Dr Kelly on the Importance of Testing For Genetic Abnormalities in GIST

Ciara Kelly, MBBCh, BAO, interim clinical director, Sarcoma Oncology Service, Memorial Sloan Kettering Cancer Center (MSKCC), discusses the treatment of patients with gastrointestinal stromal tumors (GIST), highlighting the importance of testing for genetic abnormalities and noting how she performs testing in her own clinical practice.

When treating patients with GIST, determining the optimal timing and approach for genetic testing is crucial, Kelly begins. Ideally, tumor sequencing should be performed at baseline, during recurrence, and serially in cases of metastatic disease where TKI therapies are involved, Kelly says. She states that in her practice, she prioritizes sequencing GIST tumors at baseline to identify the specific molecular subtype of the tumor, which informs the initial treatment strategy. Additionally, she noted that she performs sequencing again if there is a recurrence to reassess the tumor’s genetic profile. At certain points during the course of treatment, additional sequencing may also be considered, Kelly reports, especially if the findings may impact decisions regarding treatment adjustments.

The standard approach to molecularly characterizing GIST involves sequencing tumor tissue, a technique that has significantly evolved over the years due to advancements in sequencing technology, she continues. At MSKCC, oncologists utilize a next-generation sequencing platform to achieve precise genetic characterization of GIST tumors, she says. Another emerging sequencing method is circulating tumor DNA (ctDNA) analysis, which detects gene mutations by examining extracellular DNA released by tumor cells, Kelly explains. This technology has gained traction as an FDA-approved companion diagnostic in various cancers and is increasingly being applied to GIST cases as well, she states.

Moreover, ctDNA is becoming more prevalent in clinical trials focused on GIST, providing valuable insights into its effectiveness and utility in this disease, Kelly says. The integration of ctDNA testing into these trials has broadened the understanding of its role in managing GIST, potentially leading to more refined and personalized treatment strategies for patients in the future, she concludes.