PMID- 36995690 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20240331 IS - 2374-2445 (Electronic) IS - 2374-2437 (Print) IS - 2374-2437 (Linking) VI - 9 IP - 5 DP - 2023 May 1 TI - Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials. PG - 646-655 LID - 10.1001/jamaoncol.2023.0042 [doi] AB - IMPORTANCE: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS). OBJECTIVE: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630. DESIGN, SETTING, AND PARTICIPANTS: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes. INTERVENTION: Patients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone. MAIN OUTCOMES AND MEASURES: Overall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017. RESULTS: Overall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45). CONCLUSIONS AND RELEVANCE: This ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791). FAU - Wang, Dian AU - Wang D AD - Rush University Medical Center, Chicago, Illinois. FAU - Harris, Jonathan AU - Harris J AD - NRG Oncology Statistics and Data Management Center, American College of Radiology. FAU - Kraybill, William G AU - Kraybill WG AD - The Ohio State University, Columbus. FAU - Eisenberg, Burt AU - Eisenberg B AD - Hoag Memorial Hospital Presbyterian, Newport Beach, California. FAU - Kirsch, David G AU - Kirsch DG AD - Duke University Medical Center, Durham, North Carolina. FAU - Ettinger, David S AU - Ettinger DS AD - Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland. FAU - Kane, John M 3rd AU - Kane JM 3rd AD - Roswell Park Cancer Institute, Buffalo, New York. FAU - Barry, Parul N AU - Barry PN AD - UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania. FAU - Naghavi, Arash AU - Naghavi A AD - H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida. FAU - Freeman, Carolyn R AU - Freeman CR AD - McGill University, Montreal, Quebec, Canada. FAU - Chen, Yen-Lin AU - Chen YL AD - Massachusetts General Hospital, Boston. FAU - Hitchcock, Ying J AU - Hitchcock YJ AD - University of Utah Health Science Center, Salt Lake City. FAU - Bedi, Manpreet AU - Bedi M AD - Froedtert and The Medical College of Wisconsin, Wauwatosa, Wisconsin. FAU - Salerno, Kilian E AU - Salerno KE AD - Roswell Park Cancer Institute, Buffalo, New York. FAU - Severin, Diane AU - Severin D AD - Cross Cancer Institute, Edmonton, Alberta, Canada. FAU - Godette, Karen D AU - Godette KD AD - Emory University, Atlanta, Georgia. FAU - Larrier, Nicole A AU - Larrier NA AD - Duke University Medical Center, Durham, North Carolina. AD - Accrual for University of Texas-MD Anderson Cancer Center, Houston, Texas. FAU - Curran, Walter J Jr AU - Curran WJ Jr AD - GenesisCare. FAU - Torres-Saavedra, Pedro A AU - Torres-Saavedra PA AD - NRG Oncology Statistics and Data Management Center, American College of Radiology. FAU - Lucas, David R AU - Lucas DR AD - University of Michigan, Ann Arbor. LA - eng SI - ClinicalTrials.gov/NCT00589121 SI - ClinicalTrials.gov/NCT00002791 GR - U10 CA180822/CA/NCI NIH HHS/United States GR - U10 CA180868/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - JAMA Oncol JT - JAMA oncology JID - 101652861 SB - IM CIN - JAMA Oncol. 2023 May 1;9(5):619-621. PMID: 36995719 MH - Male MH - Adult MH - Humans MH - Middle Aged MH - Female MH - *Neoadjuvant Therapy MH - *Sarcoma/mortality MH - Prognosis MH - Progression-Free Survival MH - Disease-Free Survival PMC - PMC10064284 COIS- Conflict of Interest Disclosures: Dr Kirsch reported grants from Merck, Bristol Myers Squibb, and Xrad Therapeutics, personal fees from Lumicell Inc as a Member of Scientific Advisory Board outside the submitted work; in addition, Dr Kirsch had a patent for Lumicell with royalties paid for Intraoperative Imaging and a patent for Xrad Therapeutics issued for Radiosensitizers. Dr Barry reported consulting fees from Elsevier, co-chair of sarcoma/skin cancer radiation oncology committee outside the submitted work. Dr Torres-Saavedra reported grants from NRG Oncology SDMC Grant / NCI during the conduct of the study. No other disclosures were reported. EDAT- 2023/03/31 06:00 MHDA- 2023/05/22 06:42 PMCR- 2024/03/30 CRDT- 2023/03/30 11:32 PHST- 2023/05/22 06:42 [medline] PHST- 2023/03/31 06:00 [pubmed] PHST- 2023/03/30 11:32 [entrez] PHST- 2024/03/30 00:00 [pmc-release] AID - 2803097 [pii] AID - coi230002 [pii] AID - 10.1001/jamaoncol.2023.0042 [doi] PST - ppublish SO - JAMA Oncol. 2023 May 1;9(5):646-655. doi: 10.1001/jamaoncol.2023.0042.