TY - JOUR
T1 - Prognostic Factors After Neoadjuvant Imatinib for Newly Diagnosed Primary Gastrointestinal Stromal Tumor
AU - Cavnar, Michael J.
AU - Seier, Kenneth
AU - Gönen, Mithat
AU - Curtin, Christina
AU - Balachandran, Vinod P.
AU - Tap, William D.
AU - Antonescu, Cristina R.
AU - Singer, Sam
AU - DeMatteo, Ronald P.
N1 - Publisher Copyright:
© 2020, The Society for Surgery of the Alimentary Tract.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - GIST
KW - Gastrointestinal stromal tumor
KW - Imatinib
KW - Neoadjuvant
KW - Surgery
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U2 - 10.1007/s11605-020-04843-9
DO - 10.1007/s11605-020-04843-9
M3 - Article
C2 - 33169327
AN - SCOPUS:85095709032
SN - 1091-255X
VL - 25
SP - 1828
EP - 1836
JO - Journal of Gastrointestinal Surgery
JF - Journal of Gastrointestinal Surgery
IS - 7
ER -