Hebron University

About: Hebron University is a education organization based out in Hebron, Palestinian Territory. It is known for research contribution in the topics: Population & Cancer. The organization has 2714 authors who have published 4180 publications receiving 163736 citations.

Prognostic Effect of BRAF and KRAS Mutations in Patients With Stage III Colon Cancer Treated With Leucovorin, Fluorouracil, and Oxaliplatin With or Without Cetuximab: A Post Hoc Analysis of the PETACC-8 Trial

Abstract: Importance The prognostic value of BRAF and KRAS mutations in patients who have undergone resection for colon cancer and have been treated with combination leucovorin, fluorouracil, and oxaliplatin (FOLFOX)-based adjuvant chemotherapy is controversial, possibly owing to a lack of stratification on mismatch repair status. Objective To examine the prognostic effect of BRAF and KRAS mutations in patients with stage III colon cancer treated with adjuvant FOLFOX with or without cetuximab. Design, Setting, and Participants This study included patients with available tumor blocks of resected stage III colon adenocarcinoma who participated between December 2005 and November 2009 in the PETACC-8 phase III randomized trial. Mismatch repair, BRAF V600E, and KRAS exon 2 mutational status were determined on prospectively collected tumor blocks from 2559 patients enrolled in the PETACC-8 trial. The data were analyzed in April 2015. Intervention Patients were randomly assigned to receive 6 months of FOLFOX4 or FOLFOX4 plus cetuximab after surgical resection for stage III colon cancer. Main Outcomes and Measures Associations between these biomarkers and disease-free survival (DFS) and overall survival (OS) were analyzed with Cox proportional hazards models. Multivariate models were adjusted for covariates (age, sex, tumor grade, T/N stage, tumor location, Eastern Cooperative Oncology Group performance status). Results Among the 2559 patients enrolled in the PETACC-8 trial (42.9% female; median [range] age, 60.0 [19.0-75.0] years), microsatellite instability (MSI) phenotype, KRAS, and BRAF V600E mutations were detected in, respectively, 9.9% (177 of 1791), 33.1% (588 of 1776), and 9.0% (148 of 1643) of cases. In multivariate analysis, MSI (hazard ratio [HR] for DFS: 1.10 [95% CI, 0.73-1.64], P = .67; HR for OS: 1.02 [95% CI, 0.61-1.69], P = .94) and BRAF V600E mutation (HR for DFS: 1.22 [95% CI, 0.81-1.85], P = .34; HR for OS: 1.13 [95% CI, 0.64-2.00], P = .66) were not prognostic, whereas KRAS mutation was significantly associated with shorter DFS (HR, 1.55 [95% CI, 1.23-1.95]; P P = .008). The subgroup analysis showed in patients with microsatellite-stable tumors that both KRAS (HR for DFS: 1.64 [95% CI, 1.29-2.08], P P = .002) and BRAF V600E mutation (HR for DFS: 1.74 [95% CI, 1.14-2.69], P = .01; HR for OS: 1.84 [95% CI, 1.01-3.36], P = .046) were independently associated with worse clinical outcomes. In patients with MSI tumors, KRAS status was not prognostic, whereas BRAF V600E mutation was associated with significantly longer DFS (HR, 0.23 [95% CI, 0.06-0.92]; P = .04) but not OS (HR, 0.19 [95% CI, 0.03-1.24]; P = .08). Conclusions and Relevance BRAF V600E and KRAS mutations were significantly associated with shorter DFS and OS in patients with microsatellite-stable tumors but not in patients with MSI tumors. Future trials in the adjuvant setting will have to take into account mismatch repair, BRAF, and KRAS status for stratification. Trial Registration EudraCT 2005-003463-23

Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study

Abstract: Author(s): Cohen, Roger B; Delord, Jean-Pierre; Doi, Toshihiko; Piha-Paul, Sarina A; Liu, Stephen V; Gilbert, Jill; Algazi, Alain P; Damian, Silvia; Hong, Ruey-Long; Le Tourneau, Christophe; Day, Daphne; Varga, Andrea; Elez, Elena; Wallmark, John; Saraf, Sanatan; Thanigaimani, Pradeep; Cheng, Jonathan; Keam, Bhumsuk | Abstract: ObjectivesTreatment options for patients with unresectable or metastatic salivary gland carcinoma (SGC) are limited. Safety and efficacy of pembrolizumab for SGC expressing programmed death ligand 1 (PD-L1) were explored.Materials and methodsA cohort of patients with advanced, PD-L1-positive SGC was enrolled in the nonrandomized, multicohort, phase Ib trial of pembrolizumab in patients with PD-L1-positive advanced solid tumors (KEYNOTE-028; NCT02054806). Key inclusion criteria included recurrent or metastatic disease, failure of prior systemic therapy, and PD-L1 expression on ≥1% of tumor or stroma cells (per a prototype immunohistochemistry assay). Patients received pembrolizumab 10 mg/kg every 2 weeks for ≥2 years or until confirmed disease progression or unacceptable toxicity. Primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by investigator review.ResultsTwenty-six patients with PD-L1-positive SGC were enrolled and treated; median age was 57 years, 88% were men, and 74% had received prior therapy for recurrent/metastatic disease. Confirmed objective response rate after median follow-up of 20 months was 12% (95% confidence interval, 2%-30%), with 3 patients achieving partial response; there were no complete responses. Median duration of response was 4 months (range, 4 to 21 mo). Treatment-related adverse events occurred in 22 patients (85%), resulting in discontinuation in 2 patients and death in 1 (interstitial lung disease); those occurring in ≥15% of patients were diarrhea, decreased appetite, pruritus, and fatigue.ConclusionsPembrolizumab demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, PD-L1-positive SGC.

Factors associated with relapse after ambulatory treatment of acute exacerbations of chronic bronchitis

Abstract: This study aimed to identify the risk factors for relapse after ambulatory treatment of acute exacerbations of chronic bronchitis (AECB) that can easily be used in a primary care setting. Data were prospectively collected on 2,414 ambulatory patients with AECB from 268 general practices located throughout Spain. A multivariate model to identify risk factors independently associated with failures was developed and validated from the information recorded at the inclusion visit and at 30-days follow-up visit. A total of 507 patients relapsed (21%); of these, 84 required admission (16.5%). The multivariate model for prediction of the risk of relapse included 2,414 cases: 1,689 for the developmental sample and 725 in the validation sample. The model obtained contained three readily-obtainable variables: ischaemic heart disease (odds ratio (OR)=1.63; 95% confidence interval (CI)=1.07–2.47), degree of dyspnoea (OR=1.31; 1.14–1.50) and number of visits to the general practitioner the previous year (OR=1.07; 1.04–1.10). The model calibrated well in developmental and validation samples (goodness-of-fit tests: p=0.295 and p=0.637, respectively). Severity of the exacerbation was not associated with increased risk of relapse in either univariate or multivariate analysis. The present results suggest that baseline characteristics of the patients such as degree of dyspnoea, coexisting ischaemic heart disease and number of previous visits to the general practitioner for respiratory problems are strongly associated with increased risk of relapse after ambulatory treatment of acute exacerbations of chronic bronchitis. In contrast, exacerbation severity was not associated with clinical failure. Guidelines for management of acute exacerbations of chronic bronchitis should consider such risk factors and advocate intensive broad spectrum treatment and closer follow-up of patients exhibiting them.

Paraneoplastic Vasculitis in Patients with Solid Tumors : Report of 15 Cases

Abstract: OBJECTIVE: To review all cases of concurrent vasculitis and solid tumors diagnosed at our Department over a 15-year period and explore evidence that would support the notion of vasculitis being a true paraneoplastic syndrome. METHODS: We reviewed the records of all patients diagnosed with vasculitis and solid tumors within 12 months of each other and prospectively followed until death or our report. We analyzed the main features and outcome of vasculitis in this setting. We also reviewed all cases published in the French-English literature. RESULTS: Fifteen patients (9 men and 6 women) in whom both vasculitis and solid tumor occurred within the same 12 months were identified. Mean age was 72.5 years (range 58-84). In 7 cases the diagnosis of vasculitis antedated that of cancer, in 6 both processes were synchronously diagnosed, and in 2 vasculitis appeared after cancer diagnosis. The most common vasculitis was cutaneous leukocytoclastic vasculitis (n = 9). Other vasculitides included Henoch-Shonlein purpura (n = 2), polyarteritis nodosa (n = 1), and giant cell arteritis (n = 3). The commonest malignancies were carcinomas of urinary organs (40%), lung (26.7%), and gastrointestinal tract (26.7%). The median followup was 28.4 months (range 1-96). Thirteen of the 15 patients demonstrated concordance of disease activity and treatment response for both cancer and vasculitis. Vasculitis flared heralding tumor recurrence or progression in 7 (46.6%) cases. CONCLUSION: In our patients, resolution of vasculitis following effective treatment of the putatively linked malignancy, and recurrence of vasculitis heralding tumor recurrence or progression, provide strong evidence for vasculitis being a true paraneoplastic syndrome. Chronic or persistent vasculitis with poor response to usually effective therapy, especially in elderly patients, should raise questions about underlying malignancy.