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Interferon receptor alpha/beta is associated with improved survival after adjuvant therapy in resected pancreatic cancer.

ABSTRACT: AIM: Interferons (IFNs) are known to have antiproliferative and immunoregulatory activities that are modulated through specific cell surface ligands, known as IFN-alpha, -beta, and -gamma receptors. The presence of these receptors and their impact on response to adjuvant therapy in patients with pancreatic cancer has not been determined. PATIENTS AND METHODS: Slides were prepared from 46 patients with pancreatic adenocarcinoma. Immunohistochemistry (IHC) was subsequently used to determine the expression of IFN- alpha/beta receptor-chain 2 (IFN-alpha/betaR) and IFN-gamma receptor-chain 1 (IFN-gammaR). The correlation between IFN receptor expression, tumor characteristics, and the overall patient response to adjuvant therapy were determined analytically. RESULTS: The IHC performed for pancreatic adenocarcinoma demonstrated a high IFN-alpha/betaR expression in 4% (2/46) of patients, moderate expression in 20% (9/46) of patients, and faint or no expression in 76% (35/46) of patients. IHC confirmed a high expression of IFN-gammaR in 52% (24/46) of patients, moderate expression in 35% (16/46) of patients, and faint or no expression in the remaining 13% (6/46) of patients. Thirty-two (69.7%) patients received adjuvant therapy. Clinicopathological survey did not demonstrate any significant correlation between IFN-alpha/betaR and IFN-gammaR expression with regard to tumor size, vascular invasion, perineural invasion, lymph node metastases, or stage of disease. Use of adjuvant therapy was associated with increased survival in patients with IFN-alpha/betaR-positive tumors compared with patients with IFN-alpha/betaR-negative tumors (24 months versus 14.7 months in log rank test, p=0.012). The expression of IFN-gammaR, however, had no impact on patient survival (20 months vs 17 months; p=0.656, log rank test). CONCLUSION: IFN-alpha/betaR is associated with improved survival for patients with resectable pancreatic cancer who received adjuvant therapy.

SUBMITTER: Saidi RF

PROVIDER: S-EPMC2215399 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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Project description:ImportanceSurgery followed by adjuvant chemotherapy or chemoradiation is widely used to treat resectable pancreatic cancer. Although studies suggest initiation of adjuvant therapy within 12 weeks of surgery, there is no clear time interval associated with better survival.ObjectiveTo evaluate the ideal timing of adjuvant therapy for patients with stage I to II resected pancreatic cancer.Design, setting, and participantsThis cohort study included 7548 patients with stage I to II resected pancreatic cancer (5453 with adjuvant therapy; 2095 without adjuvant therapy) from the National Cancer Database from 2004 to 2015. Data were collected from January 2014 to December 2015 and analyzed from December 2018 to May 2019.ExposuresAdjuvant chemotherapy or chemoradiation at various time intervals.Main outcomes and measuresOverall survival (OS).ResultsA total of 7548 patients (3770 male [49.9%]; median [interquartile range] age, 67 [59-74] years) were identified from the National Cancer Database. Among 5453 patients with adjuvant therapy, a Cox model with restricted cubic splines identified the lowest mortality risk when adjuvant therapy was started 28 to 59 days after surgery. Patients were divided into early (n = 269, adjuvant therapy initiated within <28 days), reference (n = 3048, adjuvant therapy initiated within 28-59 days), and late (n = 2136, adjuvant therapy initiated after >59 days) interval cohorts. Median (interquartile range) overall follow-up was 38.6 (24.6-62.0) months. Compared with the reference interval cohort on multivariable analysis, both the early cohort (hazard ratio, 1.17; 95% CI, 1.02-1.35; P = .03) and the late cohort (hazard ratio, 1.09; 95% CI, 1.02-1.17; P = .008) were associated with worse mortality. Similarly, the reference interval cohort had improved OS compared with the early cohort in 268 propensity-matched pairs (2-year OS, 52.5% [95% CI, 46.7%-59.0%] vs 45.1% [95% CI, 39.5%-51.6%]; P = .02) and compared with the late cohort in 2042 propensity-matched pairs (2-year OS, 51.3% [95% CI, 49.1%-53.6%] vs 45.4% [95% CI, 43.3%-47.7%]; P = .01). Patients who received adjuvant therapy more than 12 weeks after surgery (n = 683) had improved OS compared with surgery alone in both multivariable analysis (hazard ratio, 0.75; 95% CI, 0.66-0.85; P < .001) and 655 propensity-matched pairs (2-year OS, 47.2% [95% CI, 43.5%-51.3%] vs 38.0% [95% CI, 34.4%-42.0%]; P < .001).Conclusions and relevancePatients with stage I to II pancreatic cancer who commenced adjuvant therapy within 28 to 59 days after primary surgical resection had improved survival outcomes compared with those with adjuvant therapy before 28 days or after 59 days. Patients who recovered slowly from surgery still benefited from delayed adjuvant therapy initiated more than 12 weeks after surgery compared with patients who underwent surgery only.

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Interferon receptor alpha/beta is associated with improved survival after adjuvant therapy in resected pancreatic cancer.

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