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

Author:

Szumera-Ciećkiewicz Anna12ORCID,Bobak Klaudia3,Spałek Mateusz J.34ORCID,Sokół Kamil12,Wągrodzki Michał1,Owczarek Daria1,Kawecka Monika12,Puton Beata1,Koseła-Paterczyk Hanna3ORCID,Rutkowski Piotr3ORCID,Czarnecka Anna M.35ORCID

Affiliation:

1. Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02781 Warsaw, Poland

2. Diagnostic Hematology Department, Institute of Hematology and Transfusion Medicine, 00791 Warsaw, Poland

3. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02781 Warsaw, Poland

4. 1st Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, 02781 Warsaw, Poland

5. Department of Experimental Pharmacology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02106 Warsaw, Poland

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.

Funder

Maria Sklodowska-Curie National Research Institute of Oncology Internal

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference63 articles.

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5. Predicting radiotherapy response for patients with soft tissue sarcoma by developing a molecular signature;Tang;Oncol. Rep.,2017

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