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Results summary of St. Jude clinical trial: 



Treatment of patients with newly diagnosed medulloblastoma, supratentorial primitive  neuroectodermal tumor, or atypical teratoid rhabdoid tumor (SJMB03)

Why was this study done?

SJMB03 studied two different ways of giving radiation therapy, along with chemotherapy (chemo) and stem cell transplant. The goal was to find out how well they work in patients with newly diagnosed medulloblastoma, primitive neuroectodermal tumor or atypical teratoid rhabdoid tumor.

Combining radiation therapy with chemo may kill more tumor cells. Autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by these treatments. It is not yet known which radiation therapy regimen combined with chemo and transplant is more effective in treating these brain tumors.

The main goal of this study is to learn as much as possible about the biology of medulloblastoma and related tumors, and the side effects of treatment. We will use that information to develop new and better ways to improve treatments.

The study also sought to answer these questions:

  • Can a new computer-based educational program help prevent at least some of the loss in reading, language and learning skills?
  • Will changes in MR images of the brain help identify patients who are more likely to have problems with learning and functioning?
  • Will a lower dose of radiation to the brain still cure the tumor?
  • What are the side effects of the treatment?
  • How can MR 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?

  1. Radiation treatments to the brain and spine
  2. Collection of blood stem cells for later use with chemo
  3. Treatment with high-dose chemo (cisplatin, vincristine and cyclophosphamide) and stem cell transplant
  4. Education

What did we learn from this study?

Hearing loss findings. One of the important things we learned in this study was about the risk of hearing loss to children who receive the chemo drug cisplatin. Scientists thought differences in patients’ genetic makeup might affect the chances of having hearing loss. The scientists checked the DNA (genetic make-up) of patients in this study and an earlier study. The researchers looked for more than 1.7 million common inherited variations in the genes. The search led to a gene called ACYP2. Some versions of this gene were linked with more than a four-fold greater risk of hearing loss. The findings may help us find out patients who are more likely to develop hearing loss due to cisplatin treatment.

Details about medulloblastoma molecular groups. We already knew that medulloblastoma tumors can be divided into four molecular groups: WNT, SHH, Group 3 and Group 4. In this study we learned more about how each group responds to treatment. We learned that all WNT, and some SHH and Group 3/4, are low risk for coming back (relapse). We also learned that some SHH and Group 3/4 are high risk.

Discoveries about relapse patterns. About one-third of children with medulloblastoma will relapse. The relapse rate varies based on factors such as the patient’s age and what type of therapy is received. We used information from this clinical trial and other samples to study relapse. We learned that 10% of tumors classified as relapsed medulloblastoma are actually a secondary malignancy. We also discovered that some tumors switch between Group 3 and Group 4 tumors.

What are the next research steps as a result of this study?

Only 1 in 8 patients with cisplatin-related hearing loss carried the ACYP2 gene variant. This suggests that other genes that we have not discovered yet also contribute to hearing loss. More research is needed to understand how the ACYP2 variations affect hearing loss from cisplatin.

This study helped us better understand risk, so we know when to reduce or increase therapy. These findings will help us better design future clinical trials for these tumors.

The findings also show the need to include molecular analysis when diagnosing and treating medulloblastoma.

How does this study affect my child?

Every childhood cancer survivor should receive long-term follow-up care. Through the St. Jude After Completion of Care clinic, your child will receive information and guidance for care after treatment. Please speak with your St. Jude doctor about specific guidelines that apply to 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.

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.

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.