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

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

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1828-1836
Number of pages9
JournalJournal of Gastrointestinal Surgery
Volume25
Issue number7
DOIs
StatePublished - Jul 2021

Bibliographical note

Funding Information:
Consulting fees from Blueprint Medicines, Novartis, Daiichi Sankyo, Loxo, and GlaxoSmithKline Pharmaceuticals (William Tap). Dr. DeMatteo has a research grant from Blueprint Medicines. The other authors have no disclosures.

Funding Information:
The investigators were supported by NIH grant R01 CA102613, the David Foundation, Betsy Levine-Brown and Marc Brown, GIST Cancer Research Fund, and David and Monica Gorin (RPD), Kristen Ann Carr Fellowship (MJC)

Publisher Copyright:
© 2020, The Society for Surgery of the Alimentary Tract.

Keywords

  • GIST
  • Gastrointestinal stromal tumor
  • Imatinib
  • Neoadjuvant
  • Surgery

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Fingerprint

Dive into the research topics of 'Prognostic Factors After Neoadjuvant Imatinib for Newly Diagnosed Primary Gastrointestinal Stromal Tumor'. Together they form a unique fingerprint.

Cite this