March 31 2023
Combined long-term survival results from nonrandomized phase II trial NRG Oncology RTOG 0630 and the ancillary analysis of the combined NRG-RTOG 0630/9514 trials indicate that pathologic complete response (pCR) is associated with improved survival outcomes for patients with localized soft tissue sarcoma (STS) who receive preoperative chemoradiotherapy or radiotherapy. This data suggests that pCR can be used as a prognostic factor for clinical outcomes in future STS research. These results were recently published in the JAMA Oncology.
NRG-RTOG 0630 and 9514 both evaluated STS patients who were receiving either preoperative image-guided radiotherapy (IGRT; 0630) or neoadjuvant chemoradiotherapy (9514). The primary objective of the combined ancillary analysis was to correlate percentage tumor viability after surgery with survival and disease outcomes for this patient population on these two studies.
“Previously, all information that researchers had regarding the prognostic impact of pCR to therapy for STS patients was limited, unclear, and often offered conflicting results. In this analysis, we strived to connect the treatment-induced pCR of STS patients receiving these relatively uniformed treatment regimens to their recently reported long-term outcomes,” stated Dian Wang, MD, PhD, FASTRO, of the Rush University Medical Center and the Lead Author of the NRG-RTOG 0630/9514 manuscript.
The long-term results of NRG-RTOG 0630 analyzed 79 patients with STS at a median follow-up of 6 years for surviving patients. The results, published in this manuscript, indicate the estimated 5-year overall survival (OS) is 62.1% (95% confidence interval [CI] 51.2-73.0) and the estimated 5-year local failure (LF) rate is 12.7% (95% CI 6.5-21.1). The 5-year distant failure rate is 45.3% (95% CI 33.8-56.0) and the 5-year disease-free survival (DFS) and distant disease-free survival rates are 47.5% (95% CI 36.4-58.6) and 52.1% (95% CI 40.9-63.3), respectively. These results have also established that the reduced target volumes that were used during this study are appropriate for preoperative IGRT.
NRG-RTOG 0630 and 9514 combined included 123 patients that were evaluable for pCR as 14 out of 51 (27.5%) on 9514 and 14 out of 72 (19.4%) on 0630 had pCR. The 5-year OS rate is 100% for patients with pCR versus 76.5% (95% CI 62.3-90.8) and 56.4% (95% CI 43.3-69.5) for patients with <pCR in 9514 and 0630, respectively and pCR is associated with improved OS (p=0.01) and DFS [hazard ratio (HR) 4.91, 95% CI 1.51-15.93; p=0.008] relative to <pCR. Five-year LF 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 <pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma are associated with worse OS [HR 2.24, 95% CI 1.12-4.45].
Further research should consider an analysis of a larger population of STS patients, delving into the correlation between hyalinization/fibrosis to oncologic outcomes, assessing imaging and pCR in relation to disease outcomes, and clarifying specific histologic types that may benefit from treatment intensification and personalized therapy to help strengthen the findings of this study.
This project was supported by grants U10CA180868 (NRG Oncology Operations) and U10CA180822 (NRG Oncology SDMC) from the National Cancer Institute (NCI).
Wang D, Harris J, Kraybill WG, et al. 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. JAMA Oncol. Published online March 30, 2023. doi:10.1001/jamaoncol.2023.0042
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.