Sarcopenic Obesity and Clinical Outcomes Among Cancer Patients
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: Oncologists are aware of the importance of obesity in both the risk for developing cancer and in shortened survival among cancer patients. Recently, there has been an increased awareness of a similar pattern of risk among individuals with reduced muscle mass. Patients with both expanded fat mass and reduced lean body mass (sarcopenia) are likely to be at greatest risk. In the current report, Prado and colleagues from Edmonton, Alberta define parameters for such a cohort using data from abdominal CT in addition to the standard determinants of obesity. Of 2115 cancer patients, approximately 15% met criteria for obesity, and of these obese cancer patients, 15% also met criteria for sarcopenia. These individuals were shown to have a very high risk for poor functional status and reduced overall survival.
Source: Prado CM, Prevalence and clinical implications of sarcopenic obesity in patients with solid tumors of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9:629-635.
The presence of obesity in individuals with reduced lean body mass (sarcopenic obesity) is predictive of morbidity and mortality in non-malignant disease1 and also toxicity to chemotherapy.2 In the current report, Prado and colleagues from Edmonton, Alberta, describe the effect of sarcopenic obesity on treatment outcome of patients with respiratory and gastrointestinal cancers.
Over a span of approximately three years, 2115 patients with solid tumors of the respiratory or gastrointestinal tract were seen at the cancer treatment center serving northern Alberta, Canada, and of these 325 (15%) were classified as obese (body mass index [BMI] > 30). For those identified as obese, available lumbar CT images were analyzed for total skeletal muscle cross-sectional area which was then used to estimate total body fat-free mass (FFM).
Of the 325 obese patients, 250 had CT images that met the criteria for analysis. 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. Of the 250 evaluable obese patients, 38 (15%) 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<0·0001). Estimated FFM showed a poor association with body-surface area (r²=0·37). The authors argued that if one assumes that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, that the wide variation in FFM could account for up to three-times difference in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population.
Commentary
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. Patients with sarcopenic obesity had poorer functional status, shorter survival (by a mean difference of 7 months), and poorer response to chemotherapy. The researchers suggest this finding might be due to greater variability in the volume of distribution of chemotherapeutic drugs in this population.
Both sarcopenia and obesity have been associated with adverse outcomes in general, and in cancer patients, specifically and the combination (sarcopenic obesity) most likely represents a "worst case scenario." But, what are the implications of this for the practicing oncologist? For patients with metabolically active cancers, empiric criteria for obesity are likely to be met less frequently than age-matched individuals without cancer. Indeed, in this study, whereas 15% were obese at the time of assessment, just 6 months earlier, 27% had been obese. Furthermore, assessing lean body mass has yet to become a routine community approach, primarily because age and sex diagnostic criteria are not established and the methodology of assessment (either by CT or DEXA) has not been standardized. Although it's likely that oncologists do not need specific data on lean body mass relative to overall weight to assess prognosis, the estimation of fat-free mass could allow better dosing of chemotherapeutic regimens by tailoring dosage to actual metabolic target tissue volumes. Furthermore, a proactive approach to physical activity and exercise along with anti-tumor treatment might be warranted in patients discovered to have sarcopenia (with or without coexisting obesity).
In an editorial accompanying the Prado article,3 Roubenoff suggested that oncologists make the effort to recognize sarcopenia. He points out that age over 70 years, difficulty getting up from a chair, and history of weight loss should prompt consideration of a CT scan to assess axial muscle mass and calls for further research to assess whether sarcopenia in the absence of obesity also confers these increased risks, and whether dose adjustments based on body-composition analysis can actually improve survival.
Certainly, it is difficult to argue against this perspective. Recognizing that sarcopenia may be as important as obesity in assessing prognosis is one thing, but considering body composition in more precise terms may ultimately be shown to improve chemotherapy effectiveness and reduce toxicity.
References
1. Roubenoff R. Sarcopenia: effects on body composition and function. J Gerontol A Biol Sci Med Sci. 2003;58(11):1012-1017.
2. Prado CM, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007;13(11):3264-3268.
3. Roubenoff R. Excess baggage: sarcopenia, obesity, and cancer outcomes. Lancet Oncol. 2008;9(7):605-607.
Oncologists are aware of the importance of obesity in both the risk for developing cancer and in shortened survival among cancer patients. Recently, there has been an increased awareness of a similar pattern of risk among individuals with reduced muscle mass.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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