Body Composition, Symptoms, and Survival in Advanced Cancer Patients Referred to a Phase I Service Henrique A. Parsons 1 *, Vickie E. Baracos 2 , Navjot Dhillon 1 , David S. Hong 1 , Razelle Kurzrock 1 1 Department of Investigational Cancer Therapeutics (A Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America, 2 Department of Oncology/Division of Palliative Care Medicine, University of Alberta, Edmonton, Alberta, Canada Abstract Background: Body weight and body composition are relevant to the outcomes of cancer and antineoplastic therapy. However, their role in Phase I clinical trial patients is unknown. Methods: We reviewed symptom burden, body composition, and survival in 104 patients with advanced cancer referred to a Phase I oncology service. Symptom burden was analyzed using the MD Anderson Symptom Assessment Inventory(MDASI); body composition was evaluated utilizing computerized tomography(CT) images. A body mass index (BMI)$25 kg/m 2 was considered overweight. Sarcopenia, severe muscle depletion, was assessed using CT-based criteria. Results: Most patients were overweight (n = 65, 63%); 53 patients were sarcopenic (51%), including 79% of patients with a BMI,25 kg/m 2 and 34% of those with BMI$25 kg/m 2 . Sarcopenic patients were older and less frequently African-American. Symptom burden did not differ among patients classified according to BMI and presence of sarcopenia. Median (95% confidence interval) survival (days) varied according to body composition: 215 (71–358) (BMI,25 kg/m 2 ; sarcopenic), 271 (99–443) (BMI,25 kg/m 2 ; non-sarcopenic), 484 (286–681) (BMI$25 kg/m 2 ; sarcopenic); 501 d (309–693) (BMI$25 kg/m 2 ; non-sarcopenic). Higher muscle index and gastrointestinal cancer diagnosis predicted longer survival in multivariate analysis after controlling for age, gender, performance status, and fat index. Conclusions: Patients referred to a Phase I clinic had a high frequency of sarcopenia and a BMI$25 kg/m 2 , independent of symptom burden. Body composition variables were predictive of clinically relevant survival differences, which is potentially important in developing Phase I studies. Citation: Parsons HA, Baracos VE, Dhillon N, Hong DS, Kurzrock R (2012) Body Composition, Symptoms, and Survival in Advanced Cancer Patients Referred to a Phase I Service. PLoS ONE 7(1): e29330. doi:10.1371/journal.pone.0029330 Editor: Eric Deutsch, Institut Gustave Roussy, France Received May 23, 2011; Accepted November 25, 2011; Published January 3, 2012 Copyright: ß 2012 Parsons et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported in part by Grant Number RR024148 from the National Center for Research Resources, a component of the NIH Roadmap for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. Competing Interests: The authors have declared that no competing interests exist. * E-mail: haparsons@gmail.com Introduction Several body composition features have been associated with the incidence, etiology, and therapeutic outcomes of cancer. Obesity, as one example, has been implicated in the etiology and prognosis of various cancers [1]. Additionally, weight loss is frequent among cancer patients, especially in advanced disease [2], and is the predominant feature of cancer cachexia [3]. Cachexia occurs in up to 80% of cancer patients [4], is a marker of poor prognosis [5,6,7], negatively impacts patients’ quality of life [8,9], and impairs their normal physical function [10]. Sarcopenia, severe muscle depletion, has received special attention in the recent cancer literature because of its association with reduced physical ability and increased mortality in noncancer patients [11,12,13,14], and unfavorable treatment outcomes, especially severe toxicity [12,15,16]. Studies in patients with malignant diseases [16,17] and non-malignant conditions [18,19] have shown that the combination of heavy body weight and sarcopenia results in particularly poor physical functional ability and clinical outcome. Various mechanisms putatively underlie muscle wasting and cachexia. Inflammation is a likely major player in the genesis of these entities, and the relationship between cachexia and cytokines has been widely studied [20,21,22,23,24]. Inflammatory pathways and cytokines have also been implicated in cancer-related symptoms [25,26,27,28], which cause severe distress and impair the quality of life of cancer patients, especially those with advanced disease. A rational hypothesis is that sarcopenia, cachexia and other cancer-related symptoms share similar underlying inflammatory mechanisms. The rapidly developing field of oncology has been driven, in part, by clinical trials, reflected by the 5,841 active and recruiting oncology phase I and II studies listed on the www.clinicaltrials.gov website as of early May 2011. Patients enrolled on these trials typically have failed to respond to multiple standard-of-care therapeutic regimens and frequently have less than a one-year expected survival [29]. Ideally, candidates for accrual to these investigations survive long enough to generate meaningful results, and have a minimum of features to confound the interpretation of results (i.e., significant symptom burden, unusual propensity for treatment toxicity). There is a dearth of research examining the relationships among body composition, the PLoS ONE | www.plosone.org 1 January 2012 | Volume 7 | Issue 1 | e29330