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

Abstract

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 × 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-1α, CD163, CD68, CD34, CD105, and γH2AFX 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-1α 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-1α, which confirmed the correlation with PR. However, high expression of γH2AFX 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: HIF1α and γH2AFX could be potential biomarkers for PR prediction after neoadjuvant treatment in STS.

Low NT5DC2 expression predicts favorable prognosis and suppresses soft tissue sarcoma progression via ECM-receptor interaction pathway

“…Soft tissue sarcoma is a compositional complex and highly heterogeneous mesenchymal malignancy which happened in all parts of the human body, at all ages, with a wide variety and different biological behaviors [18] . Despite extensive research efforts, the etiology of soft tissue sarcoma remains elusive and due to the limited efficacy of chemotherapy and radiotherapy in soft tissue sarcoma patients, surgery is still the main treatment [ 19 , 20 ]. Meanwhile, soft tissue sarcoma has high recurrence and lung metastasis rates, and patients with advanced-stage soft tissue sarcoma cannot tolerate surgery, chemotherapy or radiotherapy [ 21 , 22 ].…”

A bibliometric analysis based on hotspots and frontier trends of positron emission tomography/computed tomography utility in bone and soft tissue sarcoma

“…The delta-imaging omics histogram combined with imaging characteristics and clinical factors can be used to evaluate individual pathological reactions after preoperative chemotherapy, which is helpful to formulate appropriate chemotherapy and further treatment plans (89). In addition, Anna et al (90) proposed a biomarker for predicting NCT PR. The researchers discovered a negative correlation between PR and the expression of HIF-1a, suggesting a suboptimal treatment response.…”

“…Sarcoma cells utilize hypoxia and the DNA damage response as mechanisms to react to multidisciplinary treatment (90). The uptake of 3'-deoxy-3'-FLT ( 18 F-FLT), which is similar to the nucleotide thymidine and serves as a marker for DNA replication, has been investigated as an indicator of tumor cell growth (94).…”