9:00 am - 10:00 am
ECHA 1-134, 11405 87 Ave NW, Edmonton Alberta
Event details: A graduate exam seminar is a presentation of the student’s final research project for their degree.
This is an ALES PhD Final Exam Seminar by Pamela Klassen. This seminar is open to the general public to attend.
Zoom Link: https://ualberta-ca.zoom.us/j/9104309836?omn=95287570041
Thesis Topic: Enhancing nutrition care in advanced pancreatic cancer: Defining clinical contributors to
malnutrition progression and the impact of pancreatic enzyme replacement therapy
PhD with Dr. Vera Mazurak
Abstract:
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 of these. 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 should be implemented as part of comprehensive care to
attenuate CAM and improve the patient experience
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