Journal Article

Prognostic Factors After Neoadjuvant Imatinib for Newly Diagnosed Primary Gastrointestinal Stromal Tumor

Antonescu, Cristina R., Singer, Sam, Cavnar, Michael J., Curtin, Christina, Tap, William D., Seier, Kenneth, DeMatteo, Ronald P., Balachandran, Vinod P., Gönen, Mithat

2021

Overview

Introduction Neoadjuvant imatinib (Neo-IM) therapy may facilitate R0 resection in primary gastrointestinal stromal tumors (GISTs) that are large or in difficult anatomic locations. While response to preoperative tyrosine kinase inhibitors is associated with better outcome in metastatic GIST, little is known about prognostic factors after Neo-IM in primary GIST. Study Design Patients with primary GIST with or without synchronous metastases who underwent Neo-IM were retrospectively analyzed from a prospective maintained institutional database for Response Evaluation Criteria in Solid Tumors (RECIST), tumor viability, and mitotic rate. Overall survival (OS) was estimated by Kaplan-Meier and compared by log-rank test. Cox proportionate hazard models were used for univariate and multivariate analysis. Results One hundred and fifty patients were treated for a median of 7.1 months (range 0.2–160). By RECIST, partial response, stable disease, and progressive disease were seen in 40%, 51%, and 9%, respectively. By pathologic analysis, ≤ 50% of the tumor was viable in 72%, and the mitotic rate was ≤ 5/50HPF in 74%. On multivariate analysis, RECIST response and tumor viability were not associated with OS, while post-treatment high mitotic rate (hazard ratio (HR) for death 5.3, CI 2.3–12.4), R2 margins (HR 6.0, CI 2.3–15.5), and adjuvant imatinib (HR 0.4, CI 0.2–0.9) were ( p < 0.05). Five-year OS was 81 vs. 38% for low vs. high mitotic rate; 81, 59, and 39% for R0, R1, and R2 margins; and 75 vs 61% for adjuvant vs. no adjuvant imatinib therapy ( p < 0.05). Conclusions In primary GIST undergoing Neo-IM therapy, progression was uncommon, but substantial down-sizing occurred in the minority. High tumor mitotic rate and incomplete resection following Neo-IM were associated with poor outcome, while adjuvant imatinib was associated with prolonged survival.

• Publisher: Springer US,Springer Nature B.V
• Subject: Antineoplastic Agents - therapeutic use / Cancer surgery / Cancer therapies / Clinical trials / Gastric cancer / Gastroenterology / Gastrointestinal cancer / Gastrointestinal Neoplasms - drug therapy / Gastrointestinal Stromal Tumors - drug therapy / Humans / Imatinib Mesylate - therapeutic use / Inhibitor drugs / Medical prognosis / Medicine / Medicine & Public Health / Metastasis / Multivariate analysis / Neoadjuvant Therapy / Original Article / Prognosis / Prospective Studies / Retrospective Studies / Sarcoma / Surgery / Targeted cancer therapy / Tumors