Comprehensive Nutritional Therapy To Improve The Clinical Outcome Of Patients With Head And Neck Cancer Who Receive Radiotherapy:A Randomized Controlled Study

Background:Patients who receive radiotherapy for head and neck malignancies are prone to malnutrition,which can cause many adverse effects.The aim of this randomized controlled study was to the confirm whether patients with head and neck cancer could benefit from comprehensive nutritional therapy including intensive,individualized nutritional dietary counseling,nutritional intervention and long-term follow-up,and whether it could effectively prevent patients'weight loss and malnutrition,improve their quality of life and reduce the incidence of complications during the course of radiotherapy.The results of the study should provide clinical evidence for reasonable and standardized comprehensive nutritional therapy for head and neck cancer patients.Methods:This was a single-center,single-blind,randomized controlled clinical study.The body weight of patients was used as the main outcome indicator to calculate the sample requirements in this study.The inclusion criteria were an age between 18 and 75 years old,either male or female,conscious,with no communication barriers,and able to answer the questionnaires for the study.All patients provided written informed consent and were willing to participate in this study.The exclusion criteria were uncontrolled or severe heart,liver,lung,or kidney disease;the use of a pacemaker;patients with pleural or peritoneal effusion;diabetics;patients who had received daily oral nutrition supplementation before enrollment;those who previously received radiotherapy;those participating in other clinical investigations;and those unwilling to participate in the study,or who agreed to participate in the study but refused to provide written informed consent.Patients who met these criteria who were diagnosed with head and neck malignancies and planned to undergo radiotherapy from March2017 to December 2018 in the Daping Hospital Radiotherapy Center of the Army Medical University were included.Patients were randomly divided into study and control groups.Each patient was numbered according to the sequence of enrollment,and subjects were divided into groups using a random number table?central random method?produced by the Department of Epidemiology,College of Public Health,Zhengzhou University.A third party was informed of the enrollment number by phone after the initial screening of patients,and they provided the random number and grouping to us.The patients in the study group were given individualized and professional nutritional dietary counseling,as well as oral nutritional supplements?ONS?with an intervention duration of 12 weeks.The ONS was a 500 ml total nutrition formula?containing 500 kcal energy,21 g protein,and corresponding amounts of other nutrients?given daily.The patients in the control group were given routine nutrition education by the clinician on the basis of anti-tumor treatment.Both groups of patients provided written informed consent.The relationships between the various demographic and cancer characteristics and the nutritional status were investigated using the medical history and by conversations with the patients.The case report form was completed on site,and the data were compiled and entered into the Epidata system for archiving.The duration of radiation therapy for head and neck cancer patients is generally 6-8 weeks.When the patient was first enrolled in the study,the baseline data were recorded,and then the patient was followed up once a week for 12 weeks.After the intervention finished,each patient was followed up every3 months for 1 year.The survey contents at each follow-up mainly included:a dietary survey,anthropometric measurements?including the height,body weight,body mass index?BMI?,mid-arm circumference?MAC,non-dominant arm?,mid-arm muscle circumference?MAMC?,triceps skinfold thickness?TSF,non-dominant arm?,calf circumference?CC,left calf?,and handgrip strength?HGS,non-dominant hand??,patient-generated subjective global assessment?PG-SGA?scores,hematological indices,Karnofsky performance scores?KPS?,self-rating depression scale,and symptoms of oral mucositis.The quality of life for all participating patients was measured using the European Organization for Research and Treatment of Cancer?EORTC?QLQ-C30.The changes in body weight and nutritional status of the two groups of patients were recorded at the end of the 4^th and 8^th weeks?at the end?of radiotherapy during the nutritional intervention period,and 6 months after the end of the intervention.The quality of life,anthropometric measurements and other related indicators of the two groups of patients were compared using SPSS 21.0.Results:1.In this study,202 head and neck cancer receiving radiotherapy were continuously enrolled.Thirty patients were excluded?13 of them had a history of diabetes,8 patients had received radiotherapy multiple times,6 patients refused to participate,1 patient had a cardiac pacemaker,1 patient was younger than 18 years old and 1 patient was older than 75 years?,so a total of 172 cases were enrolled.Eleven patients were dropped out of the study because the dates of them were not collected before the first follow-up time?8 of them refused to participate in the follow-up,2 patients were found to have diabetes,and 1 patient suffered from an accidental fall and disability required the treatment to be stopped?,making the loss to follow-up rate 6.4%.Therefore,161 patients?84 in the intervention group,77 controls?were included in the final analysis.There were no significant differences in the baseline demographic information or cancer characteristics between the two groups?P>0.05?.The average age of the study group was 53.13±10.18 years old,including 58?69.0%?males and26 females?31.0%?.The average age of the control group was 51.43±10.51 years old,including 56 males?72.7%?and 21 females?27.3%?.It was found that the energy and protein intake in the independent diet of patients in both groups decreased significantly during radiotherapy based on an analysis of the dietary survey.There were no significant differences in energy and protein intake between the control and study groups at the same time points.The actual energy and protein intake of the study group were higher than in the control group because of the supplemental 500 kcal/d given per day in addition to the patient's independent diet.2.The body weight of the patients in both groups decreased during and after radiotherapy.The body weight loss at the end of the 4th and the 8th weeks and at six months compared with the baseline in the study group were 3.66±3.21%,6.93±5.17%and 7.79±5.42%,which were all lower than those in the control group?4.43±3.25%,7.75±5.40%and 8.68±6.80%?.In addition,the weights of the study group at the end of the 4th?62.06±10.02 kg?and 8th?61.24±9.27kg?weeks and at six months after the intervention?60.29±9.01kg?were all better than those of the control group at the same time points?58.13±8.62 kg,57.05±9.86 kg and55.94±8.71 kg?,and the differences were statistically significant?F=2.642,P=0.009;F=2.730,P=0.007 and F=3.012,P=0.003?.The results showed that although the body weight of patients in both groups decreased during radiotherapy,the degree of weight loss in the study group was significantly lower than in the control group,indicating that the nutritional intervention led to better weight maintenance in the patients.3.After a repeated measures of variance analysis,it was noted that there were significant differences among the BMI?F=5.287,P=0.023?,TSF?F=4.042,P=0.047?and HSG?F=4.052,P=0.047?between the study group and the control group,and the indices of the study group were significantly better than those in the control group after comprehensive nutritional therapy at the end of the 4^th and 8^th weeks of radiotherapy and at six months after radiotherapy.In the study group,the CC were significantly better than those in the control group at the end of the 4^th?F=2.112,P=0.036?and 8^th?F=2.276,P=0.024?weeks during radiotherapy.The anthropometry measurements of the study group were also higher than those of the control group.4.According to the PG-SGA scores,there were no differences in the nutritional status between the study group?2.90±3.11?and the control group?2.51±2.34?at baseline?P=0.363?.The data showed that some degree of malnutrition occured during radiotherapy,especially at the end of radiotherapy(8^th week)with the highest PG-SGA score being noted at that time point.However,the PG-SGA scores of the study group were significantly lower than the scroes of the control group?F=2.244,P=0.026?,indicating that the nutritional status in the study patients was better than in the control group.The PG-SGA scores of the study group?8.10±3.25;3.11±2.19?were also significantly lower than those in the control group?9.27±3.79;3.90±2.11?at the end of the 4^th week during radiotherapy and at six months after radiotherapy,demonstrating that the nutritional status of patients in the study group was significantly better than that in the control group.5.The depression scores?22.83±3.75?of the study group at six months after radiotherapy were significantly lower than those in the control group?24.50±5.20;P=0.032?.6.Based on a comprehensive analysis of multiple dimensions of the patients'quality of life,comprehensive nutritional therapy was found to have a significant positive effect on the overall health of patients?F=7.003,P=0.009?.Although the overall health status of patients decreased during radiotherapy,the scores of patients in the study group at the 4^th week?78.92±11.07?and 8^th week?76.77±12.49?during radiotherapy were higher than those in the control group?74.78±13.40 and 71.97±15.17,respectively?,and the differences were statistically significant?F=2.128,P=0.035 and F=2.169,P=0.032?.The same was true for the pain score?F=8.700,P=0.004?and the loss of appetite score?F=5.954,P=0.016?.7.A repeated measures analysis of variance was performed to analyze the hematological indices of both groups at each time point(4^th week and 8^th week during radiotherapy,and at six months after radiotherapy).The results showed that among the eight hematological indices examined in this study,there were no significant differences between the groups,and there was no interaction between the intervention factors and time effects(P_group*time>0.05).However,there were statistically significant differences associated with time factors for indices such as the total protein?F=3.819,P=0.028?,red blood cell count?F=8.115,P=0.000?,TLC?F=12.409,P=0.001?,hemoglobin level?F=5.209,P=0.005?,and platelet count?F=3.870,P=0.015?.As expected,this confirmed that radiotherapy affected the hematological indices,and the nutritional intervention did not significantly affect these indices.8.There was no interaction between the intervention-related factors and time effects of the KPS scores(F_group*time=2.060,P_group*time=0.105),and there were no statistically significant differences in the main effects of intervention factors?F=0.074,P=0.786?.However,there were statistically significant differences in the main effects of time factors?F=51.725,P=0.000?.However,it found that the overall functional status of the patients in the study group was better than that in the control group during the first six months after the nutritional treatment.9.Interventional factors and time effects did not interact with the development of oral mucositis?F=0.449,P=0.671?,and there were no statistically significant differences in the main effects of intervention factors?F=0.089,P=0.765?at the same time points,but the main effect of the time factor was significantly different?F=266.779,P=0.000?,which indicates that there were significant differences in the severity of oral mucositis between the two groups,although both groups showed improvements in their oral mucositis over time and after the end of radiotherapy.It also showed that the oral mucositis in both groups was the most severe at the end of radiotherapy?8 weeks?.Conclusions:1.Patients with head and neck cancer are prone to malnutrition during radiotherapy.For the patients in this study,comprehensive nutritional therapy improved the patients'body weight,as well as their PG-SGA score,quality of life,physical measurements and the depression score.2.Due to oral mucositis,dysphagia and loss of appetite,the energy and protein intake in the independent diet of patients were significantly reduced during radiotherapy.The nutritional intervention did not have an impact on the development of oral mucositis during radiotherapy in the study.More attention should be focused on the occurrence and treatment of this problem in the clinic.3.Long-term and close follow-up is necessary for head and neck cancer patients during radiotherapy,and should include professional nutritional consultations and nutritional assessments,so that any nutritional problems can be identified in a timely manner.Identifying such problems earlier and as part of routine follow-up will make it more convenient for patients to receive effective and reasonable comprehensive nutritional therapy,leading to better outcomes.