Dataset Information

Depth of response is a significant predictor for long-term outcome in advanced gastric cancer patients treated with trastuzumab.

ABSTRACT:

Purpose

We 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.

Results

From 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 C? 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 methods

Sixty-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).

Conclusions

DpR 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.

SUBMITTER: Lee CK

PROVIDER: S-EPMC5458198 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

Depth of response is a significant predictor for long-term outcome in advanced gastric cancer patients treated with trastuzumab.

Lee Choong-Kun CK Kim Seung-Seob SS Park Saemi S Kim Chan C Heo Su Jin SJ Lim Joon Seok JS Kim Hyunki H Kim Hyo Song HS Rha Sun Young SY Chung Hyun Cheol HC Park Sohee S Jung Minkyu M

Oncotarget 20170501 19

<h4>Purpose</h4>We 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.<h4>Results</h4>From 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 ...[more]

PMID: 28415714

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Project description:BACKGROUND:HER2-positive gastric cancer (GC) affects 7%-34% of patients with GC. Trastuzumab-based first-line treatment has become the standard of care for HER2-positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2-targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2-positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2-positive AGC treated with trastuzumab. PATIENTS AND METHODS:Forty-two HER2-positive GC samples from patients treated with trastuzumab-based first-line chemotherapy were selected. DNA samples were sequenced. PTEN and MET immunohistochemistry were also performed. RESULTS:Concurrent genetic alterations were detected in 97.1% of HER2-positive AGC. We found activation of PI3K/Akt/mTOR pathway in 52.4% of patients and TKR GCN gains in 38.1%. TKR GCN gains did not correlate with overall survival (OS) or progression-free survival (PFS). Multivariate Cox models showed that PI3K/Akt/mTOR activation negatively affects the effectiveness of trastuzumab-based chemotherapy in terms of OS and PFS. CONCLUSION:Our results provide for the first time a detailed molecular profile of concurrent genetic alterations in HER2-positive AGC. PI3K pathway activation could be used as a predictive marker of worse outcome in this patient population. In addition, gains in copy number of other TKR genes in this subgroup may also influence the survival benefit obtained with trastuzumab. IMPLICATIONS FOR PRACTICE:This article reports, for the first time, a detailed molecular profile of genomic alterations in patients with HER2-positive advanced gastric cancer (AGC). PI3K/Akt/mTOR signaling pathway activation seems to have a differentially negative effect on overall survival and progression-free survival in AGC treated with trastuzumab-based chemotherapy. Combining different targeted agents could be a successful therapeutic strategy to improve the prognosis of HER2-positive AGC.

Dataset Information

Depth of response is a significant predictor for long-term outcome in advanced gastric cancer patients treated with trastuzumab.

Purpose

Results

Materials and methods

Conclusions

Publications

Depth of response is a significant predictor for long-term outcome in advanced gastric cancer patients treated with trastuzumab.

Similar Datasets

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