248 - The Impact of Hypofractionated Pre-Operative Radiation Therapy on PD-L1 Expression in Soft Tissue Sarcomas

C. Clarke¹, A. C. Istl², M. Bedi³, R. Singh⁴, J. Charlson⁵, J. Neilson³, A. Wooldridge³, D. M. King³, Y. Sun³, and H. Rui³; ¹Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, ²Department of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, ³Medical College of Wisconsin, Milwaukee, WI, ⁴Vanderbilt University, Nashville, TN, ⁵Medical College of Wisconsin, Milwaukee, WI, United States

Purpose/Objective(s): Preoperative RT followed by resection is a common management for soft tissue sarcomas (STS). Standard course of RT involves 5-weeks, however, there has been a shift towards pre-op hypofractionation given phase II data showing excellent rates of local control and toxicity. There is evidence suggesting immune system plays pivotal role in treatment response for many cancers. RT has demonstrated upregulation of PD-L1 expression; however, this elevation may also trigger immunosuppression. PD-L1 induction can lead to immune escape, resulting in compromised outcomes. Th impact of hypofractionation on biomarker expression in sarcomas remains poorly elucidated. This study aims to evaluate the influence of pre-op HFRT on biomarker expression in STS as well as its implications on DMFS and OS. Materials/

Methods: A retrospective study comparing hypofractionated RT (HFRT) and standard fractionated RT (SFRT) was performed. From 2015-2022, 67 pts with localized STS of the extremity/trunk were treated with HFRT (35 Gy/5 fx) or SFRT (50 Gy/25 fx) followed by resection ~5 weeks later. Tumor immune marker profiling by multiplex histocytometry of 134 samples using a 7-color marker panel was done. CD45, CD68, PD1 and PD-L2 were also evaluated. Variables and % expression in PD-L1 in tumor between SFRT and HFRT groups were assessed. ROC analysis was performed to assess the best cut-off related to outcomes. DMFS and OS were evaluated using the KM estimate. For MVA, cox-proportional hazards test was used.
Results: Median f/u was 6 yrs. 22 pts received HFRT and 45 pts received SFRT. 2-year OS and DMFS was 85% and 73%, respectively. There was no difference in the % change of PDL-1 between pre- and post-RT in the two cohorts (6% vs 9%, p=0.43). No other immune marker was significant for survival. ROC analysis revealed PD-L1 post-RT was associated with DMFS (ROC cutoff 0.028, p= 0.04). 2-year DMFS for pts with = 2.8% expression of PD-L1 post-RT was 91% vs 65% (p=0.01, 95% CI 81.1 to 110.4). 67% of pts in the HFRT cohort had >2.8% PD-L1 expression post-RT compared to 33% in SFRT. However, on UVA, a trend of improved 2-year DMFS with HFRT (86% vs 68%, p=0.06, 95% CI 81.1 to 110.5). No variable was significant on MVA for OS, but HFRT (p=0.02) and PD-L1 expression =2.8% (p=0.03) demonstrated improved DMFS.
Conclusion: HFRT led to improvements of DMFS on MVA, despite 67% of the patients in this cohort had a PD-L1 expression > 2.8%. While additional studies are needed to further explore the influence of HFRT on the immune system, this implies that HFRT may instigate systemic positive alterations, potentially improving DMFS.

Table 1

Variable	SFRT (N=45)	HFRT (N=22)	p</b>
Age	57	60	NS
Grade	Low/Int: 11% High: 89%	Low/Int: 23% High: 77%	NS
Location	UE: 18% LE: 80% Chest Wall: 2%	Upper Extremity: 4% Lower Extremity: 91% Chest Wall: 5%	NS
Histology	Pleomorphic 37.3% Liposarcoma 15.5% Leiomyosarcoma 4.4% Other 13%	Pleomorphic 40% Liposarcoma 27% Leiomyosarcoma 18% Other 13%	NS
Stage	I: 0% II: 13% III: 86%	I:4% II: 11% III: 84%	NS
Size (mean cm)	10.5	9.2	NS
Chemo	36%	40%	NS