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Background. Consistent results are lacking as regards the comparative effectiveness of intensity-modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3DCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Patients and Methods. Patients treated with definitive radiotherapy (RT) between 2002 and 2010 were retrospectively reviewed. Overall survival (OS), local-regional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were compared among patients irradiated with different techniques. The association between RT technique and survival indexes was assessed in a Cox proportional hazard regression model. Propensity score matching (PSM) was used to balance known confounding factors. Results. A total of 652 patients were eligible for analysis, including 206 with 3DCRT and 446 with IMRT. The median OS of

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course. We report on a single institution's modern NA-CRT experience in management of localized STS. Materials/Methods: Retrospective review of localized STS patients who underwent a curative course of neoadjuvant chemotherapy and radiotherapy followed by surgical resection from a single institution was performed. Cases undergoing NA-CRT for metastatic STS or with a prior history of excision were excluded from analysis. Acute radiation toxicities were quantified using the Radiation Therapy Oncology Group (RTOG) Common Terminology Criteria for Adverse Events scoring schema. Prechemoradiation and post-chemoradiation primary disease PET/CT avidity values were collected as well as final surgical resection margin status. Using the Kaplan-Meier survival analysis, 2-year local control (LC), disease-free survival (DFS), and overall survival (OS) were estimated. Results: From 2011 to 2018, 37 consecutive cases of biopsy-proven stage IA-IIIB STS to the extremities (27), pelvis (5), paraspinal region (3), adrenal gland (1), and chest wall (1) were identified. Median radiation dose delivered was 46.8 Gy (range: 16-54 Gy), and all patients underwent conventional neoadjuvant chemotherapy with the majority receiving ifosfamide (31). Following NA-CRT, mean reduction of 67% was observed in tumor PET avidity (range: 17-100%); once resected, mean tumor necrosis of 54.0% (range: 2-100%) was observed with complete response in 16.2% (nZ6) and partial response in 75.7% (nZ28). Post-treatment resection margins were negative in all patients with 21.6% having close margin of 1 mm or less and only an additional patient needing re-excision due to an initial positive margin. At median follow-up of 32.8 months (range: 3.3-88.5 months), 2-year LC was 91.7%, DFS 71.4% and OS 92.0%. Radiation was relatively well tolerated during the course of therapy: 70.3% of patients presented with grade I/II radiation dermatitis (single case of grade 3) and 21.6% with grade 1 fatigue. There were 2 cases of delay in treatment due to radiation-related grade 2 esophagitis and abscess development requiring termination of treatment after 1600cGy; 3 other cases of treatment delays were secondary to chemotherapy-related admissions. Postsurgical complications included wound infection in 10.8% (nZ4), and wound dehiscence in 8.1% (nZ3). Conclusion: Neoadjuvant sequencing of chemoradiation in STS trimodality treatment is effective and relatively well tolerated. While this singleinstitution report of NA-CRT demonstrates outstanding resection margin status and long-term local disease control, future prospective assessment of optimal sequencing and identification of reliable prognostic biomarkers and new systemic therapies would be needed for further advancements in STS management.

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