Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy

Brain Behav Immun. 2010 Aug;24(6):968-74. doi: 10.1016/j.bbi.2010.03.009. Epub 2010 Mar 29.

Abstract

Elevations in cancer treatment-induced circulating inflammatory cytokines may be partially responsible for the development of significant symptom burden (e.g., pain, fatigue, distress, disturbed sleep) during concurrent chemoradiation therapy (CXRT). Sixty-two patients undergoing CXRT for locally advanced non-small cell lung cancer (NSCLC) reported symptoms weekly for 15 weeks via the M. D. Anderson Symptom Inventory (MDASI). Serum inflammatory cytokines were assessed weekly during therapy via enzyme-linked immunosorbent assay. Dynamic changes in cytokines and associated symptom profiles were estimated using mixed-effect models. MDASI symptom severity increased gradually as CXRT dose accumulated and peaked at week 8. Serum concentrations of interleukin (IL)-6, IL-10, and serum soluble receptor 1 for tumor necrosis factor (sTNF-R1) increased significantly by week 8 (all p<.05). During CXRT, controlled for age, sex, race, body mass index, cancer recurrence, previous treatment status, total radiotherapy dose, and CXRT delivery technique, an increase in sTNF-R1 was significantly related to an increase in the mean score for all 15 MDASI symptoms (estimate, 1.74; SE, 0.69; p<.05) and to a larger radiation dose to normal lung volume (estimate, 1.77; SE, 0.71; p<.01); an increase in serum IL-6 was significantly related to increased mean severity for the five most severe symptoms (pain, fatigue, disturbed sleep, lack of appetite, sore throat) (estimate, 0.32; SE, 0.16; p<.05). These results suggest a role for over-expressed pro-inflammatory cytokines in significant worsening of symptoms in NSCLC patients undergoing CXRT, and warrant further study to identify biological targets for ameliorating treatment-related symptom burden.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / complications*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Combined Modality Therapy
  • Cost of Illness
  • Cytokines / blood
  • Cytokines / physiology*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Longitudinal Studies
  • Lung Neoplasms / complications*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / radiotherapy
  • Male
  • Middle Aged
  • Receptors, Tumor Necrosis Factor, Type I / biosynthesis
  • Receptors, Tumor Necrosis Factor, Type I / genetics
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antineoplastic Agents
  • Cytokines
  • Interleukin-6
  • Receptors, Tumor Necrosis Factor, Type I
  • Tumor Necrosis Factor-alpha
  • Interleukin-10