BMC Cancer

Breast cancer is one of the most commonly diagnosed forms of cancer, and recent advances in treatment have led to increasing prevalence of breast cancer survivors globally. But even after completing active treatment, breast cancer survivors remain vulnerable to a range of adverse health outcomes due to high levels of physiological stress. This study investigates the relationship between sleep disturbance and allostatic load (AL) in breast cancer survivors and control subjects, using a large cohort sample drawn from the UK Biobank. Breast cancer survivors exhibited a higher mean AL at baseline (m = 2.74) compared to the control sample (m = 2.44; p < 0.01), and AL remained elevated as time elapsed following cancer diagnosis. There was a positive association at baseline between AL and symptoms of sleep disturbance in both breast cancer survivors and controls. However, cancer survivors exhibited a greater increase in levels of AL with only moderate or occasional sleep disturbance. Longitudinal analyses revealed that for both cancer survivors and controls, higher AL at baseline predicted poorer sleep quality at the next wave (r {approx} .22; p < 0.05). These findings support a bidirectional relationship between sleep disturbance and overall physiological stress, highlighting sleep as a potential target for intervention in breast cancer survivorship care.

Cognitive decline is common after cancer, but little is known regarding the etiology of this adverse effect, especially in terms of molecular mechanisms. This prospective study obtained brain imaging and cognitive testing from 50 newly diagnosed women with primary breast cancer prior to any cancer treatment and 53 female controls. Participants completed up to 7 assessments for a total time span of 9.7 +/- 0.92 years. Imaging transcriptomics was used to measure the expression of genes in the brain involved in N-methyl-D-aspartate (NMDA) and calcium-mediated neurotransmission. GRIN2A, GRIN2B, CACNA1C were significantly expressed in gray matter in both groups (R2 > 0.094, p < 0.015). GRIN2A (t = -2.72, p = 0.007) and CACNA1C (t = -2.11, p = 0.036) were significantly lower in the cancer group compared to controls across timepoints. GRIN2A declined over time in patients, and this was significantly different compared to controls ({chi}{superscript 2} = 9.73, p = 0.001). Cognitive scores were significantly lower in patients compared to controls (p = 0.002). In patients, GRIN2A were significantly associated with cognitive performance over time (p < 0.007). These findings suggest that gene expression involved in neurotransmission is disrupted in the brain among patients with breast cancer and may contribute to cognitive changes. Our results provide novel molecular insights regarding the roles of non-CNS cancer pathology and treatments in the brain related to calcium signaling and pro-survival/plasticity-related pathways. Our findings also point to potential treatments for cognitive effects of cancer.

Cancer is a significant public health issue in low--and middle-income countries, especially in Africa. While lifestyle and/or behavioral interventions such as exercise and dietary modifications are known to improve patient outcomes and quality of life, critical evidence from resource-limited settings like Africa is scanty. Here, we present a review of clinical trials on the current landscape of cancer associated lifestyle interventions in oncology in Africa. We comprehensively reviewed non-pharmacological/ lifestyle cancer-related clinical trials in Africa on ClinicalTrials.gov and ICTRP trial registries from 01 July 2005 to 30 October 2024. We employed descriptive analyses, primarily frequency and percentage, to analyze and report the data. Overall, 53 trials matching the criteria were identified. Most of the trials were in Egypt (38/53, 97.4%), Kenya (4/53,10.3%), and Nigeria (5/53, 12.9%). The top cancer types for the trials in Africa were breast 24/62, 45.3%), colorectal (6/62, 11.3%) and acute lymphoblastic leukemia (4/62, 7.5%). Concerning sponsorship, most trials were universities/academia-sponsored trials (45/53, 84.9%), locally sponsored (37/53, 69.8%), conducted among patients (88.7%), and 84.9% cancer survivors. Most trials involved physical activity interventions (25/53, 47.2%) and psychological and psychological interventions (10/53, 18.9%), with (32/53, 60.4%) trials completed and (13/53, 24.5%) trials ongoing. Non-pharmacological interventions for the management of cancer appear to be nascent in Africa. Oncology trials are needed to ensure the effectiveness of non-pharmaceutical/lifestyle interventions in Africa, especially sub-Saharan Africa (SSA). In the current era of precision medicine, pharmacological, and lifestyle interventions, it no longer suffices to assume that interventions in high--and upper-middle-income countries will be effective in low-middle-income countries, especially Africa.

BackgroundBreast cancer (BC) and colorectal cancer (CRC) are considered primary cancers that affect both male and females globally. In Malaysia, BC is the most commonly diagnosed cancer among women of all ethnic groups and CRC is the second most common cancer in males and the second most common cancer in females. This systematic review was carried out to assess cancer symptom awareness and barriers to undergoing cancer screening for BC and CRC. MethodsA pre-defined search was conducted between January 2008 and December 2018 using the following databases: MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus and Cochrane Library for relevant articles. The search was updated in June 2020. Reviewers independently performed the data extraction and quality assessment of the included study according to the Joanna Briggs Institute assessment tools. Result22 studies met the inclusion criteria (BC n=11; CRC n=11). Nine studies assessed symptom knowledge for BC and eight for CRC. Two studies described barriers towards cancer screening for BC and one for CRC. Four CRC studies assessed symptoms knowledge and cancer screening barriers. The most commonly reported BC symptoms were painless breast lump(27.6% - 90.8%), nipple discharge (1.6% - 74.5%) and pain in breast/ breast region (11.5% - 82.8%) meanwhile CRC symptoms were change in bowel habits (new-onset diarrhoea or constipation) (28.4% - 86.6%), bleeding and/or bleeding from the back passage (11.5% - 71.9%) and weight loss (9.3% - 83.4%). Financial issue (10% - 17.5%) was the most frequent blockade identified towards BC screening meanwhile fear of result (27.6% - 32.1%) for CRC screening by Malaysians. Overall the studies carried out in Malaysia, six studies on BC symptom knowledge and one study on BC screening barrier were scored as medium study quality while four studies on CRC symptom knowledge and three studies on CRC screening barriers were scored as medium study quality. ConclusionStudies described varied and overall, limited, symptom awareness and barriers towards BC and CRC screening which likely contributes to the delayed presentation of cancers in Malaysia. There is a need for improving the awareness of BC and CRC symptoms as well as the importance of screening to encourage the early presentation of symptomatic cancer patients and down-staging of cancer.

BackgroundVarious treatments exist for non-melanoma skin cancer (NMSC), but the mainstay is surgical removal. Superficial radiotherapy (SRT) is one non-surgical technique that has been used for over a century but fell out of favor due to the advent of Mohs micrographic surgery (MMS). A new technology that combines a 22 megahertz (MHz) dermal ultrasound with SRT (US-SRT) enables tumor visualization before, during, and after treatment, and demonstrates increased cure rates and reduced recurrences. MethodsWe conducted a meta-analysis comparing the local control (LC) of four studies using traditional non-image-guided forms of radiotherapy for NMSC treatment to two seminal studies utilizing high-resolution dermal ultrasound-guided SRT (HRUS-SRT). The four traditional radiotherapy studies were obtained from a comprehensive literature search used in an article published by the American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions. The meta-analysis employed a logit as the effect size indicator with Q-statistic to test the null hypothesis. ResultsLC rates for the 2 US-SRT studies were statistically superior to the 4 traditional therapies individually and collectively. When stratified by histology, statistically superior outcomes for US-SRT were observed in all subtypes with p-values ranging from p < 0.0001 to p = 0.0438. These results validated an earlier analysis using a logistic regression statistical method showing the same results. ConclusionUS-SRT is statistically superior to non-image-guided radiotherapies for NMSC treatment. This modality may represent the future standard of non-surgical treatment for early-stage NMSC.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is poised to be a leading cause of cancer-related deaths. Despite developing new treatment strategies, patient outcomes have not significantly improved. Chemoresistance has been implicated as a major contributor to ineffective treatments observed with studies suggesting combination therapy targeting multiple pathways. This study explored dysregulated genes in tumours of PDAC patients to identify targets which could be used effectively in combination with conventional therapy against cancer cells. MethodsIn this study, PCR arrays were used for gene expression profiling of tumours obtained from South African PDAC patients to identify key differentially expressed pathways and potentially new therapeutic target genes. SPP1 was selected and RNA interference was used to knock the gene down. Migration and apoptosis assays were used to evaluate the effect of the knockdown, alone and in combination with gemcitabine, on a pancreatic cancer cell line, MIA PaCa-2. Proteomic analysis using SWATH-MS was used to demonstrate potential molecular mechanisms linked to the morphological and phenotypical effects observed with treatment. ResultsWe demonstrated several genes linked to the growth factor and signal transduction signalling pathways, and identified SPP1 as a target. We observed that by combining SPP1 knockdown with conventional chemotherapy, gemcitabine, resulted in a synergistic effect, leading to an enhanced early apoptotic response. A decline of migratory and invasive capabilities of MIA PaCa-2 cells was observed upon subjecting the cancer cells to SPP1 reduction and gemcitabine treatment. Furthermore, proteomic analyses uncovered several pathways that were dysregulated by the combination therapy including both pro-and anti-tumorigenic ones. ConclusionThe study findings indicate that SPP1 could be a potential therapeutic target for PDAC, and the possible synergistic effects observed when SPP1 knockdown was combined with gemcitabine treatment suggest a potential avenue for developing more effective treatments for PDAC while exploring tumour cell adaptation for survival.

Many cancer survivors, including those with a current or previous diagnosis of cancer, experience cancer-related cognitive impairments (CRCI). CRCI can impact their ability to think quickly, clearly, make decisions and perform daily actions. There have been a variety of non-pharmacological interventions developed and trialed with the aim of reducing CRCI or mitigating its impact. The aim of this work is to provide an overall picture of the effectiveness of non-pharmacological interventions to improve cognition in cancer survivors by providing an overview and synthesis of systematic reviews. Review TitleEffectiveness of Non-Pharmacological Interventions to Improve Cognition in Cancer: An Overview of Systematic Reviews

Obesity causes a number of systemic alterations including chronic inflammation and changes in gut microbiome. However, whether these actively contribute to poor survival and therapy resistance in patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet fed pancreatic tumor bearing mice do not respond to standard of care therapy with gemcitabine and paclitaxel when compared to corresponding control diet fed mice. Upon fecal matter transplant from control mice to high fat diet fed mice, the tumors became sensitive to standard of care therapy and showed extensive cell death. Analysis of gut microbiome showed an enrichment of queuosine (Q) producing bacteria in high fat diet fed mice and an enrichment of S-adenosyl methionine (SAM) producing bacteria in control diet fed mice. Further, treatment of high fat diet fed animals with SAM recapitulated the observation with lean to obese fecal matter transplant. Additionally, treatment of pancreatic and colon cancer cell lines in vitro with Q promoted resistance to the paclitaxel and oxaliplatin respectively, while treatment with SAM promoted sensitivity to these drugs. Treatment of pancreatic cancer cells with Q showed upregulation PRDX1, that is involved in oxidative stress protection. Analysis of tumor tissues in high fat diet fed mice showed high PRDX1, low apoptosis and increased proliferation, which were reversed upon treatment with SAM as well as by lean to obese fecal matter transplant. In parallel, high fat diet fed mice showed increase in CD133+ treatment refractory population compared to the control animals. Interestingly, treatment with Q in vitro did not enrich for CD133+ population, indicating that Q mediated protection from cell death was independent of enrichment of treatment refractory cells. These observations indicated that microbial metabolite Q accumulated in high fat diet fed mice protected tumors from chemotherapy induced oxidative stress by upregulating PRDX1. This protection could be reversed by treatment with SAM. We conclude that relative concentration of S-adenosyl methionine and queuosine in fecal samples of pancreatic cancer patients can be indicative of therapy response in this disease.

BackgroundSerum aspartate transaminase (sAST) level is used routinely in conjunction with other clinical assays to assess liver health and disease. Increasing evidence suggests that sAST is associated with all-cause mortality and has prognostic value in several cancers, including gastrointestinal and urothelial cancers. Here, we undertake a systems approach to unravel molecular connections between AST and cancer prognosis, metabolism, and immune signatures at the transcriptomic and proteomic levels. MethodsWe mined public gene expression data across multiple normal and cancerous tissues using the Genotype Tissue Expression (GTEX) resource and The Cancer Genome Atlas (TCGA) to assess the expression of genes encoding AST isoenzymes (GOT1 and GOT2) and their association with disease prognosis and immune infiltration signatures across multiple tumors. We examined the associations between AST and previously reported pan-cancer molecular subtypes characterized by distinct metabolic and immune signatures. We analyzed human protein-protein interaction networks for interactions between GOT1 and GOT2 with cancer-associated proteins. Using public databases and protein-protein interaction networks, we determined whether the subset of proteins that interact with AST (GOT1 and GOT2 interactomes) are enriched with proteins associated with specific diseases, miRNAs and transcription factors. ResultsWe show that AST transcript isoforms (GOT1 and GOT2) are expressed across a wide range of normal tissues. AST isoforms are upregulated in tumors of the breast, lung, uterus, and thymus relative to normal tissues but downregulated in tumors of the liver, colon, brain, kidney and skeletal sarcomas. At the proteomic level, we find that the expression of AST is associated with distinct pan-cancer molecular subtypes with an enrichment of specific metabolic and immune signatures. Based on human protein-protein interaction data, AST physically interacts with multiple proteins involved in tumor initiation, suppression, progression, and treatment. We find enrichments in the AST interactomes for proteins associated with liver and lung cancer and dermatologic diseases. At the regulatory level, the GOT1 interactome is enriched with the targets of cancer-associated miRNAs, specifically mir34a - a promising cancer therapeutic, while the GOT2 interactome is enriched with proteins that interact with cancer-associated transcription factors. ConclusionsOur findings suggest that perturbations in the levels of AST within specific tissues reflect pathophysiological changes beyond tissue damage and have implications for cancer metabolism, immune infiltration, prognosis, and treatment personalization.

Background and AimsOver 80% of patients with pancreatic cancer experience cachexia, characterized by severe muscle and fat loss. While all the mechanistic understanding comes from preclinical models, the translatable nature of these findings to humans remains a critical gap due to the limited knowledge of human cachexia biology. MethodsWe generated matched gene and microRNA profiles from rectus abdominis muscle of 55 pancreatic ductal adenocarcinoma and 18 control subjects. Differentially expressed genes and microRNAs were identified at 1.5-fold change and p<0.05. ResultsGene expression results revealed a striking sex-specific difference at the expression and pathway levels. In both sexes, co-expression gene network analysis identified more significant modules and hub genes at 1-month of weight loss than the traditionally used six months, suggesting that gene alterations may be more dynamic in the early stages of the disease progression. When comparing hub genes from humans to experimental models of cachexia, genes such as RELA, DDX21, WDR75, PTPN1, and CRIP3 exhibited similar patterns of expression, suggesting their potential role in cachexia. microRNAs also exhibited sex-specific expression. Although several common miRNAs were identified between sexes, their gene targets differed, indicating that microRNAs may regulate gene targets in a sex-specific manner. ConclusionsThe dataset can serve as a resource for validating preclinical findings and exploring previously unexplored molecules in cachexia. Future studies will functionally characterize the role of the hub genes and microRNAs in cachexia. This is the first study to identify sex-specific genes and microRNAs from a single cancer type.

The vulnerability of cancer cells to nutrient deprivation and their reliance on specific metabolites are emerging markers in cancer research. Numerous animal studies and preclinical research have shown that fasting is both safe and feasible. As a result, many studies suggest combining fasting with chemotherapy, immunotherapy, or other treatments as a potentially promising strategy to enhance therapeutic outcomes. This article provides a comprehensive analysis of the outcome measures in randomized controlled trials that reflect the impact of fasting on cancer treatment efficacy. Additionally, it validates the relationship between fasting and relevant proteins using data from the UK Biobank, including insulin receptor (INSR), insulin-like growth factor 1 receptor (IGF1R), and insulin-like growth factor binding protein 1 (IGFBP1), and further examines the impact of changes in these proteins on cancer patient prognosis. We found that fasting improves radiological response rates by lowering glucose, insulin, and insulin-like growth factor-1 (IGF-1) levels, while increasing insulin-like growth factor binding protein (IGF-BP) levels. Fasting also reduces DNA damage in immune cells and does not lead to additional treatment-related toxicities. Thus, fasting is a safe and effective adjunctive treatment for cancer, improving therapeutic outcomes while ensuring patient safety.

IntroductionColorectal cancer (CRC) is the second most common cause of cancer death globally. Genome-wide association studies have established that cancer risk mediated through common genetic variants can be linked to variation in gene expression. Since obesity and male sex impart substantially elevated CRC risk, we studied transcriptional profiles of normal colorectal mucosa using RNA sequencing to better understand the relationship of these risk factors with gene expression levels. MethodsNormal colorectal mucosa was sampled from 365 participants (208 males, 157 females) either during surgery (n=103) or through endoscopic biopsy (n=262) from cancer patients and patients with other unrelated conditions. In total, 238 samples were used for our discovery dataset and 380 samples were obtained for the validation of our findings. The transcription analysis was done using paired-end total RNA sequencing. Data processing and gene filtering followed the Genotype-Tissue Expression (GTEx) Project pipeline v8. Differential Expression Analysis (DEA) was performed on normalised counts to evaluate effects of sex and body mass index on the total gene expression, as well as possible confounding effects of cancer presence on the gene expression in normal colorectal tissue. ResultsFollowing filtering, there were 15,465 genes available for analysis. DEA identified two genes that were significantly associated with sex and five associated with body mass index. However, whilst these nominal signals are of interest, none of the genes associated with sex remained significant in a replication dataset. Due to the missing BMI information, replication of DEA by BMI was not possible. ConclusionWe found no systematic differences in gene expression in normal colorectal epithelium between males and females, nor did we find a strong association between gene expression and BMI. Although sample size may limit our analysis, the results suggest no or limited confounding effects of BMI and sex on gene expression in normal colorectal mucosa samples.

AbstractPancreatic cancer (PC) is associated with high mortality overall. Recent literature has focused on investigating long noncoding RNAs (lncRNAs) in several cancers, but studies on their functions in PC are lacking. The purpose of this study was to identify novel lncRNAs and utilize machine learning to techniques to predict metastatic cases of PC using the identified lncRNAs. To identify significantly altered expression of lncRNA in PC, data was collected from The Cancer Genome Atlas (TCGA) and RNA-sequencing (RNA-seq) transcriptomic profiles of pancreatic carcinomas were extracted for differential gene expression analysis. To assess the contribution of these lncRNAs to metastatic progression, different ML algorithms were used, including logistic regression (LR), support vector machine (SVM), random forest classifier (RFC) and eXtreme Gradient Boosting Classifier (XGBC). To improve the predictive accuracy of these models, hyperparameter tuning was performed, in addition to reducing bias through the synthetic minority oversampling technique. Out of 60,660 gene transcripts shared between 151 PC patients, 38 lncRNAs that were significantly differentially expressed were identified. To further investigate the functions of the novel lncRNAs, gene set enrichment analysis (GSEA) was performed on the population lncRNA panel. GSEA results revealed enrichment of several terms implicated in proliferation. Moreover, using the 4 ML algorithms to predict metastatic progression returned 76% accuracy for both SVM and RFC, explicitly based on the novel lncRNA panel. To the best of my knowledge, this is the first study of its kind to identify this lncRNA panel to differentiate between non-metastatic PC and metastatic PC, with many novel lncRNAs previously unmapped to PC. The ML accuracy score reveals important involvement of the detected RNAs. Based on these findings, I suggest further investigations of this lncRNA panel in vitro and in vivo, as they could be targeted for improved outcomes in PC patients, as well as assist in the diagnosis of metastatic progression based on RNA-seq data of primary pancreatic tumors.

BackgroundHigh risk (HR) basal cell carcinoma (BCC) subtypes have been associated with high recurrence rates that is felt to be better managed surgically. Specifically, Mohs Micrographic Surgery (MMS) is considered most effective for aggressive HR BCCs and superior to traditional nonsurgical techniques, including radiation. Recently, superficial radiation therapy with high resolution ultrasound image guidance called Image Guided Superficial Radiation Therapy (IGSRT) displayed high local control (LC) rates and is an emerging non-surgical alternative to MMS for non-melanoma skin cancer (NMSC). ObjectivesWe present the largest experience in the USA on treatment of BCCs using IGSRT and specifically evaluate if there are differences in LC between HR BCC versus non-HR subtypes using this technology. MethodsA retrospective analysis was conducted on 7,994 BCC lesions treated with IGSRT in the continental United States. We compared the results of BCCs treated with IGSRT separated by HR vs non HR groups including 339 HR BCC lesions and 7655 non HR BCC lesions. High risk was defined as infiltrative, micronodular, morpheaform, and sclerosing subtypes. Non-HR BCC included superficial, nodular, and not otherwise specified (NOS) subtypes. Local control (LC) rates at two and five years were calculated with actuarial life-table and Kaplan-Meier methods and statistically compared using log rank tests. ResultsIGSRT treatment of the HR BCC group showed no recurrences with two and five-year actuarial and KM LC rates all at 100%. In comparison, the non-HR BCC cohort achieved similar two and five-year actuarial LC rates of 99.71% and 99.24% (KM LC at 99.5% and 99.23%), respectively. No statistical differences in LC rates between the two cohorts (p=0.278 each) resulted. Patients tolerated treatment well with little or rare high grade RTOG toxicity reported in both cohorts. ConclusionHR BCC may be treated just as effectively as low risk BCC using IGSRT and presents a viable alternative to MMS. The targeted approach using IGSRT, incorporating high resolution dermal ultrasound (HRDUS), appear to enhance treatment accuracy and effectiveness demonstrating high LC rates in all subtypes of BCC comparable to MMS and is a viable non-surgical option. Plain language summary Effectiveness of a non-surgical skin cancer treatment using an image guided form of radiation modality on all subtypes of basal cell skin cancerRecent studies using a non-surgical treatment combining low penetrance radiation with ultrasound called Image Guided Superficial Radiation Therapy (IGSRT) showed promise in curing Basal Cell Cancer (BCC) of the skin, which is the most common skin cancer worldwide afflicting millions annually. Recent studies on early stage (I, II) BCCs treated with IGSRT (estimated combined total of [~]1900 BCC cases) appear to rival the best surgical treatment available called Mohs Micrographic Surgery ("Mohs" or MMS). Furthermore, certain subtypes of BCC appear to behave more aggressively with worse outcomes even with surgery and is generally felt inappropriate for radiation treatment. However, BCC subtypes were not specified in previous IGSRT studies. This study presents the largest experience (using medical chart review) in approximately 8000 BCC cases treated by IGSRT across the continental United States separated by aggressive vs non-aggressive subtypes for early stages (I, II) as well as more advanced (stage III) BCC cases to evaluate the efficacy and safety. This study confirms the high cure/control rate and safety of IGSRT for all subtypes of BCC which appear equivalent with Mohs (although the study was not meant to be a head to head comparison of the 2 different modalities). Moreover, the aggressive types of BCC showed similar (if not marginally better) cure rates than the more common non-aggressive BCC subtypes. The potential benefits to patients from this study show there is now a clinically proven non-surgical treatment with the same effectiveness as surgery for the most common cancer on the planet. Key PointsO_LIThis study provides evidence that backs up using IGSRT as a viable treatment option to MMS for both high risk and non-high risk BCC cases, achieving similar local control rates for both groups. C_LIO_LIIt highlights that high risk BCC is more sensitive to radiation therapies such as IGSRT than previously believed, challenging the conventional practice of surgical treatment. C_LI

Background and ObjectiveChemotherapy-induced peripheral neuropathy (CIPN) is a complex and dose-limiting toxicity of anticancer treatments with chronic symptoms leading to increased disability and reduced quality of life. The present study evaluated clinical risk factors associated with development of chronic, severe and dose-limiting CIPN, utilising a comprehensive multi-modal battery of neuropathy assessment. MethodsBaseline clinical risk factors were investigated in patients who had completed neurotoxic chemotherapy (including taxanes, platinums and haematological cancer therapies). CIPN was assessed using neurological evaluation (Total Neuropathy Score, sural nerve conduction studies), patient reported outcome measure (EORTC QLQ-CIPN20), and clinically graded neuropathy (NCI-CTCAE). Multivariate models of risk factors associated with development of chronic, severe and dose-limiting CIPN were evaluated using backwards stepwise regression model building. ResultsThe study recruited 903 patients (age 61 (IQR 50-69) years) who were assessed 12 (IQR 6-24) months post neurotoxic treatment. 73% of patients presented with CIPN at time of assessment, with 37% having moderate to severe symptoms. 32% of patients experienced neurotoxic treatment dose modification due to CIPN. Across the various CIPN assessment approaches, risk factors for chronic CIPN included older age, diabetes diagnosis, higher BMI and prior exposure to neurotoxic treatment (all P<0.05). Risk factors for severe CIPN included older age, higher BMI, prior neurotoxic treatment and female sex (all P<0.05), whereas risk factors for dose-limiting CIPN included older age and female sex (all P<0.05). DiscussionThis study identified baseline clinical risk factors associated chronic, severe and dose-limiting CIPN. Closer monitoring of these vulnerable cohorts will allow for timely CIPN management, including referral pathways to intervention and rehabilitation therapies which will ultimately lead to improved CIPN morbidity.

BackgroundYears back, cancer was thought to be a problem limited to the developed countries. Cancer is now a disease with lots of burden, leading cause of death and disability in developing countries. Physical health is very important for the overall well-being of breast cancer survivors, since it is the visible part of the dimensions of overall health and well-being. Prior studies have examined factors leading to late detection, financial burden and experiences of caregivers of breast cancer patients in Ghana, however, none of the studies have explored how breast cancer may specifically impact the physical well-being and the quality of life of these women. This study therefore seeks to explore how breast cancer impact the physical well-being and the quality of life of these women. MethodologyThe study site and setting was the Oncology directorate at Komfo Anokye Teaching Hospital where twelve respondents were recruited for the study. Breast care survivors were purposively sampled and interviewed (face-to-face) to explore how the BC has impacted on their physical wellbeing and their Quality of Life (QoL). Demographic data were obtained before the main interview. The interviews lasted between 30minutes to 45minutes. Data was analysed using thematic analysis of key information by using NVivo data management software. ResultsParticipants described their physical wellbeing according to the way they encountered the disease from the onset through to the treatment administration. Five sub-themes emerged, namely: Fatigue/bodily weakness: impaired functional ability: pain; distorted sleep; and fertility. ConclusionFatigue, impaired functional ability, pain, distorted sleep and fertility were consistent with constructs of the Quality of Life model. These physical symptoms negatively affected the total well-being of the BCSs.

BackgroundAlthough physical activity may play a significant role in enhancing quality of life for glioma patients, its integration into clinical care remains underexplored. This study assessed the experiences, perspectives, and barriers of healthcare professionals in promoting physical activity for glioma patients. MethodsAn online survey with 19 questions was distributed to Dutch healthcare professionals registered with the Dutch Neuro-Oncology Society (LWNO). Additionally, professionals were individually asked to remind and invite their colleagues to participate. Participants provided informed consent. ResultsFifty-five professionals from 20 centers completed the survey, mainly neurologists (35%) and nurses (33%). Most professionals (58%) indicated receiving frequent questions about physical activity, particularly regarding safety and appropriate activities. Additionally, 76% stated they often proactively provide advice, typically recommending low-intensity activities like walking. Key barriers to making such recommendations included limited information materials (37%), knowledge (33%), and referral options (27%). Professionals concerns about physical activity included risks of overexertion and patient discouragement if activity would prove too challenging. Despite these challenges, 89% supported integrating physical activity into glioma care, and 56% expressed a need for specific guidelines. While professionals believe in the benefits for symptom management and quality of life, 62% were neutral about the strength of supporting evidence. ConclusionsPhysical activity is frequently discussed in glioma care, but recommendations are mostly inappropriate due to limited knowledge, resources, and guidance. Existing guidelines are rarely applied in practice. Future research should accumulate evidence, develop tailored guidelines, and equip professionals with tools to truly integrate physical activity into practice. Key pointsO_LIPhysical activity is discussed in glioma care, but recommendations are challenging C_LIO_LIBarriers included limited informational materials, knowledge and referral options C_LIO_LIThere is strong support for integrating physical activity C_LI Importance of the studyQuality of life is a major concern for glioma patients, and physical activity has emerged as a promising complementary intervention to alleviate symptoms and enhance quality of life through its positive effects on physical and mental well-being. Although healthcare professionals recognize its value and frequently discuss physical activity with patients, significant barriers persist, including limited informational materials, insufficient knowledge, and uncertainty about referral options. While the benefits of physical activity are well-established in other types of cancer with cancer-specific guidelines, such guidelines and physical activity recommendations are not implemented in glioma care. Given the lack of glioma-specific evidence on the effects of physical activity, it remains unclear whether additional guidelines should be developed at all. This study identifies both the practical challenges and the evidence gap, highlighting the urgent need for targeted research, better resources, and structured support to help professionals effectively guide glioma patients in their physical activities.

Background and AimsPancreatic ductal adenocarcinoma (PDAC) is characterized by resistance to therapy. A major contributing factor to therapeutic failure is profound desmoplasia and a well-documented hypoxic tumor microenvironment (TME). In PDAC, several therapeutic approaches, including chemotherapy and radiation alone or combined with immune checkpoint inhibitors, have shown minimal therapeutic success, placing an imperative need for the discovery and application of innovative treatments. Endoscopic ultrasound guided radiofrequency ablation (EUS-RFA) is a promising immunomodulator therapy for PDAC. In this work, we hypothesized RFA promotes local and systemic stromal and immunomodulating effects that can be identified for new combination therapeutic strategies. MethodsTo test our hypothesis, a syngeneic PDAC mouse model was performed by symmetrically injecting 100k murine KPC cells in bilateral flanks of C57BL/6 female mice. RFA treatment initiated when tumors reached 200-500 mm3 and was performed only in the right flank. The left flank tumor (non-RFA contralateral side) was used as a paired control for further analysis. ResultsRFA promoted a significant reduction in tumor growth rate 4 days after treatment in RFA treated and non-RFA side contralateral tumors from treated mice when compared to controls. Histological analysis revealed a significant increase in expression of cleaved Caspase3 in RFA treated tumors. In addition, collagen deposition and CD31+ cells were significantly elevated in RFA side and non-RFA contralateral tumors from RFA treated mice. Proteome profiling showed changes in C5a and IL-23 in RFA responsive tumors, indicating a role of RFA in modulating intratumoral inflammatory responses. ConclusionsThese data indicate RFA promotes local and systemic anti-tumor responses in a syngeneic mouse model of PDAC implicating RFA treatment for local tumors as well as metastatic disease. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

ObjectiveRecent studies have shown a potential link between gut microbiome and colorectal cancer (CRC). Initially, a wide array of research into this topic was discovered from the past decade, illustrating a keen interest in the potential causal relationship between the gut microbiome and CRC. However, the cancer research community is lacking a summarised systematic review of this kind which aims to explore the evidence linking the human gut microbiome to risk of CRC. DesignThis systematic review was carried out with two independent reviewers assessing the database outcomes from Medline and EMBASE during May 2020. A meta-analysis was undertaken studying the link between Helicobacter pylori and CRC; processed through Stata. Results31 papers were included in the systematic review, followed by 12 for the meta-analysis. From these papers, Fusobacterium and Bacteroides were reported most frequently as enriched in CRC versus control. The meta-analysis showed an Odds Ratio of 1.49 (95% CI 1.19 - 1.86), including a total of 20,001 events. This meta-analysis concluded that H. pylori infection significantly increases the risk of CRC, albeit with evidence of publication bias. ConclusionsBacteria have been discovered to increase the risk of CRC, however a definitive causal relationship cannot be concluded or excluded using case-control studies. To fully understand the potential link of the bacteria listed, alterations in research design and execution are required. The assessment found a need for a large-scale cohort study conducted over a significant period of time to thoroughly evaluate the potential relationship between gut microbiome and CRC risk. O_TEXTBOXSignificance of studyWhat is already known on this subject? [tpltrtarr]Roughly 10% of all cancer deaths in the UK are attributed to colorectal cancer (CRC), with CRC being the third most common cancer worldwide. [tpltrtarr]The risk of developing CRC has been closely linked to the composition of the gut microbiome [tpltrtarr]H. pylori is a known causative agent of gastric cancer What are the new findings? [tpltrtarr]To the best of the researchers knowledge, this is the first systematic review of this type conducted into this topic, investigating the genera/species of bacteria in the human gut microbiome and the risk of CRC. [tpltrtarr]This systematic review found a strong association between Fusobacterium and Bacteroides, amongst other species, and CRC. [tpltrtarr]The meta-analysis found a significant link between H. pylori infection and increased risk of CRC. How might this impact on clinical practice in the foreseeable future? [tpltrtarr]This systematic review provides potentially actionable evidence in the personalised management of patients to reduce their risk of CRC. [tpltrtarr]This review has highlighted the need for a large population prospective cohort study, with standardised sampling methods. [tpltrtarr]The meta-analysis reinforces the importance of H. pylori testing and eradication in those deemed at high risk of CRC C_TEXTBOX

BackgroundCachexia is defined by chronic loss of fat and muscle, is a frequent complication of pancreatic ductal adenocarcinoma (PDAC), and negatively impacts patient outcomes. Nutritional supplementation cannot fully reverse tissue wasting, and the mechanisms underlying this phenotype are unclear. This work aims to define the relative contributions of catabolism and anabolism to adipose wasting in PDAC-bearing mice. Human antigen R (HuR) is an RNA-binding protein recently shown to suppress adipogenesis. We hypothesize that fat wasting results from a loss of adipose anabolism driven by increased HuR activity in adipocytes of PDAC-bearing mice. MethodsAdult C57BL/6J mice received orthotopic PDAC cell (KrasG12D; p53R172H/+; Pdx1-cre) (PDAC) or PBS (sham) injections. Mice exhibiting moderate cachexia (9 days after injection) were fasted for 24h, or fasted 24h and refed 24h before euthanasia. A separate cohort of PDAC mice were treated with an established HuR inhibitor (KH-3, 100 mg/kg) and subjected to the fast/refeed paradigm. We analyzed body mass, gross fat pad mass, and adipose tissue mRNA expression. We quantified lipolytic rate as the normalized quantity of glycerol released from 3T3-L1 adipocytes in vitro, and gonadal fat pads (gWAT) ex vivo. Results3T3-L1 adipocytes treated with PDAC cell conditioned media (CM) had lower expression of lipolysis and lipogenesis genes than control cells, and did not display elevated lipolysis as measured by liberated glycerol. PDAC gWAT cultured ex vivo displayed decreased lipolysis compared to sham gWAT (-54.7%). PDAC and sham mice lost equivalent fat mass after a 24h fast, however, PDAC mice could not restore inguinal fat pads (iWAT) (-40.5%) or gWAT (-31.8%) mass after refeeding. RNAseq revealed 572 differentially expressed genes in gWAT from PDAC compared to sham mice. Downregulated genes (n=126) were associated with adipogenesis (adj p=0.05), and expression of adipogenesis master regulators Pparg and Cebpa were reduced in gWAT from PDAC mice. Immunohistochemistry revealed increased HuR staining in gWAT (+74.9%) and iWAT (+41.2%) from PDAC mice. Inhibiting HuR binding restored lipogenesis in refed animals with a concomitant increase in iWAT mass (+131.7%). ConclusionsOur work highlights deficient adipose anabolism as a driver of reduced lipid content in 3T3-L1 adipocytes treated with PDAC conditioned media and PDAC mice. The small molecule KH-3, which disrupts HuR binding, restored adipose anabolism in PDAC mice. This highlights HuR as a potentially targetable regulatory node for adipose anabolism in cancer cachexia.