The CRC-NORDIET study is designed to gain a better understanding of whether diet after diagnosis has impact on long-term outcomes, risk of recurrence and survival in patients with CRC. Due to lack of studies, CRC patients currently have no specific dietary
recommendations, other than the general recommendations for people who are not
diagnosed with cancer. Although observational studies suggest that diet after diagnosis may play a role, RCTs are urgently needed to confirm the potential of diet to improve outcomes in this patient population. Our study will therefore be of great importance for this group of patients.
The majority of the patients included in this work underwent nutritional assessments at a time point where cancer treatment was completed. Existing literature shows that
malnutrition is prevalent in CRC patients at the time of diagnosis, however, the high prevalence of malnutrition, FFM depletion and sarcopenia found in our population post-surgery, suggest that a significant proportion of these patients are still in need for nutritional intervention. Persistent nutritional problems may lead to continued loss of body weight and further deterioration of nutritional status, which may influence the further course of
survivorship. Although the cancer disease is cured and the patients are predicted good prognosis, decline in nutritional status may negatively impact quality of life, functional capacity and survival, as shown by Ravasco and coworkers who demonstrated that CRC patients who did not receive intensive nutritional counseling experienced decline in
nutritional status, quality of life and survival compared to the patients who received dietary counseling [45].
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Most of the studies demonstrating associations between malnutrition and sarcopenia, and clinical outcome measurements and survival in CRC patients have included high proportions of patients with locally advanced or metastatic disease. The current work provides new knowledge about the high prevalence of malnutrition and sarcopenia in a CRC population without metastatic cancer. The relationship regarding low FFM and sarcopenia and clinical outcomes and survival will be investigated in future analyses in the CRC-NORDIET study.
In the current work, we demonstrated that by using the PG-SGA categories, only half of the patients with FFM depletion and less than half of the patients with sarcopenia were
identified by this tool. Consequently, a great proportion of the patients would incorrectly be evaluated as “well nourished” if PG-SGA was used as the only assessment tool for nutritional assessment. Based on our findings, we recommend that body composition analysis should be performed in addition to the PG-SGA.
PG-SGA was developed to evaluate the patient in terms of anabolic or catabolic, with emphasis on recent changes in body weight. However, in the context of the increasing prevalence of overweight and obesity in cancer patients, and the support from studies demonstrating that lean mass depletion may be masked by weight increase and increased BMI, monitoring only body weight will exclude important information regarding body composition. For example, if the patient continues to gain weight in terms of fat at the expense of lean body mass, it may lead to increased risk of sarcopenic obesity with all the health risks associated. Although the literature is scarce in non-metastatic CRC patients, preliminary data suggest that sarcopenia is associated with reduced survival [57] , and hence, these individuals should be identified and monitored.
In clinical practice, access to sophisticated instruments such as DXA may be limited for this purpose. In the current work, it was demonstrated that use of BIA resulted in estimates of FFM that were comparable to DXA on group level when the most appropriate equations were used. Interestingly, our work demonstrated that use of the various equations resulted in significant different estimates of FFM, and moreover, that the two BIA devices gave significant differences in FFM estimates, when using the same equation. These findings imply that BIA devices should not be used interchangeably in the clinical setting.
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The results in paper 3 showed that the proportion of patients identified with low FFM according to the cutoff values by ESPEN, varied substantially depending on BIA device and equation used. Thus, some patients will not be correctly identified with low FFM as part of the malnutrition diagnosis if a suboptimal equation is used.
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5 C ONCLUSIONS
The present thesis concludes with the following:
The CRC-NORDIET study was developed and established in 2012. At the end of January 2018, 340 patients were enrolled in the study. It is estimated that the calculated sample size of 500 participants will be reached by the end of 2020. Of the 447 patients enrolled in the study so far, only 16 patients (5 %) have voluntary quitted. Based on the high retention rate in our study we suggest that the study design is conceived as feasible by the patients.
In our population with non-metastatic CRC patients, 69 % were evaluated as well nourished (PG-SGA A) and 31 % patients were categorized as malnourished (PG-SGA B). No patients were evaluated as severely malnourished (PG-SGA C). Based on BIA assessments, low FFM was identified in 29 % of the patients. Twenty-two percent were diagnosed with sarcopenia. Our findings indicate that a significant portion of the patients were in need for nutritional intervention although most of the patients had already completed their cancer treatment.
Despite that almost one third of the patients were found to have low FFM, PG-SGA did not identify these patients with sufficient sensitivity. The PG-SGA categorization classified only 50 % of the patients as malnourished (PG-SGA B). Moreover, only 64 % of the patients with low FFM were evaluated as muscle depleted by the physical examination in the PG-SGA.
Both BIA devices showed good agreement compared to the reference method DXA, when using the appropriate BIA equation. Hence, BIA may be a useful tool to identify patients with low FFM and should accompany PG-SGA in the nutritional assessment of CRC patients. It is however, important to note that selection of BIA device and BIA equation may result in significantly different estimates of FFM, and the same BIA device and equation should be used when assessments are repeated during follow-up of the patient.
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6 F UTURE PERSPECTIVES
Future analyses from the CRC study will examine the ability of the CRC-NORDIET intervention to improve nutritional status as well as to maintain or increase FFM. In cancer patients with metastatic disease, it is well established that the catabolic state favors an ongoing loss of skeletal muscle, a process that cannot be reversed by conventional nutrition care. In contrast, there is limited data concerning the ability of nutritional interventions to improve nutritional status and preserve or improve muscle mass in patients with localized cancer.
The dietary intervention in the CRC-NORDIET study was not specifically designed to achieve beneficial outcomes in terms of muscle mass. However, the dietary counseling aims to ensure adequate energy and protein intake, which is of importance to prevent weight loss and depletion of fat-free mass. Moreover, the recommended diet in the CRC-NORDIET targets a healthy body composition, including prevention of overweight and obesity. Future analyses from the CRC study will examine changes in fat-free mass assessed by BIA and DXA from baseline and during follow-up. Comparison of BIA and DXA at several time points will provide interesting information regarding the agreement between methods.
Although this work suggest that BIA should be applied in combination with PG-SGA to sufficiently identify patients with FFM depletion, it will be interesting to investigate whether the combination of PG-SGA and BIA will predict morbidity and mortality better than each method separately.
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