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Abstract For the multistage progression of prostate cancer (PCa) and resistance to immunotherapy, tumour‐associated macrophage is an essential contributor. Although immunotherapy is an important and promising treatment modality for cancer, most patients with PCa are not responsive towards it. In addition to exploring new therapeutic targets, it is imperative to identify highly immunotherapy‐sensitive individuals. This research aimed to establish a signature risk model, which derived from the macrophage, to assess immunotherapeutic responses and predict prognosis. Data from the UCSC‐XENA, GEO and TISCH databases were extracted for analysis. Based on both single‐cell datasets and bulk transcriptome profiles, a macrophage‐related score (MRS) consisting of the 10‐gene panel was constructed using the gene set variation analysis. MRS was highly correlated with hypoxia, angiogenesis, and epithelial‐mesenchymal transition, suggesting its potential as a risk indicator. Moreover, poor immunotherapy responses and worse prognostic performance were observed in the high‐MRS group of various immunotherapy cohorts. Additionally, APOE, one of the constituent genes of the MRS, affected the polarisation of macrophages. In particular, the reduced level of M2 macrophage and tumour progression suppression were observed in PCa xenografts which implanted in Apolipoprotein E‐knockout mice. The constructed MRS has the potential as a robust prognostic prediction tool, and can aid in the treatment selection of PCa, especially immunotherapy options.

Abstract Background Malnutrition, sarcopenia and frailty are distinct, albeit interrelated, conditions associated with adverse outcomes in adults with cancer, but whether they relate to multimorbidity, which affects up to 90% of people with cancer, is unknown. This study investigated the relationship between multimorbidity with malnutrition, sarcopenia and frailty in adults with cancer from the UK Biobank. Methods This was a cross‐sectional study including 4122 adults with cancer (mean [SD] age 59.8 [7.1] years, 50.7% female). Malnutrition was determined using the Global Leadership Initiative on Malnutrition criteria. Probable sarcopenia and sarcopenia were defined using the European Working Group on Sarcopenia in Older People 2 criteria. (Pre‐)frailty was determined using the Fried frailty criteria. Multimorbidity was defined as ≥2 long‐term conditions with and without the cancer diagnosis included. Logistic regression models were fitted to estimate the odds ratios (ORs) of malnutrition, sarcopenia and frailty according to the presence of multimorbidity. Results Genitourinary (28.9%) and breast (26.1%) cancers were the most common cancer diagnoses. The prevalence of malnutrition, (probable‐)sarcopenia and (pre‐)frailty was 11.1%, 6.9% and 51.2%, respectively. Of the 11.1% of participants with malnutrition, the majority (9%) also had (pre‐)frailty, and 1.1% also had (probable‐)sarcopenia. Of the 51.2% of participants with (pre‐)frailty, 6.8% also had (probable‐)sarcopenia. No participants had (probable‐)sarcopenia alone, and 1.1% had malnutrition, (probable‐)sarcopenia plus (pre‐)frailty. In total, 33% and 65% of participants had multimorbidity, including and excluding the cancer diagnosis, respectively. The most common long‐term conditions, excluding the cancer diagnosis, were hypertension (32.5%), painful conditions such as osteoarthritis or sciatica (17.6%) and asthma (10.4%). Overall, 80% of malnourished, 74% of (probable‐)sarcopenia and 71.5% of (pre‐)frail participants had multimorbidity. Participants with multimorbidity, including the cancer diagnosis, had higher odds of malnutrition (OR 1.72 [95% confidence interval, CI, 1.31–2.30; P

Abstract Aims Individuals with congenital heart disease (CHD) are at an increased risk for cancer. As cancer survival rates improve, the prevalence of late side effects, such as heart failure (HF), is becoming more evident. This study aims to evaluate the risk of developing HF following a cancer diagnosis in patients with CHD, compared with those without CHD and with CHD patients who do not have cancer. Methods CHD patients (n = 69 799) and randomly selected non‐CHD controls (n = 650 406), born in Sweden between 1952 and 2017, were identified from the Swedish National Health Registers and Total Population Register (excluding those with syndromes and transplant recipients). CHD patients who developed cancer (n = 1309) were propensity score‐matched with non‐CHD patients who developed cancer (n = 9425), resulting in a cohort of 1232 CHD patients with cancer and 2602 non‐CHD controls with cancer (after exclusion of individuals with HF prior to cancer diagnosis). In a separate analysis, CHD patients with cancer were propensity score‐matched with CHD patients without cancer (n = 68 490). A total of 1233 CHD patients with cancer and 2257 CHD patients without cancer were included in the study. Results Among CHD patients with cancer, 73 (5.9%) developed HF during a mean follow‐up time of 8.5 ± 8.7. Comparatively, in the propensity‐matched control population, 29 (1.1%) non‐CHD cancer patients (mean follow‐up time of 7.3 ± 7.5) and 101 (4.5%) CHD patients without cancer (mean follow‐up time of 9.9 ± 9.2) developed HF. CHD patients exhibited a significantly higher risk of HF post‐cancer diagnosis compared with the non‐CHD control group [hazard ratio (HR) 4.39, 95% confidence interval (CI) 2.83–6.81], after adjusting for age at cancer diagnosis and comorbidities. In the analysis between CHD patients with cancer and those without cancer, the results indicated a significantly higher risk of developing HF in CHD patients with cancer (HR 1.53, 95% CI 1.13–2.07). Conclusions CHD patients face a more than four‐fold increased risk of developing HF after a cancer diagnosis compared with cancer patients without CHD. Among CHD patients, the risk of HF is only modestly higher for those with cancer than for those without cancer. This suggests that the increased HF risk in CHD patients with cancer, relative to non‐CHD cancer patients, may be more attributable to CHD itself than to cancer treatment‐related side effects.

Abstract Young children receiving outpatient cancer care are vulnerable to undermanaged pain. App‐based solutions that provide pain treatment advice to parents in real‐time and in all environments may improve access to quality pain care. We used a parent co‐design approach involving iterative rounds of user testing and software modification to develop a usable Pain Caregiver Resource (PainCaRe) real‐time pediatric cancer pain management app. Parents of children (2–11 years) with cancer completed three standardized modules using a PainCaRe prototype. App usability and acceptability were evaluated using the validated System Usability Scale and a thematic analysis of app testing sessions and interviews. Iterative testing sessions were conducted until data saturation. Interview themes were synthesized into action items that guided revisions to PainCaRe and additional testing rounds were conducted as necessary. Twenty‐two parents participated in three testing cycles. Overall, parents described PainCaRe as an acceptable and potentially clinically useful pain management tool. Mean system usability scores were in the acceptable scale range during each testing cycle. Usability issues identified and resolved included those related to software malfunction, complicated app navigation logic, lack of clarity on pain assessment questions, and the need for pain management advice specifically tailored to child developmental stage. Using co‐design methods, the PainCaRe cancer pain management app was successfully refined for its acceptability and utility to parents. Next steps will include a PainCaRe pilot study before evaluating the impact of the app on younger children's pain outcomes in a randomized controlled trial.

Abstract Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non‐immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.

Cancer represents a profound challenge to healthcare systems and individuals worldwide. The development of multiple drug resistance is a major problem in cancer therapy and can result in progression of the disease. In our previous studies, we developed small‐molecule inhibitors targeting ubiquitin‐specific peptidase 24 (USP24) to combat drug‐resistant lung cancer. Recently, we found that the USP24 inhibitor NCI677397 induced ferroptosis, a type of programmed cell death, in drug‐resistant cancer cells by increasing lipid reactive oxygen species (ROS) levels. In the present study, we investigated the molecular mechanisms and found that the targeting of USP24 by NCI677397 increased gene expression of most lipogenesis‐related genes, such as acyl‐CoA synthetase long‐chain family member 4 (ACSL4), and activated autophagy. In addition, the activity of several antioxidant enzymes, such as glutathione peroxidase 4 (GPX4) and dihydrofolate reductase (DHFR), was inhibited by NCI677397 treatment via an increase in protein degradation, thereby inducing lipid ROS production and lipid peroxidation. In summary, we demonstrated that NCI677397 induced a marked increase in lipid ROS levels, subsequently causing lipid peroxidation and leading to the ferroptotic death of drug‐resistant cancer cells. Our study provides new insights into the clinical use of USP24 inhibitors as ferroptosis inducers (FINs) to block drug resistance during chemotherapy.

Genomic medicine has transformed the lives of patients with cancer by enabling individualised and evidence‐based clinical decision‐making. Despite this progress, the implementation of precision cancer medicine is limited by its dependence on isolated biomarkers. The development of bulk and single‐cell multiomic technologies has revealed the enormous complexity of the cancer ecosystem. Beyond the cancer cell, the tumour microenvironment, macroenvironment and host factors, including the microbiome, profoundly influence the cancer phenotype, and accounting for these enhances the resolution of precision medicine. The advent of robust multiomic profiling and interpretable machine learning algorithms mark the dawn of a new postgenomic era of personalised cancer medicine. In Precision Cancer Medicine 2.0, high‐resolution personalised clinical decision‐making is informed by the comprehensive multiomic profiling of tumour and host, integrated using artificial intelligence.

Cancer cachexia (Ccx) is a complex metabolic condition characterized by pronounced muscle and fat wasting, systemic inflammation, weakness and fatigue. Up to 30% of cancer patients succumb directly to Ccx, yet therapies that effectively address this perturbed metabolic state are rare. In recent decades, several characteristics of Ccx have been established in mice and humans, of which we here highlight adipose tissue dysfunction, muscle wasting and systemic inflammation, as they are directly linked to biomarker discovery. To counteract cachexia pathogenesis as early as possible and mitigate its detrimental impact on anti‐cancer treatments, identification and validation of clinically endorsed biomarkers assume paramount importance. Ageing was recently shown to affect both the validity of Ccx biomarkers and Ccx development, but the underlying mechanisms are still unknown. Thus, unravelling the intricate interplay between ageing and Ccx can help to counteract Ccx pathogenesis and tailor diagnostic and treatment strategies to individual needs.

Abstract A new payoff function is proposed for cancer treatment optimisation, the tumour elimination payoff (TEP), that incorporates the increase in lifespan if tumour elimination is achieved. The TEP is discounted by drug toxicity and by potential risks, such as metastasis and mutation. An approximation is used for the probability of tumour elimination, e−αN(T), giving a terminal payoff with an exponential dependence on the final tumour size N(T). The optimal solutions for this payoff for simple tumour growth models, (logistic and Gompertz growth), are determined. Using Pontryagin's maximum principle it is proved that bang–bang optimal solutions exist with a single switch; specifically delayed treatment and treat‐and‐stop solutions at maximum tolerated dose (MTD) exist. There is also a singular arc with constant tumour size. Solutions either have a high probability, respectively, low probability of tumour elimination; these correspond to a post‐treatment high probability of cure, and a high probability of relapse, respectively. Optimising over the time horizon T results in solutions that are either MTD throughout or no treatment, that is, treatment is either beneficial or detrimental. For the logistic growth model, the treatment benefit phase diagram is derived with respect to the patient's expected increase in lifespan and tumour size.

Abstract Cancer poses a significant health threat to the elderly, accounting for a substantial proportion of cancer patients aged 65 and above. As life expectancy continues to rise and the population ages, the incidence of cancer in the elderly is expected to increase further. Age is a major risk factor for the majority of common cancers, with the incidence and prevalence rising as individuals grow older. Factors such as chemoprevention and environmental carcinogen elimination may influence the process of carcinogenesis. Studies reveal that the incidence and mortality rates of various cancers in the elderly and extremely old individuals are on the rise worldwide, with most types peaking around the age of 75 to 90, followed by a sharp decline. Birth cohort and period effects also play a complex role in the connection between aging and cancer risk. Clinical trials often exclude older individuals, limiting our understanding of cancer treatments' effects on this particular age group. More research is needed to focus on the unique requirements of older adults with cancer.

A first‐in‐human trial demonstrated that a vaccine targeting the histone mutation H3K27M can induce an immune response, in a mutation‐specific manner, in patients with diffuse midline glioma. In a recent study by Boschert et al., the same group now dissects the functional immune response triggered after effective vaccination of one of the patients, who has been in remission for over 3 years. The H3K27M peptide vaccine, named H3‐vac, induces a CD4+ T‐cell‐specific immune response in this patient and expands the repertoire of polyclonal H3K27M‐specific T‐cell receptors. A clonal H3K27M‐reactive B‐cell population was also detected in the patient's cerebrospinal fluid. Importantly, the immune response is induced across various human leukocyte antigen alleleotypes, indicating the potential efficacy of the vaccine in diverse populations. By exploring in detail the immune response linked to this patient's long‐term survival, the authors prove peptide vaccinations as a viable therapeutic approach. This paves the way for personalised therapies harnessing immunogenic T‐ and B‐cell responses against different tumour types.

An immunosuppressive tumor microenvironment promotes tumor growth and is one of the main factors limiting the response to cancer immunotherapy. We have previously reported that inhibition of vacuolar protein sorting 34 (VPS34), a crucial lipid kinase in the autophagy/endosomal trafficking pathway, decreases tumor growth in several cancer models, increases infiltration of immune cells and sensitizes tumors to anti‐programmed cell death protein 1/programmed cell death 1 ligand 1 therapy by upregulation of C‐C motif chemokine 5 (CCL5) and C‐X‐C motif chemokine 10 (CXCL10) chemokines. The purpose of this study was to investigate the signaling mechanism leading to the VPS34‐dependent chemokine increase. NanoString gene expression analysis was applied to tumors from mice treated with the VPS34 inhibitor SB02024 to identify key pathways involved in the anti‐tumor response. We showed that VPS34 inhibitors increased the secretion of T‐cell‐recruitment chemokines in a cyclic GMP‐AMP synthase (cGAS)/stimulator of interferon genes protein (STING)‐dependent manner in cancer cells. Both pharmacological and small interfering RNA (siRNA)‐mediated VPS34 inhibition increased cGAS/STING‐mediated expression and secretion of CCL5 and CXCL10. The combination of VPS34 inhibitor and STING agonist further induced cytokine release in both human and murine cancer cells as well as monocytic or dendritic innate immune cells. Finally, the VPS34 inhibitor SB02024 sensitized B16‐F10 tumor‐bearing mice to STING agonist treatment and significantly improved mice survival. These results show that VPS34 inhibition augments the cGAS/STING pathway, leading to greater tumor control through immune‐mediated mechanisms. We propose that pharmacological VPS34 inhibition may synergize with emerging therapies targeting the cGAS/STING pathway.

Abstract There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia–cachexia syndrome. This review aimed to examine the dose–response effect of MA supplementation in patients with cancer‐associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer‐associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random‐effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [−0.11, 1.38], P = 0.093, I2 = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short‐term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose–response meta‐analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I2 = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P

Abstract The prevention and management of cancer therapy‐related cardiac dysfunction (CTRCD) have become increasingly important. Recent studies have revealed the crucial role of genetics in determining the susceptibility to development of CTRCD. We present a case of a 65‐year‐old woman with breast cancer who developed recurrent CTRCD following low‐dose chemotherapy, despite lacking conventional cardiovascular risk factors. Her medical history included anthracycline‐associated cardiomyopathy, and her condition deteriorated significantly after treatment with HER2‐targeted therapies. Through the use of multimodal imaging, we detected severe left ventricular systolic dysfunction. Further investigation with genetic testing revealed a likely pathogenic variant in the TNNT2 gene, suggesting a genetic predisposition to CTRCD. This case implies the potential role of genetic screening in identifying patients at risk for CTRCD and advocates for personalized chemotherapy and cardioprotective strategies.

Abstract Alterations in cellular calcium (Ca2+) signals have been causally associated with the development and progression of human cancers. Cellular Ca2+ signals are generated by channels, pumps, and exchangers that move Ca2+ ions across membranes and are decoded by effector proteins in the cytosol or in organelles. S‐acylation, the reversible addition of 16‐carbon fatty acids to proteins, modulates the activity of Ca2+ transporters by altering their affinity for lipids, and enzymes mediating this reversible post‐translational modification have also been linked to several types of cancers. Here, we compile studies reporting an association between Ca2+ transporters or S‐acylation enzymes with specific cancers, as well as studies reporting or predicting the S‐acylation of Ca2+ transporters. We then discuss the potential role of S‐acylation in the oncogenic potential of a subset of Ca2+ transport proteins involved in cancer.

Abstract Cancer stands as a leading global cause of death, with its etiology characterized by complexity and multifaceted factors. Growing research indicates a strong correlation between environmental factors and cancer incidence, underscoring the critical importance of intervening in environmental risk factors to mitigate cancer occurrence. Despite this, specialized research institutions focusing on the intersection of environment and cancer remain scarce, with global investment in cancer prevention significantly trailing behind efforts in diagnosis and treatment. Against the backdrop of rapid global climate change, industrialization, urbanization, aging populations, and the globalization of lifestyles, we proposed the concept of Environmental Oncology (EO) to address these challenges. We discussed the rationale and necessity of developing EO and presented a comprehensive research framework focusing on cancer prevention and treatment. Future EO research will aim to identify cancer causes and implement early prevention strategies using advanced scientific technologies and methods. By emphasizing multidisciplinary collaboration and integrating molecular biology at the micro level, EO will explore the relationship between external and internal environments and cancer. EO will identify potential therapeutic targets by studying the pathways through which environmental exposures lead to carcinogenesis. EO will develop early warning systems and disseminate research findings by collecting big data, employing robust statistical models, and establishing research centers.

Abstract People with diabetes mellitus (DM) and hyperglycemia are linked with cancer risk. Diabetes and cancer have been corroborated by high morbidity and mortality rates. Studies revealed that elevated levels of insulin secretions trigger insulin‐like growth factor 1 (IGF‐1) production. Moreover, IGF‐1 is a key regulator involved in promoting cancer cell progression and is linked with DM. Cancer drug resistance and ototoxic effects can adversely affect the health and lifespan of an individual. However, naturally derived bioactive compounds are gaining attention for their nontoxic properties and specific behavior. Likewise, probiotics have also been regarded as safe and successful alternatives to treat DM‐linked cancers. The present review aims to highlight the therapeutic potential and feasible functions of probiotics to mitigate or inhibit DM‐associated cancers. Meanwhile, the intracellular signaling cascades involved in promoting DM‐linked cancer are enumerated for future prospective research. However, metabolomics interactions and protein–protein interactions are to be discussed for deeper insights into affirmative principles in diabetic‐linked cancers. Drug discovery and innovative preclinical evaluation need further adjuvant and immune‐enhancement therapies. Furthermore, the results of the in silico assessment could provide scientific excellence of IGF‐1 in diabetes and cancer. Overall, this review summarizes the mechanistic insights and therapeutic targets for diabetes‐associated cancer.

Metformin and IACS‐010759 are two distinct antimetabolic agents. Metformin, an established antidiabetic drug, mildly inhibits mitochondrial complex I, while IACS‐010759 is a new potent mitochondrial complex I inhibitor. Mitochondria is pivotal in the energy metabolism of cells by providing adenosine triphosphate through oxidative phosphorylation (OXPHOS). Hence, mitochondrial metabolism and OXPHOS become a vulnerability when targeted in cancer cells. Both drugs have promising antitumoral effects in diverse cancers, supported by preclinical in vitro and in vivo studies. We present evidence of their direct impact on cancer cells and their immunomodulatory effects. In clinical studies, while observational epidemiologic studies on metformin were encouraging, actual trial results were not as expected. However, IACS‐01075 exhibited major adverse effects, thereby causing a metabolic shift to glycolysis and elevated lactic acid concentrations. Therefore, the future outlook for these two drugs depends on preventive clinical trials for metformin and investigations into the plausible toxic effects on normal cells for IACS‐01075.

Abstract Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome‐driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

Abstract The study aimed to systematically compare the effects of psychological interventions on relieving fear of cancer recurrence (FCR) by a systematic review and network meta‐analysis (NMA). The relevant randomized controlled trials were searched from China National Knowledge Infrastructure, Wanfang Database, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, Cochrane Library, Pubmed, Web of Science, CINAHL, PsycINFO, and Embase. The retrieval time was from the establishment of each database to January 23, 2024. Review Manager 5.4 software was used to evaluate the quality of each literature that met the inclusion and exclusion criteria. Stata16.0 was used for NMA. Standardized mean differences (SMDs) of patients' FCR outcomes and 95% confidence intervals (CIs) were used to determine the effects. Inconsistency test, network map, surface under the cumulative rankings curve (SUCRA), comparison‐adjusted funnel plot were performed. A total of 41 articles were included, with 4056 patients and 15 psychological interventions. Six psychological interventions (NT, Narrative Therapy; ACT, Accept and Commitment Therapy; GT, Therapy based on Gratitude‐Expanded Behavior Theory; Blend Cognitive Behavior Therapy; PERMA, PERMA Therapy; CBT, Cognitive Behavior Therapy) were effective in alleviating FCR in the short term compared with usual care, whereas the effects of ACT, GT, and CBT were sustained up to more than 3 months postintervention. NT ranked as most likely to alleviate FCR, (SUCRA: 89.8%, SMD: −2.89, 95% CI: −4.08 to −1.69), followed by ACT (SUCRA: 88.1%, SMD: −2.83, 95% CI: −4.38 to −1.27) in short‐term effects. GT ranked as most likely to alleviate FCR in long‐term effects (SUCRA: 100%, SMD: −3.35, 95% CI: −4.21 to −2.50), followed by ACT (SUCRA: 88.9%, SMD: −1.64, 95% CI: −2.36 to −0.91). However, most of the quality of evidence for pairwise comparison was rated as “very low” to “low.” The evidence can help inform evidence‐based practice and guide healthcare providers in deciding on the most effective psychological interventions for FCR, which should also be viewed with caution due to the low level of the quality.

Abstract Introduction Liver cancer presents a growing global health concern, necessitating advanced approaches for intervention. This review investigates the use and effectiveness of software navigation in interventional radiology for liver tumour procedures. Methods In accordance with Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) guidelines, a scoping review was conducted of the literature published between 2013 and 2023 sourcing articles through MEDLINE, Scopus, CINAHL and Embase. Eligible studies focused on liver cancer, utilised cone‐beam computed tomography (CBCT), and employed software for intervention. Twenty‐one articles were deemed eligible for data extraction and analysis. Results Categorised by type, software applications yielded diverse benefits. Feeder detection software significantly enhanced vessel identification, reducing non‐target embolisation by up to 43%. Motion correction software demonstrated a 20% enhancement in image quality, effectively mitigating breathing‐induced motion artefacts. Liver perfusion software facilitated efficient tumour targeting while simultaneously reducing the occurrence of side effects. Needle guide software enabled precise radiofrequency ablation needle placement. Additionally, these software applications provided detailed anatomical simulations. Overall, software integration resulted in shorter procedures, reduced radiation exposure and decreased contrast media usage. Conclusion This scoping review highlights the innovative yet relatively underexplored role of software navigation for liver tumour procedures. The integration of software applications not only enhances procedural efficiency but also bolsters operator confidence, and contributes to improved patient outcomes. Despite the current lack of uniformity and standardisation, these software‐driven advancements hold significant promise for transforming liver tumour interventions. To realise these benefits, further research is needed to explore the clinical impact and optimal utilisation of software navigation tools in interventional radiology.

Abstract Background Cancer cachexia is a life‐threatening, inflammation‐driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy. Methods The effect of AR on cancer cachexia was investigated in two distinct murine models of colorectal cancer. First, 7‐week‐old CD2F1 male mice were subcutaneously injected with colon‐26 carcinoma cells (C26) or vehicle (CT). Six days after injection, mice were treated for 5 days with AdipoRon (50 mg/kg/day; C26 + AR) or the corresponding vehicle (CT and C26). Additionally, a genetic model, the ApcMin/+ mouse, that develops spontaneously numerous intestinal polyps, was used. Eight‐week‐old male ApcMin/+ mice were treated with AdipoRon (50 mg/kg/day; Apc + AR) or the corresponding vehicle (Apc) over a period of 12 weeks, with C57BL/6J wild‐type mice used as controls. In both models, several parameters were assessed in vivo: body weight, grip strength and serum parameters, as well as ex vivo: molecular changes in muscle, fat and liver. Results The protective effect of AR on cachexia development was observed in both cachectic C26 and ApcMin/+ mice. In these mice, AR administration led to a significant alleviation of body weight loss and muscle wasting, together with rescued muscle strength (P

Abstract Background Cancer cachexia is a multifactorial metabolic wasting syndrome characterized by anorexia, unintentional loss of weight involving both skeletal muscle and adipose tissues, progressive functional impairment and reduced survival. Therapeutic strategies for this serious condition are very limited. Growth differentiation factor 15 (GDF‐15) is a cytokine that is implicated in cancer cachexia and may represent both a biomarker of cancer cachexia and a potential therapeutic target. Ponsegromab is a potent and selective humanized monoclonal antibody that inhibits GDF‐15‐mediated signalling. Preclinical and preliminary phase 1 data suggest that ponsegromab‐mediated inactivation of circulating GDF‐15 may lead to improvement in key characteristics of cachexia. The primary objective of this phase 2 study is to assess the effect of ponsegromab on body weight in patients with cancer, cachexia and elevated GDF‐15 concentrations. Secondary objectives include assessing physical activity, physical function, actigraphy, appetite, nausea and vomiting, fatigue and safety. Exploratory objectives include evaluating pharmacokinetics, pharmacodynamics, immunogenicity, lumbar skeletal muscle index and Response Evaluation Criteria in Solid Tumors. Methods Approximately 168 adults with non‐small‐cell lung, pancreatic or colorectal cancers who have cachexia and elevated GDF‐15 concentrations will be randomized in a double‐blind, placebo‐controlled study (NCT05546476). Participants meeting eligibility criteria will be randomized 1:1:1:1 to one of three dose groups of ponsegromab (100, 200 or 400 mg) or matching placebo administered subcutaneously every 4 weeks for an initial 12‐week treatment period. This is followed by optional open‐label treatment with ponsegromab of 400 mg administered every 4 weeks for up to 1 year. The primary endpoint is mean change from baseline in body weight at Week 12. A mixed model for repeated measures followed by a Bayesian Emax model will be used for the primary analysis. Secondary endpoints include physical activity, physical function and actigraphy measured by remote digital sensors; patient‐reported appetite‐related symptoms assessed by Functional Assessment of Anorexia‐Cachexia Therapy subscale scores; anorexia/appetite, nausea and vomiting, and fatigue evaluated according to questions from the Cancer‐Related Cachexia Symptom Diary; and incidence of adverse events, safety laboratory tests, vital signs and electrocardiogram abnormalities. Perspective Cancer‐related cachexia is an area of significant unmet medical need. This study will support the clinical development of ponsegromab as a novel inhibitor of GDF‐15, which may ameliorate key pathologies of cancer cachexia to improve patient symptoms, functionality and quality of life. Trial registration ClinicalTrials.gov ID: NCT05546476.

Abstract The use of patient‐reported outcomes (PROMs) of quality of life (QOL) is common in cachexia trials. Patients' self‐report on health, functioning, wellbeing, and perceptions of care, represent important measures of efficacy. This review describes the frequency, variety, and reporting of QOL endpoints used in cancer cachexia clinical trials. Electronic literature searches were performed in Medline, Embase, and Cochrane (1990–2023). Seven thousand four hundred thirty‐five papers were retained for evaluation. Eligibility criteria included QOL as a study endpoint using validated measures, controlled design, adults (>18 years), ≥40 participants randomized, and intervention exceeding 2 weeks. The Covidence software was used for review procedures and data extractions. Four independent authors screened all records for consensus. Papers were screened by titles and abstracts, prior to full‐text reading. PRISMA guidance for systematic reviews was followed. The protocol was prospectively registered via PROSPERO (CRD42022276710). Fifty papers focused on QOL. Twenty‐four (48%) were double‐blind randomized controlled trials. Sample sizes varied considerably (n = 42 to 469). Thirty‐nine trials (78%) included multiple cancer types. Twenty‐seven trials (54%) featured multimodal interventions with various drugs and dietary supplements, 11 (22%) used nutritional interventions alone and 12 (24%) used a single pharmacological intervention only. The median duration of the interventions was 12 weeks (4–96). The most frequent QOL measure was the EORTC QLQ‐C30 (60%), followed by different FACIT questionnaires (34%). QOL was a primary, secondary, or exploratory endpoint in 15, 31 and 4 trials respectively, being the single primary in six. Statistically significant results on one or more QOL items favouring the intervention group were found in 18 trials. Eleven of these used a complete multidimensional measure. Adjustments for multiple testing when using multicomponent QOL measures were not reported. Nine trials (18%) defined a statistically or clinically significant difference for QOL, five with QOL as a primary outcome, and four with QOL as a secondary outcome. Correlation statistics with other study outcomes were rarely performed. PROMs including QOL are important endpoints in cachexia trials. We recommend using well‐validated QOL measures, including cachexia‐specific items such as weight history, appetite loss, and nutritional intake. Appropriate statistical methods with definitions of clinical significance, adjustment for multiple testing and few co‐primary endpoints are encouraged, as is an understanding of how interventions may relate to changes in QOL endpoints. A strategic and scientific‐based approach to PROM research in cachexia trials is warranted, to improve the research base in this field and avoid the use of QOL as supplementary measures.

Abstract Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990–2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety‐nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C‐reactive protein (n = 22, 42.3%), interleukin‐6 (n = 16, 30.8%) and tumour necrosis factor‐α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin‐like growth factor binding protein 3 (IGFBP‐3) and insulin‐like growth factor 1 (IGF‐1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP‐3, IGF‐1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.

Abstract Background The interdependence of cytokines and appetite‐modifying hormones implicated in cancer anorexia‐cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non‐inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes. Methods Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia‐Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex‐standardized skeletal muscle index (z‐SMI) and fat mass index (z‐FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite‐modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two‐step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan–Meier analysis. Results Patients had low z‐SMI (mean = −3.78 cm2/m2; SD: 8.88) and z‐FMI (mean = 0.08 kg2/m2; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F‐1) IFN‐γ, IL‐1β, Il‐4, IL‐6, IL‐10, IL‐12, TGFβ1 (positive contribution), and IL‐18 (negative); (F‐2) IL‐8, IL‐18, MCP‐1, TGFβ1, TNF‐α (positive), and ghrelin (negative); and (F‐3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS‐1 was associated with cachexia (P = 0.002); RFS‐2, with higher CRP (P

Abstract Background Body weight and its changes have been associated with cancer outcomes. However, the associations of short‐term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short‐term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. Methods This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height‐adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight‐related indicators and compared their prognostic performance using Harrell's C‐index, integrated discrimination improvement, continuous net reclassification improvement and time‐dependent C‐index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan–Meier analysis and multivariable‐adjusted Cox regression models. Results The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow‐up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C‐index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P 10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5–10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5–10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. Conclusions The prognostic performance of peridiagnosis RWC is superior to other weight‐related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change‐related premature deaths.

Abstract Background Cachexia is prevalent in gastrointestinal cancers and worsens patient outcomes and chemotherapy compliance. We examined to what extent registered gastrointestinal cancer chemotherapy clinical trials record measures and related symptoms of cachexia as outcomes, and whether these were associated with trial characteristics. Methods Four public trial registries (2012–2022) were accessed for Phase II and/or III randomized controlled pancreatic, gastric, and colorectal cancer chemotherapy trial protocols. Trial outcome measures of overall survival and toxicity/side effects, and those related to cachexia [physical activity, weight/body mass index (BMI), dietary limitations, caloric intake, lean muscle mass] and symptoms (appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, and oral mucositis) were extracted, along with the number and types of performance status and patient‐reported outcomes (PROs) tools. Data were summarized descriptively. Chi‐square tests examined associations between outcomes and trial characteristics (cancer type, trial location, funding source, PROs tools, and commencement year). Statistical significance was set at P

Abstract Introduction Restrictive eligibility criteria in cancer drug trials result in low enrollment rates and limited population diversity. Relaxed eligibility criteria (REC) based on solid evidence is becoming necessary for stakeholders worldwide. However, the absence of high‐quality, favorable evidence remains a major challenge. This study presents a protocol to quantitatively evaluate the impact of relaxing eligibility criteria in common non‐small cell lung cancer (NSCLC) protocols in China, on the risk–benefit profile. This involves a detailed explanation of the rationale, framework, and design of REC. Methods To evaluate our REC in NSCLC drug trials, we will first construct a structured, cross‐dimensional real‐world NSCLC database using deep learning methods. We will then establish randomized virtual cohorts and perform benefit–risk assessment using Monte Carlo simulation and propensity matching. Shapley value will be utilized to quantitatively measure the effect of the change of each eligibility criterion on patient volume, clinical efficacy and safety. Discussion This study is one of the few that focuses on the problem of overly stringent eligibility criteria cancer drug clinical trials, providing quantitative evaluation of the effect of relaxing each NSCLC eligibility criterion. This study will not only provide scientific evidence for the rational design of population inclusion in lung cancer clinical trials, but also establish a data governance system, as well as a REC evaluation framework that can be generalized to other cancer studies.

Abstract Skin cancer is common and deadly, needs to be detected and treated properly. Deep learning algorithms like UNet have shown potential results in medical imaging. Such approaches still struggle to capture fine‐grained details and scale differences in skin lesions‐based occlusions' appearance, size etc. This research proposes a redesign UNet, the Multi‐Scale Pyramid Attention Network (MSPAN), to improve skin cancer lesion segmentation. The input data is processed at numerous scales with varied receptive fields. This enhances the network's ability to identify lesion locations by capturing local and global context. Attention approaches also help the network to suppress noise by focusing on informative features. We have evaluated MSPAN model on the publicly available ISIC2018 benchmark dataset for skin lesion segmentation. The method surpasses traditional UNet and other current methods in accuracy and effectiveness. The model also has a post‐processing to estimate lesion area for fast inference, making it suitable for extensive screening. Redesigned UNet with the Multi‐Scale Pyramid Attention Network improves skin cancer lesion segmentation. The model's ability to collect fine‐grained information and handle occlusions allows for more accurate skin cancer diagnosis and treatment. The MSPAN design can improve computer‐aided diagnosis systems and help dermatologists make precise clinical decisions.

Drug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug perturbations most inversely related to the disease‐associated gene signature to identify drugs that may reverse that signature. We assessed the performance and biological relevance of three approaches for constructing disease‐associated gene signatures (i.e., limma, DESeq2, and MultiPLIER) and prioritized the resulting drug repurposing candidates for four low‐survival human cancers. Our results were enriched for candidates that had been used in clinical trials or performed well in the PRISM drug screen. Additionally, we found that pamidronate and nimodipine, drugs predicted to be efficacious against the brain tumor glioblastoma (GBM), inhibited the growth of a GBM cell line and cells isolated from a patient‐derived xenograft (PDX). Our results demonstrate that by applying multiple disease‐associated gene signature methods, we prioritized several drug repurposing candidates for low‐survival cancers.

The coupling of transcription and translation enables prokaryotes to regulate mRNA stability and reduce nonfunctional transcripts. Eukaryotes evolved other means to perform these functions. Here, we quantify the disparity between gene expression and protein levels and attempt to explain its origins. We collected publicly available simultaneous measurements of gene expression, protein level, division rate, and growth inhibition of breast cancer cells under drug perturbation. We used the cell lines as entities with shared origin, different evolutionary trajectories, and cancer hallmarks to define tasks subject to specializing and trading‐off. We observed varying average mRNA and protein correlation across cell lines, and it was consistently higher for the gene products in the cancer hallmarks. The enrichment of hallmark gene products signifies the resources invested in it as a task. Enrichment based on mRNA or protein abundance corresponds to the relative resources dedicated to transcription and translation. The differences in gene‐ and protein‐based enrichment correlated with nominal division rates but not growth inhibition under drug perturbations. Comparing the range of enrichment scores of the hallmarks within each cell signifies the resources dedicated to each. Cells appear to have a wider range of enrichment in protein synthesis relative to gene transcription. The difference and range of enrichment of the hallmark genes and proteins correlated with cell division and inhibition in response to drug treatments. We posit that cancer cells may express the genes coding for seemingly nonspecialized tasks but do not translate them to the corresponding proteins. This trade‐off may cost the cells under normal conditions but confer benefits during stress.

Abstract The association of type 2 diabetes with certain cancer risk has been of great interest for years. However, the effect of diabetic medications on cancer development is not fully understood. Prospective clinical trials have not elucidated the long‐term influence of hypoglycemic drugs on cancer incidence and the safety for cancer‐bearing patients with diabetes, whereas numerous preclinical studies have shown that antidiabetic drugs could have an impact on carcinogenesis processes beyond the glycemic control effect. Because there is no evidence of the safety profile of antidiabetic agents on cancer biology, careful consideration would be required when prescribing any medicines to patients with diabetes and existing tumor. In this review, we discuss the potential influence of each diabetes therapy in cancer ‘initiation’, ‘promotion’ and ‘progression’.

ABSTRACT Introduction Health services rely upon carers to provide care for loved ones with cancer, yet many carers often feel ill‐prepared for this role. Despite a multitude of programmes to support carer mental health, programmes that help carers feel better equipped to support a person with cancer are lacking. This study aimed to address this need by adapting an evidence‐based intervention to be suitable for carers of people with cancer. Methods This study used an exploratory, qualitative design consisting of experienced‐based co‐design and an in‐depth stakeholder engagement strategy. An existing evidence‐based programme to promote resilience in the context of providing care was adapted for relevance to carers for people with cancer via two co‐design workshops with carers and healthcare professionals (n = 8). The resulting prototype programme was refined based on stakeholder consultations with staff and consumer members of cancer and carer support organisations across Australia (n = 16). Transcripts of the workshops, meetings and written feedback from carers were thematically analysed. Results Major programme developments were guided by three themes that emerged from the co‐design workshops: ‘creating value for carers’, ‘multiple contributors to carer distress’ and ‘the need for flexible implementation’. Analysis of the stakeholder consultation data showed that the themes of ‘diversity in carer journeys’ and ‘creating impact for carers’ were key to further tailoring the programme for applicability to practice. An adapted programme called ‘iCanSupport’ resulted from the process, with key adaptations being more relevant case study scenarios for carers and greater flexibility in accessing and engaging with the intervention to accommodate a range of carer circumstances. Conclusion Programmes to build skills for becoming a carer for someone with cancer are absent, yet they are desired by carers. Using co‐design provided a user‐centric approach to adapt an existing evidence‐based programme. Programme evaluation is required to determine the effectiveness of the co‐designed approach in improving carer preparedness among a range of cohorts. Patient or Public Contribution Carers and consumers with lived experience and others involved in supporting consumers made valuable contributions to co‐designing and refining the programme in addition to providing ongoing guidance in the unfolding analysis and reporting of this research.

Abstract Circulating RNAs have been investigated systematically for over 20 years, both as constituents of circulating extracellular vesicles (EVs) or, more recently, non‐EV RNA carriers, such as exomeres and supermeres. The high level of variability and low reproducibility rate of EV/extracellular RNA (exRNA) results generated even on the same biofluids promoted several efforts to limit pre‐analytical variability by standardizing sample collection and sample preparation, along with instrument validation, setup and calibration. Anticoagulants (ACs) are often chosen based on the initial goal of the study and not necessarily for the later EV and/or exRNA analyses. We show the effects of blood collection on EV size, abundance, and antigenic composition, as well on the miRNAs. Our focus of this work was on the effect of ACs on the number and antigenic composition of circulating EVs and on a set of circulating miRNA species, which were shown to be relevant as disease markers in several cancers and Alzheimer's disease. Results show that while the number of plasma EVs, their relative size, and post‐fluorescence labeling profile varied with each AC, their overall antigenic composition, with few exceptions, did not change significantly. However, the number of EVs expressing platelet and platelet‐activation markers increased in serum samples. For overall miRNA expression levels, EDTA was a better AC, although this may have been associated with stimulation of cells in the blood collection tube. Citrate and serum rendered better results for a set of miRNAs that were described as circulating markers for Alzheimer's disease, colon, and papillary thyroid cancers.

Abstract Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular‐bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular‐bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed‐effects model with jugular‐bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular‐bulb concentrations. The slope of the regression line between arterial and jugular‐bulb lactate was 0.95 (95% CI 0.93–0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57–5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor‐craniotomy patients probably does not originate from the brain.

ABSTRACT Background In this article, we review the most recent research on probiotics effects on diarrhea in both human and animal models of the condition along with the therapeutic potential of these compounds based on their findings. Recent Findings Nearly 50%–80% of cancer patients experience chemotherapy‐induced diarrhea (CID), serious gastrointestinal toxicity of chemotherapeutic and radiation regimens that leads to prolonged hospitalizations, cardiovascular problems, electrolyte imbalances, disruptions in cancer treatment, poor cancer prognosis, and death. CID is typically categorized as osmotic diarrhea. The depletion of colonic crypts and villi by radiotherapy and chemotherapy agents interferes with the absorptive function of the intestine, thereby decreasing the absorption of chloride and releasing water into the intestinal lumen. Probiotic supplements have been found to be able to reverse the intestinal damage caused by chemo‐radiation therapy by promoting the growth of crypt and villi and reducing inflammatory pathways. In addition, they support the modulation of immunological and angiogenesis responses in the gut as well as the metabolism of certain digestive enzymes by altering the gut microbiota. Conclusion Beyond the benefits of probiotics, additional clinical research is required to clarify the most effective strain combinations and dosages for preventing chemotherapy and radiotherapy diarrhea.

ABSTRACT Background The COVID‐19 pandeminc has had widespread impacts, but its specific effects on mental health and cognitive function in patients with cancer remain under‐explored. Recent Findings Data from the general population has suggested that mental health problems were frequent during the pandemic, namely during the initial stage of the outbreak. For patients with cancer, a systematic review and meta‐analysis of data published until January 2021 also showed elevated prevalence of depression and anxiety, and suggested that anxiety was more frequent than in health workers and healthy controls. Objective This systematic review aimed to synthesize existing evidence on the impact of the COVID‐19 pandemic on mental health and cognitive function in patients with cancer. Methods Studies were identified through systematic search of three electronic bibliographic databases (PubMed, Web of Science, and EBSCOHOST) with adapted search strings. We included only peer‐reviewed, nonqualitative, original research papers, published between 2019 and 2022, and reporting on mental health and/or cognition outcomes during the COVID‐19 pandemic in adult patients with cancer. Results Of 3260 papers identified, 121 full text articles were retrieved and 71 met inclusion criteria. We found that patients with cancer reported high levels of psychological distress, anxiety and depression, as well as cognitive complaints during the pandemic. However, studies were not consistent in identifying these symptoms as effects of the pandemic specific for this population. In fact, longitudinal studies did not find consistent differences between pre‐ and post‐pandemic periods and, globally, patients with cancer did not report increased severity of these mental health symptoms in relation to the general population. Conclusion Overall, while the COVID‐19 pandemic may have raised mental health challenges for patients with cancer, the diagnosis of cancer and associated treatments seemed to remain the main source of concern for these patients.

Abstract Hepatocellular carcinoma (HCC), with its increasing prevalence globally, is emerging as a major health challenge. Hepatocellular carcinoma cells exhibit both significant homogeneity and heterogeneity, governed by complex epigenomic regulations. Recently, numerous single‐cell unimodal techniques have been used to study HCC at various levelswhich have already revealed a complex interplay at genomic, transcriptomic, spatial and epigenomic levels. However, the use of single‐cell multimodal techniques combining different unimodal layers in HCC remains quite limited, necessitating further studies focusing on these methods to uncover novel markers, and mechanisms at epigenetic levels. In this commentary, we highlight how integrating multimodal approaches with epigenetic modifications can provide new insights into HCC and foster future therapeutic advancements.

Abstract Introduction As the rural–urban cancer mortality gap widens, centering care around the needs of rural patients presents an opportunity to advance equity. One barrier to delivering patient‐centered care at rural hospitals stems from limited analytic capacity to leverage data and monitor patient outcomes. This case study describes the experience of a public health cancer surveillance system aiming to fill this gap within the context of a rural cancer network. Methods To support the implementation of a novel network model intervention in Iowa, the Iowa Cancer Registry began generating hospital‐specific and catchment area reports. Then, the Iowa Cancer Registry supported adapting the network model to fit the context of Iowa's cancer care delivery system by performing data monitoring and reporting functions. Informed by a gap analysis, the Iowa Cancer Registry then identified which quality accreditation standards could be achieved with public health surveillance data and analytic support. Results The network intervention in Iowa supported 5 rural cancer centers across the state, each concurrently pursuing quality accreditation standards. The Iowa Cancer Registry's hospital and catchment‐specific reports illuminated the cancer burden and needs of rural cancer centers within the network. Our team identified 19 (of the 36 total) quality standards that can be supported by public health surveillance functions typically performed by the registry. These standards encompassed data‐driven quality improvement, patient monitoring, and reporting guideline‐concordant care standards. Conclusions As rural hospitals continue to face resource constraints, multisectoral efforts informed by data from centralized public health surveillance systems can promote quality improvement initiatives across rural communities. While our work remains preliminary, we predict that analytic support provided by the Iowa Cancer Registry will enable the rural network hospitals to focus their capacity toward developing the infrastructure necessary to deliver high‐quality care and serve the unique needs of rural cancer patients.

Abstract Exosomes are nanoscale membrane vesicles identified by electron microscopy in 1946. They are approximately 30–150 nm in size. Originally, exosomes were thought to be used to eliminate excess components from cells to maintain their normal physiology. Later, it was found that the function and targeting of specific cellular components in exosomes have important implications for the regulation of cellular communication. In the last few years, exosomes have been linked to tumors, infections, and other diseases. New advances in cancer immunotherapy have occurred as a result of the identification of exosomes of immune cell origin, expanding the existing anticancer immune response. This article details exosomes derived from dendritic cells, T lymphocytes (CD4+ T cells, CD8+ T cells, and CAR‐T cells), natural killer cells, and their promising applications in tumor therapy.

Abstract Introduction An increasing body of evidence suggests a close association between COVID‐19 infection and the safety of PD‐1/PD‐L1 inhibitor therapy in cancer patients. However, the available data concerning these impacts remain limited and occasionally contradictory. Material and Methods We conducted a retrospective analysis of cancer patients who received PD‐1/PD‐L1 inhibitor therapy at the same institution from November 2022 to May 2023. After excluding patients with missing information, a total of 224 cases were included. In our study, immune‐related adverse events (irAEs) that occurred during the hospitalization of patients were included in the analysis. Further analysis of inter‐subgroup differences was conducted following a 1:2 propensity score matching. Statistical analyses were performed using the Fisher's exact, chi‐squared, and Mann–Whitney U‐tests. Result The results showed that no statistically significant differences between the two subgroups in the incidence of irAEs, changes in immune function before and after using PD‐1/PD‐L1 inhibitors, and alterations in hepatic and renal function (p > 0.05). Conclusion Our findings suggest that infection with COVID‐19 does not significantly impact the safety of PD‐1/PD‐L1 inhibitors in cancer patients. Most cancer patients used PD‐1/PD‐L1 inhibitors during COVID‐19 infection (asymptomatic or mild infection) did not experience exacerbation of their underlying condition, nor did they exhibit a substantial increase in toxic side effects.

ABSTRACT Backgroud Cancer‐related cognitive impairment is one of the common complications in children with cancer, but our understanding of their experience with cognitive deficits remains limited. From the perspective of parents, this study aimed to explore the distress and demands faced by children with cancer‐related cognitive impairment, to provide references for developing targeted intervention strategies for cancer children. Methods We used a purposeful sampling method to conduct semi‐structured interviews with the parents of 18 children with cancer‐related cognitive impairment. The transcripts were analyzed using Colaizzi's method. Results Three categories and 11 subcategories were obtained from the data analysis, including diverse levels of cognitive impairment in children (speech communication difficulties, impaired executive function, attention deficit, and intellectual disability), persistent negative emotions (anxiety and worry, complaints and resentment, negative avoidance and positive experiences after psychological adjustment), multiple needs (need for disease information, need for professional management, and an urgent need for more external support). Conclusion Parents of children with cancer‐related cognitive impairment face a significant psychological burden, coupled with confusion and numerous inquiries regarding the symptoms and management of their children's cognitive impairment. It is imperative for medical professionals to strengthen the dissemination of information related to cancer‐associated cognitive impairments, while promptly recognizing and intervening in related symptoms. Rational allocation of resources, establishment of targeted support systems, and enhancement of social acceptance may be the key points that policymakers could consider. These efforts hold immense significance, as they play a pivotal role in elevating cognitive capabilities and enhancing the overall quality of life for children with cancer.

Abstract There is a recent trend showing an uptick in the artificial sweetener's usage, particularly the nonnourishing variety. The allure of a low‐calorie choice that lets people indulge in their sweet tooths while consuming less calories overall is what motivates this. Children's food products often contain a substantial number of artificial sweeteners due to their properties that aid in moisture retention, act as fillers, and serve as bulking agents. This article provides a comprehensive overview of artificial sweeteners and influences in human wealth. Studies have linked the use of artificial sweeteners to premature birth, highlighting the teratogenic potential of these compounds, particularly in beverages. Pregnant women who incorporate nonnutritive sweeteners into their diet during pregnancy are more likely to have children with birth defects, as indicated by studies on the subject. Artificial sweeteners should not be added to food for children because studies show that eating them while a child's body is still developing might disturb the balance of gut microbiota and cause potential problems like heart disease, stroke, and cognitive decline. The ingestion of nonnourishing sweeteners has adverse effects on the fertility of both men and women. Studies indicate that exceeding the recommended daily consumption that the FDA has set for artificial sweeteners can result in conditions of infertility for both genders. Additionally, there is a connection between the onset of cancer and the use of artificial sweeteners. Presently, a considerable amount of research relies on animal models rather than human ones, creating a notable gap in research. The limitation of extensive human model studies represents a drawback in validating results. Furthermore, there is a necessity for increased research focused on advancing techniques that can minimize the adverse effects of artificial sweeteners, making them more suitable for addressing issues related to obesity and various types of diabetes.

Abstract Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation of various biological processes. Regulation of copper levels within a narrow range is imperative for maintaining metabolic homeostasis. Numerous studies have demonstrated the significant roles of copper homeostasis and cuproptosis in health and disease pathogenesis. However, a comprehensive and up‐to‐date systematic review in this domain remains absent. This review aims to consolidate recent advancements in understanding the roles of cuproptosis and copper homeostasis in health and disease, focusing on the underlying mechanisms and potential therapeutic interventions. Dysregulation of copper homeostasis, manifesting as either copper excess or deficiency, is implicated in the etiology of various diseases. Cuproptosis, a recently identified form of cell death, is characterized by intracellular copper overload. This phenomenon mediates a diverse array of evolutionary processes in organisms, spanning from health to disease, and is implicated in genetic disorders, liver diseases, neurodegenerative disorders, and various cancers. This review provides a comprehensive summary of the pathogenic mechanisms underlying cuproptosis and copper homeostasis, along with associated targeted therapeutic agents. Furthermore, it explores future research directions with the potential to yield significant advancements in disease treatment, health management, and disease prevention.

Abstract Liquid–liquid phase separation (LLPS) has emerged as a pivotal biological phenomenon involved in various cellular processes, including the formation of membrane‐less organelles and the regulation of biomolecular condensates through precise spatiotemporal coordination of signaling pathways in cells. Dysregulation of LLPSs results in aberrant biomolecular condensates, which are widely implicated in tumorigenesis and cancer progression. Here, we comprehensively summarize the multifaceted roles of LLPS in tumor biology from the perspective of cancer hallmarks, including genomic stability, metabolic reprogramming progression, ferroptosis, and metastasis, to unveil the intricate mechanisms by which LLPS occurs in tumorigenesis. We discuss current discoveries related to therapeutic involvement and potential clinical applications of LLPS in cancer treatment, highlighting the potential of targeting LLPS‐driven processes as novel therapeutic strategies. Additionally, we discuss the challenges associated with new approaches for cancer treatment based on LLPS. This in‐depth discussion of the impact of LLPS on fundamental aspects of tumor biology provides new insights into overcoming cancer.

Abstract Patient‐centered care (PCC) is an innovative approach to the diagnosis and treatment of malignancy that aims to improve patients' experience during the management of their disease. However, despite growing interest, the concept and specifics of PCC remain unclear. This consensus document addresses this gap by providing a literature review and a clear definition of PCC and outlines its main components as observed in real‐world practice. These components include daytime diagnostic and treatment procedures, in‐hospital and community‐based infusion centers, home‐based diagnostic and treatment services, smart healthcare solutions, and integration of traditional Chinese medicine. This document delves into the implementation of PCC and explores its potential benefits.

Abstract Background While advancements in cancer treatments have improved survival rates, they also lead to adverse effects such as insomnia, which significantly impacts survivors' sleep quality. Objective This study explores the influence of cancer‐related fatigue (CRF), Fear of Cancer Recurrence (FCR), and psychological distress, with rumination serving as a mediating factor, on the insomnia experienced by cancer survivors. Methods The study involved 220 cancer survivors attending Shohada‐e‐Tajrish Hospital's oncology center in Tehran, Iran. Participants were selected through convenience sampling and completed several questionnaires: the Insomnia Severity Index, Fear of Cancer Recurrence Inventory, Cancer Fatigue Scale, Kessler Psychological Distress Scale, and Rumination Response Scale. Results The results showed that the tested model had a good fit, and the correlation matrix demonstrated significant positive correlations between CRF (0.46), FCR (0.15), psychological distress (0.55), and rumination (0.42) with insomnia in cancer survivors (p

Abstract Background The COVID‐19 pandemic prompted a surge in telehealth utilization. However, language barriers have emerged as a potential obstacle to effective telemedicine engagement, impacting millions of limited English proficient (LEP) individuals. Understanding the role of language spoken in telehealth outcomes is critical, particularly in cancer care, in which consistent follow‐up and communication are vital. The primary objective was to assess the impact of telehealth utilization and primary language spoken on clinical outcomes in cancer patients. Methods This study utilized a retrospective cohort design, encompassing cancer patients seen at the Chao Family Comprehensive Cancer Center between March 1, 2020, and December 31, 2022. The study incorporated both in‐person and telehealth visits, examining the association between encounter type and clinical outcomes. Results The study included 7890 patients with more than one outpatient visit during the study period. There was decreased telehealth utilization in non‐English speaking cancer patients throughout the pandemic. Increased telehealth utilization was associated with higher rates of admission, irrespective of cancer type. Additionally, telehealth visits were associated with longer duration of subsequent admissions compared to in‐person visits. Spanish‐speaking patients utilizing telehealth had higher rates of re‐admission compared to English speakers utilizing telehealth. Patients who died had higher rates of telehealth utilization compared to patients who survived. Conclusions and Relevance This study demonstrates that primary language spoken is associated with differences in telehealth utilization and associated outcomes in cancer patients. These differences suggest that the interplay of telehealth and language could contribute to widening of disparities in clinical outcomes in these populations. The study underscores the need to optimize telehealth usage and minimize its limitations to enhance the quality of cancer care in a telehealth‐driven era.

Abstract Objective The article aims to assess the role of stress and anxiety in relation to the level of emotional control among cancer patients. Currently cancer ranks second, after cardiovascular disease, as the most common cause of death. Moreover, it is predicted that in the coming years, cancer will become the leading cause of death worldwide. This is due to the extended lifespan of the population and also to the presence of carcinogenic factors in the surrounding environment. The emergence of cancer is a significant stressor that affects individuals in diverse ways, leading to cognitive, behavioral, and emotional consequences. In line with the adopted aim, emotional issues are the chosen area of exploration in this article. Methods The study included 102 patients. The differences between the patients' results according to various scales and the results produced by the validation group data were examined using one‐sample t‐tests. The relationships between the quantitative variables were determined using Spearman's rho coefficients, and the relationships between the quantitative and qualitative variables were verified using Kruskal‐Wallis tests. Results The participants exhibited higher anxiety suppression levels than individuals in the normalization group. They sought emotional support more frequently than the average person in the population, turned to religion, engaged in other such activities, lived in denial more often, discontinued activities, and displayed a sense of humor less frequently. The more frequently they controlled their anger, the less they sought emotional and instrumental support, catharsis, and attempted to accept the situation and cease being active. Additionally, controlling anxiety, sadness, and depression coexisted with self‐blame, denial, and compensatory actions. Conclusions Cancer patients face intense anxiety. Emotional and instrumental support, along with the ability to express and manage emotions, are crucial for these patients, especially within the context of facing the challenge of cancer. Finding constructive ways to express strong and difficult emotions prevents their accumulation and reduces the need for emotional suppression. Preventive actions should be oriented toward supporting the emotional competencies of patients.