Barry J. A. Laird

Background and Aims: Malnutrition is highly prevalent among cancer patients receiving systemic anti‐cancer therapy (SACT) and is associated with poor treatment tolerance, reduced quality of life, and increased mortality. Despite recommendations, nutritional screening in the outpatient setting is inconsistently implemented and the prognostic significance of nutritional risk identified using a validated screening tool is still unclear. This study aimed to determine the prevalence of nutritional risk among patients receiving SACT, whether their nutritional needs were being met with dietetic input, and to examine associations with clinical outcomes, including treatment toxicity, dose reduction, hospital admission, and overall survival. Methods: In this prospective observational study, adult outpatients receiving SACT were invited to complete the Patient‐Generated Subjective Global Assessment Short Form (PG‐SGA SF), a nutritional screening tool. Nutritional risk using PG‐SGA SF scores was assessed in relation to treatment toxicity, dose reduction, and hospital admission using multivariable regression models and survival was evaluated using Cox proportional hazards models, both adjusted for age, sex, metastatic disease, and performance status. Results: Of 169 participants, 24.9% were at nutritional risk, PG‐SGA SF score 4–8, and 10.7% at high risk ≥ 9, yet only 5.3% were in receipt of dietetic care. Higher PG‐SGA SF scores were independently associated with increased treatment toxicity (OR: 1.2, 95% CI: 1.1–1.3, p = 0.003) and SACT dose reductions (OR: 1.2, 95% CI: 1.0–1.3, p = 0.040). Nutritional risk was not significantly associated with 30‐day hospital admissions but was independently associated with overall survival (HR: 1.1, 95% CI: 1.0–1.2, p = 0.004). Conclusions: Nutritional risk identified using the PG‐SGA SF independently predicted treatment toxicity, dose reduction, and survival in those receiving SACT. Despite over one‐third of those meeting the criteria for dietetic intervention, only 5.3% were receiving dietetic care, indicating a substantial gap between dietetic need and provision. These results support implementation of routine screening, referral pathways, and a dedicated dietetic service integrated into oncology outpatient services.

Background and Purpose: In advanced cancer, associations among changes in body composition, cardiac wasting and prior cardiotoxic anticancer therapy have not been investigated. Experimental Approach: Using bioelectrical impedance analysis (BIA), body composition was measured in 206 patients with mostly advanced cancer without known cardiovascular disease or infection (stage III/IV: 84%, prior cardiotoxic anticancer therapy: 55%). Left ventricular (LV) mass was assessed by transthoracic echocardiography and grouped by presence of cardiac wasting according to previously established sex‐specific thresholds for LV mass adjusted for height ² (2 for women, 2 for men). BIA measurements (indexed to height ² ) included fat mass index (FMI), fat‐free mass index (FFMI), skeletal muscle mass index (SMMI), visceral fat index (VFI), total body water index (TBWI) and extracellular water index (ECWI). Key Results: Patients with cancer and cardiac wasting ( n = 88) were younger (57±15 vs 62±13 years) and more often women (68% vs 29%) compared to those without cardiac wasting ( n = 118). Patients with cardiac wasting had significantly lower FMI (−12%), FFMI (−14%), SMMI (−16%), VFI (−46%), TBWI (−13%) and ECWI (−14%). For women, FFMI was significantly associated with LV mass/height ² ( r = 0.41) and VFI for men ( r = 0.40). In the multivariable linear regression analysis, FFMI was the strongest significant predictor of cardiac wasting, with no significant interaction by sex or previous cardiotoxic therapy. Conclusions and Implications: Cardiac wasting in advanced cancer is associated with lower FFMI and VFI independent of prior cardiotoxic therapy.

Background: C-reactive protein (CRP) is a well-established marker of systemic inflammation, while Growth Differentiation Factor-15 (GDF-15) has emerged as a potential biomarker of cellular stress. Their relative perioperative dynamics remain incompletely defined. This prospective observational study aimed to explicitly characterize and compare the longitudinal dynamics of CRP and GDF-15 in patients undergoing elective knee arthroplasty. Characterizing these biomarkers in a controlled acute surgical model provides clinical relevance by mapping systemic acute-phase inflammation against cellular stress pathways, which may offer a baseline reference for evaluating chronic tissue-wasting states. Methods: This prospective observational study included 47 patients undergoing elective knee arthroplasty. After excluding nine patients with elevated baseline CRP (>10 mg/L), serial measurements of CRP and GDF-15 were analysed daily in 38 patients from pre-operation to postoperative Days 1–3. Results: CRP rose sharply after surgery, peaking on Day 3 (median: 206.0 mg/L vs. baseline: 3.0 mg/L), representing a maximal increase exceeding 6100%. GDF-15 levels also increased progressively, peaking on Day 3 (median: 1682.5 pg/mL vs. baseline: 968.8 pg/mL), which represented a statistically significant but more modest rise of 33%. CRP and GDF-15 were significantly correlated on postoperative day 1 (rs = 0.53, p = 0.001) but not days 2 and 3. Baseline GDF-15, but not CRP, was significantly associated with oral hypoglycaemic agent use and vitamin B12 supplementation. Compared to values reported in recent randomized trials of ghrelin, anti-GDF-15, and anti-IL-6 therapies, GDF-15 levels in this surgical cohort remained lower, while CRP approached levels observed in such studies. Conclusions: CRP and GDF-15 rise in parallel following surgical injury; however, GDF-15 shows a considerably lower sensitivity to the inflammatory response. These findings suggest a complementary role of GDF-15 alongside CRP in profiling the perioperative stress response. While its relatively modest acute elevation limits its utility as a primary marker of acute inflammation, this surgical stress model serves as a reference that may help contextualize biomarker profiles in chronic inflammatory or wasting conditions, such as cancer cachexia, rather than serving as a direct tool for cachexia management.

Background: Cancer significantly impacts nutritional status, thereby affecting treatment tolerance, quality of life, and survival. However, nutrition remains underutilized in oncology care. Methods: This paper describes current evidence to examine challenges, and propose strategies, for embedding nutrition into routine oncology care across the cancer continuum. Results: The complexity of cancer-related malnutrition demands simple, validated, and cancer-specific tools for nutritional screening and assessment. Terminology such as “cachexia” and “malnutrition” may not appear positive for clinicians or patients; alternatives like “nutritional fitness” are suggested. Barriers to integration include misconceptions about cachexia as solely end-of-life, poor adherence to clinical guidelines, limited training for oncologists, and lack of access to dietitians. Integration of nutrition into clinical drug trials and perioperative care (e.g., prehabilitation) is essential. Emerging tools like PRONTO and composite indices incorporating body composition and inflammation may offer practical pathways forward. Conclusion: Early and ongoing nutritional monitoring, positive communication, regulatory alignment, and education of all stakeholders, including oncologists, surgeons, and patients are critical to embedding nutrition in oncology. By reframing nutritional care as a core component of treatment rather than supportive care, outcomes can be improved and practice re-shaped.

Purpose: Nutritional care is consistently overlooked in oncology practice. It is a critical factor everyone acknowledges, but few actively address, leaving patients neglected. This article explores the challenges of ensuring optimal nutritional care in oncology. Recent findings: Significant disparities have been identified among key cancer nutrition guidelines issued by the European Society for Clinical Nutrition and Metabolism (ESPEN), the European Society for Medical Oncology (ESMO) and the American Society for Clinical Oncology (ASCO). While some emphasise comprehensive nutritional assessments, others focus on pharmacological interventions. Although aligning guideline recommendations with the Global Leadership Initiative on Malnutrition (GLIM) criteria can be complex, there are shared principles that support effective identification and management of malnutrition and cachexia in clinical settings. The key barriers that oncology health professionals face are also highlighted as these are likely to impeded good nutritional care. Summary: There is a need for a standardised, pragmatic approach in assessment and management of nutrition in patients with cancer. This will facilitate the integration of nutrition into cancer care and help overcome barriers. Emerging digital solutions may serve as a conduit to improve nutritional cancer care and enhance communication between patients and healthcare providers and streamline evidence-based nutritional care in oncology.

Cancer-associated cachexia (CAC) is a chronic wasting disease typically associated with advanced cancer, resulting in progressive and debilitating loss of function and poor tolerance to anticancer therapy. Preclinical animal models have identified various potential mechanisms and mediators, which have had limited translational success in clinical trials. This review focuses on human studies and discusses the clinical phenotyping of CAC using imaging-derived body composition, quality-of-life and functional measures, existing evidence for mediators, current therapeutic options, and future directions to advance the field. Identifying mechanisms driving CAC and targeting them are expected to improve the quality of life, treatment efficacy, and survival. Significance: CAC represents a significant clinical unmet need. Despite its high prevalence and associated mortality and morbidity, there are currently no globally approved effective therapies. This review provides a comprehensive overview of human studies aimed at defining CAC clinically and identifying mediators underlying it that are revealing effective health interventions. Furthermore, we highlight ongoing international efforts to advance our understanding of CAC.

Background: Cancer cachexia presents a significant challenge, but the ghrelin agonist anamorelin shows promise as a potential treatment. This study examined whether the baseline systemic inflammatory response (SIR) (measured by the modified Glasgow Prognostic Score [mGPS]), low BMI or greater weight loss, was associated with a differential treatment effect of anamorelin in people with cachexia and non–small‐cell lung cancer (NSCLC). Methods: ROMANA 1 and ROMANA 2 were double‐blind, placebo‐controlled, randomised Phase 3 trials that enrolled people with inoperable stage III/IV NSCLC with cachexia (≥ 5% weight loss within 6 months or body mass index [BMI] < 20 kg/m ² ). Patients were randomised 2:1 to anamorelin 100 mg once daily or placebo, for 12 weeks. This is a post hoc analysis of efficacy endpoints (body weight and body composition: lean body mass [LBM] and fat mass [FM]), stratified by baseline mGPS, BMI and weight loss and measured in the modified intent‐to‐treat pooled population. Results: Seven hundred ninety‐five patients had available data. Anamorelin improved body weight ( p < 0.001) and body composition parameters (LBM and FM, p < 0.01) in all mGPS groups. In patients with mGPS = 2, anamorelin increased weight > 5% and improved hand grip strength (HGS) and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). In patients with BMI < 20 kg/m ² at baseline or weight loss ≥ 10% in the prior 6 months, anamorelin led to significant increases in body weight from baseline ( p < 0.001) versus placebo. Patients with weight loss ≥ 10% in the prior 6 months showed the highest improvements in LBM ( p < 0.001). Patients with BMI < 20 kg/m ² at baseline showed the highest improvements in FM ( p < 0.001). Conclusion: Anamorelin improved body composition parameters in all patients, as well as physical function and symptom burden, particularly in patients with systemic inflammation, BMI < 20 kg/m ² and weight loss ≥ 10%. These results highlight that the anabolic mechanisms of anamorelin are more effective in high‐risk groups. Trial Registration: NCT identifiers: ROMANA 1: NCT01387269; ROMANA 2: NCT01387282.

Background: Cachexia is common in patients with oesophagogastric cancer. The syndrome is characterised by tissue wasting (muscle and fat), anorexia, and reduced physical function, which result from complex interactions between the tumour and its host. Heterogeneity in the diagnostic criteria used for cachexia has hindered their clinical utilisation. This study aimed to compare the two established cachexia definitions (Fearon’s consensus definition and the Global Leadership Initiative on Malnutrition [GLIM] criteria) and their relationships with survival in patients with oesophagogastric cancer. Methods: Consecutive patients newly diagnosed with oesophagogastric cancer (January 2019 to December 2020) were identified from a prospective regional database. Involuntary weight loss, BMI, CT body composition analyses, and neutrophil–lymphocyte ratios were recorded at clinical staging. These data were used to assess patients for cachexia according to Fearon and GLIM diagnostic criteria. The primary outcome of interest was overall survival. Results: Overall, 465 patients (66.9% male, median 71 years) were diagnosed with oesophagogastric cancer during the 2-year study period. Cachectic proportions differed between definitions (Fearon: 59.1% vs. GLIM: 44.1%), and only 49.1% of the 322 patients who met one set of diagnostic criteria were cachectic according to both. Patients who met the GLIM criteria were significantly more comorbid and had a poorer performance status; however, no such difference was evident when using the Fearon definition. Those patients who met either set of diagnostic criteria had shorter survival than those who met neither (p < 0.001). Following adjustment for confounders, GLIM-defined cachexia was more strongly associated with reduced survival (aHR: 1.57 [95% CI: 1.25–1.96], p < 0.001) than Fearon-defined cachexia (aHR: 1.41 [95% CI: 1.13–1.76], p = 0.002). Patients who only met the Fearon diagnostic criteria had prolonged survival (median: 363 days) when compared to those who met only GLIM (median: 158 days) or both definitions (median: 120 days). A secondary analysis of those patients who met the GLIM diagnostic criteria (n = 205) compared the three potential phenotypical criteria used in this definition. Only reduced muscle mass, and not low BMI or weight loss, was associated with poorer survival (aHR: 1.88 [95% CI: 1.15–3.07], p = 0.012) in this group. Conclusions: Cancer cachexia is strongly associated with shortened survival in patients with oesophagogastric cancer. Classification using the GLIM criteria provides more effective prognostication and this definition should be utilised in multidisciplinary patient care.