Prognostic and predictive effects of body composition in advanced malignant melanoma

• Author / Creator

  Youn, Susie

• Body composition, or the breakdown of the body into components such as skeletal muscle and adipose tissue, is increasingly recognized as an important factor impacting morbidity and survival in a variety of diseases. Body composition analysis provides both valuable prognostic information and identifies patients who may benefit from nutritional intervention and/or rehabilitation.

  The majority of body composition studies in cancer patients have been performed in those with intra-abdominal or intra-thoracic malignancies, as many body composition analysis techniques require cross-sectional imaging of the chest or abdomen. Relatively little body composition research has been done in melanoma, though patients with signs of advanced disease (stage III or IV) typically have whole-body or abdominal imaging performed as part of their staging. Baseline body composition and prevalence of factors such as sarcopenia (skeletal muscle depletion) and myosteatosis (reduced skeletal muscle density) have not been well-characterized in melanoma patients, particularly in patients with locoregional disease (stage III). This thesis includes a systematic review of current body composition research in melanoma. Existing research in melanoma has focused mostly on patients with metastatic disease and has been limited by the use of differing techniques of body composition analysis, some of which are not well-supported by the majority of body composition literature.

  Medical management of advanced melanoma has significantly changed in recent years with the emergence of immunotherapies, which have been shown to significantly improve survival in patients with metastatic disease. A growing number of studies are evaluating body composition in these patients as both a prognostic marker and predictor of immunotherapy toxicity. We performed a retrospective analysis of body composition in patients with metastatic
  melanoma receiving the immunotherapy agent nivolumab and found that myosteatosis was a strong predictor of decreased survival in these patients.

  Finally, we sought to characterize baseline body composition and its impacts on survival in patients with resectable stage III disease. A retrospective analysis was performed of a cohort of patients with resected stage III melanoma presenting to a cancer care center in Alberta, Canada from 2007-2017. Peri-operative computed tomography (CT) scans were analyzed at the third lumbar vertebrae to measure surface area of skeletal muscle and adipose tissue. Sarcopenia and myosteatosis were defined using previously published cut-offs commonly used in body composition literature. In addition, we determined cohort-specific cut-offs that significantly impacted overall survival (OS) using optimal stratification. Sarcopenia and myosteatosis defined using cohort-specific cut-offs were predictive of OS, melanoma-specific survival (MSS), and recurrence-free survival (RFS) in a multivariate model accounting for other known prognostic factors in melanoma.

  An exploratory analysis was undertaken of adipose tissue in this cohort of patients with stage III melanoma. Prognostic and predictive effects of adipose tissue are not well-understood, though emerging evidence in other cancer types suggests that an excess of visceral fat is associated with decreased survival. Unlike skeletal muscle, no cut-offs of adipose tissue associated with decreased survival have been widely adopted in the literature. We applied several methods of stratifying and analyzing measurements of adipose tissue. Though significant cut-offs of visceral adipose tissue index that impacted OS were identified using optimal stratification, these associations were only borderline significant in multivariate analyses. These results suggest a need for further research to elucidate the role of adipose tissue in melanoma.

  This thesis demonstrates that body composition, which has been identified as a significant prognostic marker in other cancer types, has a similar role in patients with advanced melanoma. Though melanoma lacks some of the more traditional risk factors for malnutrition associated with gastrointestinal malignancies, patients with resectable stage III melanoma in fact have comparable rates of sarcopenia and myosteatosis. These factors have strong negative effects on survival, independent of other known prognostic factors in melanoma. Our findings are a novel contribution to body composition research in melanoma patients, a relatively understudied field, and underscore the significant role of body composition in cancer progression and prognosis.

• Subjects / Keywords

  • melanoma
  • body composition
  • sarcopenia
  • myosteatosis

• Graduation date

  Fall 2021

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-akvb-vv20

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.