DOI: 10.1097/sla.0000000000007141 ISSN: 0003-4932

Radiographic Versus Pathology-Integrated Response for Assessing Optimal Surgical Timing After Neoadjuvant Imatinib in Patients With Locally Advanced KIT Exon 11-Mutant GIST

Tannaz Ranjbarian, Michela Del Simone, Dong-Jin Eastern Kang Sim, Mark Antkowiak, Shirley Sarno, Shumei Kato, Adam M. Burgoyne, Elena R. Fumagalli, Dario Callegaro, Paul T. Fanta, Alessandro Gronchi, Jason K. Sicklick
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Objective:

To compare radiographic and pathology-integrated metrics for defining near-maximal treatment effect after neoadjuvant imatinib in KIT exon 11-mutant gastrointestinal stromal tumor (GIST).

Summary of Background Data:

Operative timing after neoadjuvant imatinib is usually guided by radiographic shrinkage, although dimensional response may incompletely reflect biologic treatment effect.

Methods:

We retrospectively analyzed 131 patients with locally advanced KIT exon 11-mutant GIST treated with neoadjuvant imatinib followed by curative-intent resection at 2 tertiary sarcoma centers in the United States and Italy. Radiographic response was assessed across 2-month intervals using RECIST and percent tumor shrinkage. The primary timing analysis identified the earliest interval reaching 90% of peak median response within 3 to 22 months. The same framework was applied to a pathology-integrated response score (PIRS) derived from tumor shrinkage, viable tumor percentage, and necrosis.

Results:

Median age was 62 years, and 60.3% of patients were male. By RECIST, 45.8% achieved partial response and 48.9% had stable disease. Radiographic response reached a near-maximal interval at >4–6 months, whereas PIRS reached a near-maximal interval at >10–12 months. PIRS discriminated across duration groups better than RECIST ( P =0.027 vs. P =0.13). Forty patients (30.5%) with stable disease had major or near-complete PIRS. Overall survival differed across PIRS categories, whereas recurrence-free survival did not differ across PIRS or RECIST categories.

Conclusions:

Radiographic and pathology-integrated response identified different windows of near-maximal treatment effect, suggesting that size reduction alone may underestimate biologic response. The later pathology-integrated response window was not accompanied by differences in recurrence-free survival.

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