The effect of quantitative goal exercise combined with whole process refined nutrition management on the nutritional status and quality of life of head and neck cancer patients undergoing radiotherapy: an open-label, randomized, controlled trial

Abstract

Objective

To explore the clinical effect of a combined intervention comprising Quantitative Goal Exercise (QGE) and Whole-Process Refined Nutrition Management (WP-RNM) on patients with head and neck cancer undergoing radiotherapy, and to provide a basis for improving the nutritional status of these patients.

Methods

A total of 111 patients with head and neck cancer receiving radiotherapy at the First Affiliated Hospital of Air Force Medical University from September 2023 to September 2024 were selected and randomly divided into an observation group (n = 54) and a control group (n = 57). The control group received routine care, which included nutritional management, dietary guidance, health education, and conventional physiological and psychological interventions based on body weight calculations to maintain hydroelectrolyte and acid-base balance. The observation group received the combined QGE and WP-RNM intervention in addition to routine care. The QGE component consisted of a 6-week personalized program involving aerobic exercise and resistance training for limbs, prescribed as moderate-to-low intensity home-based walking sessions five times per week for at least 15 minutes each. The WP-RNM involved comprehensive nutritional screening, individualized dietary plans, and ongoing monitoring. Primary and secondary outcome measures included Body Mass Index (BMI), Patient-Generated Subjective Global Assessment (PG-SGA) score, Onodera’s Prognostic Nutritional Index (OPNI), total protein, albumin, hemoglobin, mid-upper arm circumference, triceps skinfold thickness, handgrip strength, calf circumference, and quality of life (QOL-C30).

Results

Compared to the control group, the observation group demonstrated a significantly smaller reduction in BMI at 2, 4, and 6 weeks of intervention (p < 0.001). The observation group also showed significantly greater improvement in PG-SGA scores at 3 and 5 weeks (both p < 0.001), indicating better nutritional status. Regarding objective nutritional indicators, the observation group maintained higher levels of hemoglobin (at 5 weeks, p = 0.026), total protein (at 5 weeks, p = 0.019), and albumin (at 3 weeks, p = 0.018), and experienced a slower deterioration in the OPNI (at 3 weeks, p < 0.001; at 1 month, p = 0.015). Furthermore, the observation group showed significantly greater improvement in multiple quality of life domains, including physical, role, and emotional functioning, overall health status, and symptoms such as fatigue, nausea, vomiting, and pain (all p < 0.05).

Conclusion

The integration of Quantitative Goal Exercise with Whole-Process Refined Nutrition Management alongside routine care effectively stabilized body weight, improved nutritional status, maintained objective nutritional parameters, and enhanced the quality of life in patients with head and neck cancer undergoing radiotherapy. This combined intervention represents a promising supportive care strategy worthy of clinical application.

Trial registration

This·trial was registered at ClincalTrials.gov(ChiCTR2300071214) on May 8, 2023.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13014-026-02823-y.

Introduction

Head and neck cancer (HNC) ranks as the sixth most common malignancy worldwide, with approximately 650,000 new cases and 350,000 cancer-related deaths annually, and a 5-year survival rate below 50% [1], [2]. Over 90% of these cases are classified as head and neck squamous cell carcinoma (HNSCC) [3]. China bears a substantial burden of HNC, with an annual incidence of approximately 15.34 per 100,000 individuals, accounting for about 10% of all malignant tumors in the country [1]. Current treatment strategies for HNC are determined by TNM staging and primary tumor site, and include surgery, radiotherapy (RT), chemotherapy (CT), as well as multimodal approaches incorporating targeted therapy and immunotherapy. Radiotherapy remains a cornerstone in the management of head and neck malignancies [4]. In recent years, advances in precision radiotherapy have significantly improved clinical outcomes; however, treatment-related toxicities-such as nausea, vomiting, radiation-induced oral mucositis, pain, and malnutrition-remain inadequately controlled, profoundly impairing patients’ quality of life and psychological well-being [5].

Patients with HNC undergoing RT or chemoradiotherapy (CRT) frequently experience severe nutrition-impacting symptoms and treatment-related toxicities, including trismus, xerostomia, dysphagia, and odynophagia, which adversely affect oral intake [6]. These complications could lead to unintentional weight loss and malnutrition [7]. The prevalence of malnutrition progressively increases throughout the course of radiotherapy, reaching 78% to 100% by the end of treatment [8]. Malnutrition negatively impacts the efficacy and response to radiotherapy in patients with malignancies by reducing tumor radiosensitivity, compromising the accuracy of patient positioning during RT, exacerbating radiation-induced adverse effects, decreasing treatment tolerance, prolonging overall hospitalization duration, and impairing the function of tissues and organs—thereby diminishing therapeutic outcomes and quality of life (QOL) [9].

Consequently, adequate nutritional support during RT or CRT is critical for maintaining nutritional status, QOL, immune function, and physical performance, as well as for reducing the risks of unplanned hospitalizations and mortality [10]. In China, modern clinical nutrition management has advanced significantly, and models of nutritional support continue to evolve. However, in clinical practice, nutritional support for patients identified as being at nutritional risk remains insufficient. Key challenges include delayed initiation of nutritional intervention, reliance on a single route of nutritional support, incomplete assessment metrics, and a lack of dynamic, continuous, and comprehensive nutritional care throughout the treatment trajectory. Therefore, implementing scientifically sound and individualized clinical nutritional interventions is essential to improve patients nutritional status, enhance immune function, and ultimately optimize quality of life.

Quantitative goal exercise (QGE) refers to a structured intervention that prescribes planned physical activity to accelerate recovery. Existing evidence indicates that QGE significantly improves nutritional status and quality of life (QOL) in patients following lung cancer surgery [11] and esophageal cancer surgery [12]. Moreover, physical activity has been shown to exert a positive impact on survival outcomes in patients with breast, colorectal, and prostate cancers, reducing cancer-specific mortality risk by 26% to 69% [13].

Whole-process refined nutrition management (WP-RNM) is an individualized approach that formulates precise dietary plans based on the patient’s subjective nutritional status to ensure balanced nutrient intake, thereby promoting recovery and enhancing QOL [14]. To the best of our knowledge, there are limited studies investigating the combined application of QGE and WP-RNM in nutritional interventions for patients with head and neck cancer undergoing radiotherapy.

Therefore, this study conducts a prospective clinical trial to evaluate the efficacy of integrating QGE with WP-RNM in improving nutritional status among patients with head and neck cancer receiving CRT.

Materials and methods

Clinical data

This study was an open-label, randomized (1:1) controlled trial. A total of 111 patients with head and neck cancer scheduled to receive radiotherapy at the Department of Radiation Oncology between October 2023 and March 2024 were enrolled. Using a random number table, patients were assigned to either the intervention group (n = 54) or the control group (n = 57).

The study protocol was approved by the Institutional Ethics Committee (Approval No.: KY20222067-F-1), in accordance with the Declaration of Helsinki.and registered at the Chinese Clinical Trial Registry (Registration No.: ChiCTR2300071214; Registration date: May 8, 2023). Written informed consent was obtained from all participants prior to screening for study eligibility.

Selection of study participants

Participants were screened using predefined inclusion and exclusion criteria. Inclusion criteria were as follows: Histologically confirmed primary head and neck squamous cell carcinoma (HNSCC) originating from the oral cavity, oropharynx, hypopharynx, larynx, or cervical lymph nodes; Age ≥ 18 years; Eligible for CRT with tumor stage III–IV; Full consciousness and normal mental status; Provision of written informed consent.

Exclusion criteria included: BMI < 18.5 kg/m²; History of recurrent or metastatic head and neck cancer; Presence of severe infections, endocrine disorders, cardiopulmonary or cerebrovascular diseases, or other concurrent malignancies; Contraindications to enteral nutrition or parenteral nutrition (PN); Diagnosed psychiatric illness or cognitive impairment that would impede cooperation with the intervention.

Intervention and randomization

Patients meeting the eligibility criteria were randomly assigned in a 1:1 ratio to either the intervention group or the control group. Block randomization was performed with block sizes predetermined by the statistician to ensure balanced allocation within each block. Opaque, sequentially numbered randomization envelopes—indicating group assignment and stratification factors—were prepared by the statistician and opened only after patient enrollment and provision of written informed consent. Each participant was assigned a unique study identification number maintained throughout the trial.

Control group: Patients received standard care, which included nutritional management, dietary counseling, health education, and routine physiological and psychological support delivered by physicians and nurses before initiating radiotherapy. Energy requirements were calculated based on body weight (kcal/kg), and interventions aimed to maintain fluid, electrolyte, and acid–base balance.

Intervention group: In addition to standard care, patients received a combined intervention of QGE and WP-RNM.

QGE intervention components

The attending physician and primary nurse collaborated with the patient and their family to develop an individualized QGE plan based on disease status and radiotherapy progress. After completion of radiotherapy, nurses provided detailed education on the rationale and specific content of early rehabilitation exercise post-chemotherapy. Prior to intervention initiation, a comprehensive physical assessment was conducted, followed by joint discussion with the patient and family to establish a personalized exercise prescription specifying daily quantitative targets. The purpose and components of QGE were clearly explained. Breathing exercises: Patients were instructed in diaphragmatic breathing—slow abdominal expansion during nasal inhalation, followed by a 5-second breath hold and slow exhalation. One set comprised 40 repetitions, performed 3 times per day. Physical exercise: A 6-week QGE program combining aerobic and resistance training was prescribed. Aerobic activities included walking, jogging, cycling, or aerobics. Patients performed moderate-intensity home-based walking at 60–80% of their maximum heart rate, at least 15 minutes per session, 5 days per week. Exercise prescriptions were individually tailored through team discussion based on patient tolerance and functional capacity.

WP-RNM intervention components

A multidisciplinary WP-RNM team comprising a registered dietitian, attending physician, and responsible nurse developed individualized nutrition plans based on clinical status and dietary intake. Comprehensive data—including demographic information, medical history, dietary intake, nutritional and biochemical markers, recent weight changes, symptom burden, and functional status—were collected upon admission. Patient-reported outcomes were captured via a self-assessment questionnaire, while clinician assessments incorporated metabolic stress level, age, and physical examination findings. These inputs informed the scored Patient-Generated Subjective Global Assessment (PG-SGA) [15] to classify nutritional status. Prior to implementation, the clinical significance and procedural details of WP-RNM were thoroughly explained to patients and families to ensure cooperation. Dietary plans were dynamically adjusted based on nutritional assessments conducted before and during CRT, optimizing food combinations and macronutrient ratios to achieve balanced intake. Nutritional intake was continuously monitored throughout treatment. Patients were encouraged and guided to consume nutrient-dense foods supportive of recovery, with strategies employed to enhance adherence. After discharge, attending physicians conducted regular outpatient follow-ups over a 3-month period to monitor nutritional status and provide timely, individualized dietary adjustments. The principal investigator (HA) reinforced adherence through scheduled telephone and WeChat contacts.

All outcome data were collected at baseline (prior to the first radiotherapy session) and at the final trial endpoint (Tend-Trial), defined as one month after completion of the intervention. Safety monitoring included documentation of all adverse events occurring during the study period.

Sample size calculation

All efficacy analyses were conducted according to both the intention-to-treat (ITT) and per-protocol (PP) principles. Data were entered using EpiData 3.1 with a dual-entry and double-check procedure to ensure accuracy. Statistical analyses were performed using SPSS version 24.0. Continuous variables following a normal distribution were presented as mean ± standard deviation (SD) and compared between groups using the independent-samples t-test. Non-normally distributed continuous variables were expressed as median (interquartile range) and analyzed using the Mann–Whitney U test (Wilcoxon rank-sum test). Categorical variables were reported as frequencies or percentages and compared using the chi-square test. A two-sided significance level of α = 0.05 was used for all statistical tests.

Sample size estimation was performed using PASS 15.0 software. Assuming a two-sided α of 0.05, statistical power (1 – β) of 80%, and equal allocation between the two groups, the primary outcome was defined as the change in anthropometric measures—specifically BMI—among patients undergoing head and neck radiotherapy. Based on pilot data and published literature, and accounting for two planned interim analyses (including the final analysis) with an O’Brien–Fleming alpha-spending function, the required sample size was calculated to be 49 participants per group. Anticipating a dropout rate of approximately 10%, the total target enrollment was set at 111 patients (54 in one group and 57 in the other). The actual enrollment of 111 participants therefore met the pre-specified statistical requirements.

Data collection and outcome measures

Data on histopathological diagnosis, cancer staging, and treatment regimens were extracted from medical records. The primary outcome was nutritional status assessed by BMI, a widely accepted international indicator for evaluating body weight relative to height and overall health status, calculated as:Secondary outcomes included the scored PG-SGA, serum total protein, serum albumin, and the Onodera’s Prognostic Nutritional Index (PNI). Data collection procedures encompassed face-to-face interviews, anthropometric measurements, and blood sampling at designated time points throughout the study.

Sociodemographic Characteristics and anthropometric assessment

Face-to-face interviews were conducted using a structured questionnaire to assess sociodemographic and socioeconomic status, dietary patterns, and lifestyle-related behaviors, including daily breakfast consumption, intake frequency of fruits and vegetables, cooking methods, adherence to special diets, and smoking habits. Additionally, personal medical history was collected, including family history of cancer, presence of relatives affected by head and neck cancer (HNC), tumor stage, date of diagnosis, and type of surgical intervention (if applicable).

Body weight was measured to the nearest 0.1 kg using a calibrated height–weight scale (Model SH-200 G; Zhengzhou, China). Height was recorded without shoes, and BMI was calculated as weight (kg) divided by the square of height (m²). Waist circumference was measured at the level of the superior border of the iliac crest using a non-stretchable tape measure, with measurements recorded to the nearest 0.1 cm. Calf circumference was assessed by horizontally encircling the calf with the same non-elastic tape; the tape was moved up and down the leg to identify the point of maximal girth, which was then recorded to the nearest 0.1 cm. Handgrip strength was measured using a digital dynamometer (Model EH102; Xiangshan Brand, China). Skinfold thickness was assessed at standardized anatomical sites using a skinfold caliper (Model GTQC1303813; Jiangsu, China). Safety assessments were based on adverse events reported by participants and on biochemical parameters—specifically serum urea and creatinine levels—measured during hospital visits at baseline and at the end of the trial.

Dietary intake assessment

Dietary nutrient intake was assessed using three non-consecutive 24-hour dietary recalls, including two days prior to the initiation of the intervention (with one weekend day included) and one day at the one-month follow-up after intervention completion. Participants were asked to recall all foods and beverages consumed during the previous 24 hours, including portion sizes, total energy intake, and protein consumption. They were instructed not to alter their usual eating habits during the assessment period. Standard household measuring aids—including cups, glasses, bowls, and spoons—were used to assist participants in estimating portion sizes.

Dietary data were analyzed using Nutritionist Pro™ software (Axxya Systems LLC, Version 8.01, Redmond, WA, USA), which relies on the U.S. Department of Agriculture (USDA) Standard Reference nutrient database to determine the nutritional composition of reported foods and beverages. When specific local or traditional foods were not available in the database, detailed information—including recipes, ingredients, brand names (if applicable), and preparation methods—was collected. Standardized recipes were then created and entered into Nutritionist Pro™ for nutrient analysis.

Nutritional risk assessment using PG-SGA

The scored PG-SGA was used to evaluate nutritional risk status in HNC patients at baseline (before intervention) and at the one-month endpoint of the trial. PG-SGA is a validated and reliable tool that provides a standardized reference for identifying and classifying nutritional risk in cancer patients [16]. The first section of the PG-SGA questionnaire was completed by the patient and included self-reported weight loss over the past six months and the past month. The second section was completed by a clinician and incorporated objective clinical data such as diagnosis, age, physical examination findings, and degree of metabolic stress [17]. Scores from both sections were combined to generate a total PG-SGA score, ranging from 1 to 40, with higher scores indicating greater nutritional risk. A total score of ≥ 9 is widely recognized as indicating an urgent need for nutritional intervention and dietary counseling [18]. Based on the total score, patients were categorized as well-nourished, moderately malnourished, or severely malnourished.

Assessment of serum albumin levels

Fasting blood samples (after a 12-hour fast) were collected by trained medical laboratory technicians or hospital nurses at two time points: before the start of the intervention and one month after its completion. Serum albumin concentrations were measured as a key biochemical marker of nutritional status. The reference range for serum albumin was defined as 3.5–5.0 g/dL.

Statistical analysis

All efficacy outcomes were analyzed according to both the intention-to-treat (ITT) and per-protocol (PP) principles. Data were entered into EpiData 3.1 using a dual-entry and double-verification procedure to ensure accuracy and minimize data entry errors. Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA).

Continuous variables were compared between groups or within groups over time using either the independent-samples t-test (for normally distributed data) or non-parametric tests (e.g., Mann–Whitney U test or Wilcoxon signed-rank test for non-normally distributed data), as appropriate. Categorical and ordinal variables were analyzed using chi-square tests or Fisher’s exact test when expected cell frequencies were low. All statistical tests were two-sided, and P-values ≤ 0.05 were considered statistically significant. Corresponding p-values were reported for all comparisons.

Results

Figure 1 presents the CONSORT flow diagram of participant enrollment and progression through the trial. Approximately 132 patients were initially screened for eligibility. Of these, 16 were excluded based on the predefined inclusion and/or exclusion criteria. A total of 111 eligible participants were enrolled in the study. Recruitment commenced on October 8, 2023, and follow-up continued until the end of March 2025.

Fig. 1.

CONSORT 2024 flow diagram of participant enrollment, allocation, follow-up, and analysis in a randomized controlled trial of Quantitative goal exercise combined with Whole-Process refined nutrition management for head and neck cancer patients undergoing radiotherapy

During the course of the study, 5 participants withdrew before completion due to protocol non-adherence, refusal to provide blood samples, or modification of the oncologist-prescribed treatment regimen. Consequently, 111 participants were included in the final analysis. Table 1 presents the baseline characteristics of participants in both groups. Overall, there were no statistically significant differences between the two groups.

Table 1.

Comparison of Baseline Characteristics Between the Two Groups of Patients.

Characteristics	Treatment Group	Control Group	Statistic	P value
Gender
Male	42（37.84%）	39（35.14%）	1.231a	0.267
Female	12（10.81）	18（16.22%）
Age (years)	56.52 ± 12.80	51.12 ± 13.23	1904.000b	0.031
T Stage			1.467a	0.832
T1	6（6.06%）	3（3.03%）
T2	16（16.16%）	19（19.19%）
T3	14（14.14%）	17（17.17%）
T4	12（12.12%）	12（12.12%）
N Stage			2.951a	0.708
N0	15(15.15%)	18(18.18%)
N1	17(17.17%)	12(12.12%)
N2	15(15.15%)	19(19.19%)
N3	2(2.02%)	1(1.01%)
Clinical Stage			3.922a	0.789
Ia	3（2.97%）	5（4.95%）
Ic	1（0.99%）	0（0.00%）
IIa	9（8.91%）	9（8.91%）
IIb	0（0.00%）	1（0.99%）
IIIa	17（16.83%）	20（19.80%）
IIIb	0（0.00%）	1（0.99%）
IV	19（18.81%）	16（15.84%）
Radiotherapy Days			44.251a	0.336
29–50 days	32（28.83%）	35（31.53%）
50–70 days	17（15.32%）	18（16.22%）
70–90 days	5（4.50%）	4（3.60%）
Radiotherapy Sessions			6.311a	0.788
15–30 sessions	33（30.84%）	39（36.45%）
30–36 sessions	19（17.76%）	16（14.95%）
Height (cm)	168.11 ± 8.39	167.48 ± 9.39	1609.500 b	0.677
Weight (kg)	68.11 ± 10.64	67.07 ± 14.34	1683.000 b	0.395
BMI (kg/m2)	24.17 ± 3.34	23.75 ± 3.81	1637.500 b	0.561
Body Water - Total Body Water (L)	37.51 ± 5.64	36.29 ± 7.65	1709.000 b	0.316
Body Water - Intracellular Water (L)	23.45 ± 4.16	22.36 ± 4.83	1.182 c	0.041
Body Water - Extracellular Water (L)	14.53 ± 2.50	13.90 ± 2.82	1737.000 b	0.243
Body Composition - Protein (kg)	10.10 ± 1.68	9.68 ± 2.05	0.115 c	0.024
Body Composition - Minerals (kg)	3.40 ± 0.50	3.46 ± 0.98	1595.500 b	0.739
Body Composition - Body Fat (kg)	17.06 ± 6.46	17.49 ± 6.71	−0.641 c	0.978
Body Composition - Fat-Free Mass (kg)	51.25 ± 7.43	49.68 ± 10.46	0.886 c	0.003
Body Composition - Bone Mineral Content (kg)	2.79 ± 0.40	2.76 ± 0.53	0.228 c	0.019
Muscle-Fat Analysis - Skeletal Muscle Mass (kg)	28.19 ± 4.69	26.61 ± 7.04	1767.500 b	0.178
Muscle-Fat Analysis - Muscle Mass (kg)	48.09 ± 7.23	46.59 ± 10.05	1712.500 b	0.306
Muscle-Fat Analysis - Body Fat Mass (kg)	16.96 ± 6.49	17.49 ± 6.71	−0.705 c	0.923
Basal Metabolic Rate (kcal/day)	1505.01 ± 201.17	1485.15 ± 296.40	1654.500 b	0.496
Segmental Phase Angle (°)	5.57 ± 0.82	5.36 ± 0.72	1766.000 b	0.180
PG-SGA	6.49 ± 2.27	6.47 ± 2.42	1597.000 b	0.730
Mid-Upper Arm Circumference (cm)	29.01 ± 3.68	28.13 ± 4.70	0.803 c	0.150
Triceps Skinfold Thickness (mm)	19.49 ± 4.12	19.24 ± 4.62	0.148 c	0.343
Grip Strength (kg)	35.02 ± 13.49	35.16 ± 16.05	1668.000 b	0.447
Calf Circumference (cm)	33.73 ± 3.72	33.92 ± 4.73	1400.000 b	0.619
Quality of Life Scores
Physical Functioning	83.57 ± 16.65	83.65 ± 16.65	1458.000 b	1.000
Role Functioning	97.78 ± 5.67	97.15 ± 6.28	1512.000 b	0.590
Emotional Functioning	66.04 ± 2.26	66.06 ± 2.23	1458.000 b	1.000
Cognitive Functioning	97.76 ± 6.56	96.33 ± 8.32	1567.000 b	0.277
Social Functioning	93.35 ± 9.58	93.41 ± 9.76	1466.000 b	0.953
Global Health Status	70.76 ± 8.83	70.88 ± 8.80	1478.500 b	0.894
Fatigue	2.76 ± 5.68	2.26 ± 5.40	1542.500 b	0.604
Nausea and Vomiting	1.06 ± 5.32	0.90 ± 4.99	1458.000 b	1.000
Pain	1.06 ± 4.08	1.52 ± 4.81	1432.500 b	0.481
Insomnia	1.99 ± 7.89	2.30 ± 8.44	1487.000 b	0.979
Appetite Loss	1.60 ± 7.13	1.77 ± 7.47	1486.500 b	0.982
Constipation	2.69 ± 9.08	2.40 ± 8.61	1487.000 b	0.979
Diarrhea	1.84 ± 7.61	1.93 ± 7.79	1486.500 b	0.982
Financial Difficulties	3.34 ± 10.00	3.03 ± 9.58	1487.500 b	0.976
WBC (×109/L)	5.98 ± 1.33	6.38 ± 1.88	−1.257 c	0.010
Lymphocyte Percentage (%)	0.32 ± 0.20	0.47 ± 1.34	1547.000 b	0.962
Neutrophil Percentage (%)	0.60 ± 0.10	1.82 ± 9.08	1661.500 b	0.470
Lymphocyte Absolute Count (×109/L)	1.61 ± 0.48	1.71 ± 0.65	1327.500 b	0.212
Neutrophil Absolute Count (×109/L)	3.66 ± 1.23	4.24 ± 2.33	1438.500 b	0.553
Hemoglobin (g/L)	135.78 ± 20.34	134.67 ± 14.61	−0.197 c	0.012
RBC (×101 2/L)	4.44 ± 0.65	4.53 ± 0.55	−0.998 c	0.141
Platelets (×109/L)	237.17 ± 73.01	245.65 ± 100.25	−0.244 c	0.193
Total Protein (g/L)	69.21 ± 9.30	71.36 ± 7.52	1299.000 b	0.157
Globulin (g/L)	30.30 ± 5.36	29.43 ± 4.39	1755.000 b	0.202
Albumin (g/L)	42.55 ± 8.11	43.57 ± 3.48	1231.500 b	0.070
Onodera’s Prognostic Nutritional Index	50.43 ± 8.27	52.17 ± 4.84	1165.000 b	0.027

Note: a represents the chi-square value (χ²), b represents the U value for non-parametric tests, and c represents the t value

Comparison of BMI changes between groups

As shown in Table 2, changes in body mass index (BMI) were compared across multiple time points. During the early phase of intervention (at weeks 2, 4, and 6), the decline in BMI was significantly less pronounced in the intervention group than in the control group (p < 0.001 for all time points). However, at the 1-, 2-, and 3-month follow-up assessments, the between-group differences in BMI change were no longer statistically significant (p = 0.123, 0.182, and 0.158, respectively).

Table 2.

Comparison of changes in BMI between the two groups before and after intervention

Group	Changes in BMI
	Change at 2 weeks	Change at 4 weeks	Change at 6 weeks	Change at 1 month	Change at 2 months	Change at 3 months
Treatment Group	−0.05±0.94	−0.12±1.01	−0.13±1.02	−0.33±3.58	−0.17±3.64	−0.07±3.60
Control Group	0.25 ± 4.15	−0.78±0.60	−0.88±0.75	−0.58±3.64	−0.65±4.16	−0.31±3.68
Statistic	2200.000	2609.500	2630.000	1800.000	1765.000	1778.500
P value	<0.001	<0.001	<0.001	0.123	0.182	0.158

Note:

Comparison of nutritional status (PG-SGA) between groups

As shown in the Fig. 2, baseline PG-SGA scores did not differ significantly between the two groups (p = 0.730). Following the intervention, the intervention group demonstrated a significantly greater improvement in nutritional status. Specifically, at weeks 3 and 5, the magnitude of PG-SGA score improvement was significantly greater in the intervention group than in the control group (p < 0.001). By the 1-month assessment, however, the difference between groups was no longer statistically significant(p = 0.096).

Fig. 2.

Changes in PG-SGA scores between experimental group and control group

Comparison of objective nutritional biomarkers

As summarized in Table 3 and Fig. 2, objective nutritional indicators—including hemoglobin, total protein, albumin, and Onodera’s Prognostic Nutritional Index (PNI) were analyzed.

Total protein (Fig. 3A): At week 5, total protein levels remained stable in the intervention group but declined significantly in the control group, resulting in a statistically significant between-group difference in change (p = 0.019). Hemoglobin (Fig. 3B): At baseline, hemoglobin levels were significantly lower in the intervention group (p = 0.012). However, by week 5 of intervention, the change in hemoglobin was significantly more favorable in the intervention group compared to the control group (p = 0.026). Onoderas’ PNI (Fig. 3C): Baseline PNI was lower in the intervention group (p = 0.027). Nevertheless, at both week 3 and 1 month, the deterioration in PNI was significantly less severe in the intervention group (p < 0.001 and p = 0.015, respectively). Albumin (Fig. 3D): At week 3, the decrease in serum albumin was significantly smaller in the intervention group than in the control group (p = 0.018).

Fig. 3.

Comparison of total protein, albumin, Onodera Index, and hemoglobin levels between experimental and control groups

Table 3.

Comparison of Nutritional Status Between the Two Groups Before and After Intervention

Group

Hemoglobin

Total Protein

Albumin

Onodera's Index

Pre-intervention

Δ 3w

Δ 5w

Δ 1m

Pre-intervention

Δ 3w

Δ 5w

Δ 1m

Pre-intervention

Δ 3w

Δ 5w

Δ 1m

Pre-intervention

Δ 3w

Δ 5w

Δ 1m

Treatment

135.78±20.34

-2.14±17.18

3.27±225.27

-5.89±37.32

69.21±9.30

0.90±12.60

0.03±16.39

1.70±11.93

42.55±8.11

-2.49±88.65

-3.63±88.91

-1.16±10.20

50.43±8.27

-5.05±9.12

-6.46±10.26

-4.62±11.34

Control

134.67±14.61

-4.27±16.95

-5.52±21.33

-9.46±31.26

71.36±7.52

-3.58±9.17

-4.77±11.34

-1.42±10.93

43.57±3.48

-5.34±6.68

-6.12±6.88

-1.61±6.87

52.17±4.84

-9.23±7.29

-10.06±8.03

-7.26±7.56

Statistic

-0.197

1582.500

1916.000

1773.500

1299.000

1639.500

1936.000

1695.000

1231.500

1743.500

1.858

1608.000

1165.000

1893.000

2.504

1.679

P value

0.012

0.183

0.026

0.166

0.157

0.090

0.019

0.357

0.070

0.018

0.322

0.560

0.027

<0.001

0.292

0.015

Comparison of anthropometric measurements and muscle functionality

Table 4 shows the anthropometric measurements and muscle functionality. The QGE+WP-RNM group had significantly greater arm circumference, triceps skin fold thickness, and calf circumference at 2 weeks (all p < 0.001) and 4 weeks (p < 0.001, p = 0.005, and p < 0.001, respectively) of intervention than the control group. Handgrip strength at 2 weeks and 4 weeks of intervention was significantly higher in the QGE+WP-RNM group than control group (p = 0.059 and p = 0.579, respectively). Delta changes (∆) comparisons showed the decrease in arm circumference and calf circumference of the QGE+WP-RNM group were lower than that in control group at 2 weeks (p = 0.007 and p = 0.007, respectively) and 4 weeks (p < 0.001and p < 0.001, respectively) of intervention (Table S1). The triceps skin fold thickness significantly increased in the QGE+WP-RNM group over time. However, the control group showed the opposite trend. There was a statistically significant difference in the delta changes between the two groups at 2 weeks and 4 weeks of intervention (all p < 0.001).

Table 4.

Comparison of Anthropometric Measurements Between the Two Groups Before and After Intervention

Group

Mid-Upper Arm Circumference

Triceps Skinfold Thickness

Grip Strength

Calf Circumference

Pre-intervention

Δ 2w

Δ 4w

Pre-intervention

Δ 2w

Δ 4w

Pre-intervention

Δ 2w

Δ 4w

Pre-intervention

Δ 2w

Δ 4w

Treatment group

29.01±3.68

0.77±5.10

-0.05±0.84

19.49±4.12

0.27±1.08

0.77±44.60

35.02±13.49

-1.17±8.83

-0.39±5.41

33.73±3.72

-0.20±1.51

-0.33±0.99

Control group

28.13±4.70

-0.24±0.79

-1.04±1.33

19.24±4.62

-0.23±1.83

-0.30±8.37

35.16±16.05

-0.38±2.11

-0.78±22.53

33.92±4.73

-1.27±5.46

-1.24±11.04

Statistic

0.803

1980.000

2351.500

0.148

2051.500

2450.500

1668.000

1834.000

1932.500

1400.000

1904.000

2351.500

P value

0.150

0.007

<0.001

0.343

<0.001

<0.001

0.447

0.080

0.020

0.619

0.007

<0.001

Comparison of quality of life (QOL) scores between groups

Quality of life was assessed using a validated QOL questionnaire at week 3 post-intervention (Table 5). The intervention group showed significantly better preservation of QOL across multiple domains compared to the control group. Specifically, the declines in physical functioning, role functioning, emotional functioning, and global health status were significantly smaller in the intervention group (p = 0.013, <0.001, <0.001, and <0.001, respectively). Furthermore, symptom exacerbation-including fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation-was significantly milder in the intervention group (p = 0.003, 0.004, <0.001, 0.027, 0.004, and 0.012, respectively). No significant differences were observed between the two groups in cognitive functioning, social functioning, dyspnea, diarrhea, or financial difficulties.

Discussion

Table 5.

Comparison of 3-Week Quality of Life Score Changes Between the Two Groups

Group

Physical Function

Role Function

Emotional Function

Cognitive Function

Social Function

Global Health Status

Fatigue

Nausea/Vomiting

Pain

Dyspnea

Insomnia

Appetite Loss

Constipation

Diarrhea

Financial Difficulties

Treatment group

5.65±12.62

-0.32±2.29

-0.16±1.15

-1.89±6.26

-1.88±10.68

-5.50±11.89

1.68±5.51

11.00±15.98

11.65±10.13

0.60±4.43

0.00±6.53

8.80±17.46

-1.26±9.15

-0.63±10.31

0.63±7.79

Control group

-3.14±20.93

-5.89±9.22

-4.42±6.27

-5.98±11.36

-5.02±15.52

-19.03±11.48

6.07±8.02

22.33±18.76

21.38±11.94

0.00±0.00

5.03±15.17

20.12±22.01

4.40±13.13

1.88±13.72

0.63±4.57

Statistic

1777.500

1890.000

2029.000

1704.000

1622.000

2392.500

1050.500

1014.500

821.000

1512.500

1223.000

1059.000

1276.500

1382.500

1486.000

P value

0.013

<0.001

<0.001

0.052

0.233

<0.001

0.003

0.004

<0.001

0.313

0.027

0.004

0.012

0.285

0.985

The findings of this study indicate that the intervention employed in the experimental group demonstrated a clear advantage over the control regimen in improving overall nutritional status, as assessed by the PG-SGA, and in maintaining short-term BMI stability. Notably, during the early to mid-intervention phase (weeks 3–5), this regimen more effectively stabilized or increased serum total protein and albumin levels and attenuated the deterioration of the OPNI, thereby exerting a significant protective effect on objective nutritional status of patients. More importantly, this intervention significantly improved patients’ quality of life. As early as three weeks after initiation of the intervention, patients in the experimental group exhibited a slower decline in physical, role, and emotional functioning, as well as in overall health status, and demonstrated more effective mitigation of the worsening of common cancer-related symptoms.

HNC patients at diagnosis ranges from 42% to 77% and worsens throughout the treatment course, with rates rising up to 88%. Malnutrition contributes to ineffective treatment responses, impaired functional performance, reduced quality of life, and significantly lower survival rates. The findings demonstrate that, compared with standard care, this integrated intervention significantly attenuated early-phase BMI decline during radiotherapy, improved PG-SGA scores, stabilized multiple objective nutritional biomarkers, and enhanced QOL. These results provide novel evidence-based support for comprehensive supportive care in this vulnerable patient population. The main findings of this study can be summarized as follows: Firstly, regarding body composition, the combined intervention significantly slowed the decline in BMI during the early phase of radiotherapy (weeks 2–6), consistent with prior literature. In terms of nutritional status, the intervention group showed significantly greater improvement in PG-SGA scores during mid-treatment (weeks 3–5), indicating that the combined approach effectively mitigated the onset or progression of malnutrition during radiotherapy. Secondly, for objective nutritional markers—including hemoglobin, total protein, albumin, and Onodera’s PNI—the degree of deterioration was consistently less severe in the intervention group than in the control group. Thirdly, The intervention group had significantly greater muscle functionality than the control group. Finally, the intervention group demonstrated significant advantages across multiple QOL domains.

The PG-SGA is a nutritional assessment tool specifically designed for cancer patients. Its core importance lies in its ability to accurately identify malnutrition and directly inform clinical treatment decisions, thereby improving therapeutic outcomes and survival prognosis [19]. Our study found that PG-SGA scores improved significantly more in the intervention group than in the control group at weeks 3 and 5 of radiotherapy—a finding aligned with Noronha et al. (2024). In their phase III randomized controlled trial, they reported dynamic changes in nutritional status during radiotherapy, with 41.2% of initially well-nourished head and neck cancer patients developing malnutrition during treatment [20]. Our WP-RNM strategy effectively counteracted this deterioration trend. The mechanisms underlying this benefit are likely multifactorial. WP-RNM ensured adequate energy and protein intake even during the peak of radiotherapy-induced toxicities. Concurrently, QGE enhanced nutrient utilization efficiency by stimulating muscle protein synthesis and improving insulin sensitivity. This dual-action model is supported by Wei et al. (2024), who demonstrated that the combined effect of physical activity and high-quality diet significantly reduces all-cause mortality among cancer survivors [21].

The intervention significantly attenuated early BMI loss and stabilized key nutritional biomarkers such as hemoglobin, total protein, and albumin. Which has been validated as key objective markers. This aligns with the findings of He et al. (2023), who reported that nutritional intervention was proved to be effective in enhancing energy intake while simultaneously decreasing energy expenditure in patients receiving radiotherapy for head and neck tumors. [22].

Resistance exercise, a core component of QGE, likely contributed through several pathways: mechanical loading stimulated muscle protein synthesis, counteracting radiotherapy-induced catabolism; enhanced glucose uptake by skeletal muscle improved systemic energy metabolism; and exercise-induced anti-inflammatory cytokines mitigated systemic inflammation. Together, these mechanisms helped preserve lean body mass and maintain nutritional homeostasis.

For cancer patients, maintaining adequate muscle mass is a central objective of nutritional management. Extensive research has demonstrated that reduced muscle mass is associated with increased adverse effects from radiotherapy and chemotherapy, prolonged treatment duration, diminished quality of life, and shorter overall survival [23, 24]. Compared with control group, the muscle functionality was significantly improved in the intervention group in our study. Which might bring survival benefit to these patients.

QOL is a critical endpoint in evaluating therapeutic outcomes and recovery in head and neck cancer patients. Our results show that the intervention group experienced significantly smaller declines in physical, role, and emotional functioning, as well as global health status. Moreover, symptom exacerbation-particularly fatigue, nausea/vomiting, pain, insomnia, appetite loss, and constipation-was markedly milder in the intervention group. This corroborates the work of Zhu et al. who found that standardized nutritional nursing care significantly improved QOL in this population [25]. These symptoms not only directly impair oral intake but also profoundly diminish QOL. Our intervention simultaneously improved nutritional status and alleviated these symptoms, thereby establishing a virtuous cycle in which symptom relief led to increased nutritional intake, which in turn enhanced physical capacity and functional status, ultimately resulting in improved quality of life. This further demonstrates that the regimen represents an integrated, multimodal intervention encompassing nutritional support, symptom management, and psychological care, offering benefits that substantially exceed those of conventional, nutrition-only approaches.

The mechanisms driving QOL improvements are likely synergistic: maintained nutritional status reduced the severity of radiotherapy-related toxicities; regular exercise modulated neuroendocrine function, improving mood, sleep quality, and functional capacity; and active participation in personalized exercise and dietary plans enhanced patients sense of self-efficacy and perceived control over treatment, thereby strengthening psychological resilience.

The most significant finding of this study is the synergistic interaction between QGE and WP-RNM. This synergy may manifest as follows: nutritional support provides the metabolic substrates and energy required for physical activity, while exercise enhances tissue sensitivity to nutrients and improves their metabolic utilization. As highlighted by Prof. Vanita Noronha’s team, although malnutrition is prevalent in head and neck cancer, its adverse impacts can be effectively mitigated through systematic, multimodal interventions [26].

This synergy holds substantial clinical relevance. As emphasized by Wei et al. : The combined effect of physical activity and high-quality diet demonstrates stronger protective benefits against cancer mortality than either intervention alone. Our findings extend this principle to the context of head and neck radiotherapy, providing robust evidence for the development of multidimensional supportive care protocols that integrate exercise and precision nutrition [27].

Despite its promising findings, this study has several limitations that warrant acknowledgment: First, the sample size was modest and drawn from a single tertiary center, which may limit the generalizability of the results. Future studies should employ larger, multicenter cohorts to validate these findings across diverse populations and healthcare systems. Second, although the intervention was individualized, it did not fully account for all potential effect modifiers, such as tumor subsite, detailed TNM staging, or specific radiotherapy protocols. More granular subgroup analyses could help identify patient subpopulations most likely to benefit from the combined intervention. Third, the follow-up period was limited to three months post-radiotherapy, precluding assessment of long-term outcomes. Future trials should extend follow-up duration to evaluate the impact of QGE + WP-RNM on long-term quality of life, locoregional control, progression-free survival, and overall survival. Lastly, the biological mechanisms underlying the observed benefits were not explored in depth. Future research should incorporate biomarkers of inflammation muscle metabolism and endocrine function to elucidate the molecular pathways through which combined exercise and nutrition interventions exert their protective effects. Such mechanistic insights would strengthen the scientific foundation for integrating lifestyle-based supportive care into standard oncology practice.

Conclusion

In summary, integrating quantified goal-directed exercise combined with comprehensive, individualized nutritional management into the standard care protocol for patients with head and neck cancer undergoing radiotherapy holds significant clinical value, as it preserve nutritional status, mitigate treatment-related toxicities, and enhance quality of life during radiotherapy for head and neck cancer. Future large-scale, multicenter trials are warranted to validate these findings and refine implementation strategies in diverse clinical settings.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

QGE

Quantitative Goal Exercise

WP-RNM

Process Refined Nutrition Management

BMI

Body Mass Index

PG-SGA

Patient-Generated Subjective Global Assessment

OPNI

Onodera’s Prognostic Nutritional Index

QOL-C30

quality of life

HNC

Head and neck cancer

HNSCC

Head and neck squamous cell carcinoma

RT

Radiotherapy

CT

Chemotherapy

CRT

Chemoradiotherapy

QOL

Quality of life

QGE

Quantitative goal exercise

HNSCC

Head and neck squamous cell carcinoma

PN

Parenteral nutrition

HA

Principal investigator

ITT

Intention-to-treat

PP

Per-protocol

SD

Standard deviation

Author contributions

Juanli Shi and Lina Zhao: contributed equally to this work. Juanli Shi and Geng Xiang: Study design, Data collection, Statistical analysis, Manuscript drafting. Xiaoli Long，Mai Zhang andXiao Zhang,: Literature search, Data interpretation, Manuscript revision. Meiling ChengandYangYang Yin: Patient recruitment, Clinical data acquisition. Juanli Shi，Mai Zhang and Lina Zhao: Study conception, Critical revision of the manuscript, Overall supervision. All authors approved the final version for submission.

Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

Declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the First Affiliated Hospital of Air Force Medical University (ethical approval number: KY20222067-F-1).This study was approved by the Ethics Committee of the First Affiliated Hospital of Air Force Medical University 2.0 was approved on May 20, 2022. All participants should provide written informed consent prior to randomization and are free to withdraw at any time. There are no dissemination plans of this trial.

Competing interests

The authors declare no competing interests.