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Role of mucositis in predicting gut microbiota composition in people with cancer.

Disruption of the precious ecosystem of micro-organisms that reside in the gut - the gut microbiota - is rapidly emerging as a key driver of adverse side effects/toxicities caused by numerous anti-cancer agents. Although the contribution of the gut microbiota to these toxicities is understood with ever increasing precision, the cause of microbial disruption (dysbiosis) remains poorly understood. Here, we discuss current evidence on the cause(s) of dysbiosis after cancer therapy, positioning breakdown of the intestinal mucosa (mucositis) as a central cause. Dysbiosis in people with cancer has historically been attributed to extensive antibiotic use. However, evidence now suggests that certain antibiotics have minimal impacts on the microbiota. Indeed, recent evidence shows that the type of cancer therapy used predicts microbiota composition independently of antibiotics. Given most anti-cancer drugs have modest effects on microbes directly, this suggests that their impact on the gut microenvironment, in particular the mucosa, which is highly vulnerable to cytotoxicity, is a likely cause of dysbiosis. Here, we outline evidence that support this hypothesis, and discuss the associated clinical implications/opportunities. The concept that mucositis dictates microbiota compositions provides two important implications for clinical practice. Firstly, it reiterates the importance of prioritising the development of novel mucoprotectants that preserve mucosal integrity, and indirectly support microbial stability. Secondly, it provides an opportunity to identify dysbiotic events and associated consequences using readily accessible, minimally invasive biomarkers of mucositis such as plasma citrulline.

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Supportive care measures for bispecific T-cell engager therapies in haematological malignancies.

Bispecific T-cell engager (TCE) therapies are revolutionizing the treatment of several haematological malignancies, including B-cell acute lymphoblastic leukaemia, various subtypes of B-cell non-Hodgkin lymphoma, and multiple myeloma. Due to their unique mode of action in activating endogenous T cells, they are associated with several important early side effects, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as target-specific toxicities and a significant risk of infection. Currently, supportive care measures for TCEs have largely been inferred from other T-cell therapies, such as CAR-T (chimeric antigen receptor) therapy. Further research into TCE-specific supportive care measures is needed to improve the tolerability of these therapies for patients. A key question moving forward is understanding how to predict and minimize early toxicity (cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome). Associated infection risk is a significant cause of patient morbidity, therefore a better understanding of how to optimize TCE-dosing and prophylactic measures, such as intravenous immunoglobulin and antimicrobials, will be crucial to achieving an improved balance of toxicity and efficacy. Enabling early outpatient delivery of these therapies to select patients at lower risk of toxicity may also help to improve patient experience and quality of life. Here we review up-to-date guidance and literature on existing supportive care measures for bispecific TCE therapy-related toxicities. We highlight both unique and serious side effects of TCE therapies that require improved management strategies to enable more patients to benefit from these efficacious drugs.

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Improving supportive, palliative and end of life care for teenagers and young adults with cancer in adult haematology services.

Adolescents with haematological malignancies within adult services, in the UK from 16years old, have unique needs and require developmentally targeted services and approaches to care delivery. High-risk intensive treatments are common for this cohort and a better understanding of what individualised supportive and palliative care means in this context is required. Being known and understood as an emerging adult, with particular recognition of developmental stage, is an essential component of quality measures and underpins the adolescent, and caregiver, experience when faced with an uncertain or poor cancer prognosis (UPCP). Healthcare professionals (HCPs) can experience increased emotional labour and feelings of professional inadequacy when caring for adolescents with UPCP. Therapeutic alliance improves HCPs understanding of optimum individualised care by improving communication and supported decision making. Access to training and support for HCPs is required to address the emotional impact of therapeutic alliance with teenage/adolescent and young adults (T/AYAs) with advanced cancer. Investment in therapeutic alliance, alongside robust support mechanisms and targeted training, can improve the skills, confidence and wellbeing for HCPs, and can also ensure optimum individualised care for T/AYAs with UPCP. Evidence for optimum care for adolescents with advanced cancer is relatively scarce, especially for younger T/AYAs (16-24) in the UK who sit within adult services. Further evaluation of the impact of current UK expertise, services and programs are needed to inform future development.

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Telemedicine in geriatric oncology - lessons learned from the COVID-19 experience.

Telemedicine quickly became integrated into healthcare caused by the Coronavirus 19 (COVID-19) pandemic. Rapid use of telemedicine into healthcare systems was supported by the World Health Organization and other prominent national organizations to reduce transmission of the virus while continuing to provide access to care. In this review, we explored the effect of this swift change in care and its impact on older adults with cancer. Older adults are susceptible to the COVID-19 virus caused by various risk factors, such as comorbidity, frailty, decreased immunity, and cancer increases vulnerability to infection, hospitalization, and mortality. We found three major themes emerged in the literature published in the past 18months, including access to care, telemedicine modes of communication, and the use of technology by older adults with cancer. These findings have brought insight into issues regarding healthcare disparities. The utilization of telemedicine by older adults with cancer has potential future benefits with the integration of technology preparation prior to the patient's initial visit and addressing known health disparities. The hybrid model of care provides in-person and or remote access to clinicians which may allow older adults with cancer the flexibility needed to obtain quality cancer care.

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Gastrointestinal mucositis: a sign of a (systemic) inflammatory response.

Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability. These events cause a heightened risk of bloodstream infections and lead to systemic inflammation. While studies investigating risk prediction models or therapeutics targeting GIM-related inflammation remain scarce, results have shown promise in finding biomarkers and alleviating GIM and its accompanying clinical symptoms. The findings underscore the important role of inflammation and the microbiome in GIM. Understanding the inflammatory pathways driving GIM is crucial for developing effective treatments. Further research is needed using genomics, epigenomics, and microbiomics to explore better risk prediction models or therapeutic strategies aimed at mitigating GIM-related inflammation.

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Thirty-day mortality as a metric for palliative radiotherapy in pediatric patients.

Thirty-day mortality (30DM) is an emerging consideration for determining whether terminally ill adult patients may benefit from palliative radiotherapy (RT). However, the efficacy and ethics of delivering palliative RT at the end of life (EOL) in children are seldom discussed and not well-established. Palliative RT is perhaps underutilized among patients ≤21years old with rates as low as 11%. While effective when delivered early, clinical benefit decreases when administered within the last 30days of life. Pediatric 30DM rates vary widely between institutions (0.7-30%), highlighting the need for standardized practices. Accurate prognosis estimation remains challenging and prognostic models specific to palliative pediatric patients are limited. Discordance between provider and patient/parent perceptions of prognosis further complicates decision-making. RT offers effective symptom control in pediatric patients when administered early. However, delivering RT within the last 30days of life may provide limited clinical benefit and hinder optimal EOL planning and care. Early referral for palliative RT, preferably with fewer fractions (five or fewer), along with multidisciplinary supportive care, optimizes the likelihood of maintaining patients' quality of life. Prognosis estimation remains difficult, and improving patient and family understanding is crucial. Further research is needed to refine prognostic models and enhance patient-centered care.

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Managing chronic pain after breast cancer treatments: are web-based interventions the future?

Chronic post-treatment pain in breast cancer affects a high proportion of patients. Symptom burden and financial costs are increasingly impacting patients and healthcare systems because of improved treatments and survival rates. Supporting long-term breast cancer symptoms using novel methodology has been examined, yet few have explored the opportunity to utilise these interventions for prevention. This review aims to explore the need for, range of, and effectiveness of such interventions. Three papers describe risk factors for chronic pain, with six recent papers describing the use of interventions for acute pain in the surgical setting. The evidence for the effectiveness of these interventions to improve pain management in this setting is limited but tentatively positive. The results have to take into account the variation between systems and limited testing. Multiple types of intervention emerged and appear well accepted by patients. Most assessed short-term impact and did not evaluate for reduction in chronic pain. Such interventions require rigorous effectiveness testing to meet the growing needs of post-treatment pain in breast cancer. A detailed understanding of components of web-based interventions and their individual impact on acute pain and chronic pain is needed within future optimisation trials. Their effectiveness as preventative tools are yet to be decided.

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Cancer survivor late-effects, chronic health problems after cancer treatment: what's the evidence from population and registry data and where are the gaps?

Improvements in cancer treatment have led to more people living with and beyond a cancer diagnosis but survivors may have increased health problems as they age. The purpose of this review is to critically evaluate population data exploring incidence of late effects for cancer survivors. 18 studies were identified between 2013 and 2023 that explored the impact on survivors' physical and emotional health. Patients who had been treated at least 2years previously for cancer had significant cardiovascular risk factors compared with age-matched controls. Women with breast cancer were more likely to have cardiovascular disease, including hypertension, arrythmias and congestive heart failure. This was associated with anthracyclines and/or trastuzumab as part of systemic anti-cancer therapy. Survivors of colorectal cancer were three times more likely to have acute kidney injury than age-matched controls. Stress and mood disorders were higher in survivors of testicular cancer and prostate cancer. Population studies are important to identify the 'real world' consequences of cancer and its treatment beyond clinical trials. Knowledge is critical for managing an ageing cancer population. Data to personalise cancer survivorship care, not only helps determine potential health risks, but can improve secondary prevention, emotional health, recovery, and long-term outcomes.

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