Isotretinoin has no effect on event-free survival across high-risk medulloblastoma molecular groups when added to maintenance: A secondary analysis of the Children's Oncology Group ACNS0332 data.

Background: The Children's Oncology Group (COG) study ACNS0332 examined the effect of adding carboplatin and isotretinoin to high-risk medulloblastoma therapy. Isotretinoin arms were closed early due to futility, but the effect of carboplatin was shown to vary by individual medulloblastoma subgroups. Because isotretinoin arms were closed before subgroup classification was available, a differential effect of isotretinoin among various subgroups was not examined. Here, we conduct a secondary analysis of ACNS0332 data examining the effect of isotretinoin on event-free survival (EFS) among individual medulloblastoma subgroups. Methods: Among 261 patients enrolled in ACNS0332, a subgroup was evaluable in 231 patients. Fisher's exact tests and chi-square tests were used to compare distributions of categorical variables among patients with and without exposure to isotretinoin. EFS for subgroups was estimated, and the log-rank test was used to examine differences in outcome distributions among patient groups. Results: Among 231 evaluable patients, 85 were randomized to isotretinoin, 85 were randomized to no isotretinoin, and 61 received no isotretinoin without randomization. All 4 medulloblastoma groups were identified: Randomization to isotretinoin was not associated with any difference in EFS in patients with group 3 ( Conclusions: This study confirms that isotretinoin in addition to radiation and chemotherapy did not improve EFS in pediatric high-risk medulloblastoma regardless of molecular subgroup.