Link Between pCR and Improved Survival for Patients With Soft Tissue Sarcoma

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A link between pathologic complete response (pCR) and improved survival outcomes were seen in patients with localized soft tissue sarcoma (STS) who received preoperative chemoradiotherapy or radiotherapy, according to long-term survival results from an analysis of the combined NRG-RTOG 0630/9514 trials (NCT00589121; NCT00002791).¹

At 5 years, the overall survival (OS) rate was 100% in trial NRG-RTOG 9514 for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) in NRG-RTOG 0630, and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR, respectively. This showed that pCR was associated with improved OS (P = .01) and disease-free survival (DFS; HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR.²

Additionally in trials 9514 vs 0630, the 5-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, respectively. Aside from leiomyosarcoma, liposarcoma, and myxofibrosarcoma, histologic types other than were associated with worse OS rates (HR, 2.24; 95% CI, 1.12-4.45).

Overall, these data show that pCR can be used as a prognostic factor for clinical outcomes in future research evaluating patients with STS.¹

“The goal of this analysis was to determine if complete pathology response is associated with long-term survival. In addition, we have updated the long-term results of our image-guided preoperative radiotherapy of extremity soft tissue sarcoma [RTOG 0630],” Dian Wang, MD, PhD, FASTRO, of the Rush University Medical Center and the lead author of the NRG-RTOG 0630/9514 manuscript, told Targeted Oncology^TM. "The findings showed that complete pathology response [no viable tumor cells] treated by neoadjuvant chemo-radiation or radiation alone predicts good long-term survival outcomes. Long-term results of image-guided preoperative radiotherapy [RTOG 0630] are still excellent in both clinical outcomes and advserse event profiles, which indicates peremeters used in this protocol should be considered as a standard to treat extremity soft tissue sarcoma if radiotherapy is given preoperatively."

In both the NRG-RTOG 0630 and 9514 trials, investigators evaluated patients with STS who were receiving either preoperative image-guided radiotherapy (NRG-RTOG 0630) or neoadjuvant chemoradiotherapy (NRG-RTOG 9514).¹ There were 143 eligible patients from the 0630 (n = 79) and 9514 (n = 64) trials included in the ancillary analysis of pCR. Seventy-nine patients from the 0630 trial were evaluated for long-term outcomes.

For the combined ancillary analysis of the trials, investigators assessed the primary objective of correlating percentage tumor viability after surgery with survival and disease outcomes for this patient population.

In the analysis, there were 42 (53.2%) men. A total of 68 (86.1%) were white and the mean age among patients was 59.6 (14.5) years. For the NRG-RTOG 0630 trial, there was 1 new in-field recurrence and 1 new distant failure at median follow-up of 6.0 years and since the initial report. Additionally, 123 patients were evaluable for pCR from both studies, 14 of the 51 (27.5%) patients in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR.

Additional long-term findings from the NRG-RTOG 0630 study which analyzed 79 patients with STS and had a median follow-up of 6 years for surviving patients showed that the estimated 5-year overall survival was 62.1% (95% CI, 51.2-73.0). The estimated 5-year local failure rate was 12.7% (95% CI 6.5-21.1), the 5-year distant failure rate was 45.3% (95% CI 33.8-56.0), and the 5-year DFS and distant DFS rates were 47.5% (95% CI 36.4-58.6) and 52.1% (95% CI 40.9-63.3), respectively.

Based on these results, it has been established that the reduced target volumes that were used during this study are appropriate for preoperative image-guided radiotherapy.

This ancillary analysis of 2, non-randomized, NRG-RTOG 0630 and 9514 clinical trials found that pCR correlated with improved survival in patients with STS. pCR should be considered as a prognostic factor of clinical outcomes for future studies.

Moreover, it is suggested that additional research should consider an analysis of a larger population of patients with STS to further evaluate the link between hyalinization/fibrosis to oncologic outcomes, assess imaging and pCR in relation to disease outcomes, and clarify which histologic types may benefit from treatment intensification and personalized therapy. This type of research would help strengthen the findings of this study.

"We need to investigate either radiation intensification or targeted agents that sensitize radiation to cause no viable tumor cells, which predicts for survival benefits," added Wang.

REFERENCES:

1. NRG oncology combined trial long-term results indicate that pathologic complete response is prognostic of outcomes for soft tissue sarcoma patients. News release. March 31, 2023. Accessed April 4, 2023. https://bit.ly/3K0NVGU

2. 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 [published online ahead of print, 2023 Mar 30]. JAMA Oncol. 2023;e230042. doi:10.1001/jamaoncol.2023.0042