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Peer-reviewedCC BY-NC-NDSupportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Beyond reduced intake: tumor metabolism and immune dysregulation drive cancer-related malnutrition in head and neck squamous cell carcinoma (HNSCC).

  • Vincenzo Zurlo1
  • Arianna Piccirillo2
  • Maria Luisa Marciano3
  • Monica Pontone3
  • Fabiana Raffaella Rampetta3
  • Erica Perri4
  • Francesco Perri3
4 affiliations
  1. 1Nutrition and Supportive Care Unit, ASL Napoli 3, Naples, Italy.
  2. 2Head and Neck Oncology Unit, Istituto Nazionale Tumori Di Napoli IRCCS 'G. Pascale', Naples, Italy. [email protected].
  3. 3Head and Neck Oncology Unit, Istituto Nazionale Tumori Di Napoli IRCCS 'G. Pascale', Naples, Italy.
  4. 4Medical Oncology Unit, Università Degli Studi Della Campania Luigi Vanvitelli, Caserta, Italy.
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Abstract

Cancer-related malnutrition is highly prevalent in patients with head and neck squamous cell carcinoma (HNSCC) and represents a major determinant of treatment tolerance, quality of life, and survival. Although traditionally attributed to reduced oral intake caused by dysphagia, mucositis, and treatment-related toxicity, increasing evidence indicates that malnutrition in HNSCC is largely driven by tumor-induced metabolic and inflammatory alterations. Enhanced aerobic glycolysis, systemic inflammation, and tumor-derived factors promote hypermetabolism, substrate redistribution, and progressive skeletal muscle depletion. Within this immune-metabolic framework, the tumor behaves as a metabolic sink, redirecting glucose, lipids, and amino acids from host tissues to sustain its growth, thereby contributing to energy wasting and sarcopenia independently of caloric intake. Recent clinical data support the translational relevance of this model. Imaging-based assessment of body composition at the third cervical vertebra (C3) and metabolic imaging parameters such as total lesion glycolysis (TLG) provide measurable indicators of tumor metabolic burden and its association with skeletal muscle loss and nutritional risk. Integrating metabolic imaging, inflammatory biomarkers, and body composition analysis may enable earlier identification of patients at high risk of malnutrition and treatment-related toxicity. This review integrates these complementary biological and imaging domains into a unified immune-metabolic framework for nutritional risk stratification in HNSCC. Recognizing cancer-related malnutrition in HNSCC as a tumor-driven immune-metabolic syndrome has important therapeutic implications. Early immune-metabolic nutritional strategies, rather than reactive caloric supplementation alone, may represent a key component of integrated oncologic care aimed at preserving lean body mass and improving clinical outcomes.

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Cite

BibTeXRIS
BibTeX
@article{zurlo2026beyond,
  title = {{Beyond reduced intake: tumor metabolism and immune dysregulation drive cancer-related malnutrition in head and neck squamous cell carcinoma (HNSCC).}},
  author = {Vincenzo Zurlo and Arianna Piccirillo and Maria Luisa Marciano and Monica Pontone and Fabiana Raffaella Rampetta and Erica Perri and Francesco Perri},
  journal = {Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer},
  year = {2026},
  month = oct,
  doi = {10.1007/s00520-026-11115-w},
  url = {https://europepmc.org/article/MED/42832090},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Beyond reduced intake: tumor metabolism and immune dysregulation drive cancer-related malnutrition in head and neck squamous cell carcinoma (HNSCC).
AU  - Vincenzo Zurlo
AU  - Arianna Piccirillo
AU  - Maria Luisa Marciano
AU  - Monica Pontone
AU  - Fabiana Raffaella Rampetta
AU  - Erica Perri
AU  - Francesco Perri
PY  - 2026
DA  - 2026/10/05
JO  - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
DO  - 10.1007/s00520-026-11115-w
UR  - https://europepmc.org/article/MED/42832090
AB  - Cancer-related malnutrition is highly prevalent in patients with head and neck squamous cell carcinoma (HNSCC) and represents a major determinant of treatment tolerance, quality of life, and survival. Although traditionally attributed to reduced oral intake caused by dysphagia, mucositis, and treatment-related toxicity, increasing evidence indicates that malnutrition in HNSCC is largely driven by tumor-induced metabolic and inflammatory alterations. Enhanced aerobic glycolysis, systemic inflammation, and tumor-derived factors promote hypermetabolism, substrate redistribution, and progressive skeletal muscle depletion. Within this immune-metabolic framework, the tumor behaves as a metabolic sink, redirecting glucose, lipids, and amino acids from host tissues to sustain its growth, thereby contributing to energy wasting and sarcopenia independently of caloric intake. Recent clinical data support the translational relevance of this model. Imaging-based assessment of body composition at the third cervical vertebra (C3) and metabolic imaging parameters such as total lesion glycolysis (TLG) provide measurable indicators of tumor metabolic burden and its association with skeletal muscle loss and nutritional risk. Integrating metabolic imaging, inflammatory biomarkers, and body composition analysis may enable earlier identification of patients at high risk of malnutrition and treatment-related toxicity. This review integrates these complementary biological and imaging domains into a unified immune-metabolic framework for nutritional risk stratification in HNSCC. Recognizing cancer-related malnutrition in HNSCC as a tumor-driven immune-metabolic syndrome has important therapeutic implications. Early immune-metabolic nutritional strategies, rather than reactive caloric supplementation alone, may represent a key component of integrated oncologic care aimed at preserving lean body mass and improving clinical outcomes.
SN  - 0941-4355
SN  - 1433-7339
ER  -