title: Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy.
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.
authors.affiliation: Department of Symptom Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. xswang@mdanderson.org
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Shi
authors.forename: Loretta A
authors.initials: LA
authors.lastname: Williams
authors.forename: Li
authors.initials: L
authors.lastname: Mao
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cleeland
authors.forename: Ritsuko R
authors.initials: RR
authors.lastname: Komaki
authors.forename: Gary M
authors.initials: GM
authors.lastname: Mobley
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D003131:Combined Modality Therapy; D017281:Cost of Illness; D016207:Cytokines / Q000097:blood / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D015850:Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10