Dataset Information

Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy.

ABSTRACT: PURPOSE:To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation. METHODS AND MATERIALS:We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was used to determine time to local and distant failure, overall survival, and progression-free survival. P values were calculated with the log-rank test. RESULTS:High tumor expression of c-MET was associated with a shorter time to distant failure in patients receiving neoadjuvant (n=23) or neoadjuvant therapy (n=73) (median 8.9 months vs 22.0 months, P=.0010). We then examined the ability of incorporating 2 known biomarkers, thymidylate synthase and DPC4 (SMAD4), with c-MET to risk-stratify patients. This multi-protein predictor divided our cohort into groups of similar numbers and was predictive of distant failure (median 13.4 months vs 24.2 months, P=.0094) but not of local control. CONCLUSION:c-MET is potentially predictive of distant failure. Using c-MET, DPC4, and thymidylate synthase, we developed a multi-protein predictor that could be used to risk-stratify patients and guide decisions regarding the sequencing of locoregional and systemic therapies in pancreatic cancer.

SUBMITTER: Cuneo KC

PROVIDER: S-EPMC6444352 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy.

Cuneo Kyle C KC Morgan Meredith A MA Griffith Kent A KA Hawkins Peter G PG Greenson Joel K JK Ben-Josef Edgar E Lawrence Theodore S TS Zalupski Mark M MM

International journal of radiation oncology, biology, physics 20171028 2

<h4>Purpose</h4>To determine the prognostic significance of c-MET expression and develop a predictor of distant failure in patients with resectable pancreatic cancer treated with chemoradiation.<h4>Methods and materials</h4>We used a tissue microarray to study protein expression by immunohistochemistry in 102 patients treated surgically for pancreatic cancer. Two cores per patient were blindly scored from 0 (no staining) to 3 (strong staining) by a single pathologist. The Kaplan-Meier method was ...[more]

PMID: 29229329

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Project description:Background:Neoadjuvant chemoradiation is currently standard of care in stage II-III rectal cancer, resulting in tumor downstaging for patients with treatment-responsive disease. However, the prognosis of the downstaged patient remains controversial. This work critically analyzes the relative contribution of pre- and post-therapy staging to the anticipated survival of downstaged patients. Methods:The National Cancer Database (NCDB) was queried for patients with rectal cancer treated with transabdominal resection between 2004 and 2014. Stage II-III patients downstaged with neoadjuvant radiation were compared with stage I patients treated with definitive resection alone. Patients with positive surgical margins were excluded. Overall survival was evaluated using both Kaplan-Meier analyses and Cox proportional hazards models. All statistical tests were two-sided. Results:A total of 44 320 patients were eligible for analysis. Survival was equivalent for patients presenting with cT1N0 disease undergoing resection (mean survival = 113.0 months, 95% confidence interval [CI] = 110.8 to 115.3 months) compared with those downstaged to pT1N0 from both cT3N0 (mean survival = 114.9 months, 95% CI?=?110.4 to 119.3 months, P = .12) and cT3N1 disease (mean survival = 115.4 months, 95% CI?=?110.1 to 120.7 months, P = .22). Survival statistically significantly improved in patients downstaged to pT2N0 from cT3N0 disease (mean survival = 109.0 months, 95% CI?=?106.7 to 111.2 months, P < .001) and cT3N1 (mean survival = 112.8 months, 95% CI?=?110.0 to 115.7 months, P < .001), compared with cT2N0 patients undergoing resection alone (mean survival = 100.0 months, 95% CI?=?97.5 to 102.5 months). Multiple survival analysis confirmed that final pathologic stage dictated long-term outcomes in patients undergoing neoadjuvant radiation (hazard ratio [HR] of pT2 = 1.24, 95% CI?=?1.10 to 1.41; HR of pT3 = 1.81, 95% CI?=?1.61 to 2.05; HR of pT4 = 2.72, 95% CI?=?2.28 to 3.25, all P ? .001 vs pT1; HR of pN1 = 1.50, 95% CI?=?1.41 to 1.59; HR of pN2 = 2.17, 95% CI?=?2.00 to 2.35, both P < .001 vs pN0); while clinical stage at presentation had little to no predictive value (HR of cT2 = 0.81, 95% CI?=?0.69 to 0.95, P = .008; HR of cT3 = 0.83, 95% CI?=?0.72 to 0.96, P = .009; HR of cT4 = 1.02, 95% CI?=?0.85 to 1.21, P = .87 vs cT1; HR of cN1 = 0.96, 95% CI?=?0.91 to 1.02, P = .19; HR of cN2 = 0.96, 95% CI?=?0.86 to 1.08, P = .48 vs cN0). Conclusions:Survival in patients with rectal cancer undergoing neoadjuvant radiation is driven by post-therapy pathologic stage, regardless of pretherapy clinical stage. These data will further inform prognostic discussions with patients.

Dataset Information

Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy.

Publications

Prognostic Value of c-MET Expression in Patients With Pancreatic Cancer Receiving Adjuvant and Neoadjuvant Chemoradiation Therapy.

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