotherapy=== | ===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, and 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 (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins). |
− | **Round vincristine '''down''' to the nearest 0.1 mg. | + | **Round vincristine '''down''' to the nearest 0.1 mg. |
− | '''7-week course''' | + | '''7-week course''' |
====References==== | ====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 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 | ||
− | |||
==Maintenance Regimen A== | ==Maintenance Regimen A== | ||
Cycles 1, 2, 4, 5, 7, 8 | Cycles 1, 2, 4, 5, 7, 8 | ||
===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 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. | ||
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**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''' | '''6-week cycle''' | ||
− | |||
====References==== | ====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 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 | ||
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===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. | ||
− | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 2 | + | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 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)]]. | **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 15-30 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. | **Can be given via continuous infusion starting 15-30 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, and 8. | + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, and 8. |
− | **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 course''' | '''6-week course''' | ||
− | |||
====References==== | ====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 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 Standard Dose CSRT/Standard Volume Boost= | |
− | = | ||
*Ages 3+ | *Ages 3+ | ||
*All patients must begin therapy within 31 days of surgery. | *All patients must begin therapy within 31 days of surgery. | ||
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*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions. | *Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions. | ||
*Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions. | *Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions. | ||
− | |||
===Chemotherapy=== | ===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, and 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 (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins). |
− | **Round vincristine '''down''' to the nearest 0.1 mg. | + | **Round vincristine '''down''' to the nearest 0.1 mg. |
− | '''7-week course''' | + | '''7-week course''' |
====References==== | ====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 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 | ||
− | |||
==Maintenance Regimen A== | ==Maintenance Regimen A== | ||
Cycles 1, 2, 4, 5, 7, 8 | Cycles 1, 2, 4, 5, 7, 8 | ||
===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 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. | ||
Line 85: | Line 73: | ||
**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''' | '''6-week cycle''' | ||
− | |||
====References==== | ====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 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 | ||
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===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. | ||
− | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 2 | + | *[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 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)]]. | **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 15-30 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. | **Can be given via continuous infusion starting 15-30 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, and 8. | + | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, and 8. |
− | **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 course''' | '''6-week course''' | ||
− | |||
====References==== | ====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 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== | ==Chemoradiotherapy== | ||
===XRT=== | ===XRT=== | ||
Line 115: | Line 98: | ||
For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. | For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. | ||
===Chemotherapy=== | ===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, and 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 (per institution) once on day 1, 8, 15, 22, 29, and 36 (Once a week starting within one week of the start of CSRT). |
− | **Round vincristine '''down''' to the nearest 0.1 mg. | + | **Round vincristine '''down''' to the nearest 0.1 mg. |
− | |||
'''6-Week Course''' | '''6-Week Course''' | ||
− | |||
===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:''' 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, 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:''' 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 | ||
− | |||
==Maintenance Cycle== | ==Maintenance Cycle== | ||
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. | 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. | ||
===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[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 and 8. | + | *[[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 and 8. |
**Round vincristine '''down''' to the nearest 0.1 mg. | **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 and 3. | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2 and 3. | ||
**[[Cyclophosphamide (Cytoxan)]] should be 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 Course''' | '''28-Day Course''' | ||
− | |||
===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:''' 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, 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:''' 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 Regimen B= | |
− | = | ||
==Chemoradiotherapy== | ==Chemoradiotherapy== | ||
===XRT=== | ===XRT=== | ||
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For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. | For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. | ||
===Chemotherapy=== | ===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, and 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 (per institution) once on day 1, 8, 15, 22, 29, and 36 (Once a week starting within one week of the start of CSRT). |
− | **Round vincristine '''down''' to the nearest 0.1 mg. | + | **Round vincristine '''down''' to the nearest 0.1 mg. |
**Administer prior to Carboplatin | **Administer prior to Carboplatin | ||
− | *[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes given daily 1 - 4 hours prior to radiation therapy (Total of 30 doses). | + | *[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes given daily 1 - 4 hours prior to radiation therapy (Total of 30 doses). |
− | **[[Carboplatin (Paraplatin)]] first dose administered on the first day of radiation therapy. | + | **[[Carboplatin (Paraplatin)]] first dose administered on the first day of radiation therapy. |
**[[Carboplatin (Paraplatin)]] should be '''HELD''' if radiation treatment is not given. | **[[Carboplatin (Paraplatin)]] 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 (Paraplatin)]] should be given prior to the final radiation fraction. | ||
− | |||
'''6-Week Course''' | '''6-Week Course''' | ||
− | |||
#'''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:''' 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, 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:''' 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 | ||
− | |||
==Maintenance Cycle== | ==Maintenance Cycle== | ||
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. | 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. | ||
===Chemotherapy=== | ===Chemotherapy=== | ||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[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 and 8. | + | *[[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 and 8. |
**Round vincristine '''down''' to the nearest 0.1 mg. | **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 and 3. | *[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2 and 3. | ||
**[[Cyclophosphamide (Cytoxan)]] should be 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 Course''' | '''28-Day Course''' | ||
− | |||
===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:''' 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, 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:''' 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 | ||
− | |||
=Adjuvant therapy= | =Adjuvant therapy= | ||
− | |||
==Carboplatin, Cyclophosphamide, Etoposide, Methotrexate, Vincristine {{#subobject:ea894c|Regimen=1}}== | ==Carboplatin, Cyclophosphamide, Etoposide, Methotrexate, Vincristine {{#subobject:ea894c|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
Line 182: | Line 152: | ||
|} | |} | ||
===Regimen {{#subobject:9134b2|Variant=1}}=== | ===Regimen {{#subobject:9134b2|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
!style="width: 25%"|Study | !style="width: 25%"|Study | ||
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
Line 198: | Line 168: | ||
*[[Methotrexate (MTX)]] | *[[Methotrexate (MTX)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | |||
===References=== | ===References=== | ||
# Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. [https://www.nejm.org/doi/10.1056/NEJMoa042176 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758008 PubMed] | # Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. [https://www.nejm.org/doi/10.1056/NEJMoa042176 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758008 PubMed] | ||
− | |||
==Cisplatin, Lomustine, Vincristine {{#subobject:3d292d|Regimen=1}}== | ==Cisplatin, Lomustine, Vincristine {{#subobject:3d292d|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
Line 208: | Line 176: | ||
|} | |} | ||
===Regimen {{#subobject:2067d9|Variant=1}}=== | ===Regimen {{#subobject:2067d9|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
!style="width: 20%"|Years of enrollment | !style="width: 20%"|Years of enrollment | ||
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*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 0 | *[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 0 | ||
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 7, 14 | *[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 7, 14 | ||
− | |||
'''8 cycles (see note)''' | '''8 cycles (see note)''' | ||
− | |||
===References=== | ===References=== | ||
# '''COG A9961:''' Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. [https://doi.org/10.1200/JCO.2006.06.4980 link to original article] '''contains partially verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16943538 PubMed] NCT00002875 | # '''COG A9961:''' Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. [https://doi.org/10.1200/JCO.2006.06.4980 link to original article] '''contains partially verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16943538 PubMed] NCT00002875 | ||
− | |||
==Cyclophosphamide & Vincristine/Cisplatin & Etoposide {{#subobject:852402|Regimen=1}}== | ==Cyclophosphamide & Vincristine/Cisplatin & Etoposide {{#subobject:852402|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
Line 241: | Line 206: | ||
|} | |} | ||
===Protocol {{#subobject:1a3d99|Variant=1}}=== | ===Protocol {{#subobject:1a3d99|Variant=1}}=== | ||
− | {| class="wikitable" style="width: 40%; text-align:center;" | + | {| class="wikitable" style="width: 40%; text-align:center;" |
!style="width: 25%"|Study | !style="width: 25%"|Study | ||
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
Line 255: | Line 220: | ||
*[[Cyclophosphamide (Cytoxan)]] | *[[Cyclophosphamide (Cytoxan)]] | ||
*[[Vincristine (Oncovin)]] | *[[Vincristine (Oncovin)]] | ||
− | |||
'''28-day cycle for 2 cycles, alternating with part 2''' | '''28-day cycle for 2 cycles, alternating with part 2''' | ||
− | |||
====Chemotherapy, part 2==== | ====Chemotherapy, part 2==== | ||
*[[Cisplatin (Platinol)]] | *[[Cisplatin (Platinol)]] | ||
*[[Etoposide (Vepesid)]] | *[[Etoposide (Vepesid)]] | ||
− | |||
'''28-day cycle for 1 cycle, alternating with part 1''' | '''28-day cycle for 1 cycle, alternating with part 1''' | ||
− | |||
===References=== | ===References=== | ||
# Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. [https://www.nejm.org/doi/10.1056/NEJM199306173282401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8388548 PubMed] | # Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. [https://www.nejm.org/doi/10.1056/NEJM199306173282401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8388548 PubMed] | ||
− | |||
==VCP {{#subobject:3dy31n|Regimen=1}}== | ==VCP {{#subobject:3dy31n|Regimen=1}}== | ||
{| class="wikitable" style="float:right; margin-left: 5px;" | {| class="wikitable" style="float:right; margin-left: 5px;" | ||
Line 274: | Line 234: | ||
VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rednisone | VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rednisone | ||
===Regimen {{#subobject:ytacgn|Variant=1}}=== | ===Regimen {{#subobject:ytacgn|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: 100%; text-align:center;" | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
!style="width: 20%"|Years of enrollment | !style="width: 20%"|Years of enrollment | ||
Line 294: | Line 254: | ||
*[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> IV once on day 1 | *[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14 | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14 | ||
− | |||
'''6-week cycle for 8 cycles''' | '''6-week cycle for 8 cycles''' | ||
− | |||
===References=== | ===References=== | ||
#'''CCG-921:''' Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. [https://doi.org/10.1200/jco.1999.17.3.832 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10071274/ PubMed] | #'''CCG-921:''' Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. [https://doi.org/10.1200/jco.1999.17.3.832 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10071274/ PubMed] | ||
− | |||
[[Category:Medulloblastoma regimens]] | [[Category:Medulloblastoma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Pediatric neurologic neoplasms]] | [[Category:Pediatric neurologic neoplasms]] |
Revision as of 05:31, 4 February 2022
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COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Chemoradiotherapy
XRT
- Craniospinal External beam radiotherapy 23.4 Gy in 13 daily fractions
- Tumor Bed Boost External beam radiotherapy 30.6 Gy in 17 daily fractions.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins).
- Round vincristine down to the nearest 0.1 mg.
7-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. link to original article NCT00085735
Maintenance Regimen A
Cycles 1, 2, 4, 5, 7, 8
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 1 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, and 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.
6-week cycle
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. link to original article NCT00085735
Maintenance Regimen B
Cycles 3, 6, and 9
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV given over 1 hour on Days 1 and 2.
- Mesna (Mesnex) 360 mg/m2/dose IV over 15 to 30 minutes on Days 1 and 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 15-30 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/m2 (maximum dose of 2 mg) IV once per day on days 1, and 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. link to original article NCT00085735
COG ACNS0331 Standard Dose CSRT/Standard Volume Boost
- Ages 3+
- All patients must begin therapy within 31 days of surgery.
Chemoradiotherapy
XRT
- Craniospinal External beam radiotherapy 23.4 Gy in 13 daily fractions.
- Posterior Fossa Boost External beam radiotherapy 30.6 Gy in 17 daily fractions.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins).
- Round vincristine down to the nearest 0.1 mg.
7-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. link to original article NCT00085735
Maintenance Regimen A
Cycles 1, 2, 4, 5, 7, 8
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 1 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, and 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.
6-week cycle
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. link to original article NCT00085735
Maintenance Regimen B
Cycles 3, 6, and 9
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV given over 1 hour on Days 1 and 2.
- Mesna (Mesnex) 360 mg/m2/dose IV over 15 to 30 minutes on Days 1 and 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 15-30 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/m2 (maximum dose of 2 mg) IV once per day on days 1, and 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. 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 full protocol as this depends on site of metastases and disease stage.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, and 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
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. link to original article 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. link to original article NCT00392327
Maintenance Cycle
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.
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 (per institution) once on days 1 and 8.
- Round vincristine down to the nearest 0.1 mg.
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 1 hour once on days 2 and 3.
- Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2.
28-Day Course
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. link to original article 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. link to original article NCT00392327
COG ACNS0332 Regimen B
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 full protocol as this depends on site of metastases and disease stage.
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, and 36 (Once a week 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 given daily 1 - 4 hours prior to radiation therapy (Total of 30 doses).
- Carboplatin (Paraplatin) first dose administered on the first day of radiation therapy.
- Carboplatin (Paraplatin) 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.
6-Week Course
- 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. link to original article 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. link to original article NCT00392327
Maintenance Cycle
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.
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 (per institution) once on days 1 and 8.
- Round vincristine down to the nearest 0.1 mg.
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV over 1 hour once on days 2 and 3.
- Cyclophosphamide (Cytoxan) should be given at least 24 hours after Cisplatin on day 2.
28-Day Course
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. link to original article 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. link to original article NCT00392327
Adjuvant therapy
Carboplatin, Cyclophosphamide, Etoposide, Methotrexate, Vincristine
back to top |
Regimen
Study | Evidence |
---|---|
Rutkowski et al. 2005 | Non-randomized |
Preceding treatment
Chemotherapy
- Carboplatin (Paraplatin)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Methotrexate (MTX)
- Vincristine (Oncovin)
References
- Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. link to original article PubMed
Cisplatin, Lomustine, Vincristine
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Packer et al. 2006 (COG A9961) | 1996-2000 | Phase 3 (C) | Cisplatin, Cyclophosphamide, Vincristine | Did not meet primary endpoint of EFS |
Note: neither the cycle length nor the exact dosing instructions for vincristine are clear from the manuscript.
Preceding treatment
- Surgery, then radiotherapy
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Lomustine (CCNU) 75 mg/m2 PO once on day 0
- Vincristine (Oncovin) 1.5 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 7, 14
8 cycles (see note)
References
- COG A9961: Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. link to original article contains partially verified protocol PubMed NCT00002875
Cyclophosphamide & Vincristine/Cisplatin & Etoposide
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Protocol
Study | Evidence |
---|---|
Duffner et al. 1993 | Non-randomized |
Total duration of treatment is 12 to 24 months.
Preceding treatment
- Surgical resection or biopsy
Chemotherapy, part 1
28-day cycle for 2 cycles, alternating with part 2
Chemotherapy, part 2
28-day cycle for 1 cycle, alternating with part 1
References
- Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. link to original article PubMed
VCP
back to top |
VCP: Vincristine, CCNU (Lomustine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zeltzer et al. 1999 (CCG-921) | 1986-1992 | Phase 3 (C) | 8-in-1 | Superior PFS |
Preceding treatment
- Surgery, then Vincristine & RT
Chemotherapy
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15
- Lomustine (CCNU) 100 mg/m2 IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
6-week cycle for 8 cycles
References
- CCG-921: Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. link to original article contains verified protocol PubMed