Comparison between preoperative chemoradiation versus neoadjuvant chemotherapy with postoperative radiation for extremity soft-tissues sarcomas.
Authors: Aguiar Samuel , Menezes Jacqueline , Mello Celso Lopes , Silva Maria Leticia Gobo , Nakagawa Suely Akiko , Stevanato Paulo Roberto , Bezerra Tiago , Kupper Bruna , Takahashi Renata , Marques Tomas Mansur , Lopes Ademar 
Published: June 2022

e23527

Background: Extremity soft-tissues sarcomas are a rare entity that represent 1% of solid tumors in adults. Surgery is the main treatment and limb sparing resection with adjuvant radiotherapy (RT) is associated with good local control. However, high rates of distant relapses motivated the evaluation of adjuvant systemic treatment protocols. We aim to compare survival rates between two cohorts of patients treated with two different preoperative protocols. Methods: An observational comparative cohort study were carried out. Two cohorts of patients with high grade, larger then 5.0 cm, and non-metastatic soft tissue sarcomas of extremities, treated with two distinct preoperative institutional protocols, in two different periods of time, were compared. Group 1 included patients treated in the period from January, 1995 to December, 2004, when patients with high risk extremities soft tissue sarcomas were submitted to preoperative radiation therapy (a total dose of 30 Gy) concomitant with doxorubicin (60 mg/m2); this protocol included adjuvant chemotherapy with doxorubicin and ifosfamide. Group 2 included patients treated in the period from April, 2005 to July, 2012, when our group changed the preoperative protocol to neoadjuvant chemotherapy without radiation, with four cycles doxorubicin (60 mg/m2 per cycle) and ifosfamide (9.000 mg/m2 per cycle), followed by surgery, and postoperative radiation. Data from the group 1 were retrospectively collected, and data from group 2 were from our prospective database. Results: Eighty-eight patients were included (37 in group 1 and 51 in group 2). There were no statistical differences between the groups with regards to age, gender, location and tumor size. Predominant histological subtypes were synovial sarcoma (27.3%), pleomorphic sarcoma (15.9%), leiomyosarcoma (11.4%) and liposarcoma (8%). Relapses occurred in 60.5% of patients, most in the lungs (48.1%). Amputation rates were 14.3% in the group 1 and 4.5% in the group 2. Five-year local recurrence free survival was 81.7% for the group 1 and 91.7% for the group 2. There was no difference in median overall survival when comparing group 1 and 2 (47 versus 78 months, respectively; IC 95 3.967 – 132.033; p = 0.49), but our data showed higher recurrence free survival in group 2 (19 versus 132 months; IC 95 5.9 – 60.09; p = 0.025, respectively). Among patients from the group 2, whom presented less than 10% of viable tumor cells in the surgical specimens (good responders), no local or distant recurrences have occurred. Conclusions: In our retrospective analysis, neoadjuvant chemotherapy was associated with greater recurrence free survival in patients with high-grade extremity soft tissue sarcomas as compared to neoadjuvant chemoradiation. For patients with high risk of distant relapse, neoadjuvant chemotherapy should be considered after a multidisciplinary discussion.