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An exploration into the relationship of body composition parameters and survival outcomes in patients with resectable colorectal cancer

  • Author / Creator
    Hopkins, Jessica Jean
  • Both tumor biology and host-specific factors play an important role in the prognosis of colorectal cancer. Body composition is an emerging patient-specific factor, which is currently being elucidated. Opportunistic analysis of pre-existing staging computed tomography scans can be used to quantify skeletal muscle and adipose tissue area (cm2), as well as average skeletal muscle radiodensity (Hounsfield Units). Skeletal muscle area at the third lumbar vertebrae is highly correlated with total body skeletal muscle mass, and can be used as a surrogate marker. Severe loss of skeletal muscle mass, or sarcopenia, has been shown to be predictive of worse perioperative and long-term outcomes in colorectal cancer. Reduced skeletal muscle radiodensity, as a measure of myosteatosis, has also been shown to be associated with worse survival outcomes. Those patients with sarcopenia are more likely to experience dose-reductions and dose-limiting toxicities during chemotherapy regimens. Therefore, skeletal muscle mass, as measured from cross-sectional imaging, may play a role in personalized dosing of chemotherapy. Furthermore, sarcopenia and myosteatosis have been shown to be associated with poor survival after surgical resection. Unfortunately, there is significant variation in methodology, which prevents comparison between many of the published studies. This thesis included a large cohort of stage I-III colorectal cancer patients treated with curative intent. All included patients had a preoperative CT scan and were seen at a cancer clinic in Northern Alberta. The primary aim was to quantify effects of sarcopenia and myosteatosis on long-term survival outcomes. A composite phenotype was defined to characterize patients as having sarcopenia alone, myosteatosis alone or concurrent sarcopenia and myosteatosis. The effect of adipose tissue on survival outcomes was also assessed. Skeletal muscle and adipose tissue mass and skeletal muscle radiodensity were also quantified from 2-year surveillance scans. The rates of change over time, along with presence of sarcopenia at follow-up were then analyzed for their effects on disease recurrence and survival after completion of disease surveillance. Using cohort specific cut-offs for sarcopenia, myosteatosis, visceral obesity and total adiposity, several conclusions were reached. Sarcopenia was highly predictive of worse overall, recurrence-free and cancer-specific survival. Myosteatosis was predictive of worse overall survival and cancer specific survival. Using a composite phenotype, concurrent presence of sarcopenia and myosteatosis was predictive of significantly worse overall, recurrence-free and cancer-specific survival in an adjusted model. These results were not affected by presence of absence of visceral obesity or elevated total adiposity. Furthermore, in those patients who survived to their 2-year surveillance scan without evidence of disease recurrence; changes in body composition parameters were quantified. On average, all patients were losing skeletal muscle mass and radiodensity, but gaining adipose tissue. Patients who were sarcopenic at the time of diagnosis, or those patients who lost muscle mass over time had significantly worse overall survival, while increased adiposity had a protective effect. The presence of both sarcopenia and muscle loss over time resulted in increased all-cause mortality. Overall, this thesis demonstrates that skeletal muscle mass and radiodensity are easily obtainable and quantifiable measurements that can act as reliable prognostic factors in stage I-III colorectal cancer patients treated with curative intent. Furthermore, their change over time may help predict those patients who will have worse survival outcomes following evidence of late disease recurrence. Identification of sarcopenia and ongoing muscle loss together, represents an increased risk profile, from which patients may benefit from extended disease surveillance. Furthermore, patients found to have sarcopenia at time of diagnosis would be appropriate candidates for an intervention to improve muscle mass and radiodensity, with hopes of improving long-term survival outcomes.

  • Subjects / Keywords
  • Graduation date
    Fall 2018
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3P55DZ7K
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.