Atrt-11. Irs-Iii: Long-Term Follow-Up Shows Favorable Outcomes and Durable Responses for Localized Atypical Teratoid Rhabdoid Tumor (Atrt)

Abstract BACKGROUND IRS-III-based chemotherapy is a long-standing treatment approach for ATRT, which mostly affects infants under the age of 3. We provide long-term outcomes from three high-volume pediatric centers, including a subgroup of patients treated with “moderately-delayed” radiation therapy (RT). METHODS We performed a retrospective analysis of 60 patients treated between 1999-2021. Patients at Boston and Sydney Children’s Hospitals received per-protocol early chemoradiation during induction cycles 3-4, while patients at Children’s Hospital of Philadelphia received moderately-delayed RT with temozolomide post 6 induction cycles. Demographic, clinical and outcome data were collected. RESULTS Median age at diagnosis was 2.3 years (range:0.5-19.5) with median follow-up 2.7 years (range:0.1-15.5); however, 20/60 patients were followed 5 years (median 10.4, range:5.1-15.5). Thirty-six patients (60%) underwent gross or near-total resection; 14 (23%) had metastatic disease. Seventeen (28%) did not receive RT due to progression, toxicity, or provider discretion; 27 (45%) received focal and 17 (28%) craniospinal RT. For the entire cohort, 5- and 10-year PFS were both 30% (95%CI: 19-42). OS were 38% (95%CI: 27-51) and 31% (95%CI: 19-43), respectively. For patients with localized disease, 5-year PFS and OS were 38% (95%CI: 24-52) and 45% (95%CI: 30-56), respectively. Patients with metastatic disease had 5-year PFS and OS of 0% and 19% (95%CI: 3-43), with no long-term survivors. In multivariate analysis, RT was a statistically significant prognostic factor. However, treatment field (focal vs. CSI), RT timing (early vs. moderately-delayed), patient age, resection extent, or metastatic status were not significant. CONCLUSIONS Our results suggest that IRS-III should remain a standard of care approach for localized ATRT, based on the favorable survival outcomes with the longest follow up of any published ATRT regimen to date. In addition, it highlights the importance of RT for localized disease and proposes it can be given after induction without compromising outcomes, reducing treatment-related toxicity.