2996 - Does Pre-Operative Hypofractionated Radiotherapy Improve Survival in Soft Tissue Sarcomas?

J. Hirshberg¹, A. C. Istl², C. Clarke³, J. Neilson⁴, A. Wooldridge⁴, R. Singh⁵, D. M. King⁴, J. Charlson⁶, and M. Bedi⁴; ¹Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, ²Department of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, ³Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, ⁴Medical College of Wisconsin, Milwaukee, WI, ⁵MCWAH, Milwaukee, WI, ⁶Cancer Center-Froedtert Hospital, Medical Collegue of Wisconsin, Milwaukee, WI

Purpose/Objective(s): Pre-operative RT is often used in the management of soft tissue sarcoma (STS), which has shown to lead to excellent rates of local control. Hypofractionated radiation (HFRT) has been shown to have comparable safety and efficacy to standard fractionated RT (SFRT) in many phase 2 trials and has potential radiobiologic and temporal advantages. However, it is not yet known if these benefits translate to improved oncologic outcomes. In this study, we retrospectively analyze patients with extremity and truncal STS who received pre-operative SFRT or HFRT to determine if HFRT is associated with distant metastases-free survival (DMFS) and Overall Survival (OS). Materials/

Methods: Patients with localized Stage I-III STS of the extremity and superficial trunk treated between 2015-2022 were retrospectively analyzed. Pre- and post-operative pathologic samples were analyzed to assess treatment effect by a trained musculoskeletal pathologist. Patients received either SFRT or HFRT 4-6 weeks prior to surgery. The HFRT and SFRT doses were 35Gy/5fx, and 50Gy/25fx, respectively. Patient, tumor, and treatment variables were evaluated (Table 1) and DMFS and OS were evaluated using the Kaplan-Meier estimate. For multivariate analysis (MVA), cox-proportional hazards test was used.
Results: Sixty-seven patients with matched biopsy and resection samples were reviewed. Median follow up was 5.9 years. Most had Stage III (86%) and Grade-3 (84%) STS. Most were treated with SFRT (67%, n=45) compared to HFRT (33%, n=22). There were no significant differences between HFRT and SFRT cohorts. For all patients, the 2-year OS and DMFS were 85% and 73%, respectively. The 2-year DMFS for those treated with HFRT was 85.7% vs 64% with SFRT (p=0.0569, 95%CI 79.9-109.2) On MVA, KPS (p=0.004, 95% CI 2.4-107.7), HFRT (p=0.0241 95% CI 0.005-0.69), and necrosis (p=0.0083 95%CI 2.03-119.3) were significantly associated with DMFS, and KPS (p=0.007 95%CI 2.04-94.2) and necrosis (p=0.014 95%CI 1.6-70.5) were significantly associated with OS.
Conclusion: In this study, HFRT did not improve OS as compared to SFRT. Nevertheless, a notable significance on MVA emerged indicating that HFRT is linked to improved DMFS. Future studies with larger populations of SFRT and HFRT patients are warranted to corroborate these findings. However, this research indicates the promise of HFRT, suggesting not only radiobiological and temporal advantages, but also potential benefits in DMFS.

Abstract 2996 – Table 1

	SFRT (n=45)	HFRT (n=22)	p-value
Age	57	60	0.27
Grade	Low/Int: 11.1% High: 88.9%	Low/Int: 22.7% High: 77.3%	0.48
Location	Upper Extremity: 17.8% Lower Extremity: 80% Chest Wall: 2.2%	Upper Extremity: 4.5% Lower Extremity: 91% Chest Wall: 4.5%	0.26
Histology	Pleomorphic 37.7% Liposarcoma 26.6% Leiomyosarcoma 4.6% Other 31.1%	Pleomorphic 40.2% Liposarcoma 27.3% Leiomyosarcoma 18.2% Other 14.1%	0.63
Stage	I: 0% II: 13.7% III: 86.3%	I:4.0% II: 11.0% III: 85.0%	0.42
Size (mean)	10.5cm	9.2cm	0.76
Neoadjuvant Chemo	36%	40%	0.79