Predictive Biomarkers of Pathological Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Soft Tissue Sarcomas

Background: Marginally resectable and unresectable soft tissue sarcomas (STS) remain a therapy challenge due to the lack of highly active treatment. The aim of the study was to identify a biomarker to predict the pathological response (PR) to preplanned treatment of these STSs. Methods: In the phase II clinical trial (NCT03651375), locally advanced STS patients received preoperative treatment with a combination of doxorubicin-ifosfamide chemotherapy and 5 x 5 Gy radiotherapy. PR to the treatment was classified using the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group recommendations. We have chosen HIF-1a, CD163, CD68, CD34, CD105, and ?H2AFX proteins, rendering different biological phenomena, for biomarker study. Results: Nineteen patients were enrolled and in four cases a good PR was reported. The high expression of HIF-1a before surgery showed a negative correlation with PR, which means a poor response to therapy. Furthermore, the samples after surgery had decreased expression of HIF-1a, which confirmed the correlation with PR. However, high expression of ?H2AFX positively correlated with PR, which provides better PR. The high number of positive-staining TAMs and the high IMVD did not correlate with PR. Conclusions: HIF1a and ?H2AFX could be potential biomarkers for PR prediction after neoadjuvant treatment in STS.

Automated summary

In the study of preplanned treatment in soft tissue sarcoma (STS) patients, HIF1a and ?H2AFX were identified as potential biomarkers for predicting pathological response (PR) after neoadjuvant treatment.