Head and neck squamous cell carcinoma (HNSCC) is a great global health issue and is regarded as the seventh most common cancer in the world with approximately 700,000 new diagnoses and 350,000 deaths annually. It is the leading cancer in males in India, causing almost a quarter of all incidence of Indian cancer. Primary causes or etiology include the consumption of tobacco and alcohol and infection with human papillomavirus (HPV) [1,2]. Treatment of locally advanced non-metastatic disease is standard with concurrent chemoradiation, which, while increasing locoregional control, has significant treatment-related toxicity. These toxicities, particularly mucositis and dysphagia, invariably lead to suboptimal nutritional intake [3,4]. Malnutrition is an ubiquitous and significant problem amongst this patient population, both as a consequence of the treatment effects during the acute phase and because of tumour site [5]. A greater than 7% deterioration in BMI over a period of six months is an established indicator of poor nutritional health, able to blunt immune function, increase the infection and hospitalisation rate, and potentially lead to treatment interruptions [6,7]. As such, nutritional health is an overriding determining factor in the tolerance to treatment and eventual outcome. This is an observational, prospective study, which shall attempt to investigate the independent influence of pre-treatment body mass index on response to treatment, toxicity profiles, and survival in patients with HNSCC undergoing definitive concurrent chemoradiation [8].

Study Design and Setting This was a prospective, single-institutional observational study performed in the Department of Radiotherapy of R. G. Kar Medical College and Hospital, Kolkata, India. The study was designed to evaluate the effect of pre-treatment body mass index (BMI) on head and neck cancer patient outcomes who received definitive chemoradiation. The period of study was September 2022 to June 2024, with at least six months' follow-up of the last recruited patient in both arms to permit ultimate analysis of data. Study Population The study population was biopsy-documented in new cases of head and neck squamous cell carcinoma presented to the outpatient department. Patients were eligible if they were 20 to 70 years old, had a performance status of 0 to 2 by ECOG, and were going to undergo platinum-based concurrent chemoradiation. Exclusion criteria were important and included a history of radiotherapy or chemotherapy, evidence of distant metastases, non-squamous histology on pathology, prior malignancy, uncontrolled comorbidity, and refusal by the patient. The sample size was calculated to be around 150 patients on the basis of the institution's annual registration patterns. Treatment Protocol Concurrent chemoradiation was given to all patients. The radiation therapy was administered with intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) methods. Patients were immobilized in the supine position in a thermoplastic mould. Simulation CT scans were employed for target volume delineation, such as the gross tumour volume (GTV), clinical target volume (CTV), and planning target volume (PTV), with a 5 mm margin being applied to the CTV to create the PTV. Organs at risk (OARs) were contoured per guidelines. The radiation therapy dose prescribed was 66–70 Gy in 30–35 fractions in 6–7 weeks. Radiation was given using 6 MV photon beams, and the planning aim was that 95% of the PTV should be treated to 95% of the prescribed dose. Cone-beam CT image guidance was used routinely for setup verification. Simultaneous chemotherapy was given in the form of intravenous cisplatin weekly in a dose of 40 mg/m² for 6–7 weeks, if renal function (creatinine clearance ≥60 ml/min) and hematological indices were within normal limits. Monitoring of the blood counts and renal function was done once a week during treatment. Data Collection and Measurements The key variable of interest was pre-treatment BMI, computed as weight in kilograms divided by height squared in meters (kg/m²). BMI was classified by World Health Organization criteria: underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9), and obese (≥30). BMI was assessed within 14 days of the start of treatment, four weeks post-initiation of chemoradiation, and within one week of treatment completion. Treatment response was determined at six weeks from completion of chemoradiation with Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Endpoints were the overall response rate (ORR) and disease control rate (DCR). Acute toxicities (within 90 days of initiation of treatment) and late toxicities (beyond 90 days) were assessed with the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Progression-free survival (PFS) was measured as the interval from the initiation of treatment to documented disease progression or death from any cause. Statistical Analysis Data were summarized and analyzed using SPSS version 21. Categorical data were reported as percentages and contrasted with the chi-squared test. Continuous data were reported as mean ± standard deviation and contrasted with independent t-tests. Survival analysis for PFS was conducted by the Kaplan-Meier method, with contrasts being made by the log-rank test. A p-value of ≤0.05 was considered significant. Ethical Considerations The protocol was approved by the Institutional Ethics Committee prior to patient recruitment. All participants provided written informed consent.

Patient and Disease Characteristics A total of 150 patients were entered on the study and 149 completed the concurrent chemoradiation course and were included in the final analysis. The patient population was mostly male (82.6%) with a median age of 54 years (range: 24-70 years). The most common (91.9%) patients had tobacco history, and the majority (54.4%) had alcohol abuse. The majority of patients had an adequate performance status, with 73.2% having ECOG 1. The oropharynx (40.0%) was the most common primary site for the tumor, followed by the hypopharynx (24.0%) and oral cavity (18.0%). The disease was mostly advanced at the time of presentation, with 69.7% of patients presenting in stage IVA and 40.3% clinical T3 tumor. The baseline clinical and demographic profile of the study sample is illustrated in Table 1. Table 1: Baseline Demographic and Clinical Characteristics of the Study Population (n=149) Characteristic Category Number (%) Sex Male 123 (82.6%) Female 26 (17.4%) Age (years) 20-30 5 (3.4%) 31-40 18 (12.1%) 41-50 39 (26.2%) 51-60 56 (37.6%) 61-70 32 (21.5%) Tobacco Use Yes 137 (91.9%) No 12 (8.1%) ECOG Performance Status 1 109 (73.2%) 2 40 (26.8%) Primary Tumor Site Oropharynx 60 (40.3%) Hypopharynx 36 (24.2%) Oral Cavity 27 (18.1%) Larynx 21 (14.1%) Nasopharynx 5 (3.4%) Clinical Stage I 2 (1.3%) II 16 (10.7%) III 18 (12.1%) IVA 104 (69.8%) IVB 9 (6.0%) Distribution of Pre-Treatment Body Mass Index Pre-treatment Body Mass Index (BMI) was determined for all patients. BMI category distribution stratified by gender and primary tumor site is shown in Table 2. More male patients (38.2%) were overweight or obese (BMI ≥25.0 kg/m²) than female patients (46.2%), although the female sample size was small. On tumor site analysis, the oropharynx and oral cavity maximally included patients with a BMI ≥25.0 kg/m². Table 2: Distribution of Pre-Treatment Body Mass Index by Gender and Primary Tumor Site Category BMI <18.5 (Underweight) BMI 18.5–24.9 (Normal) BMI ≥25.0 (Overweight/Obese) Gender Male (n=123) 12 (9.8%) 64 (52.0%) 47 (38.2%) Female (n=26) 0 (0.0%) 14 (53.8%) 12 (46.2%) Tumor Site Oropharynx (n=60) 7 (11.7%) 30 (50.0%) 23 (38.3%) Oral Cavity (n=27) 2 (7.4%) 19 (70.4%) 15 (55.6%) Hypopharynx (n=36) 2 (5.6%) 15 (41.7%) 10 (27.8%) Larynx (n=21) 1 (4.8%) 11 (52.4%) 9 (42.9%) Nasopharynx (n=5) 0 (0.0%) 3 (60.0%) 2 (40.0%) Association Between BMI and Treatment Response Response to treatment was measured at 1.5, 3, and 6 months following treatment according to RECIST v1.1 criteria. A definite relationship was seen between pre-treatment BMI and response to treatment. Subjects with a higher pre-treatment BMI (≥25.0 kg/m²) always showed a better complete response (CR) rate than those with normal or reduced BMI. As can be seen in Figure 1, at follow-up at 6 months, most of the patients who achieved a CR (79 out of 97, 81.4%) belonged to the higher BMI group. In contrast, locoregional failure was more common among patients with a BMI <18.5 kg/m². In addition, the association between disease stage and BMI was examined. As illustrated in Figure 2, patients with more advanced nodal disease (N2/N3) were most frequently in the normal BMI group (54.4%), while a greater BMI occurred more frequently in patients with earlier-stage disease. This indicates that increased BMI could be connected with a distinct disease profile or biology.

This potential observational study supports the increasing evidence that pre-treatment nutritional status, quantified as Body Mass Index (BMI), is an independent prognostic factor in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive chemoradiation. Our results illustrate a definite correlation between elevated pre-treatment BMI and enhanced locoregional control, having a statistically significant p-value of 0.03 [9]. In particular, patients with a BMI ≥25 kg/m² had significantly fewer locoregional failures (2.68%) than those with normal BMI (10.07%) and most dramatically compared to underweight patients (3.36%). This is consistent with the literature, such as Park et al.'a prospective cohort study that also reported a strong correlation between BMI and prognosis for HNSCC [10,11]. The age and gender profile of our cohort, with a predominance of males (82.6%) and a mean age of 52.65 years, conforms to epidemiological trends presented by other Indian and international studies [12]. Yet, the pattern of primary sites of tumors in our study, with oropharyngeal cancers being the most common (40.26%), varies from elderly Indian series which identified the larynx as the leading site. This transformation can be a reflection of evolving etiological patterns, including increased prevalence of human papillomavirus-related oropharyngeal cancers [13]. The improved results noted in patients with an elevated BMI might be due to superior nutrition stores, which may contribute to better tolerance to the considerable toxicities of concurrent chemoradiation, thus decreasing therapy breaks and enhancing drug delivery. Although it is possible that lower BMI could be a surrogate for more aggressive disease or higher tumor burden, our analysis did try to control for this by examining BMI in different T and N stages [14]. The fact that there still remained a significant association after controlling for this indicates that the impact of BMI might be independent to some extent. A low BMI probably indicates a catabolic state imposed by the tumor, which can impair immune response and tissue repair, the key to treatment response and recovery [15]. In summary, our research supports the utility of pre-treatment BMI as a low-cost, accessible, and easy-to-use prognostic factor in HNSCC. These results highlight the essential role of detailed nutritional evaluation and intervention as part of multidisciplinary care for these patients. Optimization of nutritional status before starting aggressive treatment regimens such as chemoradiation may have the potential to enhance therapeutic response and survival. Randomized controlled trials should be the focus of future studies to identify whether proactive nutritional support to optimize BMI is directly beneficial in increasing locoregional control as well as overall survival.

This prospective study illustrates an important correlation between pre-treatment body mass index (BMI) and locoregional control in head and neck cancer patients treated with chemoradiation. Statistical analysis in a series of 149 patients, which were mostly male with oropharyngeal primaries, showed that increased pre-treatment BMI was associated with better treatment outcome. Patients with BMI ≥25 kg/m² had a significantly lower rate of locoregional failure (2.68%) than those with a normal BMI (10.07%) and underweight patients (3.36%), a result confirmed by a significant chi-square test p-value of 0.03. Although these findings highlight the prognostic significance of nutritional status, confirmation by larger prospective studies with longer follow-up is needed before concluding the effect of pre-treatment BMI on long-term survival.

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