Unravelling energy expenditure and body composition in cancer patients during and after initial treatment
Authors:   , Van Soom Timia 
Published: July 2024

This dissertation aimed to unravel how the presence of a tumor and its treatment affect resting energy expenditure (REE) and body composition in patients with cancer, more specifically in patients with and survivors of breast cancer. Secondly, we intent to contribute to the developing technologies in calorimetry assessments to facilitate metabolic research, and to promote the clinical application of indirect calorimetry (IC). By understanding the resting energy requirements, individual rehabilitation strategies based accurate measures of REE can be developed to improve the energy balance and prevent deterioration of body composition. Chapter 1 of this thesis includes a general introduction on the burden of breast cancer, explains more about metabolic reprogramming inherent to the disease, and clarifies energy metabolism and energy expenditure in health and disease. Furthermore, different methods for conducting calorimetric assessments are briefly discussed. The introduction concludes with the general aims and outline of this thesis. Chapter 2 reviewed the literature to examine the current knowledge on the impact of cancer and chemotherapy on REE and body composition in various cancer types. The results revealed a large variety in REE, with significant changes during treatment presenting a U-shaped curve. Initial tumor burden and the metabolic impact of chemotherapy were postulated to participate to the heterogeneity of REE. Body composition changed concurrent with the energetic requirements. REE predicted by the Harris- Benedict equation (HBEq) seems to underestimate REE by IC, addressing the need for adequate measures of REE. This literature review study disclosed many tumor types, with different methodologies concerning the calorimetric assessments. Lack of metabolic studies in specific cancer types and during different stages of the disease and treatment, were identified as main gap in literature. Inaccessibility to appropriate measurement tools might be one reason for the lack of metabolic studies. In literature, indirect calorimetry is often the method of choice for conducting metabolic assessments. Current practices, however, are cumbersome, and require expensive equipment and specialized staff, which limit its use. New developments in technology can lead to more user-friendly devices which can promote its application. In Chapter 3, the validity of a new basic respiratory room to measure energy expenditure was examined. A comparison study was conducted to investigate if the room was 1) capable to equally measure energy expenditure under the same resting conditions as with the standard assessment by ventilated hood, and 2) to examine its ability to detect minute changes in activity. The results of this study led to a safe and valid implementation of the room as assessment modality in the studies discussed in chapter 4. Chapter 4 presents the findings on REE and body composition in patients with breast cancer in the tumor-bearing state, at mid-treatment, and in 1-, 3, and 5-year survival after treatment ending. To test the hypothesis that alterations are present, the results of patients and survivors were compared with a matched healthy control group. The results in section 4.1 reveal that women who are diagnosed with breast cancer experience higher REE, suggested to be caused by tumor burden with C-reactive protein and tumor size as possible predictors. Hypermetabolism is present in 50% of the patients, a novelty that can be explained by timing of our assessments. After 12 sessions of paclitaxel chemotherapy, REE remained elevated while fat-free mass decreased. We suggest that this decline results from muscle wasting, involving catabolic processes that uplift REE. Moreover, fatigue deteriorated during treatment. The higher fatigue levels correlated with measures of energy expenditure, which is a new finding that 15 can entail a possible clinical meaning. The results discussed in section 4.2 show a duality between absolute measures of REE and REE adjusted by fat-free mass. From our findings, we emphasize the importance of body composition and promote REE adjusted by fat-free mass when interpreting energy requirements. The small increase in REE found, albeit within normality ranges from healthy controls, is suggested to result from inter-individual varieties in impact of metabolic dysfunctions on REE. The latter dysfunctions, related to obesity and high adiposity body phenotypes, were present in 60% of the survivors. The interaction between survival and fat mass on REE is, in this light, an intriguing result. This dissertation ends with a final Chapter 5, containing a general discussion. From our studies, we conclude that REE is elevated in the breast cancer-bearing state and remains elevated at mid-treatment, although its etiology might be different. We suggest that tumor burden initially uplifts REE, with Creactive protein, along with tumor size, as predictor. The specific energetic demand of breast cancer was graded as ‘low’. After chemotherapy, loss of fat-free mass was most notable, suggested to be caused by muscle wasting which increases REE. Concordant with the loss of fat-free mass, fatigue worsened as well. Fatigue correlated with measures of energy expenditure which may carry a clinical meaning that needs to be further studied. Furthermore, breast cancer survivors experience normal levels of REE during de 5-year survival period after treatment, but can be metabolically compromised due to the presence of metabolic dysfunctions (dyslipidemia (hypercholesterolemia and hypertriglyceridemia) or medication, hypertension (or medication), insulin resistance (or medication), increased adiposity (FM>30% of total BW, with BMI>25.0 kg/m2), or increased blood glucose). Failing to adapt nutritional intake with energy requirements leads to changes in body weight, that is, in case of breast cancer, mostly experienced as weight gain predominated by fat mass. Current dietary strategies are mostly based on predictions of REE (HBEq), although they underestimate the true energy requirements as measured by IC. With our findings on the respiratory room, we intend to promote its use in metabolic research, and later on in clinical practice. Our results provide scientific basis for further research on specific nutritional requirements during and in the aftercare of breast cancer. We promote that supportive strategies should be based on lifestyle interventions, balancing energy intake and energy expenditure, with the ultimate goal to support body composition and prevent metabolic deterioration.