A new study found that patients with certain types of mutations to exon 11 of the KIT gene are at increased risk of recurrence for gastrointestinal stromal tumor (GIST) after complete resection. The study was published in Therapeutic Advances in Medical Oncology.
The results demonstrated that 18 out of 36 patients (50%) with KIT exon 11 deletion or deletion/insertion involving codon 557 and/or 558 (Del-557/558) had recurrence within 7 years of resection. This was compared to 7 out of 26 (26.9%) patients with deletion/insertion in codons other than 557 and/or 558 (Del-No-557/558), or 4 out of 34 (11.8%) patients with duplication, insertion, or single-nucleotide-variant mutations (No-Del).
When comparing the 3 groups of mutations, Del-557/558 patients also had shorter median recurrence-free survival (mRFS) times of 86.9 months compared to Del-No-557/558 (mRFS, 148.02 months) and No-Del groups (mRFS, 155 months; P <.001).
Within the group of Del-557/558 patients who experienced relapse, 14 of the 18 patients (77.8%) had deletions that involved both codons 557 and 558.
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In terms of risk category, 55.5% of Del-557/558 patients were classified as high-risk compared to 15.4% of Del-No-557/558 or 44.1% of No-Del patients (P =.008).
“In patients with localized GISTs completely resected we showed that KIT exon 11 deletions or deletion/insertion involving both codons 557 and 558 are genotypes indicative of more aggressive tumor behavior and higher risk of recurrence: the KIT exon 11 deletion or deletion/insertion, when involving only one of 557 or 558 codons, resembles the more indolent prognostic behavior of tumor-carrying deletion outside 557 and 558 codons, supporting the importance of considering the PV type and codon location in routine risk stratification,” the authors concluded.
The study also found that patients at intermediate risk with Del-557/558 had a similar worse prognosis than high-risk patients in the Del-No-557/558 and No-Del groups, and should be considered for adjuvant treatment with imatinib.
A total of 96 patients with localized GISTs and KIT exon 11 mutations were included in the study between January 2005 and December 2020. The median follow-up time for the study was 92 months (range, 10-190 months) with a 7-year RFS rate of 69.8%.
Incorvaia L, Badalamenti G, Fanale D, et al. Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs). Ther Adv Med Oncol. 2021;13. doi.17588359211049779