Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer

Caan, Bette J.; Feliciano, Elizabeth M. Cespedes; Prado, Carla M.; Alexeeff, Stacey; Kroenke, Candyce H.; Bradshaw, Patrick T.; Quesenberry, Charles P.; Weltzien, Erin; Castillo, Adrienne; Olobatuyi, Taiwo A.; Chen, Wendy Y.

doi:10.1001/jamaoncol.2018.0137

Cited by 382 publications

(409 citation statements)

References 20 publications

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“…Several studies have demonstrated the influence of low muscle mass (sarcopenia) and/or poor muscle quality (low radiodensity) on cancer prognosis, reporting prognostic cut‐off values based on the statistical method of optimal stratification for respective parameters. Optimizing a cut‐value by minimizing the P ‐value, however, can lead to bias, namely, an overestimation of the prognostic impact as the cut‐offs so determined heavily dependent on the case mix in the respective study populations, for example, according to age, gender, ethnicity, cancer type, and stage, and consequently cannot be applied uniformly in different cohorts as exemplified by considerable different cut‐off values reported in an Asian cohort compared with North American cohorts . In addition, defining a low‐risk group and a high‐risk group based on a cut‐value is conceptually misleading if the prognostic impact is in fact linear: It falsely suggests that there are two qualitatively different subgroups, although in reality, the hazard just varies proportional to the measurement.…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

Hacker¹,

Hasenclever

Linder³

et al. 2019

J cachexia sarcopenia muscle

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Background Body fat and/or muscle composition influences prognosis in several cancer types. For advanced gastric and gastroesophageal junction cancer, we investigated which body composition parameters carry prognostic information beyond well‐established clinical parameters using robust model selection strategy such that parameters identified can be expected to generalize and to be reproducible beyond our particular data set. Then we modelled how differences in these parameters translate into survival outcomes. Methods Fat and muscle parameters were measured on baseline computed tomography scans in 761 patients with advanced gastric or gastroesophageal junction cancer from the phase III EXPAND trial, undergoing first‐line chemotherapy. Cox regression analysis for overall survival (OS) and progression‐free survival (PFS) included body composition parameters and clinical prognostic factors. All continuous variables were entered linearly into the model as there was no evidence of non‐linear prognostic impact. For transferability, the final model included only parameters that were picked by Bayesian information criterion model selection followed by bootstrap analysis to identify the most robust model. Results Muscle and fat parameters formed correlation clusters without relevant between‐cluster correlation. Mean muscle attenuation (MA) clusters with the fat parameters. In multivariate analysis, MA was prognostic for OS (P < 0.0001) but not for PFS, while skeletal muscle index was prognostic for PFS (P = 0.02) but not for OS. Worse performance status Eastern Cooperative Oncology Group (ECOG 1/0), younger age (on a linear scale), and the number of metastatic sites were strong negative clinical prognostic factors for both OS and PFS. MA remained in the model for OS (P = 0.0001) following Bayesian information criterion model selection in contrast to skeletal muscle index that remained prognostic for PFS (P = 0.009). Applying stricter criteria for transferability, MA represented the only prognostic body composition parameter for OS, selected in >80% of bootstrap replicates. Finally, Cox model‐derived survival curves indicated that large differences in MA translate into only moderate differences in expected OS in this cohort. Conclusions Among body composition parameters, only MA has robust prognostic impact for OS. Data suggest that treatment approaches targeting muscle quality are unlikely to prolong OS noticeably on their own in advanced gastric cancer patients, indicating that multimodal approaches should be pursued in the future.

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Section: Discussionmentioning

confidence: 99%

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

Hacker¹,

Hasenclever

Linder³

et al. 2019

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…This observation has been confirmed in two large cohort studies of 3241 females with breast cancer and 3262 males and females with colorectal cancer, where low abdominal muscle cross-sectional area was observed in 34-42% of patients, and this was independently associated with a 27-41% higher risk of overall mortality. 35 Another approach is to model the joint effects of muscle and adiposity using phenotype methods. 47 The use of body composition quantified with clinical imaging is, however, not without limitation.…”

Section: Body Mass Indexmentioning

confidence: 99%

The evolution of body composition in oncology—epidemiology, clinical trials, and the future of patient care: facts and numbers

Brown

Feliciano

Caan

2018

J cachexia sarcopenia muscle

Self Cite

128

115

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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.

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“…In patients with acute and chronic illness, depleted skeletal muscle (SM) mass, also referred to as sarcopenia, is a condition associated with underlying disease processes and adverse outcomes . Imaging technologies like dual‐energy x‐ray absorptiometry and computed tomography (CT) are considered gold‐standard references for body composition assessment in research.…”

Section: Introductionmentioning

confidence: 99%

Tutorial: A Step‐by‐Step Guide (Version 2.0) for Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross‐Sectional Computed‐Tomography Image Using the National Institutes of Health ImageJ

Gomez-Perez

McKeever

Sheean

2019

J Parenter Enteral Nutr

103

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Background In patients with acute and chronic illness, depleted skeletal muscle (SM) mass, also referred to as sarcopenia, is a condition associated with an underlying disease process and adverse outcomes. Because of software upgrades and errors related to installation, clarifications and a revised tutorial were needed for calculating SM cross‐sectional area (CSA) using the National Institutes of Health (NIH) ImageJ. Methods A pilot study was conducted to determine the usability of the tutorial version 2.0. Eight adults (≥18 years of age) who had no previous experience or background in body composition or computed‐tomography imaging and owned a personal laptop computer (Mac or PC) were included in the pilot study. Participants were tested on the completion of 4 tasks: (1) installation of software, (2) updating the software, (3) following revised tutorial (version 2.0), and (4) transferring information from the software to a spreadsheet for calculation of SM CSA. Results All participants completed the tutorial and all assigned tasks, 4/4 (100%). However, 38% (3/8) of the participants made errors while cutting and pasting values from the ImageJ results box to a spreadsheet for calculating SM CSA. Conclusion The tutorial version 2.0 was easy to follow and provided sufficient information for adults to install, update, and perform the steps of body composition for the NIH ImageJ software without major issues. Care should be taken when cutting and pasting results from the software as well as when using the Microsoft Excel spreadsheet for calculating SM CSA.

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Association of Muscle and Adiposity Measured by Computed Tomography With Survival in Patients With Nonmetastatic Breast Cancer

Cited by 382 publications

References 20 publications

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

Prognostic role of body composition parameters in gastric/gastroesophageal junction cancer patients from the EXPAND trial

The evolution of body composition in oncology—epidemiology, clinical trials, and the future of patient care: facts and numbers

Tutorial: A Step‐by‐Step Guide (Version 2.0) for Measuring Abdominal Circumference and Skeletal Muscle From a Single Cross‐Sectional Computed‐Tomography Image Using the National Institutes of Health ImageJ

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