Associations between patient-reported late effects and systemic cytokines in long-term survivors of head and neck cancer treated with radiotherapy

J Cancer Surviv. 2023 Aug;17(4):1082-1093. doi: 10.1007/s11764-022-01273-1. Epub 2022 Nov 9.

Abstract

Purpose: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects.

Methods: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls.

Results: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls.

Conclusions: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls.

Implications for cancer survivors: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.

Keywords: Head and neck cancer survivors; Health-related quality of life; Late effects; Patient-reported outcomes; Pro-inflammatory cytokines; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cancer Survivors*
  • Cross-Sectional Studies
  • Cytokines* / blood
  • Deglutition Disorders* / blood
  • Deglutition Disorders* / epidemiology
  • Fatigue Syndrome, Chronic* / blood
  • Fatigue Syndrome, Chronic* / epidemiology
  • Female
  • Head and Neck Neoplasms* / radiotherapy
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Quality of Life
  • Surveys and Questionnaires
  • Xerostomia* / blood
  • Xerostomia* / epidemiology

Substances

  • Cytokines