title: Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study.
abstract: OBJECTIVE
  Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach.
  
  
  METHODS
  Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45-50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity.
  
  
  RESULTS
  Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident.
  
  
  CONCLUSIONS
  This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted.
authors: School of Medical Sciences, University of Adelaide, Adelaide, Australia. joanne.bowen@adelaide.edu.au.
authors: J M
authors: JM
authors: Bowen
authors: School of Medicine, University of Adelaide, Adelaide, Australia.
authors: I
authors: I
authors: White
authors: Discipline of Surgery, University of Adelaide, Adelaide, Australia.
authors: L
authors: L
authors: Smith
authors: Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia.
authors: A
authors: A
authors: Tsykin
authors: School of Medicine, University of Adelaide, Adelaide, Australia.
authors: K
authors: K
authors: Kristaly
authors: Discipline of Surgery, University of Adelaide, Adelaide, Australia.
authors: S K
authors: SK
authors: Thompson
authors: School of Medicine, Flinders University, Bedford Park, Australia.
authors: C S
authors: CS
authors: Karapetis
authors: RAH Cancer Centre, Royal Adelaide Hospital, Adelaide, Australia.
authors: H
authors: H
authors: Tan
authors: Discipline of Surgery, University of Adelaide, Adelaide, Australia.
authors: P A
authors: PA
authors: Game
authors: Department of Surgery, Flinders University, Adelaide, South Australia, Australia.
authors: T
authors: T
authors: Irvine
authors: Department of Surgery, Flinders University, Adelaide, South Australia, Australia.
authors: D J
authors: DJ
authors: Hussey
authors: Department of Surgery, Flinders University, Adelaide, South Australia, Australia.
authors: D I
authors: DI
authors: Watson
authors: School of Medicine, University of Adelaide, Adelaide, Australia.
authors: D M K
authors: DM
authors: Keefe
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005720:Gamma Rays; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy; D010865:Pilot Projects; D012333:RNA, Messenger / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin; D005472:Fluorouracil
keywords: Chemoradiation; Esophageal cancer; Mucositis; RT-PCR; Toxicity