R. D. Shelby1, L. Suarez-Kelly1, P. Y. Yu1, T. M. Hughes1, C. G. Ethun2, T. B. Tran3, G. Poultsides3, D. M. King7, M. Bedi7, T. C. Gamblin7, J. Tseng4, K. K. Roggin4, K. Chouliaras5, K. Votanopoulos5, B. A. Krasnick6, R. C. Fields6, R. E. Pollock1, J. H. Howard1, K. Cardona2, V. P. Grignol1 1Ohio State University,Columbus, OH, USA 2Emory University School Of Medicine,Atlanta, GA, USA 3Stanford University,Palo Alto, CA, USA 4University Of Chicago,Chicago, IL, USA 5Wake Forest University School Of Medicine,Winston-Salem, NC, USA 6Washington University,St. Louis, MO, USA 7Medical College Of Wisconsin,Milwaukee, WI, USA
Introduction: The addition of radiation to surgery has improved limb-salvage rates for deep extremity sarcomas. Timing of delivery in a neo-adjuvant (NA) vs adjuvant strategy remains an area of study. We sought to evaluate the effect of NA radiation on patients with deep extremity sarcomas from a multi-institutional database.
Methods: A retrospective review of all adult patients with deep extremity sarcomas who underwent surgical resection at 7 U.S institutions from 2000-2016 was performed. Categorical variables were compared using chi-square test. Continuous variables were compared using two-sample t-tests. To assess the impact of radiation on recurrence free survival (RFS) and overall survival (OS) Cox proportional hazard regression models were used. Multivariate analysis was performed for all statistically significant categories to evaluate association with OS and RFS.
Results: 1483 patients with surgically resected deep extremity sarcomas were identified. Average tumor size was 15cm; the most common histology was undifferentiated pleomorphic sarcoma. 723 (50%) patients had surgery only, 419 (29%) had NA radiation and 311(21%) had adjuvant radiation. Most patients who received radiotherapy had grade 3 tumors (82% NA vs 81% adjuvant vs 60% surgery, p<0.0001). Patients receiving NA radiation were more likely to have a history of radiation (7% NA vs 2% adjuvant vs 4% surgery, p=.0060) and undergo core biopsy for diagnosis (67% NA vs 31% adjuvant vs 34% surgery, p<0.0001) than those who had surgery first. More patients in the NA and surgery alone group underwent radical resection (92% NA vs 83% surgery vs 78% adjuvant p<0.0001). The radiotherapy groups had significantly more limb-sparing operations (98% adjuvant vs 94% NA vs 87% surgery, p<0.0001). NA radiation increased post-operative complications (34% NA vs 24% surgery vs 16% adjuvant, p<0.0001) and the need for tissue flap reconstruction (38% NA vs 24% surgery vs 22% adjuvant, p<0.0001). NA radiotherapy led to more negative margins on frozen (87%% NA vs 79% surgery vs 72% adjuvant, p<.0001) and final pathology (90% NA vs 79% surgery vs 75% adjuvant, p<.0001). There were significantly fewer local recurrences in the NA group (14% vs 17% adjuvant vs 27% surgery, p=0.001). The surgery only group had the fewest metastatic recurrences (52% vs 72% NA vs 62% adjuvant, p=0.001). OS and RFS were better in the groups receiving radiation, although not statistically significant. On multivariate analysis there was no factor independently associated with survival.
Conclusion: In this large multi-institutional study, radiotherapy (adjuvant and NA) improves limb salvage rates. NA radiation improves margin status and local recurrence rates, however with increased post-operative complications. There were no other differences related to timing of radiotherapy. Our findings are consistent with other smaller studies.