Deck, Jared

Abstract Background Children’s Oncology Group ACNS0333 treated atypical teratoid/rhabdoid tumor (ATRT) with surgery, chemotherapy (induction and consolidation) and radiation therapy (RT). M0 had focal RT and M+ had physician-selected focal RT or craniospinal (CSI). Methods Forty patients (29 M0, 11 M+) received RT. Pre-RT chemotherapy response was complete, partial, or stable disease. RT timing (age/stage-based) was pre-consolidation (RT-first) or post-consolidation (consolidation-first). Event-free survival (RT-EFS), overall survival (RT-OS), and cumulative incidence of local relapse (CILR) or distant relapse (RT-CIDR) were calculated. Analyses included log-rank tests and relative hazard rates with 95% confidence intervals to estimate proportional hazards regression. Results Four-year RT-EFS was 56.8% and 4-year RT-OS was 58.8% focal RT: 34 patients, CSI: 6 patients). A trend for superior RT-EFS for M+ compared to M0 (P = .0625, RHR 0.26; 95% CI 0.06-1.18) was shown. RT-EFS was improved for consolidation-first compared to RT-first timing (P = .037, RHR 0.43; 95% CI 0.13-1.37). Pre-RT chemotherapy response was associated with improved RT-EFS (P = .031) and RT-OS (P = .0069). Four-year RT-CILR was 7.84%; no differences in RT-CILR were shown for higher primary RT dose (≥5400 cGy, P = .38) or gross total resection (P = .80). 4-year RT-CIDR was 27.8% for M0 and 9.1% for M+ patients (P = .22). M+ had CSI (n = 6) or focal RT (n = 5). Fatal necrosis potentially-attributable to RT occurred in 3 RT-first patients (occuring either 1.6, 4.6, or 16.2 months post-treatment). Conclusions RT with intensive systemic therapy showed promising survival outcomes and effective primary disease control in ATRT. Sequencing RT prior to myeloblative chemotherapy, rather than post-consolidation, may be associated with increased risk of fatal radionecrosis.

AbstractPurposeRadiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta‐analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI).MethodsAfter abstract screening, 25 studies (1995–2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double‐reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre‐radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded.ResultsThe 2‐ and 4‐year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow‐up of 2 years (range 0.3–13.5). The median age was 2 years (range 0.2–19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre‐radiation chemotherapy response (p < .001), and high‐dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre‐radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI.ConclusionChemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.