Enhancing nutrition care in advanced pancreatic cancer: Defining clinical contributors to malnutrition progression and the impact of pancreatic enzyme replacement therapy

• Author / Creator

  Klassen, Pamela

• Introduction:
  Advanced pancreatic cancer (aPC) is an incurable disease in which palliative chemotherapy is offered to extend life. Most patients will experience cancer-associated malnutrition (CAM), marked by ongoing skeletal muscle loss and associated with poor survival and patient distress. CAM progression is unpredictable; some patients maintain muscle while others waste rapidly, and clinical factors associated with the latter are not well defined. In addition to reduced oral intake and altered metabolism, malabsorption due to pancreatic enzyme insufficiency (PEI) may contribute to both symptom burden and CAM progression. Pancreatic enzyme replacement therapy (PERT) is inconsistently applied to manage PEI in aPC, and PERT’s impacts on symptom burden and skeletal muscle loss have not been evaluated during chemotherapy. The overall aim of this research was to further collective understanding of risk factors for rapid muscle loss in people with aPC and contribute to the limited literature about the role of PERT as a component of nutrition therapy.
  Methods:
  A population-based data set was developed by linking multiple provincial health data sources from Alberta, Canada. For all patients who received standard chemotherapy for aPC in Alberta from 2013-2019, data included demographics, diagnosis, tumour specifics, cancer-directed treatments, tumour response, pharmaceutical use, dietitian contacts, routinely recorded weights, and overall survival were collected. Computed-tomography (CT)-defined measurements of skeletal muscle and adipose tissue were included for patients who had CT scans up to 12 weeks prior to chemotherapy (baseline CT) and 8-16 weeks after chemotherapy initiation (endpoint CT). The contributions of patient-, treatment-, and tumour-related factors to skeletal muscle and total adipose tissue change between baseline and endpoint were examined using multivariable linear regression. Prevalence and timing of dietitian involvement, PERT use and dose were described for patients alive at 60 days and compared according to year and treatment centre. In the subset with muscle measurements, muscle loss was defined as loss greater than measurement error and the relationship between PERT use, dose and skeletal muscle loss was explored using multivariable logistic regression.
  To understand the impact of PERT on symptoms, patients with aPC and suspected PEI were recruited to a prospective observational study from 2021-2023. PERT was prescribed as per usual care with ongoing support from an oncology dietitian. Symptom change on the PEI Questionnaire (PEI-Q) was compared between pre-PERT and first reassessment (at 1 or 3 months) using paired t-tests and exact McNemar’s tests.
  Results:
  504 patients received standard chemotherapy for aPC from 2013-2019; muscle and adipose measurements were available for 210. In the first 12 weeks of palliative chemotherapy, FOLFIRINOX regimen contributed to greater muscle loss while GEM/NAB regimen was associated with greater adipose loss. Tumour progression was a high-magnitude contributor to both tissue losses. Higher body mass index (BMI) was associated with greater loss of both tissues while male sex was associated only with greater muscle loss.
  Among patients alive at 60 days (n=435), the prevalence of PERT use increased provincially from 44% in 2013-2017 to 71% in 2018-2019. While prevalence of PERT use increased at both treatment centres, dose prescribed and estimated dose consumed increased at only at Centre A. Dietitian involvement increased to 65% in 2018-2019 compared to < 40% in 2013, with no difference between centres at any time point. Among 210 patients with muscle measurements, 81 initiated PERT within the first 6 weeks of chemotherapy. Estimated consumed dose < the cohort median (75 000 USP lipase units/day) was associated with 5.4-fold greater odds of muscle loss compared to higher doses.
  Twenty-three patients on dietitian-directed PERT completed the prospective study from 2021-2023. Abdominal symptoms were more prominent than bowel symptoms at baseline and abdominal domain score improved significantly from baseline to first reassessment after PERT initiation. There was a significant decrease in the prevalence of moderate/severe PEI between baseline and first reassessment.
  Conclusions:
  Tumour response, chemotherapy regimen, sex, BMI, PEI and PERT use/dose are factors that impact the progression of CAM in aPC. Dietitians are increasingly involved in aPC care and are well positioned to support PERT use as an integral component of symptom management and nutritional optimization. CAM progression is not inevitable, and early interventions such as PERT and intensive dietetic support should be trialed as part of comprehensive care to attenuate CAM and improve the patient experience.

• Subjects / Keywords

  • oncology nutrition
  • cancer cachexia
  • pancreatic exocrine insufficiency
  • pancreatic cancer

• Graduation date

  Fall 2024

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-qr6a-mg32

• License

  This thesis is made available by the University of Alberta Library 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.