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Experts Investigate Value of Chromosomal Complexity in Imatinib Treatment for High-Risk GIST

Investigators sought to determine if chromosomal complexity could be used as a biomarker in de-escalation of adjuvant imatinib treatment, presented at the 2021 ASCO Annual Meeting. 

Though investigators hypothesized that high-risk GISTs with few chromosomal aberrations had a favorable outcome, and may not benefit from adjuvant therapy, results presented the Chromosomal complexity was strongly correlated with poor RFS in localized, high-risk GIST.

GIST patients undergoing surgical resection of their primary tumor between 1998 and 2020 were identified in the sarcoma database at Oslo University Hospital. Within said database, included all samples with available karyotype analysis made on fresh tumor tissue. To note, karyotypes were categorized as simple if they had ≤5 chromosomal changes, and complex if there were > 5 chromosomal aberrations.

Chromosomal aberrations were in fact detected in 226 tumors. Of which, 181 80.1 % were gastric. The most recurrent resulting imbalances included loss of 14q (75.9 %), 22q (43.5 %), 1p (36.6 %), and 15q (29.6 %).

136 tumors (60.2 %) had simple karyotypes, though 90 (39.8 %) were complex. Cytogenetically complex tumors were found to be larger (P< 0.001), had a higher mitotic count (P= 0.009), and were more often non-gastric (P< 0.001).

“A strong association was found amongst chromosomal complexity and risk classification, according to the modified NIH criteria (P< 0.001). Additionally, 65.5 % of high-risk tumors within the study were karyotypically complex compared to 37 of 144 (25.7 %) tumors that were not high-risk. In the high-risk group, 17 patients experienced disease recurrence, of whom one had a simple and 16 had a complex tumor karyotype”, stated Dr. Boye and fellow investigators.

“Estimated 5-year RFS for patients with simple tumor karyotypes was 94 % compared to 51 % for patients with cytogenetically complex tumors (P= 0.004). Adjuvant and/or neoadjuvant imatinib treatment was administered to 40 high-risk patients with a median treatment duration of 33 months (range 2-60 months). A complex karyotype was associated with poor RFS both in patients with (P= 0.016) and without (P= 0.046) adjuvant imatinib”-they continued.

Chromosomal complexity was strongly associated with poor RFS in localized, high-risk GIST. Recurrences were infrequent for tumors with simple karyotypes, indicating that de-escalation of adjuvant imatinib treatment should be further explored in patients with cytogenetically simple GISTs.

To conclude, investigators reports chromosomal complexity was strongly correlated with poor RFS in localized, high-risk GIST. -Alexis Hyams

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