3328 - Retrospective Comparison of PULSAR vs. SAbR in Combination with Immunotherapy for Renal Cell Carcinoma

Purpose/Objective(s): Personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) is an emerging radiation strategy designed to allow for adaptation, lower risk to OARs and leverage potential benefits of an ongoing anti-tumor immune response by mimicking a cancer vaccination schedule. We hypothesize that PULSAR has immunogenic advantages over standard regimen SAbR when used in combination with immunotherapy in the treatment of RCC. This retrospective study compares clinical outcomes between PULSAR + immunotherapy (IO) and SABR + IO in patients with RCC treated at a single institution.

Materials/Methods: A retrospective review was conducted of patients with RCC treated at the UT Southwestern Medical Center with either PULSAR (doses > 5Gy given at least 7 days apart) or SAbR in the setting of ongoing IO between 2010-2025. Thirteen consecutive patients treated with PULSAR were matched to 16 patients treated with SAbR based on clinical and disease characteristics, including age, disease burden, and line of systemic therapy. The primary endpoint was time to next systemic therapy escalation (TTNSTE), defined from the date of first RT fraction to initiation/addition/switch of systemic anti-cancer therapy due to inadequate disease control, as documented in the medical record. Changes due solely to toxicity or planned discontinuation were not counted as events. To mitigate immortal time bias related to PULSAR delivery, a prespecified landmark analysis at 28 days from RT start was performed, with time-to-event measured from the landmark forward. Additionally, we assessed time to radiographic progression, defined as time from RT start to first documented progression at any site. In each case, death was handled as a competing event. We also report on local control and toxicity graded with CTCAEv5.

Results: Median follow up for SAbR cohort was 24.8 months (IQR: 8.8 to 39.8) while PULSAR cohort was 21.4 months (IQR: 15.4 to 31.9). Local control of irradiated lesions was observed in 93.8% compared to 100% for PULSAR cohort (p=1). Grade =3 treatment-related toxicity occurred in 0% of patients treated with PULSAR and 12.5% of patients treated with SAbR (p=0.48). Median TTNSE was 8.1 months for patients treated with PULSAR and 27.7 month for patients treated with SAbR (p=0.36). Time to radiographic progression at any site was 8.1 months in the PULSAR, and 5.4 months in the SAbR (p=0.77).

Conclusion: This retrospective analysis evaluates differences in radiographic response patterns and time to next systemic agent between PULSAR and SABR when combined with IO for RCC. Main findings, though limited by small cohorts, show that patients treated with PULSAR vs. SAbR in combination with IO have similar responses in terms of progression at any site. Furthermore, patients treated with PUSLAR had lower rates of Grade = 3 toxicities. The findings of this study may inform future prospective investigations exploring optimal radiation fractionation strategies to enhance immunotherapeutic outcomes in RCC.