Background: A body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression.Methods: An international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0–4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade.Results: One thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in −2 log likelihood (P < 0.001) and persisted after adjustment for age, sex, and cancer type and stage (P < 0.001). Median survival decreased across the weight loss grades ranging from 407 days (95% CI 312–502)—weight loss grade 0 to 119 days (95% CI 93–145)—weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%).Conclusions: The WLGS is related to survival, cachexia domains, and the likelihood of progression. Adding certain cachexia domains to the WLGS improves prognostic accuracy.

Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell’s c-statistic and receiver operating characteristic curve analysis. Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3–5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. ClinicalTrials.gov Identifier: NCT01362816 .

There is no consensus on the optimal endpoint(s) in cancer cachexia trials. Endpoint variation is an obstacle when comparing interventions and their clinical value. The aim of this systematic review was to summarize and evaluate endpoints used to assess appetite and dietary intake in cancer cachexia clinical trials. A search for studies published from 1 January 1990 until 2 June 2021 was conducted using MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Eligible studies examined cancer cachexia treatment versus a comparator in adults with assessments of appetite and/or dietary intake as study endpoints, a sample size ≥40 and an intervention lasting ≥14 days. Reporting was in line with PRISMA guidance, and a protocol was published in PROSPERO (2022 CRD42022276710). This review is part of a series of systematic reviews examining cachexia endpoints. Of the 5975 articles identified, 116 were eligible for the wider review series and 80 specifically examined endpoints of appetite (65 studies) and/or dietary intake (21 studies). Six trials assessed both appetite and dietary intake. Appetite was the primary outcome in 15 trials and dietary intake in 7 trials. Median sample size was 101 patients (range 40–628). Forty‐nine studies included multiple primary tumour sites, while 31 studies involved single primary tumour sites (15 gastrointestinal, 7 lung, 7 head and neck and 2 female reproductive organs). The most frequently reported appetite endpoints were visual analogue scale (VAS) and numerical rating scale (NRS) (40%). The appetite item from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30/C15 PAL (38%) and the appetite question from North Central Cancer Treatment Group anorexia questionnaire (17%) were also frequently applied. Of the studies that assessed dietary intake, 13 (62%) used food records (prospective registrations) and 10 (48%) used retrospective methods (24‐h recall or dietary history). For VAS/NRS, a mean change of 1.3 corresponded to Hedge's g of 0.5 and can be considered a moderate change. For food records, a mean change of 231 kcal/day or 11 g of protein/day corresponded to a moderate change. Choice of endpoint in cachexia trials will depend on factors pertinent to the trial to be conducted. Nevertheless, from trials assessed and available literature, NRS or EORTC QLQ C30/C15 PAL seems suitable for appetite assessments. Appetite and dietary intake endpoints are rarely used as primary outcomes in cancer cachexia. Dietary intake assessments were used mainly to monitor compliance and are not validated in cachexia populations. Given the importance to cachexia studies, dietary intake endpoints must be validated before they are used as endpoints in clinical trials.

Appetite loss is prevalent in patients with advanced cancer and negatively affects their quality of life. However, understanding of the factors associated with appetite loss is limited. The current study aims to explore characteristics and therapeutic interventions used for patients with and without appetite loss admitted to an acute palliative care unit. Patient characteristics and patient-reported outcome measures (PROMs), using the 11-point numeric rating scale (NRS 0–10), were registered. Descriptive statistics, independent samples T-tests and chi-square tests were utilized for data analysis. Of the 167 patients included in the analysis, 62% (104) had moderate to severe appetite loss at admission, whereof 63% (66) improved their appetite during their hospital stay. At admission, there was a significant association between appetite loss and having gastrointestinal cancer, living alone, poor performance status and withdrawn anticancer treatment. Patients with appetite loss also experienced more nausea, depression, fatigue, dyspnea and anxiety. In patients with improved appetite during hospitalization, mean decrease in NRS was 3.4 (standard error (SE) 0.27). Additionally, patients living alone were more likely to improve their appetite. Appetite improvement frequently coincided with alleviation of fatigue. Understanding these associations may help in developing better interventions for managing appetite loss in patients with advanced cancer.

Background: Systemic inflammation is crucial in cancer cachexia, but the optimal measurement method remainsunclear. This study compares markers of systemic inflammation (MoSI) in predicting weight loss in patients withmetastatic cancer.Methods: This prospective, observational multi-center study involved patients undergoing radiotherapy forbone metastases. Baseline assessments included demographics, clinical characteristics, previous weight loss,and appetite loss. MoSI included: C-reactive protein (CRP), albumin, white blood cells, neutrophil-to-lymphocyteratio, monocyte-to-lymphocyte ratio, interleukin-6 (IL-6), modified Glasgow Prognostic Score (mGPS), andPrognostic Nutritional Index. Body weight was recorded at baseline, 3, and 8 weeks post-radiotherapy. Multiplelinear regression assessed MoSI’s predictive ability for weight loss, adjusting for previous weight loss, appetiteloss, and primary tumour type. Goodness-of-fit was assessed using adjusted R2.Results: Out of 574 recruited patients, 540 and 470 were analyzed at 3 and 8 weeks, respectively. The median age(IQR) was 67 (15), 330 (61%) were male, and 397 (74%) had a Karnofsky performance status ≥70. In a base modelwithout MoSI, significant predictors of weight loss at 3 weeks were appetite loss and urological, lung, and gastrointestinalcancer (adjusted R2 of 0.064), while at 8 weeks, urological and lung cancer were significant (adjusted R2of 0.035). At 3 weeks, all MoSI significantly improved the base model, with adjusted R2 between 0.078 and 0.091.At 8 weeks: CRP, mGPS, albumin and IL-6 improved the model; however only CRP and mGPS retained an adjustedR2 of ~0.09.Conclusions: All MoSI predicted weight loss, but CRP and mGPS were the most optimal.