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Human cytomegalovirus and Epstein-Barr virus infection impact on 18F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

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 (18F-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).

Conclusion

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.

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Acknowledgments

This study was financed in part by a research grant from Mutua Madrileña Biomedical, Foundation Institute Health Research Marañón (study code CMF, FMM 06-02).

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Instituto de Radiomedicina, Santiago, Chile

    Claudio V. Sole

  2. Department of Oncology, Hospital General Universitario Gregorio Marañón, C/ Doctor Esquerdo, 46, 28007, Madrid, Spain

    Felipe A. Calvo

  3. School of Medicine Complutense University, Madrid, Spain

    Claudio V. Sole, Felipe A. Calvo, Emilio Alvarez & Jose L. Carreras

  4. Department of Pathology, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Emilio Alvarez

  5. Institute for Sanitary Research, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Felipe A. Calvo & Emilio Alvarez

  6. Institute of Oncology, Hospital Provincial de Castellon, Castellon de la Plana, Spain

    Carlos Ferrer & Enrique Ochoa

  7. School of Medicine Cardenal Herrera-CEU University, Castellon de la Plana, Spain

    Carlos Ferrer

  8. Department of Radiology and Medical Physics, Hospital General Universitario Gregorio Marañón, Madrid, Spain

    Jose L. Carreras

Authors
  1. Claudio V. Sole
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  2. Felipe A. Calvo
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Corresponding author

Correspondence to Felipe A. Calvo.

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Sole, C.V., Calvo, F.A., Ferrer, C. et al. Human cytomegalovirus and Epstein-Barr virus infection impact on 18F-FDG PET/CT SUVmax, CT volumetric and KRAS-based parameters of patients with locally advanced rectal cancer treated with neoadjuvant therapy. Eur J Nucl Med Mol Imaging 42, 186–196 (2015). https://doi.org/10.1007/s00259-014-2910-8

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  • DOI: https://doi.org/10.1007/s00259-014-2910-8

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