Back to 2026 Abstracts
Biologic Plateau Guides Surgical Timing in KIT Exon 11 GIST: No Added Benefit from Prolonged Therapy by Site or Mutation
*Tannaz Ranjbarian1, *Michela Del Simone
2, *Mark Antkowiak
1, *Shirley Sarno
1, *Shumei Kato
3, *Adam M. Burgoyne
3, *Elena R Fumagalli
4, *Dario Callegaro
2, *Paul T. Fanta
3, Alessandro Gronchi
2, Jason Sicklick
11Surgery, University of California, San Diego, San Diego, California; 2Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; 3Medical Oncology, University of California, San Diego, San Diego, California; 4Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan
Background:Neoadjuvant imatinib is increasingly utilized for managing gastrointestinal stromal tumors (GIST) to enable safer, organ-sparing resections. However, the optimal treatment duration and whether it should vary by tumor site, mutation subtype, or pathology remains undefined.
Methods:We retrospectively analyzed 131 patients with localized, resectable
KIT exon 11-mutant GIST treated with neoadjuvant imatinib at two centers. Tumor size reduction was defined by the percent change from baseline imaging to post-resection pathologic size. A Gaussian-derivative method identified the biologic plateau of response. SHAP machine learning, multivariable regression, and Kaplan-Meier analysis evaluated clinical, pathologic, and molecular predictors. Subgroup analyses assessed the impact of treatment duration across tumor sites.
Results:Median treatment duration was 304 days (IQR 198-407). Tumor size reduction correlated with duration (R
2=0.08, P<0.001), plateauing at ~202 days (
Panel A). Duration was the only independent predictor of reduction (β=-0.028/day, P=0.008); tumor site (P=0.23) and mutation subtype (Kruskal-Wallis P=0.935) did not correlate. Interaction testing showed no effect of duration by site (Kruskal-Wallis P=0.096; ANOVA P=0.097). Rectal tumors received the longest treatment (median 379.5 days) yet showed no additional reduction beyond the plateau (median reduction <202 days: -34.3% vs. ≥202 days: -36.0%, P=0.73). Across all sites, extended therapy beyond 202 days did not yield significant gains in the stomach (P=0.16) or duodenum (P=0.31). Importantly, patients treated >202 days did not have prolonged survival (log-rank P=0.857;
Panel B). Among pathologic features, only viable tumor percentage showed weak correlation with size reduction (r=0.25, P=0.019) while necrosis (r=0.19, P=0.083) and mitotic index (r=0.08, p=0.45) did not.
Conclusion:For the first time, we report a biologic treatment plateau at ~6.6 months (202 days) following neoadjuvant imatinib in patients with
KIT exon 11 GIST. Continued therapy beyond this point may offer diminishing returns, without associated improvement in survival or pathologic response, unless the tumor is continuing to shrink. These findings support a biology-guided surgical approach: resect once goals are met and the plateau is reached, streamlining care and avoiding overtreatment based on anatomy alone.
Back to 2026 Abstracts
