Purpose: To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF MT ) status in metastatic colorectal cancer (mCRC). Experimental Design: A pooled analysis of four phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data.Results

Negative costimulation on T cells is exploited by both prostate cancer and melanoma to evade antitumor immunity. Blocking such mechanisms restores antitumor immunity as was demonstrated by the improved survival of patients with metastatic melanoma after treatment with an antibody blocking the CTLA-4 inhibitory receptor (ipilimumab). Enhanced expression of another inhibitory immunoreceptor, programmed death-1 (PD-1), and its ligand, PD-L1, was found to correlate with a poor prognosis in prostate cancer and melanoma. PD-1-blocking antibodies are being developed to modulate antitumor immune responses. To support preclinical and clinical development of anti-PD-1 therapy, we sought to develop biomarker assays that can detect the effect of PD-1-blocking agents in whole blood and peripheral blood mononuclear cells. In this study, we assessed the effect of PD-1 blockade in modulating super antigen (staphylococcus enterotoxin B)-induced and recall antigen (tetanus toxoid)-induced T-cell reactivity in vitro using whole blood and peripheral blood mononuclear cells from patients with advanced melanoma, prostate cancer, and healthy controls. PD-1 blockade was found to shift antigen-induced cellular reactivity toward a proinflammatory Th1/Th17 response, as evidenced by enhanced production of interferon γ, interleukin (IL)-2, tumor necrosis factor α, IL-6, and IL-17 and reduced production of the Th2 cytokines IL-5 and IL-13. It is interesting to note that suppression of Th2 responsivity was seen with whole blood cells only from patients with cancer. Taken together, we identified novel biomarker assays that might be used to determine the functional consequences of PD-1 blockade in peripheral blood cells from patients with cancer. How these assays translate to the local antitumor response remains to be established in a clinical setting.

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Postoperative radiotherapy and maxillary or mandibular tumor involvement are the highest contributing risk factors to decreasing MMO and the subsequent development of trismus after oral cancer treatment.

In this clinical 6-year follow-up study subjects with shortened dental arches (SDA, n = 55), characterized by the absence of molar support, are compared with subjects with complete dental arches (CDA, n = 52) with respect to items concerning craniomandibular dysfunction and oral comfort. In addition, a small group of subjects with SDA and removable partial dentures in the lower jaw (SDA + RPD, n = 19) is included in this study. Oral comfort is defined using the following criteria: (i) absence of pain and distress, meaning the absence of signs and symptoms of craniomandibular dysfunction: (ii) chewing ability; and (iii) appreciation of the appearance of the dentition in relation to absent posterior teeth. Additionally, complaints about the free-end RPD are described. It is concluded that: (i) a SDA (consisting of 3-5 occlusal units, OU) is not a risk factor for CMD and is able to provide long-term sufficient oral comfort; and (ii) free-end RPD (in the lower jaw) in SDA do not prevent CMD and do not improve oral function in terms of oral comfort.