The Obesity Paradox in Cancer—Moving Beyond BMI

Shachar, Shlomit Strulov; Williams, Grant R.

doi:10.1158/1055-9965.epi-16-0439

Cited by 128 publications

(74 citation statements)

References 51 publications

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“…CT scans are readily available for colorectal cancer patients for both staging and surveillance, commercially available programs (25) are currently available to assess body composition, and abbreviated (43) and automated (44) assessment methods are emerging. In the era of precision medicine, we need to move beyond BMI and utilize more precise body composition techniques to assess muscle (45) mass, as well as directly measure adiposity to help to guide treatment plans to optimize survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Caan

Meyerhardt

Kroenke

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

292

283

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Background Body composition may partially explain the U-shaped association between BMI and colorectal cancer (CRC) survival. Methods Muscle and adiposity at CRC diagnosis and survival were examined in a retrospective cohort using Kaplan Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality (OM) and CRC specific mortality (CRCsM). Results Forty-two percent of patients were sarcopenic. During 6.0 years of follow-up, 788 deaths occurred, including 433 from CRC. Sarcopenic patients had a 27% (HR 1.27; 95% CI 1.09, 1.48) higher risk of OM, than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of OM (HR 1.64; 95% CI 1.05, 2.57) when compared to females with adequate muscle and lower adiposity. The lowest risk of OM was seen in patients with a BMI between 25-<30-kg/m2, a range associated with the greatest number of patients (58.6%) who were not at increased risk of OM due to either low muscle or high adiposity. Conclusions Sarcopenia is prevalent among non-metastatic CRC patients, and should, along with adiposity be a standard oncological marker. Impact Our findings suggest a biological explanation for the obesity paradox in CRC and refute the notion that the association between overweight and lower mortality is due solely to methodological biases.

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Section: Discussionmentioning

confidence: 99%

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Caan

Meyerhardt

Kroenke

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

292

283

View full text Add to dashboard Cite

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“…Body mass index is an imprecise measure of body composition, and monitoring BMI changes may be insufficient to promptly identify occult body composition changes . We found that changes in SMI and TATI were weakly correlated with the change in BMI, and changes in SMD and SMG showed no correlation with the BMI.…”

Section: Discussionmentioning

confidence: 99%

“…Changes in body composition during cancer therapy have been associated with treatment‐related toxicity, physical inactivity, malnutrition, cancer invasiveness, and cancer therapy, which in turn could influence patient outcomes . Therefore, the prognostic value of body composition measurements in stage III EC needs to be evaluated.…”

Section: Introductionmentioning

confidence: 99%

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Lee

Lin

et al. 2019

J cachexia sarcopenia muscle

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Background Treatment‐related toxicities and decreased levels of patient performance during cancer therapy might contribute to body composition changes and thereby impact outcomes. However, the effect of longitudinal body composition changes on outcomes in patients with advanced endometrial cancer is unknown. This study investigated the association between body composition changes during staging surgery and adjuvant chemoradiotherapy and outcomes in patients with stage III endometrial cancer. Methods Pretreatment and post‐treatment computed tomography (CT) images of 131 patients with stage III endometrial cancer who were treated between 2008 and 2016 were analysed. All CT images were contrast enhanced and acquired according to the standardized protocol. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and total adipose tissue index were measured from two sets of CT images obtained at the level of the third lumbar vertebra. The skeletal muscle gauge was calculated by multiplying SMI by SMD (SMI × SMD). Predictors of overall survival and progression‐free survival were identified using Cox regression models. Results The median follow‐up was 50.6 (range 12.1–117.0) months. Overall, body mass index (BMI) changes during treatment were 0.4% per 210 days (95% confidence interval: −0.6 to 1.4; P = 0.41), and patients experienced an average SMD loss of 2.1% per 210 days (95% confidence interval: −4.0 to −0.2; P = 0.03). Weight loss and SMD loss ≥5% were observed in 23 (17.6%) and 54 (41.2%) patients, respectively. The changes in SMD did not correlate with those in BMI (Spearman's ρ for SMD, −0.13; P = 0.13). SMD change (per 1 Hounsfield unit/210 days decrease) was independently associated with poorer overall survival (hazard ratio: 1.32, 95% confidence interval: 1.14–1.52; P < 0.001) and progression‐free survival (hazard ratio: 1.28, 95% confidence interval: 1.12–1.43; P < 0.001). Our results did not show association between survival and pretreatment myosteatosis and sarcopenia or changes in SMI and total adipose tissue index during treatment. The pretreatment skeletal muscle gauge was associated with treatment modifications such as delays, dose reductions, and discontinuation of chemotherapy. Conclusions Skeletal muscle radiodensity decreased significantly during treatment and was independently associated with poorer survival in patients with stage III endometrial cancer who underwent staging surgery and adjuvant chemoradiotherapy. SMD loss was occult and occurred independently of BMI change.

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“…Although increased body mass index (BMI) has been shown to be protective for some patients with cancer , there is evidence suggesting that obesity contributes to oncologic development and progression via chronic inflammation . It suffices to say that BMI is an imperfect biomarker of body composition as it relates to cancer outcomes . Recently, Young et al (2019) examined the role of skeletal muscle mass and adiposity on clinical outcomes in a cohort of patients with melanoma who received anti–programmed cell death protein 1 monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Combined Effect of Sarcopenia and Systemic Inflammation on Survival in Patients with Advanced Stage Cancer Treated with Immunotherapy

et al. 2019

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Background Sarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy. Methods We performed a retrospective review of 90 patients enrolled on immunotherapy‐based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias‐adjusted log‐rank test. A four‐level risk stratification was used to create low‐risk (PLR <242 and nonsarcopenic), intermediate‐risk (PLR <242 and sarcopenic), high‐risk (PLR ≥242 and nonsarcopenic), and very‐high‐risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival. Results Most patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high‐risk, high‐risk, and intermediate‐risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65–27.01; p < .001; HR, 5.32; CI, 1.96–14.43; p = .001; and HR, 4.01; CI, 1.66–9.68; p = .002, respectively) and progression‐free survival (HR, 12.29; CI, 5.15–29.32; p < .001; HR, 3.51; CI, 1.37–9.02; p = .009; and HR, 2.14; CI, 1.12–4.10; p = .022, respectively) compared with low‐risk patients. Conclusion Baseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy‐treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents. Implications for Practice Sarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk‐stratification system that combined sarcopenia and platelet‐to‐lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression‐free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk‐stratify patients who are beginning treatment with immunotherapy.

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The Obesity Paradox in Cancer—Moving Beyond BMI

Cited by 128 publications

References 51 publications

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

Combined Effect of Sarcopenia and Systemic Inflammation on Survival in Patients with Advanced Stage Cancer Treated with Immunotherapy

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