Why was this study done?
SJMB03 studied 2 ways of giving radiation therapy, along with chemotherapy (chemo) and stem cell transplant. We wanted to find out how well these treatments work in patients with these newly diagnosed cancers:
- Medulloblastoma
- Primitive neuroectodermal tumor
- Atypical teratoid rhabdoid tumor
Giving radiation therapy along with chemo may kill more tumor cells. These treatments destroy cells that form blood, and autologous stem cell transplant may be able to replace these cells. We don’t know yet which treatment combination works best for these brain tumors.
This study helped us learn more about the biology of these tumors and treatment side effects. We will use this information to develop new and better treatments.
We also wanted to answer these questions:
- Can a new computer-based educational program help prevent patients from loss of reading, language, and learning skills?
- Can brain changes, detected by MRI, identify those who might develop problems with learning and functioning?
- Will a lower dose of radiation to the brain still treat the tumor?
- What are the side effects of the treatment?
- Can MRI imaging help us learn more about how to diagnose, treat, and monitor these diseases?
- How does the body break down and remove certain drugs?
- What can we learn about this treatment by studying the spinal fluid of patients?
When was this study done?
The study opened in August 2003 and closed to accrual in March 2013.
What did the study consist of?
- Radiation treatments to the brain and spine
- Collection of blood stem cells for later use with chemo
- Treatment with stem cell transplant and high-dose chemo (cisplatin, vincristine, and cyclophosphamide)
- Education
What did we learn from this study?
- Hearing loss: We learned more about the risk of hearing loss for children who receive cisplatin. We thought differences in their genes (DNA) might affect the risk of hearing loss. This study and an earlier study checked patients’ DNA to look for gene changes. We looked for more than 1.7 million common differences passed down through families. We found changes to the gene ACYP2 that were linked with more than a 4-fold greater risk of hearing loss. These findings may help doctors identify patients at risk for hearing loss when treated with cisplatin.
- Molecular groups: Medulloblastoma tumors fall into 4 groups based on specific (molecular) features. These groups are:
- WNT
- SHH
- Group 3
- Group 4
This study taught us more about each group’s response to treatment. There was a low risk for cancer relapse in treated patients in the WNT group, and some SHH and Group 3/4 treated patients. We also learned that some SHH and Group 3/4 are high-risk.
Relapse patterns. About 1 out of 3 children with medulloblastoma will get cancer relapse. The relapse rate depends on their age and type of therapy. We studied relapse using information from this clinical trial and other samples. We found that 10% of the medulloblastoma tumors were a secondary malignancy from cancer spread. We also found that some tumors switch between Group 3 and Group 4.
Memory and processing speed. Children with medulloblastoma are at risk for learning and memory problems due to their disease and treatment. We wanted to find out how radiation therapy to different areas of the brain affects patients’ memory and processing speed. We found that higher radiation doses in those areas is linked to not doing well on tests of memory and processing speed.
What are the next research steps as a result of this study?
- Hearing loss: Only 1 in 8 patients with cisplatin-related hearing loss had the ACYP2 gene variant. This suggests there might be other genes involved in hearing loss. More research will help us understand how ACYP2 variations affect hearing loss after treatment with cisplatin.
- Molecular groups: This study helped us better understand risk and when to reduce or increase therapy. These findings will help us better design clinical trials for these tumors.
- Relapse patterns: The findings show the value of adding molecular analysis when diagnosing and treating medulloblastoma.
- Memory and processing speed: Information learned in this study will help doctors better plan radiation therapy. We hope to reduce learning and memory problems while achieving the best possible cure rates.
How does this study affect my child?
Every childhood cancer survivor should have long-term follow-up care. In the St. Jude After Completion of Therapy Clinic, we will give your child information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines for your child.
For more information
Please talk with your child’s St. Jude doctor about questions or concerns you have as a result of this study.
Publications generated from this study:
Common variants in ACYP2 influence susceptibility to cisplatin-induced hearing loss. Xu H, Robinson GW, Huang J, Lim JY, Zhang H, Bass JK, Broniscer A, Chintagumpala M, Bartels U, Gururangan S, Hassall T, Fisher M, Cohn R, Yamashita T, Teitz T, Zuo J, Onar-Thomas A, Gajjar A, Stewart CF, Yang JJ.. Nat Genet 2015;47:263-6.
https://www.ncbi.nlm.nih.gov/pubmed/25665007
Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P Jr, Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V, Northcott PA. J Clin Oncol. 2021 Mar 1;39(7):807-821.
https://pubmed.ncbi.nlm.nih.gov/33502920/
Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE, Chintagumpala M, Mahajan A, Su J, Bouffet E, Bartels U, Schechter T, Hassall T, Robertson T, Nicholls W, Gururangan S, Schroeder K, Sullivan M, Wheeler G, Hansford JR, Kellie SJ, McCowage G, Cohn R, Fisher MJ, Krasin MJ, Stewart CF, Broniscer A, Buchhalter I, Tatevossian RG, Orr BA, Neale G, Klimo P Jr, Boop F, Srinivasan A, Pfister SM, Gilbertson RJ, Onar-Thomas A, Ellison DW, Northcott PA. J Clin Oncol. 2021 Mar 1;39(7):822-835.
https://pubmed.ncbi.nlm.nih.gov/33405951/
Association Between Brain Substructure Dose and Cognitive Outcomes in Children with Medulloblastoma Treated on SJMB03: A Step Toward Substructure-Informed Planning. Acharya S, Guo Y, Patni T, Li Y, Wang C, Gargone M, Ashford JM, Wilson L, Faught A, Reddick WE, Patay Z, Gajjar A, Conklin HM, Merchant TE. J Clin Oncol. 2022 Jan 1;40(1):83-95.
https://pubmed.ncbi.nlm.nih.gov/34714708/