2049 - Early Outcome of Presto: A Phase I-II Trial of Short Course PRE-Operative Radiotherapy for Soft Tissue Sarcoma

Purpose/Objective(s): Standard preoperative radiotherapy (50 Gy in 25 fractions) for soft tissue sarcoma (STS) achieves excellent local control with acceptable major wound complication rates. Several institutions have explored hypofractionated preoperative radiotherapy using various dose-fractionation schedules. This phase I-II single-institution study reports early oncologic outcomes of a 5-fraction preoperative radiotherapy regimen delivering 35 Gy to the gross tumor volume (GTV) (EQD2 64.2 Gy, a/ß = 4 Gy) to enhance tumor response. This is the first trial to evaluate oncologic outcomes in STS using distinct dose levels for the GTV and clinical target volume (CTV).

Materials/Methods: Patients with localized STS of the extremities or superficial trunk received preoperative radiotherapy in 5 fractions on alternate days, followed by surgical resection 4 to 6 weeks later. The prescribed dose was 35 Gy in 5 fractions to the gross tumor volume (GTV) and 30 Gy in 5 fractions to the clinical target volume (CTV), using standard margins defined by RTOG 0630. The primary endpoint was radiation toxicity, including wound complications, skin fibrosis, and joint stiffness. Secondary endpoints included limb functional outcomes, local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS).

Results: Fifteen patients participated in this study from June 2020 to December 2023, with a median age of 60 years (range 35–74). Lesions were located in the upper extremities (3), lower extremities (10), and in the superficial trunk area (2). The median tumor size was 7.5 cm (2.2–16.5 cm), with myxofibrosarcoma being the most common histology (53.3%). R0 resection was achieved in 93.3% of cases, and the median time from radiotherapy to surgery was 33 days (25–46). With a median follow-up of 27 months (14–50), major wound complications occurred in 4 patients (26.7%), one of whom required reoperation. Two patients needed drains and intravenous antibiotics for infected seromas, and one required a VAC dressing for an infected wound. Fibrosis Grade 2 was observed in 3 patients, with no higher grades reported. There were no cases of Grade = 2 joint stiffness or edema. The 3-year local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) rates were 100%, 77.9%, and 85.7%, respectively. The one-year Toronto Extremity Salvage Score and Musculoskeletal Tumour Society mean scores were 155 and 31, respectively.

Conclusion: This early assessment of a single-institution phase I-II study investigating hypofractionated preoperative radiotherapy delivering 35 Gy in 5 fractions to the gross tumor volume (GTV) demonstrated excellent local control, favorable acute and long-term toxicity profiles, and positive functional outcomes. This dose-fractionation schedule is convenient for patients and optimally utilizes resources. We will continue to study this pre-operative scheme both as a standalone treatment and in combination with systemic therapy.