title: Human cytomegalovirus and Epstein-Barr virus infection impact on (18)F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy.
abstract: OBJECTIVE
  It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic ((18)F-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer.
  
  
  METHODS
  HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox proportional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93%, 74% and 71%, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p = 0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p < 0.01) and EBV infection (p < 0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p <0.01) and HCMV/EBV co-infection (p = 0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p = 0.88 and 0.73), HCMV infection (p = 0.84 and 0.79), and EBV/CMV coinfection (p = 0.24 and 0.39).
  
  
  CONCLUSIONS
  This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and restaging. Further toxicity profile findings will help to determine the best candidates for specific supportive treatment during pelvic chemoradiotherapy in patients with locally advanced rectal cancer.
authors.affiliation: Department of Radiation Oncology, Instituto de Radiomedicina, Santiago, Chile.
authors.forename: Claudio V
authors.initials: CV
authors.lastname: Sole
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Calvo
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrer
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez
authors.forename: Jose L
authors.initials: JL
authors.lastname: Carreras
authors.forename: Enrique
authors.initials: E
authors.lastname: Ochoa
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D003586:Cytomegalovirus Infections / Q000150:complications / Q000000981:diagnostic imaging*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000000981:diagnostic imaging*; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D020360:Neoadjuvant Therapy; D049268:Positron-Emission Tomography; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012004:Rectal Neoplasms / Q000150:complications / Q000000981:diagnostic imaging* / Q000235:genetics / Q000628:therapy; D014057:Tomography, X-Ray Computed; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins