Imaging the tumour microenvironment in rectal cancer: Decline in tumour blood flow during radiotherapy predicts good outcome

• DOI: 10.1016/j.phro.2023.100417
• Publication Date: 2023-01-23T07:26:05Z
• Authors: Kine Mari Bakke; Sebastian Meltzer; Endre Grøvik; Anne Negård; Stein Harald Holm...; Lars Tore Gyland ...; Arne Engebret Færden; Lars Gustav Lycka...; Frida Marie Ihle ...; Atle Bjørnerud; Kjell-Inge Gjesdal; Anne Hansen Ree; Kathrine Røe Redalen
• Keywords: R895-920; 610; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Blood flow; 3. Good health; Perfusion; Medical physics. Medical radiology. Nuclear medicine; 03 medical and health sciences; 0302 clinical medicine; Response assessment; Original Research Article; Rectal cancer; RC254-282; MRI

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).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.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.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.