Mateusz J Spałek1, Hanna Koseła-Paterczyk2, Aneta Borkowska2, Michał Wągrodzki3, Anna Szumera-Ciećkiewicz4, Anna M Czarnecka5, Patricia Castaneda-Wysocka6, Iwona Kalinowska2, Jan Poleszczuk7, Edyta Dąbrowska-Szewczyk8, Andrzej Cieszanowski6, Piotr Rutkowski2. 1. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. Electronic address: mateusz.spalek@pib-nio.pl. 2. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 3. Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 4. Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Diagnostic Hematology Department, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. 5. Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. 6. Department of Radiology I, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. 7. Department of Computational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland. 8. Department of Medical Physics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland; Biomedical Physics Division, Faculty of Physics, University of Warsaw, Warsaw, Poland.
Abstract
PURPOSE: There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity. METHODS AND MATERIALS: We conducted a single-arm prospective clinical trial. Treatment combined 1 cycle of AI with subsequent 5 × 5 Gy radiotherapy within 1 week, followed by 2 cycles of AI and surgery. The primary endpoint was to assess the number of patients in whom en bloc R0 resection was achieved. RESULTS: Forty-six patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Forty-two received the planned protocol treatment. In 2 patients, the treatment was prematurely stopped because of the toxicity of chemotherapy. One patient died of septic shock because of severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ Common Terminology Criteria for Adverse Events 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but they were severe in only 6 patients. CONCLUSIONS: Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted.
PURPOSE: There is no standard treatment for marginally resectable soft tissue sarcomas (STSs) of the extremities and trunk wall, and current approaches produce unsatisfactory results. We hypothesized that the combination of doxorubicin-ifosfamide (AI) chemotherapy and 5 × 5 Gy hypofractionated radiotherapy can generate a higher ratio of limb-sparing or conservative surgeries with negative microscopic margins (R0) and acceptable treatment toxicity. METHODS AND MATERIALS: We conducted a single-arm prospective clinical trial. Treatment combined 1 cycle of AI with subsequent 5 × 5 Gy radiotherapy within 1 week, followed by 2 cycles of AI and surgery. The primary endpoint was to assess the number of patients in whom en bloc R0 resection was achieved. RESULTS: Forty-six patients met the eligibility criteria. Three patients had resectable lung metastases at baseline. Forty-two received the planned protocol treatment. In 2 patients, the treatment was prematurely stopped because of the toxicity of chemotherapy. One patient died of septic shock because of severe bone marrow suppression after the second AI cycle; a second death was not related to treatment for STS. Three patients underwent amputation. In 72% of patients in the intention-to-treat analysis, we achieved en bloc R0 resections. Grade 3+ Common Terminology Criteria for Adverse Events 4.03 chemotherapy toxicity requiring dose reduction or treatment interruption occurred in 15 patients. Wound complications occurred in 18 patients, but they were severe in only 6 patients. CONCLUSIONS: Preoperative AI combined with 5 × 5 Gy radiotherapy is a promising method for the management of marginally resectable STS. This protocol enables a high ratio of R0 limb-sparing or conservative surgeries. Further evaluation of this strategy is warranted.
Authors: David Boyce-Fappiano; Ethan P Damron; Ahsan Farooqi; Devarati Mitra; Anthony P Conley; Neeta Somaiah; Dejka M Araujo; J Andrew Livingston; Ravin Ratan; Emily Z Keung; Christina L Roland; B Ashleigh Guadagnolo; Andrew J Bishop Journal: Adv Radiat Oncol Date: 2022-02-05
Authors: Siyer Roohani; Felix Ehret; Marta Kobus; Anne Flörcken; Sven Märdian; Jana Käthe Striefler; Daniel Rau; Robert Öllinger; Armin Jarosch; Volker Budach; David Kaul Journal: Radiat Oncol Date: 2022-09-14 Impact factor: 4.309