Progress in determining response to treatment in gastrointestinal stromal tumor

ABSTRACT

Introduction: Gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal tumor of the gastrointestinal system. Multiple advances in the management of GIST from the discovery of KIT/PDGRA and other genetic alterations have led to the development of multiple tyrosine kinase inhibitors. Response assessment in GIST is determined with iRECIST (Response Evaluation Criteria in Solid Tumors), PERCIST (PET response criteria in solid tumors), or Choi criteria. Molecular genotyping of the tissue samples is the recent standard for diagnosis, treatment, and response to treatment.

Areas covered: In this study, we provide a brief overview of the history of the GIST, molecular sequencing, available treatment options and clinical trials, radiologic response assessment, and the role of ctDNA in response evaluation.

Expert opinion: Future GIST management is related to the development of sensitive assays to detect genetic alterations for initial diagnosis, treatment selection, monitoring the response to treatment, resistant mutations, and predicting survival.

KEYWORDS:

• Gastrointestinal stromal tumor
• mutational/molecular analysis
• primary/secondary mutation
• ctDNA
• tyrosine kinase inhibitors
• response

Article highlights

• Radiologic response assessment in GIST is performed using iRECIST, PERCIST, and Choi criteria

• Targeted genetic alterations such as KIT/PDGFRA and tyrosine kinase inhibitors are the current mainstay of diagnosis and management

• Assessment of response to tyrosine kinase inhibitors is dependent on primary and secondary resistance mutations in KIT/PDGFRA

• Tumor next-generation sequencing (NGS) and circulating tumor DNA have roles in tissue diagnosis, prognosis, assessment of tumor heterogeneity, clonal evolution, intra-tumor heterogeneity, and tumor mutational burden

Declaration of interest

Ty Subhawong has served as a consultant for Argos & Agios Pharmaceuticals. Jonathan Trent serves as consultant for Blueprint Medicines, Deciphera, Epizyme and Daiichi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.