Risk-adapted therapy for young children with newly diagnosed brain and central nervous system tumors (SJYC07)
Why was this study done?
Children with brain and central nervous system tumors usually receive radiation therapy. Very young children who get this treatment may have lasting problems with their thinking, learning, and growing. In this study, we delayed or avoided using radiation therapy when possible.
Chemo is used to try to shrink tumors in young children. This treatment gives their brain more time to develop before they get radiation. Chemo may even prevent the need for radiation.
The study's main goals were to:
- Study how well this treatment works on brain tumors in young children
- Better identify groups of tumor types
- Help predict which patients may respond to treatment and which patients may have a higher risk for relapse (tumor coming back)
- Learn more about the genetic makeup (genes or DNA) of brain tumors in young children
When was this study done?
The study opened in November 2007 and closed in April 2017.
What did the study consist of?
Doctors treated patients based on their risk group. There were 3 groups:
- Low risk
(1) Surgeons removed as much tumor as possible.
(2) All patients got 4 rounds of chemo with these drugs:
Patients with high-risk disease also received vinblastine.
(3) Doctors gave therapy based on risk groups:
Low-risk patients had 2, 4-week cycles of cyclophosphamide, etoposide, and carboplatin.
Intermediate-risk patients had focal radiation therapy to the area of the tumor.
High-risk patients had topotecan and cyclophosphamide.
(4) Finally, all patients received cyclophosphamide, topotecan, and erlotinib.
What did we learn from this study?
- One out of every 3 children in this study was alive 5 years later with no sign of a tumor.
- The survival rates for the children were:
- Low-risk, 55%
- Intermediate risk, 24.6%
- High-risk, 16.7%
- This risk-based approach to treatment did not improve event-free survival for all of the young children with medulloblastoma.
- Studying the genetic makeup of these tumors is important.
- Some patients with sonic hedgehog (SHH) subgroup tumors had special features known as methylation patterns. Their survival improved by 51% compared to those without the special feature.
- We found two new subtypes in the SHH subgroup: iSHH-I and iSHH-II. Children with iSHH-II had better event-free survival rates than those with iSHH-I. This outcome occurred without radiation, intraventricular chemo, or high-dose chemo.
- Young children with brain tumors may have cognitive difficulties, which can affect their quality of life. This is usually seen as trouble remembering, learning new things, and concentrating. These problems are partially due to the tumor's location and surgery. The risk of these problems was higher for:
- Younger age at treatment
- Less access to financial, educational, social, or health care resources (lower socioeconomic status)
- Children with a condition known as hydrocephalus (fluid build-up in the brain)
Findings from this study will help doctors plan treatment. They will also help us find new ways to reduce the risk of long-term cognitive problems.
What are the next research steps as a result of this study?
By studying the genes (DNA) of the tumors, we can better understand them. We will use the results of SJYC07 to plan future clinical trials. This information will help us find new ways to group these tumors and to plan new risk-based studies. We will also develop new ways to lower the risk of cognitive problems in survivors.
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 Care 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:
Risk-adapted therapy for young children with medulloblastoma (SJYC07): therapeutic and molecular outcomes from a multicentre, phase 2 trial. Robinson GW, Rudneva VA, Buchhalter I, Billups CA, Waszak SM, Smith KS, Bowers DC, Bendel A, Fisher PG, Partap S, Crawford JR, Hassall T, Indelicato DJ, Boop F, Klimo P, Sabin ND, Patay Z, Merchant TE, Stewart CF, Orr BA, Korbel JO, Jones DTW, Sharma T, Lichter P, Kool M, Korshunov A, Pfister SM, Gilbertson RJ, Sanders RP, Onar-Thomas A, Ellison DW, Gajjar A, Northcott PA. Lancet Oncol. 2018 Jun;19(6):768-784. doi: 10.1016/S1470-2045(18)30204-3. Epub 2018 May 16.
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. doi: 10.1200/JCO.20.01359. Epub 2021 Jan 27.
Predictors of Cognitive Performance Among Infants Treated for Brain Tumors: Findings From a Multisite, Prospective, Longitudinal Trial. Ali JS, Ashford JM, Swain MA, Harder LL, Carlson-Green BL, Miller JM, Wallace J, Kaner RJ, Billups CA, Onar-Thomas A, Merchant TE, Gajjar A, Conklin HM. J Clin Oncol. 2021 Jul 20;39(21):2350-2358. Epub 2021 May 4.