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Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

ABSTRACT: BACKGROUND:Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer mortality in the United States. More than 80% of patients present with distant metastasis precluding surgical eligibility. Even among patients with localized disease deemed eligible for surgical resection, the median survival is only 22.8 months due to high recurrence rates. Identification of a biomarker correlated with patient specific prognosis upon initial diagnosis can serve as a way to individualize treatment options. METHODS:We performed a retrospective cohort study analyzing pathology of patients who underwent curative intent surgery for PDAC at Geisinger Medical Center from 1998-2011 to identify whether the expression of KOC can be predictive of patient specific prognosis. Tissue microarrays of specimens were assessed by immunohistochemistry. RESULTS:A total of 62 patients are included. Comparisons between groups on overall survival (OS) and progression free survival (PFS) are estimated using the Kaplan-Meier method and the log-rank test. Each biomarker was represented as low and high expression by categorizing the expression score at <4+ or >4+, based on intensity and extent of cells stained. 40 deaths occurred in the sample. Distant metastasis and differentiation (well/moderate vs. poor) were related to OS (P=0.0120, P=0.0086). Twenty-nine patients progressed in their disease. High/low KOC expression were significantly related to PFS (P=0.0556). Patients with a high KOC expression were more than 2 times more likely to progress compared to those with a low KOC expression (HR =2.04; 95% CI: 0.97, 4.29). CONCLUSIONS:Our data is suggestive of KOC being a useful prognostic biomarker for identifying those patients with PDAC who have a high risk for early progression and distant metastasis. Larger studies are needed to determine whether KOC can be a therapeutic target in the treatment of pancreatic cancer. Furthermore, considering high KOC expressers had a worse PFS than their counterparts, investigation regarding the use of KOC expression as a biomarker to preselect patients who may benefit most from neoadjuvant chemotherapy is warranted.

SUBMITTER: Johnson B

PROVIDER: S-EPMC5177588 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

Johnson Benny B Khalil Maged M Blansfield Joseph J Lin Fan F Zhu Shaobo S Kirchner H Lester HL Weir Alva B AB

Journal of gastrointestinal oncology 20161201 6

<h4>Background</h4>Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer mortality in the United States. More than 80% of patients present with distant metastasis precluding surgical eligibility. Even among patients with localized disease deemed eligible for surgical resection, the median survival is only 22.8 months due to high recurrence rates. Identification of a biomarker correlated with patient specific prognosis upon initial diagnosis can serve as a way to individualize ...[more]

PMID: 28078135

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Project description:ImportanceAmpullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined.ObjectiveTo determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype.Design, setting, and participantsThis multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates.ExposuresAdjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy.Main outcomes and measuresOverall survival.ResultsA total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41).Conclusions and relevanceAdjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

Project description:BackgroundThe goal of surveillance testing is to enable curative salvage therapy through early disease detection, however supporting evidence in gastroesophageal adenocarcinoma is limited. We evaluated frequency of successful salvage therapy and outcomes in patients who underwent surveillance.MethodsA single-site, retrospective cohort study was conducted to identify all patients who received curative resection for gastroesophageal adenocarcinoma. Surveillance testing were those investigations not triggered by abnormal symptoms, physical examination, or blood tests. Successful salvage therapy was any potentially curative therapy for disease recurrence which resulted in postrecurrence disease-free survival ?2 years. Time-to-event data were analyzed using the Kaplan-Meier method and log rank tests.ResultsBetween 2011 and 2016, 210 consecutive patients were reviewed. Esophageal (14%), gastroesophageal junction (40%), and gastric adenocarcinomas (45%) were treated with surgery alone (29%) or multimodality therapy (71%). Adjuvant therapy was administered in 35%. At median follow-up of 38.3 months, 5-year overall survival (OS) rate was 56%. Among 97 recurrences, 53% were surveillance-detected, and 46% were symptomatic. None was detected by surveillance endoscopy. Median time-to-recurrence (TTR) was 14.8 months. Recurrences included locoregional only (4%), distant (86%), and both (10%). Salvage therapy was attempted in 15 patients, 4 were successful. Compared to symptomatic recurrences, patients with surveillance-detected recurrences had longer median OS (36.2 vs 23.7 months, P = .004) and postrecurrence survival (PRS, 16.5 vs 4.6 months, P < .001), but similar TTR (16.2 vs 13.3 months, P = .40) and duration of palliative chemotherapy (3.9 vs 3.3 months, P = .64).ConclusionsAmong patients surveyed, 96% of recurrences were distant, and salvage therapy was successful in only 1.9% of patients. Longer OS in patients with surveillance-detected compared to symptomatic recurrences was not associated with significant earlier disease detection, and may be contributed by differences in disease biology. Further prospective data are warranted to establish the benefit of surveillance testing in gastroesophageal adenocarcinoma.

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Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

Publications

Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

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