The OxyTarget study

The OxyTarget study – Functional MRI of Hypoxia-Mediated Rectal Cancer Aggressiveness [ClinicalTrials NCT01816607] (PI: Røe Redalen) aims to identify novel imaging biomarkers of hypoxia-induced rectal cancer aggressiveness, in order to reliably predict patients with poor response to chemoradiotherapy and high risk of poor metastasis-free survival at time of diagnosis. Study accrual commenced fall-term 2013 and study participation is offered to all rectal cancer patients treated at Akershus University Hospital.

Collection of tumor biopsies and whole-tissue surgical specimens provide unique opportunities for correlating MRI parameters with immunohistological markers of tumor hypoxia and large-scale molecular profiling analysis. Various blood samples are collected and an integral component of the project is characterization of circulating exosomes as ‘liquid biopsy’ biomarkers within the context of RRNEV [www.extracellularvesicles.no].

The portfolio of functional MRI sequences employed includes diffusion-weighted (DW) MRI, dynamic contrast-enhanced (DCE) MRI, blood oxygenation level dependent (BOLD) MRI, dynamic susceptibility contrast (DSC) MRI and MR spectroscopy. The DCE MRI and DSC MRI sequences are implemented into one split dynamic sequence where images are acquired during a single contrast agent injection, providing both high spatial- and high temporal resolution images. All of these sequences will provide a range of intratumoral characteristics, including tissue structure, metabolism, angiogenesis, permeability, perfusion, and tumor hypoxia, in addition to detailed morphology.

One subproject is to use functional MRI data as input to radiotherapy plans to explore how hypoxic imaging data may be utilized to optimize radiotherapy planning and predict treatment outcome. Such information may have clinical applicability for how rectal cancer patients should be stratified to treatment individualization, such as radiation dose escalation to hypoxic tumor components through application of intensity-modulated radiotherapy or boosting techniques.

PUBLICATIONS

Meltzer S, Bjørnetrø T, Lyckander LG, Flatmark K, Dueland S, Samiappan R, Johansen C, Kalanxxhi E, Ree AH, Redalen KR. Circulating exosomal miR-141-3p and miR-375 in metastatic progression of rectal cancer. Transl Oncol 2019; 12(8): 1038-44.
Bakke KM, Grøvik E, Meltzer S, Negård A, Holmedal SH, Mikalsen LTG, Lyckander LG, Ree AH, Gjesdal KG, Redalen KR, Bjørnerud A. Comparison of Intravoxel incoherent motion imaging and multiecho dynamic contrast-based MRI in rectal cancer. J Magn Reson Imaging 2019; 50(4): 1114-24.
Bjørnetrø T, Redalen KR, Meltzer S, Thusyanthan NS, Samiappan R, Jegerschöld C, Handeland KR, Ree AH. An experimental strategy unveiling exosomal microRNAs 486-5p, 181a-5p and 30d-5p from hypoxic tumour cells as circulating indicators of high-risk rectal cancer. J Extracell Vesicles 2019; 8(1): 1567219, DOI: 10.1080/20013078.2019.1567219
Bousquet PA, Meltzer S, Sønstevold L, Esbensen Y, Dueland S, Flatmark K, Sitter B, Bathen TF, Seierstad T, Redalen KR, Eide L, Ree AH. Markers of mitochondrial metabolism in tumor hypoxia, systemic inflammation, and adverse outcome of rectal cancer. Transl Oncol 2019; 12(1): 76-83.
Grøvik E, Redalen KR, Storås TH, Negård A, Holmedal SH, Ree AH, Meltzer S, Bjørnerud A, Gjesdal KI. Dynamic multi-echo DCE- and DSC-MRI in rectal cancer: low primary tumor R2* peak is significantly associated with lymph node metastasis. J Magn Reson Imaging 2017; 46(1): 194-206.

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