Abstract
PurposeWe aimed to determine and compare the predictive values of depth of response (DpR) and early tumor shrinkage (ETS) on long-term outcomes in gastric cancer patients treated with trastuzumab.ResultsFrom a total of 368 computed tomography examinations, DpR and ETS were evaluated. DpR was a significant tumor-size metric in predicting PFS and OS, and showed better discriminatory ability (higher Cτ indices, 0.6957 for PFS; 0.7191 for OS) than ETS. DpR ≥ 45% (vs. < 45%) was the optimal cutoff value, as it was best able to identify patients with longer PFS (median 9.0 vs. 6.3 months, hazard ratio [HR] = 0.608; 95% confidence interval [CI]: 0.335 to 1.104; P = 0.102) and OS (median 23.5 vs. 13.1 months, HR = 0.441; 95% CI: 0.203 to 0.955; P = 0.038).Materials and MethodsSixty-one gastric cancer patients who received first-line trastuzumab-based chemotherapy were assessed for DpR and ETS. We employed Kaplan-Meier estimates, log-rank tests, Cox proportional hazards regression models, time-dependent receiver operating characteristics, and Youden's J index to evaluate and determine cutoff values of DpR and ETS as predictors of progression-free survival (PFS) and overall survival (OS).ConclusionsDpR and ETS were significant predictors of long-term outcomes in gastric cancer patients treated with first-line trastuzumab. Validation in prospective trials with larger patient populations is needed.
Highlights
Gastric cancer, the second leading cause of cancerrelated deaths worldwide, remains a major health problem despite a global decrease in its incidence [1]
depth of response (DpR) ≥ 45% was the optimal cutoff value, as it was best able to identify patients with longer progression-free survival (PFS) and overall survival (OS)
DpR and early tumor shrinkage (ETS) were significant predictors of long-term outcomes in gastric cancer patients treated with first-line trastuzumab
Summary
The second leading cause of cancerrelated deaths worldwide, remains a major health problem despite a global decrease in its incidence [1]. Aside from well-known surrogate end-points for OS, such as progression-free www.impactjournals.com/oncotarget survival (PFS) and objective response rate, other metrics based on tumor size have recently been investigated. These include early tumor shrinkage (ETS) and depth of response (DpR), both of which are indicators of the percentage change in tumor size at a designated time point from the baseline. ETS, defined as change in tumor size at the time of first response evaluation, has been proposed to be associated with long-term outcomes in various cancer types and regimens, mainly colorectal cancer [4,5,6,7,8,9,10]. While there have been separate studies on the association of DpR or ETS and cancer patient prognosis, there has been no study evaluating DpR or ETS as predictive factors for survival outcome within one treatment cohort, in gastric cancer patients
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