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

Among 598 patients with thymoma (452 found in the literature and 146 from the Mayo Clinic), 422 (71%) suffered from 493 other diseases suspected of being associated with thymoma; 423 of these cases involved disorders of immunity. In contrast, there were only 21 patients (12%) each with one case of these other diseases among 177 Mayo Clinic patients with parathyroid adenoma; 19 of these involved immunity disorders. The total of 423 cases of diseases related to disorders of immunity included, among others, myasthenia gravis (44%), cytopenias (21%), cancer (17%), hypogammaglobulinemia (6%), polymyositis (5%), and systemic lupus erythematosus (2%). These findings merit consideration of thymoma together with certain diseases as a syndrome rather than as a spectrum of coincidental diseases.

The spectrum of diseases associated with thymoma. Coincidence or syndrome

To provide basic information about occurrence and outcome of essential thrombocythemia (ET) and agnogenic myeloid metaplasia (AMM), we used the Rochester Epidemiology Project medical record linkage system for residents of Olmsted County, Minnesota. We identified all residents who were diagnosed with ET or AMM from 1976 to 1995. Community inpatient and outpatient medical records were reviewed to verify the diagnosis of ET or AMM, and patients were followed passively through their medical records to determine the outcome after diagnosis. We identified 39 cases of ET and 21 of AMM, with age- and sex-adjusted incidence rates of 2.53 and 1.46 cases/100,000 population annually, respectively. The respective median ages at diagnosis were 72 and 67 years. The female-to-male ratios were 1.8 and 1.6 for ET and AMM, respectively, and when adjusted for age, there was no difference in risk. The median follow-up period was 62.9 months for ET and 33.2 months for AMM. Five- and 10-year survivals were 74.4% and 61.3%, respectively, for ET and were significantly lower than expected for age-matched controls (P = 0.012). Prognosis was worse for AMM, with a median progression time of 7 months and a 3-year survival of 52.4%. This was significantly worse than for age-matched controls (P < 0.001). This study provides population-based incidence and comparative survival figures in ET and AMM.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291096-8652%28199905%2961%3A1%3C10%3A%3AAID-AJH3%3E3.0.CO%3B2-I

Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995.

Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients.

Anagrelide is a member of the imidazo (2,1-b) quinazolin-2-one series of compounds, with a powerful antiaggregating effect on platelets. During studies in humans, anagrelide in small doses has produced thrombocytopenia. We therefore evaluated it in the treatment of thrombocytosis, and to date, platelet levels in 15 of 17 patients with primary thrombocythemia, 2 patients with polycythemia vera and thrombocytosis, and 1 patient with chronic granulocytic leukemia and thrombocytosis have been well controlled with the use of this agent. Induction doses of 1.0 to 1.5 mg given orally every six hours have produced a decrease in the platelet count, starting on day 5 and reaching a normal level by day 12. Side effects of anagrelide have been minimal. Maintenance therapy with 1.5 to 4.0 mg a day has continued to control the platelet count in patients for up to 28 months. This new agent appears promising in the treatment of thrombocytosis in patients with chronic myeloproliferative disease.

Murray N. Silverstein

Papers

Prognostic effect of weight loss prior tochemotherapy in cancer patients

The spectrum of diseases associated with thymoma. Coincidence or syndrome

Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995.

Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients.

Anagrelide: A New Drug for Treating Thrombocytosis