Summary To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] 2 ) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(10)70218-7.pdf

Definition and classification of cancer cachexia: an international consensus

Summary Background Emerging evidence on body composition suggests that sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in non-malignant disease and also of toxicity to chemotherapy. We aimed to assess the prevalence and clinical implications of sarcopenic obesity in patients with cancer. Methods Between Jan 13, 2004, and Jan 19, 2007, 2115 patients with solid tumours of the respiratory or gastrointestinal tract from a cancer treatment centre serving northern Alberta, Canada, were identified. Available lumbar CT images of the obese patients were analysed for total skeletal muscle cross-sectional area; these values were also used to estimate total body fat-free mass (FFM). Findings Of the 2115 patients initially identified, 325 (15%) were classified as obese (body-mass index [BMI] ≥30). Of these obese patients, 250 had CT images that met the criteria for analysis. The remaining 75 patients were recorded as without assessable scans. Obese patients had a wide range of muscle mass. Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis: 38 (15%) of 250 patients who had assessable CT images that met the criteria for analysis were below these cut-offs and were classified as having sarcopenia. Sarcopenic obesity was associated with poorer functional status compared with obese patients who did not have sarcopenia (p=0·009), and was an independent predictor of survival (hazard ratio [HR] 4·2 [95% CI 2·4–7·2], p r 2 =0·37). Assuming that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, we estimated that individual variation in FFM could account for up to three-times variation in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population. Interpretation This study provides evidence of the great variability of body composition in patients with cancer and links body composition, especially sarcopenic obesity, to clinical implications such as functional status, survival, and potentially, chemotherapy toxicity. Funding Canadian Institutes of Health Research (Ottawa, ON, Canada), Alberta Cancer Board (Edmonton, AB, Canada), and Translational Research Training in Cancer (Edmonton, AB, Canada).

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(08)70153-0.pdf

Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study.

Purpose Emerging evidence suggests muscle depletion predicts survival of patients with cancer. Patients and Methods At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Results Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P .001).

Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.

ESPEN guidelines on nutrition in cancer patients

Human body composition is important in numerous cancer research domains. Our objective was to evaluate clinically accessible methods to achieve practical and precise measures of body composition in...

https://www.focusopvoeding.nl/wp-content/uploads/2016/02/Mourtzakis-2008-a-practical-and-precise-way-to.pdf

A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care

https://www.amjmed.com/article/S0149-2918(05)80001-3/pdf

Prognostic effect of weight loss prior tochemotherapy in cancer patients

The effectiveness of DTIC in the treatment of Grade III and IV astrocytomas was analyzed in two phases. In the first phase, 14 patients (Group A) with progressive neurologic dysfunction following primary treatment were treated with DTIC alone (8 patients) or in combination with CCNU or methyl CCNU (6 patients) and evaluated for change in neurologic status. Five of the 8 treated with DTIC responded symptomatically for a median duration of 18 weeks, and 3 of 6 treated with the combination of drugs responded for a median duration of 12 weeks. In the second phase, 15 patients (Group B) were treated within 4 weeks of surgical resection with radiation therapy and adjuvant chemotherapy with DTIC and/or MeCCNU. These patients were followed for survival and compared to a historical control group of 15 patients (Group C) treated with surgery and radiation only. The drug-treated group had a median survival of 55 weeks, compared to 35 weeks for the control group. Hematologic toxicity was life threatening in 2 of 14 patients treated with combination drugs, but mild with DTIC alone. DTIC appears to be active against malignant astrocytomas. Survival may be lengthened by combining chemotherapy with surgery and radiation therapy.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197510%2936%3A4%3C1269%3A%3AAID-CNCR2820360412%3E3.0.CO%3B2-%23

Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).

Charles Rosenbaum

Papers

Prognostic effect of weight loss prior tochemotherapy in cancer patients

Treatment of grade III and IV astrocytoma with dimethyl triazeno imidazole carboxamide (DTIC, NSC-45388) alone and in combination with CCNU (NSC-79037) or methyl CCNU (MeCCNU, NSC-95441).