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537 Integrative analysis of DCE-MRI and gene expression profiles in patients with cervical cancer undergoing pelvic exenteration
  1. Hanna Valstad1,2,
  2. Tord Hompland3,
  3. Christina S Fjeldbo3,
  4. Tone Skeie-Jensen1,
  5. Brynhildur Eyjolfsdottir1,
  6. Gunnar B Kristensen1,4,
  7. Kjersti V Lund5,6,
  8. Heidi Lyng3,7 and
  9. Kristina Lindemann1,2
  1. 1Department of Gynaecological Oncology, Division of Cancer Medicine, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
  2. 2Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
  3. 3Department of Radiation Biology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
  4. 4Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway
  5. 5Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
  6. 6Department of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
  7. 7Department of Physics, University of Oslo, Oslo, Norway


Introduction/Background Patients with cervical cancer undergoing pelvic exenteration still face poor prognosis as almost half of the patients recur. There is a clear need for better understanding of prognostic biomarkers to identify those patients with a high likelihood to benefit from exenterative surgery.

Methodology This retrospective cohort study included 19 patients with cervical cancer treated with pelvic exenteration at Oslo University Hospital (OUH). All patients had diagnostic dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and accessible tumour material for gene expression profiling. The image parameters Ktrans and ve (fractional volume), reflecting tumor perfusion and extracellular extravascular space, respectively, were calculated for each voxel of the DCE-MR images, using the Tofts pharmacokinetic model. RNA was extracted from paraffin-embedded tissue and analysed with RNA-sequencing, using the QuantSeq technology. Gene expression profiles of patients with and without recurrence were compared, and the differentially expressed genes were subjected to gene set enrichment analysis (GSEA). Clinical data including complete follow up was available in the quality assurance database.

Results After a median follow up time of 5 years for non-recurrent patients, 10 patients had recurred. There was no significant association between tumor volume and recurrence. Patients with recurrence had significantly higher Ktrans on DCE-MRI compared to patients without recurrence (p=0.002). There was no significant difference in ve between the two patient groups. Totally 62 genes were found to be significantly upregulated and 17 genes were downregulated in patients with recurrence. GSEA analysis of the upregulated genes showed significant enrichment of biological processes related to vascular function.

Conclusion Increased tumor perfusion measured on DCE-MRI is a possible poor prognostic factor for patients with cervical cancer undergoing pelvic exenteration. Gene expression pattern supports this role of neovascularization and abnormal blood vessels in prognosis. If these findings can be validated, this may help to select patients to exenterative surgery.

Disclosures KL: Receipt of grants/research supports: GSK, research funding paid to

Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisai

GK: Stockholder: Novo Nordic

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