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Objective The purpose of this umbrella review was to assess the associations between sarcopenia and adverse health‐related outcomes. Design An umbrella review of meta‐analyses of observational studies. Setting and Participants Patients with sarcopenia and controls without sarcopenia were included. Measures The PubMed, Web of Science and Embase were searched for relevant systematic review and meta‐analysis. AMSTAR and GRADE system were used for methodological quality and evidence quality assessments, respectively. Results Totally 54 outcomes extracted from 30 meta‐analyses were analyzed. Twenty out of 21 prognostic outcomes indicated that sarcopenia was significantly associated with poorer prognosis of gastric cancer, hepatocellular cancer, urothelial cancer, head and neck cancer, hematological malignancy, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, esophageal cancer, and ovarian cancer. Besides, 10 out of 16 postoperative outcomes suggested that sarcopenia significantly increased the risk of multiple postoperative complications and prolonged the length of hospitalization of patients with digestive cancer. In age‐related outcomes, sarcopenia significantly increased the risk of dysphagia, cognitive impairment, fractures, falls, hospitalization, and all‐cause mortality of elderly populations. Moreover, sarcopenia was also associated with higher level of albuminuria, risk of depression, and several metabolic diseases. Conclusions and Implications Sarcopenia significantly affected a wide range of adverse health‐related outcomes, particularly in patients of tumor and elderly populations. Because evidences of most outcomes were rated as “low” and “very low,” more prospective cohort studies are required in the future. Sarcopenia significantly affected a wide range of adverse health‐related outcomes, particularly in patients of tumor and elderly populations. Besides, associations between sarcopenia and risk of metabolic diseases, depression and albuminuria were also noticeable.

Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population‐based data from the Cancer Registry of Norway for the years 2005‐2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality. In publications on cancer research, a common statement is that 90% of cancer deaths are caused by metastases, data underlying this assertion has been lacking. Using the nation‐wide, population based Norwegian Cancer Registry, we found that two of three of the deaths from solid tumors were registered with metastases as contributing cause of death, with substantial variation between tumor groups.

Traditional Chinese medicine (TCM) has been practiced for thousands of years and at the present time is widely accepted as an alternative treatment for cancer. In this review, we sought to summarize the molecular and cellular mechanisms underlying the chemopreventive and therapeutic activity of TCM, especially that of the Chinese herbal medicine‐derived phytochemicals curcumin, resveratrol, and berberine. Numerous genes have been reported to be involved when using TCM treatments and so we have selectively highlighted the role of a number of oncogene and tumor suppressor genes in TCM therapy. In addition, the impact of TCM treatment on DNA methylation, histone modification, and the regulation of noncoding RNAs is discussed. Furthermore, we have highlighted studies of TCM therapy that modulate the tumor microenvironment and eliminate cancer stem cells. The information compiled in this review will serve as a solid foundation to formulate hypotheses for future studies on TCM‐based cancer therapy. In this review, we try to summarize the molecular and cellular mechanisms underlying traditional Chinese medicine treatment from the perspective of gene to cell regulation. In the gene regulation, we emphasize the expression of oncogene and tumor suppressor genes, and epigenetic modifications; in the cell regulation, we highlight the effects of TCM treatment on the cancer stem cells and tumor microenvironment.

Background Early diagnosis of liver metastasis is of great importance for enhancing the survival of colorectal adenocarcinoma (CAD) patients, and the combined use of a single biomarker in a classier model has shown great improvement in predicting the metastasis of several types of cancers. However, it is little reported for CAD. This study therefore aimed to screen an optimal classier model of CAD with liver metastasis and explore the metastatic mechanisms of genes when applying this classier model. Methods The differentially expressed genes between primary CAD samples and CAD with metastasis samples were screened from the Moffitt Cancer Center (MCC) dataset GSE131418. The classification performances of six selected algorithms, namely, LR, RF, SVM, GBDT, NN, and CatBoost, for classification of CAD with liver metastasis samples were compared using the MCC dataset GSE131418 by detecting their classification test accuracy. In addition, the consortium datasets of GSE131418 and GSE81558 were used as internal and external validation sets to screen the optimal method. Subsequently, functional analyses and a drug‐targeted network construction of the feature genes when applying the optimal method were conducted. Results The optimal CatBoost model with the highest accuracy of 99%, and an area under the curve of 1, was screened, which consisted of 33 feature genes. A functional analysis showed that the feature genes were closely associated with a “steroid metabolic process” and “lipoprotein particle receptor binding” (eg APOB and APOC3). In addition, the feature genes were significantly enriched in the “complement and coagulation cascade” pathways (eg FGA, F2, and F9). In a drug‐target interaction network, F2 and F9 were predicted as targets of menadione. Conclusion The CatBoost model constructed using 33 feature genes showed the optimal classification performance for identifying CAD with liver metastasis. APOB, APOC3, FGA, F2, F9, and NKX2‐3 were potential biomarkers for classification of CAD with liver metastasis. Menadione might be a promising anti‐metastatic drug of CAD cells through functioning its role at sites of F2 and F9. CatBoost model constructed by 33 feature genes showed the optimal classification performance for identifying CAD liver metastasis.

Breast cancer patients often experience symptoms that adversely affect their quality of life. It is understood that many of these symptoms tend to cluster together: while they might have different manifestations and occur during different phases of the disease trajectory, the symptoms often have a common aetiology that is a potential target for intervention. Understanding the symptom clusters associated with breast cancer might usefully inform the development of effective care plans for affected patients. The aim of this paper is to provide an updated systematic review of the known symptom clusters among breast cancer patients during and/or after cancer treatment. A search was conducted using five databases for studies reporting symptom clusters among breast cancer patients. The search yielded 32 studies for inclusion. The findings suggest that fatigue‐sleep disturbance and psychological symptom cluster (including anxiety, depression, nervousness, irritability, sadness, worry) are the most commonly‐reported symptom clusters among breast cancer patients. Further, the composition of symptom clusters tends to change across various stages of cancer treatment. While this review identified some commonalities, the different methodologies used to identify symptom clusters resulted in inconsistencies in symptom cluster identification. It would be useful if future studies could separately examine the symptom clusters that occur in breast cancer patients undergoing a particular treatment type, and use standardised instruments across studies to assess symptoms. The review concludes that further studies could usefully determine the biological pathways associated with various symptom clusters, which would inform the development of effective and efficient symptom management strategies.

Tisagenlecleucel (tisa‐cel) is a second‐generation autologous CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed/refractory (R/R) large B‐cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa‐cel in the standard‐of‐care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa‐cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa‐cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non‐relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow‐up of 14.1 months from CAR T‐cell infusion, median progression‐free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa‐cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses. This article provides real‐world European data on the results of relapsed/refractory large B‐cell lymphoma patients treated with tisagenlecleucel.

Background Adaptive magnetic resonance imaging‐guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. Methods We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high‐dose (biologically effective dose [BED10] >70) and standard‐dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan‐Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT. Results Median follow‐up was 17 months. High‐dose patients (n = 24, 55%) had statistically significant improvement in 2‐year OS (49% vs 30%, P = 0.03) and trended towards significance for 2‐year FFLF (77% vs 57%, P = 0.15) compared to standard‐dose patients (n = 20, 45%). FFDF at 18 months in high‐dose vs standard‐dose groups was 24% vs 48%, respectively (P = 0.92). High‐dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21‐0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72‐0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard‐dose group and did not occur in the high‐dose group. Conclusions Patients treated with dose‐escalated MRgRT demonstrated improved OS. Prospective evaluation of high‐dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted. Adaptive magnetic resonance imaging (MRI)‐guided radiation therapy (RT) is a novel method to deliver dose‐escalated RT to inoperable pancreatic tumors. Dose‐escalated adaptive MRI‐guided RT improved survival without compromising safety.

Population‐based data on metastatic patterns are lacking because cancer registries seldom record metastases. This study uses a novel population‐based approach to identify metastases and describes metastatic pathways from 14 common primary cancers to 12 specific metastatic sites. A total of 179 581 patients with metastatic cancer were identified from the Swedish Cancer Registry and metastatic sites were identified using the Cause of Death Register and the National Patient Register. Patterns of metastatic spread were described across age and sex. In men, colorectal cancer was the main source of lung, peritoneal, and liver metastases. Lung cancer was the main origin of pleural and nervous system metastases. Prostate cancer dominated bone metastases but had minor contribution to other metastatic sites. Among women, breast cancer was the dominant origin of most metastatic sites, with the exception of peritoneum which was ruled by metastases from the ovary. As other exceptions, for nervous system metastases, lung cancer was the origin of metastases somewhat more frequently than breast cancer and for liver metastases, colorectal cancer was the main origin instead of breast cancer. The present achievement was to implement the first nationwide description of clinical landscape of cancer metastases, with an aim to serve as a reliable source for clinicians and researchers. This study uses a novel population‐based approach to identify metastases and describes metastatic pathways from 14 common primary cancers to 12 specific metastatic sites. The present achievement was to implement the first nationwide description of clinical landscape of cancer metastases, with an aim to serve as a reliable source for clinicians and researchers.

Background Inflammation is a hallmark of cancer, and systemic markers of inflammation are increasingly recognised as negative prognostic factors for clinical outcome. Neutrophil‐to‐lymphocyte ratio (NLR) is readily available from routine blood testing of patients diagnosed with cancer. Methods Peer‐reviewed publications from PubMed/MEDLINE, Web of Science and EMBASE were identified according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines. Hazard ratios (HR) for overall survival (OS) and surrogate endpoints (SE; comprising disease‐, recurrence‐ and progression‐free survival) were pooled using a random effects model. Additional analysis was carried out to further investigate NLR as an independent prognostic factor and account for heterogeneity. Results Seventy‐one eligible papers comprising 32,788 patients were identified. High NLR was associated with poor clinical outcomes. Significant publication bias was observed, and larger studies also adjusted for more covariates. Correcting for publication bias in multivariate studies brought our best estimate for true effect size to HR = 1.57 (95% CI 1.39–1.78; p < 0.0001) for OS and to HR = 1.38 (95% CI 1.16–1.64; p = 0.0003) for SE. Conclusions NLR is confirmed as an easily available prognostic biomarker in colorectal cancer, despite the limitations of some studies previously reporting this finding. As such, it should be routinely collected in prospective clinical trials. While more standardised and rigorous large‐scale studies are needed before high NLR can be fully assessed as an independent predictor of CRC progression and outcome, the data suggest that it may be used to highlight individuals with tumour‐promoting inflammatory context. Systemic inflammation is increasingly recognised as a key determinant of cancer survival. Consequently, readouts of inflammatory status have received immense research focus lately as potential prognostic factors. In this report, the authors explore a simple full‐blood‐count‐derived metric, the neutrophil‐to‐lymphocyte ratio (NLR), as a prognostic factor in colorectal cancer. Based on 71 publications, accounting for 32,788 patients, high NLR emerges as a readily available predictor of poor clinical outcome both for overall survival and surrogate endpoints, such as disease or progression‐free survival.

Background A combination of programmed cell death protein‐1 (PD‐1)/programmed cell death ligand‐1 (PD‐L1) inhibitors and radiotherapy (RT) is increasingly being used to treat non‐small‐cell lung cancer (NSCLC). However, the safety and efficacy of this approach remains controversial. We performed a systematic review and meta‐analysis to summarize the related research. Methods We searched the China Biology Medicine, EMBASE, Cochrane Library, and PubMed databases for all the relevant studies. The Stata software, version 12.0 was used for the meta‐analysis. Results The study included 20 clinical trials that enrolled 2027 patients with NSCLC. Compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT was associated with prolonged overall survival (OS) (1‐year OS: odds ratio [OR] 1.77, 95% confidence interval [CI] 1.35–2.33, p = 0.000; 2‐year OS: OR 1.77, 95% CI 1.35–2.33, p = 0.000) and progression‐free survival (PFS) (0.5‐year PFS: OR 1.83, 95% CI 1.13–2.98, p = 0.014; 1‐year PFS: OR 2.09, 95% CI 1.29–3.38, p = 0.003; 2‐year PFS: OR 2.47, 95% CI 1.13–5.37, p = 0.023). Combination therapy also improved the objective response rate (OR 2.76, 95% CI 1.06–7.19, p = 0.038) and disease control rate (OR 1.80, 95% CI 1.21–2.68, p = 0.004). This meta‐analysis showed that compared with non‐combination therapy, combination therapy using PD‐1/PD‐L1 inhibitors and RT did not increase the serious adverse event rates (≥grade 3); however, this approach increased the rate of grade 1–2 immune‐related or radiation pneumonitis. Subgroup analyses revealed that the sequence of PD‐1/PD‐L1 inhibitors followed RT outperformed in which concurrent PD‐1/PD‐L1 inhibitor and RT followed PD‐1/PD‐L1 inhibitor. Combination of stereotactic body RT or stereotactic radiosurgery with PD‐1/PD‐L1 inhibitors may be more effective than a combination of conventional RT with PD‐1/PD‐L1 inhibitors in patients with advanced NSCLC. Conclusion Combination therapy using PD‐1/PD‐L1 inhibitors and RT may improve OS, PFS, and tumor response rates without an increase in serious adverse events in patients with advanced NSCLC. However, combination therapy was shown to increase the incidence of mild pneumonitis. Radiotherapy combined with PD‐1/PD‐L1 inhibitors in the treatment of advanced NSCLC showed clinical long‐term survival benefit and short‐term efficacy benefit, and might not increase the serious adverse events.