Sarcopenia is underrecognized in nonmetastatic breast cancer and occurs in over one-third of newly diagnosed patients. Measures of both sarcopenia and adiposity from clinically acquired CT scans in nonmetastatic patients provide significant prognostic information that outperform BMI and will help to guide interventions to optimize survival outcomes.

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.

Prediagnosis inflammation was associated with at-diagnosis sarcopenia. Sarcopenia combined with inflammation nearly doubled risk of death, suggesting that these commonly collected biomarkers could enhance prognostication. A better understanding of how the host inflammatory/immune response influences changes in skeletal muscle may open new therapeutic avenues to improve cancer outcomes.

Despite a greater risk of cancer associated with higher BMI, overweight (BMI 25-<30 kg/m 2 ) and class I obese (BMI 30-<35 kg/m 2 ) patients often have a paradoxically lower risk of overall mortality after a cancer diagnosis, a phenomenon called the "obesity paradox." Only when patients exceed a BMI !35 kg/m 2 are elevations in mortality risk consistently noted. This paradox has been dismissed as the result of methodologic bias, which we will describe and debate here. However, even if such bias influences associations, there is growing evidence that body composition may in part explain the paradox. This phenomenon may more accurately be described as a BMI paradox. That is, BMI is a poor proxy for adiposity and does not distinguish muscle from adipose tissue, nor describe adipose tissue distribution. Low muscle mass is associated with higher risk of recurrence, overall and cancerspecific mortality, surgical complications, and treatment-related toxicities. Patients with who are overweight or obese have on average higher levels of muscle than their normal-weight counterparts. Also, there is some evidence that patients with moderate levels of subcutaneous adipose tissue may have lower mortality. More research utilizing body composition is needed to clarify the effects of adiposity on cancer mortality. Cancer Res; 78(8); 1906-12.Ó2018 AACR. BMI and SurvivalOverweight (body mass index, BMI: 25-<30 kg/m 2 ) and obesity (!30 kg/m 2 ) are established cancer risk factors. They are associated with a host of metabolic and endocrine changes implicated in cancer development including insulin resistance, systemic inflammation, and alterations in hormone levels and growth factors. Many of these pathways are also implicated in cancer progression, suggesting that overweight and obese patients should have a higher risk of cancer mortality. Yet, in many cancers, including lymphoma (1), leukemia (2), colorectal (3), gastric (4, 5), and renal (3, 6), cancers, a higher BMI at diagnosis has not been associated with a higher mortality risk, or it has exhibited a protective association, leading to an apparent "obesity paradox." In other cancer sites such as in postmenopausal breast cancer (7), there is often a J-shaped relationship of BMI and mortality; obese patients have a higher risk of death compared with normal-weight patients, but the elevation in risk does not approach the magnitude of risk observed in underweight patients. Further, in studies with large sample sizes that distinguish classes of obesity, this increased risk often does not emerge until patients exceed a BMI !35 kg/m 2 (i.e., class IIþ obesity; ref. 8). In a recent pooled analysis of clinical treatment trials, there was no cancer or treatment combination in which overweight (BMI !25 kg/m 2 )patients had a higher risk of death compared with normal-weight patients (overall mean HR 0.96; P ¼ 0.06). This was true across tumor sites (breast, prostate, bladder, ovarian, lung, kidney, colorectal, and hematologic) and stages (both nonmetastatic and metastatic). In fa...

There is growing interest from the oncology community to understand how body composition measures can be used to improve the delivery of clinical care for the 18.1 million individuals diagnosed with cancer annually. Methods that distinguish muscle from subcutaneous and visceral adipose tissue, such as computed tomography (CT), may offer new insights of important risk factors and improved prognostication of outcomes over alternative measures such as body mass index. In a meta‐analysis of 38 studies, low muscle area assessed from clinically acquired CT was observed in 27.7% of patients with cancer and associated with poorer overall survival [hazard ratio: 1.44, 95% CI: 1.32–1.56]. Therapeutic interventions such as lifestyle and pharmacotherapy that modify all aspects of body composition and reduce the incidence of poor clinical outcomes are needed in patients with cancer. In a meta‐analysis of six randomized trials, resistance training exercise increased lean body mass assessed from dual‐energy X‐ray absorptiometry [mean difference (MD): +1.07 kg, 95% CI: 0.76–1.37; P < 0.001] and walking distance [MD: +143 m, 95% CI: 70–216; P < 0.001] compared with usual care control in patients with non‐metastatic cancer. In a meta‐analysis of five randomized trials, anamorelin (a ghrelin agonist) significantly increased lean body mass [MD: +1.10 kg, 95% CI: 0.35–1.85; P = 0.004] but did not improve handgrip strength [MD: 0.52 kg, 95% CI: −0.09–1.13; P = 0.09] or overall survival compared with placebo [HR: 0.99, 95% CI: 0.85–1.14; P = 0.84] in patients with advanced or metastatic cancer. Early screening to identify individuals with occult muscle loss, combined with multimodal interventions that include lifestyle therapy with resistance exercise training and dietary supplementation combined with pharmacotherapy, may be necessary to provide a sufficient stimulus to prevent or slow the cascade of tissue wasting. Rapid, cost‐efficient, and feasible methods to quantify muscle and adipose tissue distribution are needed if body composition assessment is to be integrated into large‐scale clinical workflows. Fully automated analysis of body composition from clinically acquired imaging is one example. The study of body composition is one of the most provocative areas in oncology that offers tremendous promise to help patients with cancer live longer and healthier lives.

In patients with CRC, those with low SMD were found to have elevated risks of disease-specific and overall mortality, independent of MM or adiposity. Clinical practice should incorporate body composition measures into the evaluation of the health status of patients with CRC. Cancer 2018;124:3008-15. © 2018 American Cancer Society.

IMPORTANCE Given the risks of postoperative morbidity and its consequent economic burden and impairment to patients undergoing colon resection, evaluating risk factors associated with complications will allow risk stratification and the targeting of supportive interventions. Evaluation of muscle characteristics is an emerging area for improving preoperative risk stratification.OBJECTIVE To examine the associations of muscle characteristics with postoperative complications, length of hospital stay (LOS), readmission, and mortality in patients with colon cancer. DESIGN, SETTING, AND PARTICIPANTSThis population-based retrospective cohort study was conducted among 1630 patients who received a diagnosis of stage I to III colon cancer from January 2006 to December 2011 at Kaiser Permanente Northern California, an integrated health care system. Preliminary data analysis started in 2017. Because major complication data were collected between 2018 and 2019, the final analysis using the current cohort was conducted between 2019 and 2020.EXPOSURES Low skeletal muscle index (SMI) and/or low skeletal muscle radiodensity (SMD) levels were assessed using preoperative computerized tomography images. MAIN OUTCOMES AND MEASURESLength of stay, any complication (Ն1 predefined complications) or major complications (Clavien-Dindo classification score Ն3), 30-day mortality and readmission up to 30 days postdischarge, and overall mortality. RESULTSThe mean (SD) age at diagnosis was 64.0 (11.3) years and 906 (55.6%) were women. Patients with low SMI or low SMD were more likely to remain hospitalized 7 days or longer after surgery (odds ratio [OR], 1.33; 95% CI, 1.05-1.68; OR, 1.39; 95% CI, 1.05-1.84, respectively) and had higher risks of overall mortality (hazard ratio, 1.40; 95% CI, 1.13-1.74; hazard ratio, 1.44; 95% CI, 1.12-1.85, respectively). Additionally, patients with low SMI were more likely to have 1 or more postsurgical complications (OR, 1.31; 95% CI, 1.04-1.65) and had higher risk of 30-day mortality (OR, 4.85; 95% CI,. Low SMD was associated with higher odds of having major complications (OR, 2.41; 95% CI, 1.44-4.04).CONCLUSIONS AND RELEVANCE Low SMI and low SMD were associated with longer LOS, higher risk of postsurgical complications, and short-term and long-term mortality. Research should evaluate whether targeting potentially modifiable factors preoperatively, such as preserving muscle mass, could reverse the observed negative associations with postoperative outcomes.

Background For many chemotherapy regimens dosed on body surface area (BSA), patients are dose-reduced, delayed, or discontinue treatment, reducing survival. Consideration of body composition may be useful in individualizing chemotherapy dosing, but few studies examine the association of body composition with chemotherapy tolerance in colon cancer. Methods We identified non-metastatic colon cancer patients diagnosed from 2006–2011 at Kaiser Permanente who received FOLFOX as initial adjuvant chemotherapy (n=533). We quantified patients’ muscle mass using clinically-acquired computed tomography (CT) scans and quantified chemotherapy doses, treatment dates, and related toxicities using the electronic medical record. In logistic regression models adjusting for age, sex, and stage, we examined associations of muscle tertiles with early discontinuation (<6 cycles), treatment delay (≥3 days off-schedule ≥3 times), and/or dose reduction (relative dose intensity≤0.70, based on planned treatment). Results Average age at diagnosis was 58.7 years, body surface area (BSA) was 1.9 m2, and body mass index was 28.7 kg/m2. Compared to the highest sex-specific tertile of muscle, patients in the lowest tertile were more likely to experience toxicities had twice the risk of adverse outcomes on FOLFOX: odds ratios (OR) and 95% Confidence Intervals (95%CI) were OR=2.34 (95%CI: 1.04, 5.24; p-trend=0.03) for early discontinuation, OR=2.24 (95%CI: 1.37, 3.66; p-trend=0.002) for treatment delay and OR=2.28 (95%CI: 1.19, 4.36; p-trend=0.01) for dose reduction. Conclusions Lower muscle mass is associated with greater toxicity and poor chemotherapy adherence on FOLFOX. Many chemotherapy drugs are dosed on BSA: treatment may be better individualized if muscle mass is considered.