Cancers
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Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. ⋯ Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.
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Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. ⋯ Moreover, it also induced the secretion of cytokines, such as IFN-γ and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens.
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To identify the predictive factors of recurrence and survival in an unselected population of Western patients who underwent multimodal percutaneous thermal ablation (PTA) for small Hepatocellular Carcinomas (HCCs). ⋯ IDR was associated with tumor aggressiveness, suggesting a metastatic mechanism. Besides AFP association with LTP, IDR, RFS and OS, treatment-naïve patients had longer RFS, and multi-nodularity was associated with shorter RFS and OS. Steatotic HCC, identified on pre-treatment MRI, independently predicted longer OS, and needs to be further explored.
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Preclinical evidence has shown increased expression of mu opioid receptor 1 (MOR-1) in colorectal cancer although its association with disease-free and overall survival (DFS and OS) has not been investigated. We hypothesized that MOR-1 was overexpressed in tumor samples compared to normal tissue and this was associated with decreased DFS and OS. We carried out a retrospective study assessing the association of MOR-1 tumor expression with long-term outcomes by immunohistochemistry in normal and tumor samples from 174 colorectal cancer patients. ⋯ No associations were found between MOR-1 expression and OS or postoperative complications. These findings suggest that although MOR-1 is over-expressed in colorectal cancer samples there is no association to increased risk of recurrence or mortality. Future studies are warranted to elucidate the role of cancer stage, genetic polymorphism, and quantitative assessment of MOR-1 over-expression on long-term outcomes in colorectal cancer.
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Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer-particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. ⋯ We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77; mean difference: -0.22) and EORTC QLQ-C30 (47.7 versus 58.4; mean difference: -10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23; mean difference: -21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7; mean difference: -9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.