Researchers have discovered that pathologic complete responses may be associated with improved survival outcomes for patients with localized soft-tissue sarcoma who received preoperative chemoradiotherapy or radiotherapy, according to a novel study published by Wang et al in JAMA Oncology. The new findings suggest that pathologic complete responses can be used as a prognostic factor for clinical outcomes in future soft-tissue sarcoma studies.
Background
“Previously, all information that researchers had regarding the prognostic impact of [pathologic complete responses] to therapy for patients [with soft-tissue sarcoma] was limited, unclear, and often offered conflicting results. In this analysis, we strived to connect the treatment-induced [pathologic complete responses] of patients [with this disease] receiving these relatively uniformed treatment regimens to their recently reported long-term outcomes,” explained first study author Dian Wang, MD, PhD, FASTRO, Professor of Radiation Oncology at the Rush University Medical College.
Study Methods and Results
In the nonrandomized phase II NRG Oncology RTOG 0630 trial and the NRG Oncology RTOG 9514 trial, the researchers evaluated patients with soft-tissue sarcoma who were receiving either preoperative image-guided radiotherapy or neoadjuvant chemoradiotherapy. The primary objective of the ancillary analysis of the combined 0630/9514 trials was to correlate the percentage of postsurgical tumor viability with survival and disease outcomes for this patient population in both studies.
In the 0630 trial, the researchers analyzed 79 patients with soft-tissue sarcoma and found that the estimated 5-year overall survival rate was 62.1% (95% confidence interval [CI] = 51.2%–73.0%) and the estimated 5-year local failure rate was 12.7% (95% CI = 6.5%–21.1%). Additionally, the 5-year distant failure rate was 45.3% (95% CI = 33.8%–56.0%), and the 5-year disease-free survival and distant disease–free survival rates were 47.5% (95% CI = 36.4%–58.6%) and 52.1% (95% CI = 40.9%–63.3%), respectively. The researchers also established that the reduced target volumes used during this study were appropriate for preoperative image-guided radiotherapy.
Combined, NRG-RTOG 0630 and 9514 included 123 patients who were eligible for inclusion in the new analysis—with 27.5% (n = 14/51) of patients from the 9514 study and 19.4% (n = 14/72) of patients from the 0630 trial demonstrating pathologic complete responses. The 5-year overall survival rate was 100% for patients with pathologic complete responses vs 76.5% (95% CI = 62.3%–90.8%) and 56.4% (95% CI = 43.3%–69.5%) for patients with less than pathologic complete responses in the 9514 trial and 0630 trial, respectively. The researchers also found that pathologic complete responses were associated with improved overall survival (P = .01) and disease-free survival (hazard ratio [HR] = 4.91, 95% CI = 1.51–15.93; P = .008) relative to patients with less than pathologic complete responses. Further, the 5-year local failure rate was 0% in patients with pathologic complete responses vs 11.7% (95% CI = 3.6%–25.1%) and 9.1% (95% CI = 3.3%–18.5%) in those with less than pathologic complete responses in the 9514 trial and 0630 trial, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were possibly associated with worse overall survival (HR = 2.24, 95% CI = 1.12–4.45).
Conclusions
The researchers emphasized that larger studies of patients with soft-tissue sarcoma may be needed to examine the correlation between hyalinization/fibrosis and oncologic outcomes, assess imaging and pathologic complete responses in relation to disease outcomes, and clarify specific histologic types that may benefit from treatment intensification and personalized therapy.
Disclosure: The research in this study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
