1069 - Preoperative Hypofractionated Radiotherapy with Locoregional Hyperthermia in Recurrent and Radiation-Associated Sarcomas: Final Results of a Phase 2 Clinical Trial

M. J. Spalek¹, A. Borkowska², M. Telejko³, and P. Rutkowski¹; ¹Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland, ²Department of Microbiology, Molecular Genetics and Genomics, Centre for Advanced Materials and Technology at the Warsaw University of Technology, Warsaw, Poland, ³Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland

Purpose/Objective(s): The role of perioperative treatment in radiation-associated sarcomas (RAS) and sarcoma recurrence in a previously irradiated volume (IRS) remains uncertain. Re-irradiation is rarely used due to fear of late toxicity. We hypothesized that the combination of preoperative or definitive radiotherapy (RT) of 12x 3 Gy with or without simultaneous boost, combined with regional hyperthermia (HT) twice weekly, would not lead to significant late toxicity in RAS/IRS patients. Materials/

Methods: We conducted a prospective, single-arm phase 2 clinical trial. We included patients with locally advanced or oligometastatic RAS/IRS. The treatment consisted of three weeks of RT, 3 or 3.5 Gy per fraction, combined with locoregional HT, followed by surgery or observation. The choice of boost or no-boost regimen was based on resectability. The regimen would be considered safe, significant late RT-related toxicity (CTCAE grade 3+ 5.0) occurred in less than 20% of patients 18 months after RT. We planned to enroll 20 patients based on Wilson’s method for calculation of confidence intervals. We aimed to create a biological dose sum of all radiotherapy plans if available and feasible.

Results: We included 20 patients (RIS n=8, IFRS n=12). Twelve patients from planned 15 underwent surgery. Two patients with potentially resectable tumors did not undergo surgery due to COVID-related reasons. One patient preferred not to undergo surgery after the preoperative no-boost regimen. The remaining five patients were deemed unresectable at the enrollment and received the simultaneous boost. The median follow-up was 30 months. Late toxicity included limited limb mobility in two patients (grades 1 and 2), grade 1 skin fibrosis in four patients and chronic skin ulceration (grade 2) in two patients. No patient developed late grade 3+ toxicity. Seven patients who received the no-boost regimen experienced local failure. No patients receiving the boost regimen experienced local progression. Eight patients had distant metastases. Four patients died.

Conclusion: Our study suggests that combining moderately hypofractionated RT with locoregional HT is safe for RAS/IRS patients. Additionally, the boost may be important for acceptable local control.