Chemotherapy‐induced nausea and vomiting (CINV) is one of the most problematic adverse events that affects the well‐being of cancer patients. Risk factors for CINV and its elimination are necessary ...to increase the indications for and effectiveness of chemotherapy. We enrolled 1549 chemotherapy‐naïve patients in two phase II trials and one phase III trial of palonosetron between 2005 and 2007. Treatment failure (any emetic episodes or any administration of rescue medication) and/or nausea, and their associations with patient factors were evaluated in acute and in delayed phases using univariate and multivariate analyses. Female gender (odds ratio, 95% confidence interval: 2.96, 2.09–4.20), age <55 years (2.56, 1.94–3.37), non‐habitual alcohol intake (1.90, 1.43–2.51) and non‐smoker (1.40, 1.04–1.90) were associated with treatment failure in the acute phase. In contrast, only female gender (1.88, 1.34–2.64) was associated with treatment failure in the delayed phase. The number of risk factors was significantly associated with CINV in both acute and delayed phases. Patient risk factors were significantly associated with CINV. Depending on the relationship between CINV‐related risk factors and a tailored antiemetic treatment, high‐risk patients defined by the listed risk factors may be candidates for future clinical trials.
Abstract
Immune checkpoint inhibitors have demonstrated significant clinical benefits in many cancers, and the use of these drugs is rapidly expanding. Unfortunately, these agents can induce a wide ...range of immune-related adverse events through the activation of immune responses in non-target organs, including the cardiovascular system. Among cardiovascular immune-related adverse events, myocarditis is the most established and biologically plausible cardiac complication of immune checkpoint inhibitors therapy with immune-related pathophysiology. In contrast, atherosclerotic cardiovascular diseases, such as myocardial infarction and ischemic stroke, were not previously recognized as a part of the immune-related adverse event spectrum. However, there is now increasing preclinical and clinical evidence that suggests a possible correlation between immune checkpoint inhibitors therapy and atherosclerotic cardiovascular events, and cardiovascular disease is increasingly recognized as a toxicity of ICIs. Results from animal studies suggest that the blockade of the cytotoxic T-lymphocyte antigen 4 or programmed cell death protein 1 pathway plays a relevant role in promoting the progression of atherosclerotic lesions. Several clinical studies have reported an increased incidence of atherosclerotic vascular events after immune checkpoint inhibitor administration. Our findings suggest that clinicians should (i) recognize that immune checkpoint inhibitors can exacerbate atherosclerosis, (ii) consider the management of cardiovascular risk factors and (iii) perform periodic screening in patients receiving immune checkpoint inhibitors.
Abstract
Cancer and cardiovascular disease share several risk factors. Clonal heamatopoiesis, a novel risk factor associated with both diseases, has received increasing attention in the fields of ...cardiology, heamatology and oncology. Clonal heamatopoiesis of indeterminate potential refers to the presence of at least one driver mutation in the heamatopoietic cells of peripheral blood without heamatological malignancy. Clonal heamatopoiesis of indeterminate potential is a common age-related condition that affects up to 60% of individuals aged > 80 years. Importantly, clonal heamatopoiesis of indeterminate potential carriers have a 2- to 4-fold higher risk of developing cardiovascular disease than non-carriers. Therefore, we performed an up-to-date review of clonal heamatopoiesis and its association with various forms of cardiovascular disease, including atherosclerotic disease, heart failure, aortic stenosis and pulmonary hypertension. In addition, we reviewed experimental studies that examined the causality and directionality between clonal heamatopoiesis and cardiovascular disease. Lastly, we discussed future research directions that will aid in the design of personalized therapies and preventive strategies for individuals with clonal heamatopoiesis. This review showed that clonal heamatopoiesis of indeterminate potential is a common condition, especially in older patients, and is associated with an increased risk of cardiovascular disease and worse prognosis. However, further research is needed to determine whether anti-inflammatory therapies or therapies that can reduce or eliminate clone size are effective in preventing cardiovascular disease in patients with clonal heamatopoiesis of indeterminate potential.
In this review, we summarized the close association between clonal heamatopoiesis and cardiovascular diseases and explored the mechanisms by which clonal heamatopoiesis exacerbates heart disease.
Cardiac dysfunction that develops during or after completion of cancer therapy is a growing health concern that should be addressed in a multidisciplinary setting. Cardio-oncology is a new discipline ...that focuses on screening, monitoring and treating cardiovascular disease during and after cancer treatment. A baseline cardiovascular risk assessment is essential. For high-risk patients, a tailored and detailed plan for cardiovascular management throughout treatment and beyond should also be established. Anthracycline and/or trastuzumab-containing chemotherapy and chest-directed radiation therapy are well known cardiotoxic cancer therapies. Monitoring for the development of subclinical cardiotoxicity is crucial for the prevention of clinical heart failure. Detecting a decreased left ventricular ejection fraction after cancer therapy might be a late finding; therefore, earlier markers of cardiac injury are being actively explored. Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins and natriuretic peptides) are possible candidates for this purpose. An important method for preventing heart failure is the avoidance or minimization of the use of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the treatment with its potential cardiotoxicity. If patients develop cardiac dysfunction or heart failure, they should be treated in accordance with established guidelines for heart failure. Cancer survivors who have been exposed to cardiotoxic cancer therapies are at high risk of developing heart failure. The management of cardiovascular risk factors and periodic screening with cardiac imaging and biomarkers should be considered in high-risk survivors.
Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with ...advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.
Intermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes, including signal transduction and gene expression patterns, arising from specific oncogenotypes and cell ...lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here, we quantified metabolic features, mostly from the 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression, and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.
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•Cell-autonomous metabolic diversity is reported in over 80 lung cancer cell lines•Heterogeneous metabolic phenotypes support lung cancer cell growth•Relating metabolic and molecular data uncovers new aspects of metabolic regulation•Some metabolic features predict sensitivity to chemotherapy and targeted agents
Metabolic reprogramming influences therapeutic sensitivity in cancer, but the scope of metabolic diversity among cancer cells is unknown. Chen et al. characterized metabolic phenotypes in over 80 non-small cell lung cancer cell lines and then used genomics, transcriptomics, proteomics, and therapeutic sensitivities to uncover relationships between metabolism and orthogonal processes.
Hepatitis B virus reactivation (HBV-R) is a serious complication that can occur in patients with resolved HBV infection during cancer chemotherapy. We examined the levels of HBV surface antibody ...(HBsAb) and HBV core antibody (HBcAb) to assess the incidence of HBV-R in cancer patients including hematopoietic stem cell transplantation (HSCT) and rituximab administration. This retrospective cohort study included 590 patients with resolved HBV infection. The incidence of HBV-R was evaluated 761.5 (range, 90–3898) days after the inititiation of chemotherapy. Of the patients, 13 (2.2%) developed HBV-R after the start of chemotherapy. All 13 patients exhibited lower HBsAb (<100 mIU/mL) levels at baseline. A higher level of HBcAb (≥100 cut off index (C.O.I.)) was a possible risk factor for HBV-R as well as HSCT and rituximab administration. The simultaneous presence of HBsAb <100 mIU/mL and HBcAb ≥100 C.O.I. increased the risk of HBV-R by 18.5%. Patients treated with rituximab were at a higher risk of HBV-R (18.4%) despite having HBcAb <100 C.O.I. Our results suggest that assessment of HBsAb and HBcAb levels prior to the chemotherapy is important for identifying patients at high risk of HBV-R, especially in solid cancers without HSCT and rituximab administration.
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