Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome. (January 2023)

• Record Type: Journal Article
• Authors: Bakke, Kine Mari; Meltzer, Sebastian; Grøvik, Endre; Negård, Anne; Holmedal, Stein Harald; Mikalsen, Lars Tore Gyland; Færden, Arne Engebret; Lyckander, Lars Gustav; Julbø, Frida Marie Ihle; Bjørnerud, Atle; Gjesdal, Kjell-Inge; Ree, Anne Hansen; Redalen, Kathrine Røe
• Is Part Of: Physics and imaging in radiation oncology. Volume 25(2023)
• Publication Date: 2023-01
• Subjects: Perfusion -- Blood flow -- MRI -- Rectal cancer -- Response assessment; Radiotherapy -- Periodicals; Radiation dosimetry -- Periodicals; Cancer -- Imaging -- Periodicals; Oncology -- Periodicals; 615.842
• DOI: 10.1016/j.phro.2023.100417
• Languages: English
• ISSNs: 2405-6316

Abstract

Graphical abstract: Highlights: Tumour perfusion was measured by magnetic resonance imaging in rectal cancer. A decline in tumour perfusion during radiotherapy predicted favourable outcome. The perfusion measurements were supported by CD34 staining of tumour specimens. Abstract: Background and purpose: Measuring rectal tumour response to radiation is pivotal to restaging patients and for possibly stratification to a watch-and-wait strategy. Recognizing the importance of the tumour microenvironment, we investigated a less explored quantitative imaging marker assessing tumour blood flow (BF) for its potential to predict overall survival (OS). Materials and methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for quantification of tumour BF before either 25x2 Gy (n = 18) with concomitant chemotherapy or 5x5 Gy (n = 6). CD34 staining of excised tumour tissue was performed and baseline blood samples were analysed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumour volumes were measured before and after treatment. After subsequent surgery, ypTN scoring assessed tumour response. Cox regression for 5-year OS analysis and t -test for group comparisons were performed. Results: The change in tumour BF (ΔBF) during neoadjuvant radiotherapy was a significant marker of OS, whereas tumour stage and volume were not related to OS. All patients with >20 % decline in BF were long-term survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline LDH (p = 0.032) and ANGPT-2 (p = 0.028) levels. Conclusion: MRI-assessed tumour ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential quantitative imaging biomarker for treatment stratification. Blood LDH and ANGPT-2 indicate that non-responding tumours may have a hypoxic microenvironment resistant to radiotherapy.