Response Evaluation of Neoadjuvant Therapies in Sarcoma

Abstract

Sarcoma is a complex and heterogeneous disease with a rapidly evolving treatment landscape. With a growing emphasis on neoadjuvant therapy as a way to improve surgical and oncologic outcomes, our approach to monitor treatment efficacy must also continue to evolve. This is paramount to both clinical trial design, where endpoints must accurately reflect disease outcomes, and individual patient, whose treatment response informs therapeutic decisions. In the era of personalized medicine, the response to neoadjuvant treatment in sarcoma remains most effectively gauged by pathologic review following surgical resection. Although measures of pathologic complete response most effectively predict outcome, the requisite surgical excision precludes their use in real-time monitoring of neoadjuvant treatment response. Current image-based metrics such as RECIST and PERCIST have been utilized in many trials; however, they are limited by their unilateral measurement approach. More effective tools are needed to better measure the response to therapy prior to neoadjuvant regimen completion, so that the medication or regimen may be best tailored to patient response in an ongoing fashion. Delta-radiomics and circulating tumor DNA (ctDNA) represent promising novel tools for real-time monitoring of treatment efficacy. These metrics have been shown to predict pathologic complete response and disease progression at a superior level to traditional CT-based guidelines. Delta-radiomics is currently being utilized in a clinical trial among soft tissue sarcoma patients in which radiation dosage is adjusted based on radiomic data. The ability of ctDNA to detect molecular residual disease is also under study in multiple clinical trials, although none in the field of sarcoma. Future directions in the field include the use of ctDNA and molecular residual disease testing among sarcoma patients, as well as increased utilization of delta-radiomics, to more effectively monitor neoadjuvant treatment response prior to surgical resection.