In a study reported in the Journal of Clinical Oncology, Kumar et al identified outcomes and patterns of relapse in pediatric patients with medulloblastoma. The investigators found that time to relapse and postrelapse survival was associated with subgroup and that the majority of relapses involve conservation of the involved medulloblastoma subgroup.
Study Details
The study involved data from infants and children in the multicenter SJMB03 and SJYC07 clinical trials of risk-adapted treatment. Patients in SJMB03 were aged ≥ 3 to 21 years and received postsurgical craniospinal irradiation followed by high-dose chemotherapy. Patients in SJYCo7 were aged < 3 years and received postsurgical induction and consolidation therapy followed by maintenance chemotherapy. A largely independent multi-institutional cohort with paired primary and relapsed tumor specimens was assessed to identify molecular features of relapse.
“Clinical behavior of relapsed medulloblastoma must be contextualized in terms of upfront therapies and molecular classifications.... Degree and patterns of molecular conservation at relapse vary by subgroup.”— Kumar et al
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Key Findings
Relapse was observed in 72 (22%) of 329 patients in SJMB03 and 52 (66%) of 79 in SJYC07. Relapse was most common among patients with group 3 tumors, occurring in 40% and 92% of patients in the two trials, with no relapses observed among patients with wingless (WNT) tumors.
Relapse included distal disease in 79% of patients. However, 38% of patients with sonic hedgehog (SHH) tumors experienced isolated local relapse.
Median time to relapse was 1.64 years in SJMB03 and 0.72 years in SJYC07. In SJMB03, time to relapse varied by molecular subgroup (P = .00087), including 2.79 years for patients with group 4 tumors (hazard ratio [HR] = 3.01, 95% confidence interval [CI] = 1.67–5.41) and 1.23 years for SHH tumors (HR = 2.41, 95% CI = 1.20–4.81) vs 0.91 years for group 3 tumors. Time to relapse also varied by molecular subgroup in SJYC07 (P = .039), primarily reflecting longer duration in group 4 vs group 3 tumors (HR = 2.74, 95% CI = 1.14–6.60).
Median postrelapse survival was 1.14 years in SJMB03 and 2.12 years in SJYC07. In SJMB03, survival varied by subgroup (P = .016), with median durations of 2.27 years for group 4 tumors (HR = 2.39, 95% CI = 1.29–4.42) and 1.06 years for SHH tumors (HR = 1.90, 95% CI = 0.94–3.83) vs 0.44 years for group 3 tumors. No variation by subgroup was observed in SJYC07 (P = .88).
Postrelapse radiation therapy among SJYC07 patients not receiving prior radiation therapy was associated with long-term survival, particularly among patients with SHH and group 3 tumors. Repeated radiation therapy in SJMB03 patients was associated with a smaller survival benefit.
In the cohort of 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma central nervous system malignancies. Among the remaining 118 patients, diagnostic tumors were WNT in 1 (1%), SHH in 48 (41%), group 3 in 22 (19%), and group 4 in 46 (39%). Medulloblastoma subgroup was conserved at relapse in 113 patients (96%); five patients with initial group 4 tumors relapsed with group 3 tumors. Molecular subtypes were conserved in 80% of patients with SHH and groups 3 and 4 tumors.
The investigators concluded, “Clinical behavior of relapsed medulloblastoma must be contextualized in terms of upfront therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.”
Paul A. Northcott, PhD, of the Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the American Lebanese Syrian Associated Charities, Alexander and Margaret Stewart Trust, American Association for Cancer Research, St. Baldrick’s Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
