From association to intervention: a pilot randomized controlled feeding trial to test the feasibility of a carbohydrate-restricted, high-fat diet in head and neck cancer patients undergoing radiotherapy

Taha, Hania Maher

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https://hdl.handle.net/2142/120422 Copy

Description

Title

From association to intervention: a pilot randomized controlled feeding trial to test the feasibility of a carbohydrate-restricted, high-fat diet in head and neck cancer patients undergoing radiotherapy

Author(s)

Taha, Hania Maher

Issue Date

2023-04-27

Director of Research (if dissertation) or Advisor (if thesis)

Arthur, Anna E

Doctoral Committee Chair(s)

Pan, Yuan-Xiang

Committee Member(s)

• Holscher, Hannah D.
• Miller, Michael

Department of Study

Food Science & Human Nutrition

Discipline

Food Science & Human Nutrition

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• head and neck cancer
• nutrition
• survival
• recurrence
• diet
• low carbohydrates
• high unsaturated fats
• randomized controlled trial
• pilot study
• association
• intervention
• feasibility
• clinical outcomes

Abstract

Low-carbohydrate, high-fat diets have been recently hypothesized to benefit outcomes in cancer patients. This has not yet been explored in head and neck cancer (HNC), an understudied cancer including tumors of the oral cavity, pharynx, and larynx, with a poor survival rate of 67%. The location of HNC and its treatment modalities often cause symptoms that might affect patients’ eating abilities, including difficulty swallowing or chewing, dry mouth, and pain. These symptoms often reduce patients’ oral and caloric intake, leading to malnutrition and/or sarcopenia. Malnutrition, sarcopenia, and symptom burden are associated with poor quality of life, response to therapy, and survival in adults diagnosed with HNC. After gastrointestinal cancers, malnutrition is the second most prevalent among HNC patients. About 30% of HNC patients are already malnourished prior to the start of oncologic treatment, while approximately 44-88% develop malnutrition after the completion of treatment. Sarcopenia is prevalent among 16-71% of HNC patients. The Academy of Nutrition and Dietetics Oncology Evidence-based Nutrition Practice Guideline for Adults recommends early and intensive nutritional intervention in adults with cancer to optimize treatment outcomes. Our previous observational studies showed that prior to initiating head and neck squamous cell carcinoma (HNSCC) treatment, a self-reported diet low in total carbohydrates, total sugar, and simple carbohydrates might have beneficial effects on the risk of all-cause mortality. Further, research demonstrated the ketogenic diet benefits in cancer patients, but the extremity of this diet makes adherence difficult. To date, there are limited guidelines for HNC medical nutritional therapy (MNT) beyond recommending adequate calorie and protein intake. Although several cancer centers provide nutritional services to cancer patients as a requirement to maintain their accreditation, beyond that, there are no standard of care guidelines. Nutrition intervention studies in HNC have mainly focused on providing oral liquid nutritional supplements like Ensure (© 2023 Abbott) and Boost (© 2023 Nestlé), nutritional counseling, and motivational interviewing during cancer treatment; however, none have focused on the diet macronutrient composition before or during treatment as part of MNT. Our long-term purpose of this research is to develop a supportive therapeutic diet with specific macronutrient composition for improving the quality of life and clinical outcomes in HNC patients. The overall objective of this dissertation was to further test the hypothesis that macronutrient composition consumption influences HNC outcomes. The first aim of this dissertation was to build on our team’s previous research and determine how intakes of various fat subtypes before cancer treatment are associated with recurrence and mortality in adults diagnosed with HNSCC. This was a secondary analysis longitudinal cohort study that involved 476 newly-diagnosed HNSCC patients recruited into the University of Michigan Head and Neck Specialized Program of Research Excellence (SPORE) study. Multivariable Cox Proportional Hazards models were used to determine the association between different fat subtypes and the risk of mortality and recurrence. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated for each tertile of fat subtypes compared with the lowest tertile. We adjusted for age, sex, smoking status, HPV status, tumor site, cancer stage, and total caloric intake. Findings suggest that a pretreatment high long-chain fatty acids (LCFAs) intake was associated with a reduced all-cause mortality risk (HR: 0.55; 95% CI: 0.34-0.91, P-trend: 0.02); a pre-treatment high unsaturated fatty acids intake was associated with a reduced all-cause mortality risk (HR: 0.62, 95% CI: 0.40-0.97, P-trend: 0.04) and HNSCC-specific mortality risk (HR: 0.51, 95% CI: 0.29-0.90, P-trend: 0.02); and high pretreatment intakes of omega-3 polyunsaturated fatty acids (ω3 PUFAs) (HR: 0.56; 95% CI: 0.35-0.91, P-trend: 0.02) and omega-6 (ω6 PUFAs) (HR: 0.57; 95% CI: 0.34-0.94, P-trend: 0.02) were significantly associated with a reduced all-cause mortality risk. No significant associations existed between other fat types and recurrence or mortality risk. The second aim of this dissertation was to determine the feasibility of implementing a carbohydrate-restricted, high-fat (CRHF) diet in newly-diagnosed HNC patients undergoing definitive radiotherapy (RT). This was a pilot, single-blinded, randomized controlled feeding trial that involved 13 newly-diagnosed HNC patients recruited from Augusta Victoria Hospital in East Jerusalem, Palestine. Participants were randomized to either the CRHF diet arm (N = 6) and received meals composed of ~30% carbohydrates, ~45% fats, and ~25% proteins; or to the Standard Diet (SD) arm (N = 7) and received meals composed of ~50-52% carbohydrates, ~30% fats, and ~18-20% proteins. Three meals per day were provided to all participants for 2 weeks before RT and 6-7 weeks during RT, with adequate calories (25 – 30 kcal/kg) estimated for weight maintenance. The final sample size included nine participants who completed all study activities. Feasibility outcomes included recruitment, retention, intervention adherence, acceptability, and absence of adverse events. The secondary outcomes were changes in weight and body composition. Kruskal Wallis Test was used to determine differences between the two arms. Findings revealed that the enrollment rate was 65%, and the retention rate was 69%. Two participants in the CRHF diet arm dropped out at the beginning of the study, and two participants in the SD arm discontinued intervention mid-study. Compliance to all meals was 67.9% (54.2% - 78.6%) for the CRHF diet arm and 81.8% (50.8% - 90.7%) for the SD arm. Participants reported satisfaction with meal quality. There were no adverse effects reported during the study period. There was no significant difference between the two arms in the diet feasibility. Participants with higher compliance to either diet had significantly less weight loss during RT than those with lower compliance (P=0.02). A non-significant but greater percent weight loss was observed in the CRHF diet arm compared to the SD arm. Conversely, the CHRF diet arm maintained more lean body mass and lost more fat mass compared to the SD arm. Lastly, Aim 3 of this dissertation aimed to report the preliminary effects of this pilot/feasibility randomized controlled trial (RCT) on HNC secondary outcomes, including nutritional status, body composition, symptom burden, and health-related quality of life (HRQOL). A per-protocol analysis was performed, including 4 participants in the CRHF arm and 5 in the SD arm. Potential differences within and between study arms were assessed. Outcomes were assessed at T0 (baseline), T1 (2 weeks), and T2 (1.5-2 months post-RT). Nutritional status was assessed using a patient-generated subjective global assessment (PG-SGA) tool; body composition was assessed using bioelectrical impedance (BIA); symptom burden was assessed using the Memorial Symptom Assessment Survey (MSAS); and HRQOL was assessed using EORTC QLQ-H&N43. Kruskal Wallis Test was used to compare between arms and Friedman’s Test was used to compare within arms. An alpha of < 0.05 was considered for significance. There were no significant differences between the study arms in nutritional status, body composition, symptom burden, or HRQOL. The HRQOL was significant for the CRHF diet arm across time-points. Maintenance in nutritional status was observed throughout the study for both study arms. At T2, 56% of participants were well-nourished, and 44% were moderately malnourished. None of the participants developed sarcopenia throughout the study period. Although the CRHF diet arm had lower means of phase angle and skeletal muscle mass index (SMMI) than the SD arm, it had a lower prevalence of malnutrition, fewer reported symptoms, and better HRQOL at all time-points. Nevertheless, at the end of the study, the average phase angle degree for both arms was > 5.0, and all participants maintained relatively low scores of symptom burden and HRQOL. In summary, the macronutrient composition of the diet before and during RT may affect HNC outcomes. Our longitudinal observational study suggests that HNC patients who consume a diet high in unsaturated fats before cancer treatment might have a reduced mortality risk. Due to the small sample size, our RCT could not detect significant differences between the CRHF diet and the SD. However, we conclude that both diets were feasible and that providing nutritious meals with oral nutrition supplements as needed to HNC patients before and during RT may have beneficial effects on HNC outcomes, including maintaining nutritional status and minimizing overall weight and muscle mass loss. This pilot RCT was the first step in determining if a CRHF diet is effective in HNC patients. These preliminary results and lessons learned can be used to develop an adequately powered efficacy trial to determine the best supportive MNT for HNC patients before and during RT.

Graduation Semester

2023-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Hania Maher Taha

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