Nutritional management and oral health-related outcomes in head and neck cancer treated with radiotherapy or chemoradiotherapy: a systematic review

Abstract

Background

Head and neck cancers are frequently diagnosed at a locally advanced stage and are commonly treated with radiotherapy or chemoradiotherapy, which significantly affect oral function and nutritional intake. Treatment delivery is often compromised by malnutrition, which affects 30–50% of patients at diagnosis and up to 90% during therapy. Despite its impact on treatment tolerance and continuity, the optimal nutritional strategy during radiotherapy or chemoradiotherapy remains unclear. This systematic review evaluated the possible influence of oral nutritional supplements, percutaneous endoscopic gastrostomy or nasogastric tube feeding on treatment delivery and tolerance, oral health-related outcomes including mucositis, dysphagia, and oral intake in patients with head and neck cancer receiving radiotherapy or chemoradiotherapy.

Methods

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included adult patients with head and neck cancer treated with radiotherapy or chemoradiotherapy who required nutritional support. Methodological quality was assessed using an adapted version of the Mixed Methods Appraisal Tool (MMAT).

Results

Thirty-one studies were included. Mucositis, as well as dysphagia and impaired oral intake, remained the most significant oral health-related outcomes, even with the implementation of multiple nutritional support measures. Early use of oral nutritional supplements was associated with fewer treatment interruptions, particularly before escalation to enteral feeding. Prophylactic percutaneous endoscopic gastrostomy appeared to be associated with reduced weight loss, fewer unplanned hospitalizations, and higher treatment completion rates, but these findings should be interpreted with caution given the observational nature of the available evidence. Nasogastric tube feeding was associated with fewer device-related complications and lower long-term dependence; however, heterogeneity across studies and the predominance of gastrostomy-focused evidence limited direct comparative conclusions.

Conclusions

Nutritional support is closely linked to oral function and treatment delivery during radiotherapy or chemoradiotherapy for head and neck cancer. Proactive strategies may improve treatment continuity in high-risk patients, but comparative evidence remains insufficient to define the optimal enteral approach. High-quality randomized trials integrating oral health-related outcomes are needed to inform evidence-based, nutrition-integrated clinical practice.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-026-08352-0.

Introduction

Head and neck cancers (HNC) represent a major global health burden, accounting for more than 1.4 million new cases and nearly 500,000 deaths worldwide in 2020 [1]. The majority of cases are squamous cell carcinomas arising in the oral cavity, oropharynx, hypopharynx, or larynx, predominantly affecting men aged 50–60 years [2]. Rarer forms include both epithelial (e.g., salivary gland, sinonasal, nasopharyngeal, neuroendocrine, odontogenic, and ear tumors) and non-epithelial malignancies (e.g., mucosal melanomas, sarcomas) [3]. Tobacco, alcohol, and human papillomavirus (HPV), especially in oropharyngeal cancer, are established risk factors [4]. Most patients are diagnosed with locally advanced disease, typically managed with surgery followed by radiotherapy (RT) or chemoradiotherapy (CRT), or exclusive CRT when surgery is not feasible [5].

Malnutrition is a major concern in HNC, affecting 30–50% of patients at diagnosis and up to 90% during RT or CRT [6, 7]. The Global Leadership Initiative on Malnutrition (GLIM) defines it as the combination of at least one phenotypic criterion (e.g., involuntary weight loss, low body mass index, muscle depletion) and one etiologic criterion (e.g., reduced food intake, malabsorption, inflammation) [8]. Causes are multifactorial, including anorexia, dysphagia, mucositis, xerostomia, trismus, odynophagia, and dysgeusia [9–11], all of which directly impair oral intake. Malnutrition during RT is associated with a twofold increase in mortality [12], as well as impaired treatment response, reduced immune function, delayed healing, and diminished quality of life [13]. Nutritional support is therefore a critical component of HNC clinical management.

Nutritional interventions in HNC include oral nutritional supplements (ONS), nasogastric tube (NGT), percutaneous endoscopic gastrostomy (PEG), and, less commonly, jejunostomy. ONS are typically used in patients with preserved oral intake and moderate malnutrition. NGT feeding is preferred for short-term enteral support (less than four weeks), while PEG is recommended for longer durations, or when NGT is poorly tolerated or contraindicated. Jejunostomy is rarely used, mostly in patients at high risk of aspiration or following upper gastrointestinal surgery [14, 15].

Despite general recommendations, no high-level evidence definitively supports one modality over another, and clinical practice remains highly variable [16, 17].

This systematic review aims to synthesize and compare the nutritional, treatment-related, functional, and oral health-related outcomes of PEG, NGT, and ONS in patients with HNC receiving RT or CRT.

Methodology

Bibliographic research strategy

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [18]. The review protocol was not registered in PROSPERO.

Electronic databases, including PubMed, Web of Science, ScienceDirect, and PsycINFO, were consulted to retrieve relevant articles published between January 1, 2005 and January 1, 2026. To optimize the search on PubMed, the MeSH Database was used, allowing the identification of Medical Subject Headings (MeSH) terms such as “Head and Neck Neoplasms,” “Malnutrition,” “Enteral Nutrition,” “Radiotherapy,” and “Chemoradiotherapy.” Boolean operators “AND” and “OR” were applied to appropriately combine search terms. Equivalent keyword combinations adapted to each database were used for Web of Science, ScienceDirect, and PsycINFO.

No language restrictions were initially applied during the search to minimize selection bias; however, only English-language full-text articles were retained during the screening phase.

Detailed search strategies, including keywords and filters, are presented in Appendix A: Search Strategies.

Eligibility criteria

Inclusion criteria

1. Adult patients with operated or locally advanced HNC (any histological subtype) undergoing treatment with either adjuvant or exclusive RT, or concurrent CRT (adjuvant or exclusive).

2. Nutritional management through enteral nutrition (via NGT or PEG) or oral nutritional supplementation.

3. Studies reporting outcomes related to nutritional status, weight changes, treatment-related toxicities, treatment completion, survival, oral intake and/or oral function.

4. Peer-reviewed original research studies (e.g., prospective or retrospective cohort studies and randomized controlled trials) published between January 2005 and January 2026.

5. The full text was available in English.

Exclusion criteria

1. Patients diagnosed with cancers other than head and neck cancer, pediatric patients (under 18 years of age), or patients receiving surgical treatment only without radiotherapy or chemoradiotherapy.

2. Studies focusing on parenteral nutrition as the sole method of nutritional management, or not adressing any form of nutritional support.

3. Studies reporting exclusively on biomarkers or outcomes unrelated to clinical or nutritional aspects.

4. Non-original research articles (e.g., conference abstracts, narrative reviews, theses, dissertations, case reports), or articles published before January 1, 2005 or after January 1, 2026.

5. Articles whose full text was unavailable or not written in English.

Study selection

After duplicate removal, study selection proceeded in two stages. First, titles and abstracts were independently screened by three reviewers (CWB, CB, and AH) according to predefined eligibility criteria. Full-text articles were then retrieved and assessed for eligibility by the same reviewers. Disagreements were resolved through discussion until consensus was reached. The overall selection process was documented according to PRISMA 2020 guidelines and is summarized in a flow diagram (Fig. 1).

Fig. 1.

PRISMA flowchart of systematic search results

Data extraction and analysis

A standardized data extraction form was developed based on the objectives of the review and was piloted on a subset of studies to ensure consistency and reliability. Data extraction was performed independently by two reviewers (CWB and CB) and cross-checked by a third reviewer (AH) to ensure accuracy.

The following variables were systematically extracted for each included study:

• Study characteristics: first author, year of publication, study design, sample size.

• Patient characteristics: number, age, sex distribution, disease type.

• Treatment modalities: RT alone or concomitant CRT, exclusive or adjuvant.

• Nutritional management: type of nutritional support (ONS, NGT, PEG), timing of intervention (prophylactic versus reactive).

• Adverse events: device-related complications associated with nutritional support, including type, grade, and incidence when available.

• Nutritional outcomes: mean weight loss (percentage or kilograms), BMI variation (kg/m2).

• Treatment-related outcomes: treatment-related toxicities (according to the Common Terminology Criteria for Adverse Events (CTCAE)), treatment completion, overall survival (OS), progression-free survival (PFS).

• Functional and oral health-related outcomes : oral intake, swallowing function, long-term feeding dependence. Treatment-related toxicities affecting the oral cavity, such as mucositis or dysphagia, were considered in both categories due to their direct impact on oral function.

All extracted data were organized in a structured Microsoft Excel database for subsequent analysis. Missing or unreported data points were explicitly annotated and considered during narrative synthesis and interpretation.

Regular research team meetings were held during the data extraction and synthesis phases to refine coding frameworks, resolve disagreements, and ensure thematic saturation. Where appropriate, summary tables were created to visually present study characteristics, nutritional interventions, and outcomes.

Quality appraisal

The methodological quality of included studies was appraised using an adapted version of the Mixed Methods Appraisal Tool (MMAT) [19], with a predefined selection of domains tailored to the objectives of this review. Five methodological domains were evaluated: appropriateness of the research design, representativeness of the study sample, adequacy of data collection methods, risk of non-response bias, and appropriateness of statistical analysis. These domains were selected a priori based on their relevance to the study designs included and their consistency with MMAT principles. Each criterion was rated as “Yes” or “No”. In accordance with MMAT recommendations, no overall score was calculated, and quality appraisal was used to inform the interpretation of findings rather than to exclude studies.

Three reviewers (CWB, CB, AH) independently conducted the assessments, with discrepancies resolved through discussion to ensure consistency. The full quality assessment is presented in Appendix B.

Data synthesis

Given the expected variability in study designs, outcome definitions, measurement methods, and follow-up durations, a quantitative synthesis was not performed.

Heterogeneity was explored qualitatively by examining differences in study design, patient populations, outcome definitions, measurement methods, and follow-up durations. Outcomes were grouped into predefined domains: adverse events, nutritional outcomes (weight loss, BMI variation), treatment-related outcomes (toxicities, treatment completion, survival), and functional and oral health-related outcomes (oral intake, swallowing function, long-term feeding dependence).

A structured narrative synthesis was conducted within each domain to identify patterns across studies while accounting for variations in study design and reporting.

Results

The initial database search yielded 362 records published between 2005 and 2026. After duplicate removal, 323 studies were screened. Title and abstract screening excluded 277 records. The remaining 46 articles underwent full-text assessment using predefined eligibility criteria (Fig. 1). Five studies were excluded due to ineligible patient populations, two did not report relevant clinical or nutritional outcomes, five had an ineligible study design, and three could not be retrieved in full text. Overall, 31 studies were included in the final synthesis [20–50] (Fig. 1).

Study characteristics

Included studies comprised two randomized controlled trials [21, 29], 11 prospective cohort studies [20, 22, 25, 27, 30, 32, 33, 36, 41, 49, 50], 17 retrospective cohort studies [23, 24, 26, 28, 31, 34, 35, 37–40, 42–45, 47, 48], and one two-year audit [46]. For analytical clarity, studies were grouped into four thematic categories: six studies focused on ONS [20–25], 19 investigated PEG [26–44], three assessed NGT feeding [45–47], and three provided direct comparisons across these modalities [48–50]. Across all studies, most patient populations were predominantly male, with the majority presenting with locally advanced HNC. Nutritional outcomes—primarily mean weight loss and body mass index (BMI) changes—were most often assessed at the end of RT or CRT, with a few studies extending follow-up to 3 or 6 months. Treatment-related, functional and oral health-related outcomes were reported with variable granularity across studies [20–50]. The MMAT assessment of the 31 studies revealed moderate to high methodological quality, with most studies meeting the majority of methodological criteria. The most common limitations were related to the suitability of data collection methods and the adequacy of statistical analyses for addressing the stated research questions (Appendix B).

Oral Nutritional Supplements (ONS)

Six studies investigated ONS, typically initiated prior to or at the start of treatment [20–25]. Four of these studies compared ONS to dietary counseling alone [21–24]. When oral intake was insufficient, escalation to enteral nutrition followed institutional protocols (Table 1).

Table 1.

Oral Nutritional Supplements (ONS) Studies

Authors and year	Study design	Patients Characteristics	Disease type	Treatment modalities	Nutritional management	Adverse Event	Nutritionnal outcomes	Treatment-related outcomes	Functional and oral health-related outcomes
Cardellini et al., 2024 [20]	Prospective Cohort Study	No. : 60 Age1 : 59.3 Sex2 : 43 M, 17 F	HNC	CRT (Exclusive or adjuvant)	ONS	ND	BMI variation : - After CRT : 25.4 to 23.5 (p = 0.016) - At 3 mo. : 23.5 to 23.3 (p = 1)	TC : - RT : 100% - CT : 96.4% OS at 1 year : 73.3% PFS at 1 year : 65%	Mucositis : 27.3% Dysphagia : 30.9% Odynophagia : 30.9%
Cereda et al., 2018 [21]	Randomized Controlled Trial	No. : 159 Age : 66.5 (ONS), 63.8 (Control group) Sex : 114 M, 45 F	HNC	RT or CRT (Exclusive or adjuvant)	ONS vs. Control group	ND	MWL : 1.9 kg (ONS) vs. 3.5 kg (Control group) (p = 0.006)	TC : Dose reduction or complete suspension : 9% (ONS) vs. 22% (Control group) (p = 0.029)	Mucositis : 1% Mucositis (ONS) vs. 96% (Control group) (p = 0.21)
Kapala et al., 2021 [22]	Prospective Cohort Study	No. : 153 Age : 58 Sex : 122 M, 31 F	HNC	CRT (Exclusive or adjuvant)	ONS vs. Control group	ND	MWL : 5.26 kg (ONS) vs. 7.5 kg (Control group) (p = 0.006)	TT : Infection, deterioration of renal and hepatic function, cytopenias… (≤ 70 years old) : 14.9 (ONS) vs. 27.9 (Control group) (p = 0.03) TC : Dose reduction : 14,1% (ONS) vs. 26,12% (Control group) (p < 0,001)	ND
Lee et al., 2008 [23]	Retrospective Cohort Study	No. : 79 Age : 56 (ONS), 58 (Control group) Sex : 64 M, 15 F	HNC	RT or CRT (Exclusive)	ONS vs. Control group	ND	MWL : - After CRT : 6.7% (ONS) vs. 10.7% (Control group) (p = 0.007) - After RT : 6.1% (ONS) vs. 10.1% (Control group) (p = 0.008)	ND	ND
Paccagnella et al., 2009 [24]	Retrospective Cohort Study	No. : 33 Age : 58.5 Sex : 24 M, 9 F	HNC	CRT (Exclusive)	ONS vs. Control group	ND	MWL : - After CRT : 4.63% (ONS) vs. 8.10% (Control group), (p = 0.0026) - At 6 mo. : 2.35% (ONS) vs. 9.55% (Control group), (p = 0.0077)	TT : 16.1% Hospital admission for mucositis (ONS) vs. 41.4% (Control group), (p = 0.03) TC : - CT : 96.7% (ONS) vs. 93.9% (Control group), (no significant difference) - RT breaks > 5 days : 30,3% (ONS) vs. 63.6% (Control group), (p = 0.007)	Mucositis : 45.5% G3-4 Mucositis (ONS) vs. 39.4% (Control group), (no significant difference)
Valentini et al., 2012 [25]	Prospective Cohort Study	No. : 21 Age : 56.1 Sex : 18 M, 3 F	HNC	CRT (Exclusive)	ONS	ND	MWL : decrease from 70.1 kg to 64.7 kg at the end of CRT (p < 0.0001)	TT : - 33% G3 Skin dermatitis - 2% G4	G3-G4 Mucositis : 33.3% G3 Dysphagia : Five cases

Abbreviations BMI Body Mass Index (kg/m2), CRT Chemo-Radiotherapy, CT Chemotherapy, G Grade, HNC Head and Neck Cancer, Mo Month(s), MWL Mean weight loss, NGT NasoGastric Tube, ND Not Detailed, ONS Oral nutritional supplements, OS Overall Survival, PEG Percutaneous endoscopic gastrostomy, PFS Progression Free Survival, RT Radiotherapy, TC Treatment Completion, TT Treatment-Related Toxicity

¹ : Mean or median age in years. ² : M for male, F for female

Adverse events

No ONS-related adverse events were specifically reported across studies [20–25].

Nutritional outcomes

Reported benefits of early ONS included reduced weight loss (absolute differences ranging from 1.6 to 2.2 kg and up to 4% lower mean loss compared to controls) [21–24].

Treatment-related outcomes

Early ONS was associated with fewer unplanned hospitalizations (16.1% vs. 41.4%, p = 0.03) and lower systemic toxicity among those under 70 years (14.9% vs. 27.9%, p = 0.03) [22, 24]. In addition, patients receiving early ONS had higher treatment completion rates than controls, with fewer dose reductions or interruptions [21, 24]. Only one study provided survival outcomes: 1-year OS of 73% and PFS of 65% [20].

Functional and oral health-related outcomes

Mucositis was the most frequently reported oral health-related outcome, occurring in up to 96% of cases, with no significant difference compared with the control group [21, 24]. One study reported dysphagia and odynophagia in 30.9% of cases [20].

PEG-based nutritional support

Nineteen studies evaluated PEG, whether placed prophylactically (P-PEG) before treatment initiation or reactively (R-PEG) during or after treatment in response to nutritional decline. In most studies focusing on P-PEG, enteral feeding was initiated once patients met clinical indicators of malnutrition [26–44]. Two studies compared standard P-PEG (feeding initiated when clinically indicated) to immediate P-PEG feeding (initiated before any signs of malnutrition) [28, 29]. Seven studies compared P-PEG to a non-enterally fed control group [26, 30, 31, 37, 38, 43, 44]. Six studies explored P-PEG alone [27, 33, 34, 36, 39, 41]. One study compared P-PEG with total enteral nutrition, additional oral intake, and a control group [32]. Two studies compared P-PEG to R-PEG [35, 40], and one study compared P-PEG, R-PEG, and a control group [42] (Table 2).

Table 2.

Percutaneous Endoscopic Gastrostomy (PEG) studies

Authors	Study design	No. of patients	Disease type	Treatment modalities	Nutritional management	Adverse Event	Nutritionnal outcomes	Treatment-related outcomes	Functional and oral health-related outcomes
Assenat et al., 2011 [26]	Retrospective Cohort Study	No. : 139 Age1 : 51.9 (P-PEG), 55 (Control group) Sex2 : 115 M, 24 F	HNC	CRT (Exclusive or adjuvant)	P-PEG vs. Control group	P-PEG : Abdominal pain or infection : 4,3% One patient developed a wall abcess	MWL : 1 kg (P-PEG) vs. 5 kg (Control group) (p < 0.001)	TC : 62.3% (P-PEG) vs. 41% (Control group) (p = 0.01) OS at 1 year : 69% (both groups, no statistical differences between the 2 groupes)	ND
Atasoy et al., 2012 [27]	Prospective Cohort Study	No : 23 Age : 53 Sex : 17 M, 6 F	HNC	CRT (Exclusive or adjuvant)	P-PEG	Buried Bumper Syndrome : 4%	MWL : 2.78 kg	TT : - 82.6% Nausea/vomiting - 4.3% Infection TC : - CT : 78.3% - RT : 100%	Mucositis : 100% Dysphagia : 100%
Blake et al., 2022 [28]	Retrospective Cohort Study	No. : 111 Age : 61.7 (Immediate feeding), 60.3 (Standard) Sex : 94 M, 17 F	HNC	CRT (Exclusive or adjuvant)	P-PEG Feeding timing : Delayed vs. Immediate	ND	MWL : 9.9% (Immediate initiation) vs. 11.1% (Delayed) (p = 0.338)	ND	ND
Brown et al., 2017 [29]	Randomized Controlled Trial	No. : 131 Age : 60.5 Sex : 115 M, 16 F	HNC	CRT (Exclusive or adjuvant)	P-PEG Feeding timing : Delayed vs. Immediate	No statistically significant difference was observed between the two groups	MWL : 10.8% (Immediate initiation) vs. 10.9% (Delayed) (p = 0.624)	TT : 57% unplanned admissions (Immediate initiation) vs. 47% (Delayed) (p = 0.270) TC : - RT : 95% (Immediate initiation) vs. 100% (Delayed) (p = 0.102) - CT : 98% (Immediate initiation) vs. 95% (Delayed) (p = 0.407) OS at 1 year : 5 deaths (Immediate initiation) vs. 6 (Delayed) (p = 0,946) PFS at 1 year : 10 disease relaps (Immediate iniation) vs. 19 (Delayed) (p = 0,135)	ND
Brown et al., 2018 [30]	Prospective Cohort Study	No. : 130 Age : 59.1 Sex : 114 M, 16 F	HNC	CRT (Exclusive or adjuvant)	P-PEG vs. Control group	ND	MWL : 7% (P-PEG) vs. 9% (Control group) (p = 0.048)	TT : 75% unplanned admissions (P-PEG) vs. 82% (Control group) (p = 0.029)	ND
Chen et al., 2010 [31]	Retrospective Cohort Study	No. : 120 Age : ND Sex : ND	HNC	CRT (Exclusive)	P-PEG vs. Control group	ND	MWL : 8% (P-PEG) vs. 14% (Control group) (p < 0.001)	TT : G3 + acute toxicity (hematologic, mucositis, xerostomia) : 60% (P-PEG) vs. 57% (Control group) (p = 0.59) TC : Missed treatment days : 5 (P-PEG) vs. 6 (Control group) (p = 0.54) OS at 3 year : 66% (P-PEG) vs. 69% (Control group) (p = 0.54)	High-Grade Dysphagia - 3 mo. : 46% (P-PEG) vs. 27% (Control group) (p = 0.01) - 6 mo. : 34% (P-PEG) vs. 5% (Control group) (p = 0.001)
Dechaphunkul et al., 2022 [32]	Prospective Cohort Study	No. : 116 Age : 52.4 Sex : 98 M, 18 F	HNC	CRT (Exclusive)	P-PEG with total enteral nutrition vs. P-PEG with oral intake vs. Control group	P-PEG : Overall infection rate : 14,7%	MWL : 8.9% (total enteral nutrition) vs. 5.28% (additional oral intake) vs. 12.7% (Control group) (p = 0.085)	ND	PEG dependence - Median time : 6.9 mo. (Total enteral nutrition) vs. 5.6 mo. (Additional oral intake) (p = 0.023) - Tube dependence at 6 mo. : 51% (total enteral nutrition) vs. 17% (additional oral intake) (p = 0.002) - Tube dependence at 12 mo. : 12.9% (total enteral nutrition) vs. 5% (additional oral intake) (p = 0.186)
Della Valle et al., 2018 [33]	Prospective Cohort Study	No. : 35 Age : 60 Sex : 20 M, 15 F	HNC	RT alone or CRT (Exclusive or adjuvant)	P-PEG	ND	MWL : - At 1 mo. : 0.1% - At 3 mo. : 1.4% - At 6 mo. : 1.2% (p = 0.8517)	ND	Ability to eat - At the start of CRT : 60% - At 1 mo. : 34,3% - At 3 mo. : 34,3% - At 6 mo. : 51,4% (p = 0,0261)
Fong et al., 2023 [34]	Retrospective Cohort Study	No. : 49 Age : 60 Sex : 36 M, 13 F	HNC	RT alone or CRT (Exclusive or adjuvant)	P-PEG	Peristomal infection : 20% Bowel perforation and ileus : 2%	MWL : 5.6%	TT : 26.5% non-elective hospitalisation TC : Treatment break (2 days) : 1 patient	PEG dependence : Median use : 97 days Late dysphagia (3 years) : 6 patients
Kao et al., 2022 [35]	Retrospective Cohort Study	No. : 11 473 Age : 61.8 Sex : 11 361 M, 112 F	HNC	CRT (exclusive or adjuvant)	P-PEG vs. R-PEG	ND	BMI variation after 6 mo. : -3.3 (P-PEG) vs. -3.5 (R-PEG) (p = 0.06)	TT : 0.24 Hospitalizations rate per mo. (P-PEG) vs. 0.35 (Reactive PEG) (p < 0.001) Median OS (mo.) : 48.2 (P-PEG) vs. 47.2 (R-PEG) (HR 0, 97%, CI 0.89–1.04)	ND
Moleiro et al., 2016 [36]	Prospective Cohort Study	No. : 47 Age : 58 Sex : 41 M, 6 F	HNC	CRT (exclusive)	P-PEG	Peritonitis : 2% Buried bumper : 2% Peristomal infection : 36%	MWL at 30 days : - 76% lost weight and 22% lost > 10% of their initial weight - 11% maintained weight - 13% gained weight	ND	PEG dependence - Mean period of PEG use : 131 days - Mean duration of exclusive nutrition by PEG : 71 days - Long-term PEG need at one year : 19%
Neves et al., 2023 [37]	Retrospective Cohort Study	No. : 90 Age : 59.56 Sex : 76 M, 14 F	HNC	CRT (exclusive)	P-PEG vs. Control group	ND	BMI variation : no significant effect of PEG tube placement on BMI (p = 0.799).	TC : CT : 90% (P-PEG) vs. 66.7% (Control group) in the subgroup with baseline BMI < 18.5 kg/m2 OS and PFS : not statistically significant (p = 0.57 and p = 0.497, respectively).	ND
Peerawong et al., 2012 [38]	Retrospective Cohort Study	No. : 219 Age : 50.7 (PPEG), 48.7 (Control group) Sex : 152 M, 67 F	HNC	CRT (exclusive)	P-PEG vs. Control group	ND	MWL : - 9% (P-PEG) vs. 15.3% (Control group) (statistical signifiant calculated with Chi-squared test) - 29% developed ≥ 10% weight loss (P-PEG) vs. 74% (Control group) (p = 0.003)	TT : - 14.3% grade 3 hypokalemia (P-PEG) vs. 50% (Control group) (p = 0.002) TC : - RT : 96% (P-PEG) vs. 95% (Control group), no significant differences - CT : 79% (P-PEG) vs. 71% (Control group), no significant differences	ND
Raykher et al., 2009 [39]	Retrospective Cohort Study	No. : 163 Age : 58 Sex : 121 M, 42 F	HNC	CRT (exclusive or adjuvant)	P-PEG	Admission due to abdominal pain, infection, bleeding (n) : 15 Feeding-Related Complications : 28% constipation, 16% nausea, 10% vomiting, 5% diarrhea, 3% reflux symptoms	BMI variation : - Overweight patients : BMI of 27.3 +/- 1.5 to 24.6 +/- 2.7 (p < 0.001) - Obese patients : BMI of 33.0 +/- 3.4 to 28.4 +/- 4.8 (p < 0.001) - Normal BMI : BMI of 22.5 +/- 1.7 to 21.4 +/- 2 (p < 0.001) - Underweight patients : BMI of 17.7 +/- 1.1 to 19.1 +/- 2.2 (p = 0.09)	TT : - 45% Nausea - Hospitalizations unrelated to PEG : 46% TC : CRT interruption : 7%	Xerostomia : 73% Dysphagia : 70% Mucositis : 70% Decreased taste : 22% PEG dependence - Mean period of use : 251 +/- 317 days (range 19-1949 days) - 6 mo. : 42% - 12 mo. : 18%
Rutter et al., 2010 [40]	Retrospective Cohort Study	No. : 111 Age : 58 Sex : 92 M, 19 F	HNC	CRT (exclusive)	P-PEG vs. R-PEG	ND	MWL : - During CRT, P-PEG had significantly lower percentage weight-loss (p < 0.001, R = 0.495) - At 6 weeks : 14.8 pounds (P-PEG) vs. 26.2 pounds (R-PEG) (p = 0.003) - At 6 mo. : 12.2 pounds (P-PEG) vs. 26.7 pounds (R-PEG) (p = 0.011)	TT : - Decrease in total inpatient days in the P-PEG group (R = 0.21, p = 0.012) - Lower risk of admission for nutritionnal deficits in the P-PEG group (R = 0.26, p = 0.01) 2-year OS : 71% (p = 0.3) 2-year PFS : 52% (p = 0.5)	PEG dependence Median time : 4 mo. Disease control was the only predictor of PEG dependence following the completion of CRT.
Silander et al., 2010 [41]	Prospective Cohort Study	No. : 64 Age : 63 Sex : 43 M, 21 F	HNC	RT or CRT (exclusive or adjuvant)	P-PEG	Peristomal infection : 6,9% PEG tube fall out (n) : 1 Explorative laparotomy (n) : 1	MWL after 6 mo. : - 11.2% (8.8 kg) - 62% lost ≥ 10% of their baseline weight BMI evolution : 24.9 to 22.2 at 6 mo.	ND	PEG dependence : Mean period of use : 180 days Dysphagia at one year : All patients except four could manage to eat a normal or semi-solid diet
Thirayan et al., 2021 [42]	Retrospective Cohort Study	No. : 103 Age : 59 Sex : 90 M, 13 F	HNC	RT or CRT (exclusive or adjuvant)	P-PEG vs. R-PEG vs. Control group	No statistically significant difference was observed between P-PEG and R-PEG	MWL : No statistically-significant differences in weight loss were seen between groups	TT : 48% unplanned admissions during RT (P-PEG) vs. 87% (R-PEG) vs. 52% (Control group) (p = 0.03) TC : - RT delays (days) : 1.1 (R-PEG) vs. 0.4 (Control group) (p = 0.009) vs. 0.7 (P-PEG) (p = 0.18) - CT : 62% (P-PEG group) vs. 20% (R-PEG) vs. 63% (Control group) (p = 0.009) OFS and PFS : no significant difference between groups (p = 0.43 and p = 0.60 respectively)	PEG dependence : no significant differences between P-PEG and R-PEG
Xu et al., 2021 [43]	Retrospective Cohort Study	No. : 266 Age : 45 Sex : 200 M, 66 F	HNC	CRT (exclusive)	P-PEG vs. Control group	ND	ND	5-year OS : 84% (P-PEG) vs. 56.6% (Control group) (p = 0.026) 5-year PFS : 76% (P-PEG) vs. 45.6% (Control group) (p = 0.020)	ND
Yamazaki et al., 2016 [44]	Retrospective Cohort Study	No. : 27 Age : 69 (P-PEG), 70 (Control group) Sex : 25 M, 2 F	HNC	RT with Cetuximab	P-PEG vs. Control group	ND	MWL : - 8.8% (P-PEG) vs. 9.6% (Control group) - ≥ 10% weight-loss : 27% (P-PEG) vs. 75% (Control group) (p = 0.013)	TT : 7% leukopenia (P-PEG) vs. 67.5% (Control group) (p = 0.002). TC : RT : 100% in both grups 1-year PFS : 33.3% (P-PEG) vs. 33.3% (Control group) (p = 0.934) 1-year OS : 93.3% (P-PEG) vs. 73.3 (Control group) (p = 0.055)	Mucositis : - 47% Grade 3–4 mucositis (P-PEG) vs. 83% (Control group) (p = 0.058) PEG dependence : - Median time : 10.3 mo. - 46.6% removal within a year

Abbreviations BMI Body Mass Index (kg/m2), CRT Chemo-Radiotherapy, CT Chemotherapy, G Grade, HNC Head and Neck Cancer, Mo Month(s), MWL Mean weight loss, NGT NasoGastric Tube, ND Not Detailed, ONS Oral nutritional supplements, OS Overall Survival, PEG Percutaneous endoscopic gastrostomy, P-PEG Prophylactic Percutaneous endoscopic gastrostomy, PFS Progression Free Survival, R-PEG Reactive Percutaneous endoscopic gastrostomy, RT Radiotherapy, TC Treatment Completion, TT Treatment-Related Toxicity

¹ : Mean or median age in years. ² : M for male, F for female

Adverse events

Peristomal infections were the most common complication, reaching 36% in one study, though severe PEG-related events (e.g., buried bumper syndrome, peritonitis) remained rare (~ 2%) [34, 36].

Nutritional outcomes

P-PEG was associated with reduced weight loss during treatment. In two comparative studies, the proportion of patients experiencing ≥ 10% weight loss was 24–29% in the P-PEG groups versus 74–75% in controls [38, 44]. Greater reductions in weight loss were reported when oral intake was preserved alongside enteral feeding [32]. No additional benefit was observed with immediate versus standard timing of feeding initiation in either study [28, 29]. Among three studies comparing P-PEG to R-PEG, only one reported a significant reduction in weight loss in the prophylactic group [40].

Treatment-related outcomes

Treatment-related toxicity was generally similar between groups, but unplanned hospitalizations were less frequent with P-PEG compared to controls (75% vs. 82%, p = 0.029) or compared to R-PEG (48% vs. 87%, p = 0.03) [30, 42]. While CRT completion was higher in one study (62.3% in the P-PEG group vs. 41% in controls, p = 0.01) [26], this benefit was not consistently observed in others [29, 38, 42]. In contrast, R-PEG was associated with lower chemotherapy completion rates [38]. Timing of enteral nutrition initiation had no measurable impact on treatment completion [29]. No consistent survival benefit was observed, and only one study reported improved OS and PFS in the P-PEG group [43].

Functional and oral health-related outcomes

Despite PEG placement, mucositis remained highly prevalent, affecting 70% to 100% of patients [27, 39]. Prophylactic PEG was also associated with xerostomia (73%) and dysgeusia (22%) in one cohort [39]. Severe mucositis (grade ≥ 3–4) was significantly less frequent in the P-PEG group than in controls (47% vs. 83%) [44].

At one year, 18–19% of patients remained PEG-dependent, regardless of timing [36, 39], with persistent use primarily associated with poor disease control [40]. PEG dependence was significantly reduced when enteral feeding was combined with continued oral intake (51% vs. 17% at 6 months, p = 0.002) [32]. One study reported a markedly higher rate of dysphagia at 6 months in the P-PEG group compared to controls (34% vs. 5%, p = 0.001) [31].

Nasogastric Tube (NGT) feeding

Three studies assessed NGT feeding (Table 3) [45–47]. NGTs were inserted reactively, based on nutritional status.

Table 3.

Nasogastric Tube (NGT) studies

Authors	Study Design	No. of Patients	Disease Type	Treatment Modalities	Nutritional Management	Adverse Events	Nutritional Outcomes	Treatment-related outcomes	Functional and oral health-related outcomes
Clavel et al., 2011 [45]	Retrospective Cohort Study	No. : 253 Age1 : 57.5 Sex2 : 197 M, 56 F	HNC	CRT (exclusive)	NGT	ND	• MWL : 10.4%	TT : 43% Dermatitis, 29% Hospitalization TC : - RT : 97% RT - CT breaks : 13% 3-year OS : 82.8% 3-year PFS : 77.8% No survival difference was observed for all comparisons between NGT and control groups.	Mucositis : 67% NGT dependence : - Median time : 40 days. 3 - % of the patients were still dependent on enteral feeding at 6 mo.
Sheth et al., 2013 [46]	2-year audit	No. : 32 Age : 57.2 Sex : 27 M, 5 F	HNC	RT or CRT (exclusive or adjuvant)	NGT	Mean lenght of hospital stay for those admitted for NGT : 13 days No major complications from NGT insertion	ND	TC : None of the patients had their treatment stopped or delayed as a result of nutrition-related issues	NGT dependence - At 6 mo. : 90% had their tube removed and were managing full nutritional requirements orally - 86% of these required a modified consistency diet - 3 patients required a gastrostomy tube (ongoing dysphagia, disease progression limiting oral intake)
Zeng et al., 2025 [47]	Retrospective Cohort Study	No. : 856 Age : 56 Sex : 596 M, 260 F	HNC	CRT	NGT vs. PN	ND	MWL : 2,23% (NGT) vs. 4,82% (PN) (p = 0,027)	TT : - 17,3% Electrolyte Disturbance (NGT) vs. 25,2% (PN) (p = 0,041) - 5,7% Infection (NGT) vs. 14,1% (PN) (p = 0,028) TC : - RT : 100% (NGT) vs. 96,5% (PN) (p = 0,038) - Mean CRT cycles : 3 (NGT group) vs. 2 (PN) (p = 0,025) PFS post-radiotherapy : No statistically difference was observed between the groups	Mucositis - 77,4% Mucositis of ≥ grade 2 (NGT) vs. 94,1% (PN) (p = 0,032)

Abbreviations BMI Body Mass Index (kg/m2), CRT Chemo-Radiotherapy, CT Chemotherapy, HNC Head and Neck Cancer, Mo. Month(s), MWL Mean weight loss, NGT NasoGastric Tube, ND Not Detailed, ONS Oral nutritional supplements, OS Overall Survival, PFS Progression Free Survival, PN Parenteral Nutrition, RT Radiotherapy, TC Treatment Completion, TT Treatment-Related Toxicity

¹ : Mean or median age in years

² : M for male, F for female

Adverse events

No NGT-specific adverse events were reported across studies [45–47].

Nutritional outcomes

The mean weight loss during CRT was 10.4% and 2.23% [45, 47]. One study compared NGT with parenteral nutrition (PN) and reported a significantly lower mean weight loss in the NGT group [47].

Treatment-related outcomes

No nutrition-associated treatment delays were reported [46]. In contrast, CRT completion rates and the median number of CRT cycles were significantly higher in the NGT group than in the PN group [47]. Three-year OS and PFS were 82.2% and 77.8%, respectively, in the NGT group, with no significant differences compared to controls [45].

Functional and oral health-related outcomes

A 67% incidence of mucositis was reported among patients with NGT [45]. In direct comparison with parenteral nutrition, NGT feeding was associated with fewer cases of mucositis grade ≥ 2 (77.4% vs. 94.1%) [47].

Long-term NGT dependence remained low, ranging from 3% to 10% at 6 months, with a median duration of 40 days [45, 46]. Sheth et al. compared their findings with regional institutional data on PEG use, reporting fewer complications and faster oral intake recovery with NGT, although three patients ultimately required secondary PEG placement [46].

Comparative evaluation of nutritional modalities

Three studies compared nutritional support strategies in HNC patients undergoing RT or CRT (Table 4) [48–50]. Two studies compared P-PEG with nutritional counseling with reactive NGT placement based on clinical need [49, 50]. One study compared four approaches: P-PEG, R-PEG, NGT, and no artificial nutrition [48].

Table 4.

Comparative studies (PEG vs. NGT vs. ONS)

Authors	Study Design	No. of Patients	Disease Type	Treatment Modalities	Nutritional Management	Adverse Events	Nutritional Outcomes	Treatment-related outcomes	Functional and oral health-related outcomes
Nugent et al., 2010 [48]	Retrospective Cohort Study	No. : 196 Age1 : ND Sex2 : 149 M, 47 F	HNC	RT alone or CRT (exclusive)	NGT vs. P-PEG vs. R-PEG vs. Control group	ND	MWL : The method of enteral feeding did not statistically influence weight difference at the end of treatment	TC : The method of enteral feeding did not statistically influence unscheduled radiotherapy treatment interruptions	ND
Pramyothin et al., 2016 [49]	Prospective Cohort Study	No. : 95 Age : 56.4 (P-PEG), 53.4 (Control group) Sex : 75 H, 20 F	HNC	CRT (exclusive or adjuvant)	P-PEG vs. Control group (Nutritional counseling and NGT if required)	P-PEG : - Exit site infection (n) : 2 - Tube occlusion requiring tube revision (n) : 1	MWL : - 3.1 kg (P-PEG) vs. 4.8 kg (Control Group) (p = 0.04) - Weight loss ≥ 10% : 4% (P-PEG) vs. 24% (Control Group) (p = 0.03)	TT : - 8% Hematological toxicity (P-PEG) vs. 11% (Control group) TC : - RT breaks : 8% patients (P-PEG) vs. 10% (Control group) (p = 0.77) - CT breaks : 40% patients (P-PEG) vs. 41% (Control group) (p = 0.90)	Mucositis - 16% severe mucositis (P-PEG) vs. 13% (Control group)
Soria et al., 2017 [50]	Prospective Cohort Study	No. : 40 Age : 59 (P-PEG), 63 (Control group) Sex : 33 M, 7 F	HNC	RT or CRT (exclusive)	P-PEG vs. Control group (Nutritional counseling and NGT if required)	No severe complications were reported associated to enteral feeding No infections after PEG placement were encountered	MWL : No significant changes in weight (p = 0.338) BMI variation : No significant changes in BMI (p = 0.314)	ND	Feeding tube dependency : Patients in the PEG group received enteral nutrition support for a longer period of time (p = 0.007)

Abbreviations BMI Body Mass Index (kg/m2), CRT Chemo-Radiotherapy, CT Chemotherapy, HNC Head and Neck Cancer, MWL Mean weight loss, NGT NasoGastric Tube, ND Not Detailed, ONS Oral nutritional supplements, OS Overall Survival, PFS Progression Free Survival, PEG Percutaneous endoscopic gastrostomy, P-PEG Prophylactic Percutaneous endoscopic gastrostomy, RT Radiotherapy, TC Treatment Completion, TT Treatment-Related Toxicity

¹ : Mean or median age in years

² : M for male, F for female

Adverse events

Adverse events were not reported in comparative studies.

Nutritional outcomes

The four-arm study did not identify significant differences in weight loss between groups [48]. In contrast, one study comparing P-PEG to NGT reported significantly lower rates of severe weight loss (≥ 10%) in the P-PEG group (4% vs. 24%, p = 0.03) [49].

Treatment-related outcomes

Data comparing oral and treatment-related toxicities between groups were scarce. No significant differences in treatment completion were reported across groups [48, 49]. Survival outcomes were not reported in comparative studies.

Functional and oral health-related outcomes

P-PEG was associated with a longer duration of enteral feeding compared to NGT [50] .

Discussion

This systematic review critically appraises current nutritional interventions in HNC patients undergoing RT or CRT. While PEG, NGT, and ONS remain widely used, clear indications and comparative guidance remain insufficiently defined. This synthesis provides an up-to-date overview of nutritional care strategies, highlighting prevailing practices and unresolved challenges that may inform future research.

Adverse events

PEG placement was associated with higher rates of procedure-related complications, such as peristomal infections, although serious adverse events were rare [34, 36]. ONS and NGT were generally well tolerated, suggesting a more favorable safety profile. These findings emphasize the importance of a risk-benefit approach when selecting nutritional strategies. In patients at elevated risk for PEG-related complications, ONS or NGT may be considered as alternative options, provided that reliable clinical criteria can be applied to guide selection.

Nutritional outcomes

Among all interventions, P-PEG appeared to be associated with the most consistent benefit in minimizing weight loss, supporting its role as a preventive approach against treatment-related malnutrition. These nutritional outcomes are closely linked to oral health, as mucositis and dysphagia directly impair oral intake and contribute to weight loss.

However, this apparent superiority may be confounded by the disproportionate number of PEG-focused studies and underlying selection factors [26–44]. In contrast, data on NGT remain limited, and direct comparative evidence between PEG and NGT is scarce, precluding robust comparative conclusions [45, 46].

Early use of ONS improved short-term nutritional parameters but appeared insufficient as standalone support in high-risk patients, supporting its integration into a tiered nutritional program preceding escalation to enteral support. Overall, while PEG appears to have clinical utility, the current evidence lacks sufficient methodological balance and comparative depth to define a universally superior nutritional strategy.

Treatment-related outcomes

Nutritional support, particularly P-PEG and early ONS, was associated with improved RT/CRT completion and reduced unplanned hospitalizations [21, 24, 26, 42]. These findings highlight the potential benefit of early and structured nutritional intervention in supporting treatment delivery and limiting complications. Conversely, R-PEG was associated with lower chemotherapy completion rates and more frequent treatment delays, suggesting an adverse effect of delayed nutritional support [42]. A meta-analysis by Zhang et al. similarly reported that P-PEG was associated with the lowest rates of treatment interruption and hospitalization compared to R-PEG and NGT [51]. Although no treatment-related interruptions were reported in NGT studies, insufficient comparative data preclude firm conclusions [46]. Notably, few studies assessed patient-reported outcomes such as quality of life or swallowing function. Including these endpoints in future research will be essential to more fully capture the clinical value of early nutritional support in HNC care.

Most studies lacked sufficient statistical power to detect survival differences, and survival outcomes were neither uniformly collected nor consistently reported. An association between P-PEG and improved OS and PFS was reported in a single study only, precluding any definitive conclusions [43].

Functional and oral health-related outcomes

Oral health-related outcomes encompass both treatment-related toxicities and functional impairments affecting the oral cavity and swallowing function, and are closely interconnected with nutritional status in patients with head and neck cancer. Oral toxicities such as mucositis and dysphagia directly impair oral intake and contribute to malnutrition, while nutritional interventions may in turn influence treatment tolerance and the ability to maintain oral feeding.

Although these outcomes were reported in the majority of studies, substantial variability exists in the definitions, grading systems, and documentation of these events, which significantly limits the ability to synthesize and compare findings across investigations. Mucositis is consistently recognized as one of the most frequent and clinically consequential treatment-related toxicities in this population, reflecting the well-established mucosal injury induced by combined chemoradiotherapy (CRT) [20, 21, 24, 25, 27, 31, 39, 44, 45, 47, 49].

However, oral health-related outcomes were often reported as secondary endpoints, with inconsistent assessment of key functional measures such as swallowing function and maintenance or recovery of oral intake. This likely reflects the primary focus of most studies on nutritional and treatment-related outcomes, rather than a specific evaluation of oral health. Beyond mucositis, functional outcomes such as dysphagia, maintenance of oral intake, and feeding tube dependence were inconsistently reported, despite their importance for long-term functional recovery. Recent literature in head and neck cancer further emphasizes the relevance of these functional outcomes, including swallowing function and feeding tube dependence, as key determinants of patient recovery and quality of life [52].

As a result, the limited and heterogeneous reporting of these outcomes may partly explain why nutritional strategies appear to improve treatment delivery without consistently demonstrating benefits on oral toxicities.

Some evidence indicates that prophylactic PEG or NGT may reduce the incidence of severe mucositis compared with standard care or parenteral nutrition; however, comparative data evaluating different modes of nutritional support remain extremely limited, preventing definitive conclusions about the relative effectiveness of these approaches [44, 47]. Persistent high rates of mucositis despite current supportive care highlight an urgent and unmet need for enhanced preventive and therapeutic strategies.

PEG was associated with prolonged enteral feeding duration, which may be associated with persistent dysphagia and raises concerns regarding long-term functional impairment. However, evidence remains inconclusive. A randomized trial by Axelsson et al. reported no increased risk of long-term dysphagia in HNC patients receiving P-PEG [53]. Our findings suggest that early oral intake in PEG-fed patients, when clinically feasible, may be associated with reduced long-term tube-feeding dependence. Developing standardized predictive tools for long-term dysphagia could improve patient selection and help tailor nutritional strategies to individual risk profiles.

Overall, the close interplay between nutritional status, swallowing function, and oral intake underscores the need for future studies to better integrate oral health-related outcomes when evaluating nutritional strategies.

Short- and long-term outcomes

Taken together, these findings suggest that nutritional interventions in patients with head and neck cancer provide important short-term benefits, particularly in terms of weight maintenance, improved treatment completion, and reduction of unplanned hospitalizations. These findings support the role of early and proactive nutritional support in enhancing treatment tolerance and reducing acute treatment-related complications.

However, these short-term benefits must be balanced against potential long-term consequences. Several studies suggest that enteral feeding strategies, particularly PEG, may be associated with prolonged feeding tube dependence and persistent dysphagia, potentially reflecting delayed recovery of swallowing function and reduced maintenance of oral intake.

This apparent discrepancy may be partly explained by differences in patient selection, as patients receiving PEG often present with more advanced disease or higher baseline risk of dysphagia. In addition, early reliance on enteral feeding may reduce the use of oral intake during treatment, which could contribute to long-term functional impairment.

Overall, these findings highlight a time-dependent trade-off between short-term improvements in nutritional and treatment-related outcomes and long-term functional consequences, which should be carefully considered in clinical decision-making.

Patient-centered perspective

In the present review, the primary focus was placed on nutritional and treatment-related outcomes, particularly weight loss, as these represent the most consistently reported and comparable endpoints across studies.

However, this focus reflects both the scope of the review and the structure of the available literature, rather than the full spectrum of clinically meaningful outcomes. Endpoints such as swallowing function, maintenance of oral intake, and quality of life are of major importance, as they directly impact long-term functional recovery and patient autonomy.

The limited and inconsistent reporting of these outcomes highlights an important gap in the current evidence base. While weight-based outcomes remain central for evaluating nutritional interventions, their relevance as primary endpoints can be questioned when not integrated with functional and patient-centered measures.

Future research should therefore aim to better incorporate these outcomes to ensure that nutritional strategies are aligned with meaningful clinical goals.

Strengths and limitations

A key strength of this review lies in its inclusive synthesis of multiple nutritional interventions, including ONS, PEG (prophylactic and reactive) and NGT. By applying strict inclusion criteria and rigorous data extraction, this review provides a comprehensive evaluation of nutritional, clinical, and survival outcomes. The structured thematic analysis integrates nutritional and treatment-related metrics, offering a pragmatic overview that bridges clinical practice and current guideline recommendations.

Several limitations should be acknowledged. First, the review protocol was not registered in PROSPERO, which may limit transparency regarding protocol deviations. Nevertheless, the methodology was predefined and strictly followed in accordance with PRISMA 2020 guidelines.

The predominance of retrospective and non-randomized studies introduces inherent sources of bias. In particular, indication bias is likely to have influenced the observed associations, as the decision to initiate PEG was not randomized but based on clinical judgment. Consequently, patients receiving PEG may have had more advanced disease, poorer baseline nutritional status, or a higher risk of dysphagia, leading to potential confounding of the observed associations.

Therefore, the reported associations between PEG and outcomes such as reduced weight loss or improved treatment completion should be interpreted with caution, as they may reflect underlying patient characteristics rather than a true causal effect of the intervention. In addition, selection and survivorship biases may have contributed to an overestimation of the benefits associated with nutritional interventions.

This review is limited by substantial clinical and methodological heterogeneity across included studies. Differences in patient populations (tumor sites, histological subtypes), treatment settings (adjuvant versus definitive), and treatment modalities (RT versus CRT) may have affected comparability and the interpretation of findings. In addition, variability in outcome definitions, measurement methods, and follow-up durations limited direct comparisons and precluded quantitative synthesis.

Radiotherapy techniques likely varied across studies (2D, 3D, IMRT, VMAT), potentially influencing treatment-related toxicities and oral health-related outcomes; however, these parameters were inconsistently reported and unavailable in most studies, preventing any meaningful assessment of their impact. Similarly, the distinction between prophylactic PEG placement and the actual initiation of enteral feeding was often unclear, which may have affected the interpretation of nutritional and functional outcomes.

Although a structured narrative approach was used to group outcomes and identify consistent patterns, these sources of heterogeneity should be considered when interpreting the findings, as they may limit the robustness and generalizability of the conclusions.

Furthermore, the distribution of interventions across studies was unbalanced, with a predominance of studies evaluating PEG compared to NGT. This overrepresentation may influence the interpretation of results, while the limited number of direct comparative studies between PEG and NGT represents a significant evidence gap. Therefore, any comparative interpretation between PEG and NGT should be considered highly limited.

Future research should aim to standardize outcome definitions and reporting, and to provide higher-quality comparative data to enable more reliable conclusions.

Future directions and clinical implications

This review underscores the need for randomized trials directly comparing nutritional strategies, particularly PEG versus NGT, using clinically relevant endpoints, including weight loss, treatment toxicity, quality of life, swallowing function, and survival. Standardizing the timing of nutritional intervention and adopting consistent definitions of malnutrition are essential to improve comparability across studies. These findings are consistent with concerns raised by Xin Chen et al., who emphasized the urgent need for further high-quality evidence [54]. Recent literature has also highlighted the importance of treatment tolerance and supportive care in optimizing survival outcomes in patients with oral and oropharyngeal cancers, reinforcing the role of multidisciplinary management in this population [55].

In the last few years, technological developments in the medical field have been rapid and continuously evolving. One of the most revolutionizing breakthroughs has been the introduction of the Internet of Things (IoT) concept into medical practice. IoT-based technologies may facilitate remote monitoring, telemedicine, and early detection of treatment-related complications, potentially improving supportive care and nutritional monitoring in patients undergoing radiotherapy or chemoradiotherapy [56].

Similarly, advances in 18 F-FDG PET-CT–based radiotherapy planning have improved tumor delineation, staging accuracy, and treatment personalization. These approaches may help optimize radiation delivery and potentially reduce treatment-related toxicities affecting oral function and nutritional intake in head and neck cancer patients [57, 58].

In addition, 3D printing technologies are increasingly being integrated into medical practice. This additive manufacturing approach allows the conversion of digital models into physical objects, facilitating surgical planning, education, and personalized treatment strategies. These innovations may contribute to improved multidisciplinary management and functional preservation in head and neck cancer care [59].

From a clinical perspective, an important unresolved question concerns the identification of patients who would benefit most from prophylactic PEG placement and the selection between PEG and NGT in routine practice. However, the current evidence does not allow the establishment of clear, evidence-based criteria for patient selection or optimal nutritional strategy. Clinical decision-making therefore remains largely individualized, based on factors such as baseline nutritional status, tumor stage, expected treatment-related toxicity, and risk of dysphagia.

Taken together, these results highlight the complexity of nutritional decision-making in HNC patients and reinforce the need for individualized, evidence-based strategies that balance efficacy, safety, and long-term functional outcomes.

Conclusion

A tailored, stepwise nutritional approach, beginning with early ONS and escalating to enteral feeding as clinically indicated, may support treatment completion, reduce unplanned hospitalizations, and mitigate treatment-related toxicities in HNC patients undergoing RT or CRT. Prophylactic PEG appears to be associated with reduced weight loss and higher rates of treatment completion ; however, these findings should be interpreted with caution given the observational nature of the available evidence and the potential for indication bias. Concerns regarding long-term dysphagia and feeding tube dependence also remain. NGT may be associated with fewer device-related complications and lower long-term dependence, but comparative data on treatment delivery and survival remain limited, preventing definitive conclusions regarding their relative superiority. Oral toxicities, such as mucositis, persist as a critical, unresolved challenge, with current nutritional interventions offering no definitive evidence of clinical benefit. Overall, high-quality randomized studies are needed to clarify the optimal timing, sequencing, and selection of nutritional strategies in routine clinical practice.

Abbreviations

CRT

Chemoradiotherapy

CTCAE

Common terminology criteria for adverse events

GLIM

Global leadership initiative on malnutrition

HNC

Head and neck cancers

HPV

Human papillomavirus

MMAT

Mixed methods appraisal tool

NGT

Nasogastric tube

ONS

Oral nutritional supplements

OS

Overall survival

P-PEG

Prophylactic PEG

PEG

Percutaneous endoscopic gastrostomy

PFS

Progression-free survival

PN

Parenteral nutrition

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

R-PEG

Reactive PEG

RT

Radiotherapy

Authors’ contributions

C.B. performed the literature search, study selection, data analysis, and drafted the manuscript. C.W.B. and A.H. contributed to the study design, data interpretation, and critically revised the manuscript. All authors reviewed and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declarations

Ethics approval and consent to participate

This review did not directly involve human participants and did not require approval from an ethics committee or institutional review board.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.