Associations of Skeletal Muscle With Symptom Burden and Clinical Outcomes in Hospitalized Patients With Advanced Cancer

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  • 1 Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, and
  • 2 Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;
  • 3 Department of Radiology, Charité-Universitätsmedizin Berlin, Berlin, Germany; and
  • 4 Department of Statistics, Massachusetts General Hospital and Harvard Medical School,
  • 5 Dana-Farber Cancer Institute,
  • 6 Department of Radiology, Brigham and Women’s Hospital,
  • 7 Massachusetts General Hospital and Brigham and Women’s Hospital Center for Clinical Data Science, and
  • 8 Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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Background: Low muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle radiodensity (quality). We sought to describe the associations of muscle mass and radiodensity with symptom burden, healthcare use, and survival in hospitalized patients with advanced cancer. Methods: We prospectively enrolled hospitalized patients with advanced cancer from September 2014 through May 2016. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire-4 [PHQ-4]) symptoms. We used CT scans performed per routine care within 45 days before enrollment to evaluate muscle mass and radiodensity. We used regression models to examine associations of muscle mass and radiodensity with patients’ symptom burden, healthcare use (hospital length of stay and readmissions), and survival. Results: Of 1,121 patients enrolled, 677 had evaluable muscle data on CT (mean age, 62.86 ± 12.95 years; 51.1% female). Older age and female sex were associated with lower muscle mass (age: B, –0.16; P<.001; female: B, –6.89; P<.001) and radiodensity (age: B, –0.33; P<.001; female: B, –1.66; P=.014), and higher BMI was associated with higher muscle mass (B, 0.58; P<.001) and lower radiodensity (B, –0.61; P<.001). Higher muscle mass was significantly associated with improved survival (hazard ratio, 0.97; P<.001). Notably, higher muscle radiodensity was significantly associated with lower ESAS-Physical (B, –0.17; P=.016), ESAS-Total (B, –0.29; P=.002), PHQ-4-Depression (B, –0.03; P=.006), and PHQ-4-Anxiety (B, –0.03; P=.008) symptoms, as well as decreased hospital length of stay (B, –0.07; P=.005), risk of readmission or death in 90 days (odds ratio, 0.97; P<.001), and improved survival (hazard ratio, 0.97; P<.001). Conclusions: Although muscle mass (quantity) only correlated with survival, we found that muscle radiodensity (quality) was associated with patients’ symptoms, healthcare use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address adverse muscle changes in oncology.

Submitted April 23, 2020; accepted for publication July 8, 2020. Published online January 29, 2021.

Previous presentation: This study was presented at the 2020 ASCO Virtual Scientific Program; May 29–31, 2020. Abstract 7006.

Author contributions: Study concept and design: All authors. Data acquisition, analysis and interpretation: All authors. Manuscript preparation: All authors. Critical revision: All authors. Final approval of manuscript: All authors.

Disclosures: Dr. Roeland has disclosed that he receives consulting fees from Mitobridge Inc., DRG Consulting, Asahi Kasei Pharmaceuticals, Napo Pharmaceuticals, American Imaging Management, Immuneering Corporation, and Prime Oncology; is a scientific advisor for Heron Pharmaceuticals, Vector Oncology, and Helsinn Pharmaceuticals; and has served as a member on data safety monitoring boards for Oragenics, Inc., Galera Pharmaceuticals, and Enzychem Lifesciences Pharmaceutical Company. Dr. Fintelmann has disclosed that he has received royalties from Massachusetts General/Brigham & Women’s. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the NCI of the NIH under award number K24 CA181253.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

These authors are co-first authors.

These authors are co-last authors.

Correspondence: Ryan Nipp, MD, MPH, Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Yawkey Center, Suite 7E, Boston, MA 02114. Email: RNipp@MGH.Harvard.edu

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