A prospective randomized controlled trial evaluating a postoperative nutritional intervention in patients with oral cancer
This randomized clinical trial was approved by the local ethics committee Ethik- Kommission an der medizinischen Fakultät der RWTH Aachen (registration number: EK 253/18) on 18/11/2018 and registered in the German Register of DRKS clinical trials (registration number: DRKS00016020, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016020) on 22/11/2018. The authors assure that the work described has been performed in accordance with the World Medical Association’s Code of Ethics (Declaration of Helsinki) for human experiments. Figure 1 illustrates the education pathway.
After institutional approval and informed consents, a total of 46 patients with oral cancer from the Oral and Maxillofacial Surgery Clinic were randomized into two groups. One group received additional postoperative nutritional support in the form of nutritional supplementation and care by a nutritional assistant. The second group received only standard nutrition and regular checkups.
The exclusion criteria for this study were: recurrences or secondary tumors of the oral cavity, cancer of the head and neck without oral involvement, previous radiotherapy in the operating room, chemotherapy in the last 12 months, manifest deficiency diseases or having a influence on the quality and/or quantity of food ingested, massive cognitive deficits and age
66 laboratory parameters in the areas of hematology, coagulation, clinical chemistry, vitamins, trace elements, iron metabolism and thyroid were determined in both groups at five time points ( preoperative, one day postoperative, before discharge, 3 and 6 months after surgery). Weight and BMI were collected at four time points (preoperative, one day postoperative, before discharge, 3 and 6 months postoperative). To assess postoperative discomfort and patient-specific aspects, both groups documented comparable questionnaires before discharge and after three and six months postoperatively.
Intervention and study process
After informing the patient and excluding contraindications, preoperative blood samples and weight determinations were performed in both study groups. Intervention patients also received initial nutritional counseling.
After surgical removal of the tumor with simultaneous coverage of the microvascular defect, the intervention patients were seen by a nutritionist in the intensive care unit on the first postoperative day. Food intake was controlled and optimized immediately postoperatively via the gastric tube or if it was already planned preoperatively via a PEG system. Parenteral nutrition, vitamins and trace elements were supplemented as needed. Depending on swelling status, swallowing function, and type and extent of resection, the diet was oralized as soon as possible. Feeding of patients in the control group by gastric tube or PEG was monitored only by intensive care unit staff. There was no additional vitamin or trace mineral supplementation and no additional professional advice from a nutritionist.
Intervention patients continued to receive 30-minute professional nutritional counseling and BIA measurement on four occasions (preoperative, before discharge, 3 and 6 months after surgery). Dietitians worked with patients to create a nutrition plan and educated them about diets high in protein and fiber. They also motivated the patients to increase their daily physical activity.
Blood samples were taken to determine parameters and questionnaires were distributed to assess postoperative complaints and patient-specific aspects in both groups at the time points before discharge and three and six months postoperatively.
From the first postoperative day, the patients of the intervention received a supplementary diet rich in fiber and protein and, depending on laboratory parameters, individual micronutrient supplementation.
The self-created questionnaires are used to assess baseline characteristics, postoperative complaints and nutritional aspects, as well as to evaluate patient nutritional counseling. They are not validated and have not been used in any other study before. However, the questionnaires were based on nutritional scores (Subjective Global Assessment (SGA), Nutritional Risk Core (NRS 2000)) and questions from other studies.2,11,12,13. Responses to patient-specific aspects were scored on a scale of 0 (low) to 10 (high).
In addition to the standard arranged food, the intervention patients received 1 bottle of the protein-containing diet (Fortimel Extra 200 ml, high-energy protein rich) per day. It is a high-calorie, fiber-containing, balanced drinkable food with an energy content of 400 kcal, 18 g of protein and 5 g of soluble fibre. The replacement is made during the period of hospitalization. In the post-hospitalization period, the prescription was made for reduced levels of protein and albumin. If there was a lack of micronutrients, substitution was made with multivitamin preparations A–Z from Doppelherz (0-1-0), Decristol 20,000 1 × week, vitamin B12 1000 μg (0-1-0) , zinc tablets 40 mg (1–0-0), calcium tablets 1000 mg (0–1-0) and/or iron tablets 100 mg (0-1-0). Vitamin and trace element supplementation was based on laboratory values. During the inpatient stay, intake was monitored by study investigators, while supplementation in the post-hospitalization period was determined by questionnaires.
Laboratory and BIA measurements were defined as primary endpoints. Secondary endpoints were set as questionnaire results on postoperative discomfort and patient-specific aspects.
The existing literature on postoperative nutritional intervention in patients with head and neck cancer was reviewed to derive a sensitive sample size range. The case size was set at 50 (25/25) patients and is comparable to similar prospective randomized studies on the subject14,15,16,17.
The statistical program G*Power (Heinrich Heine University, Düsseldorf, Germany) was used for the calculation of the sample. With an alpha value of 0.05 (two-sided) and a statistical power of 80%, there was a required sample size of 44 patients (22/22) to conduct this study in order to reject the null hypothesis regarding the effect of additional nutritional intervention. power of 80% and a confidence interval of 95%.
The inclusion and exclusion criteria chosen allowed the constitution of homogeneous study groups. Comparable studies did not distinguish between primary tumors and recurrences/secondary tumors and included all subgroups of patients with head and neck tumors without subgroup analysis14,15,16,17.
The distribution of the groups was made by block randomization. Study patients whose initial surgical treatments occurred on a Monday or Tuesday were included in the control group. Study patients whose operations took place on a Wednesday, Thursday or Friday were included in the intervention group. Patients did not know which group they would be assigned to at the time of randomization.
Data processing and statistics
Statistical evaluation and graph creation were performed using GraphPad Prism version 9.0.0 for Windows, GraphPad Software, San Diego, CA, USA, www.graphpad.com. The normality of the data was checked using the D’Agostino-Pearson normality test.
For statistical analysis between the two groups, two-tailed t-test was used for normally distributed values and Mann-Whitney test was used for non-parametric distributed values. For within-group analysis, the one-tailed t-test was performed for normally distributed values and the Mann-Whitney test for nonparametric distributed values. The analysis of nominal distributions was performed using Fisher’s exact test for low values and using the Chi-Square test for higher values.
A p-a value ≤ 0.05 was set as the significance level. Mean values ± standard deviations were determined for all data.