Abstract 5269: Imaging the tumor microenvironment in rectal cancer: Decline in tumor blood flow (BF) during neoadjuvant treatment predicts excellent outcome
Authors: Bakke Kine M. , Meltzer Sebastian , Grøvik Endre , Negård Anne , Holmedal Stein H. , Lyckander Lars G. , Færden Arne E. , Bjørnerud Atle , Gjesdal Kjell-Inge , Ree Anne H. , Redalen Kathrine R. 
Published: June 2022

Abstract
Introduction: A watch-and-wait strategy for rectal cancer patients may possibly omit surgery after neoadjuvant treatment. To optimally stratify patients for such strategy, reliable and preferably non-invasive biomarkers that repeatedly can assess neoadjuvant therapy response are needed. Recognizing the importance of the tumor microenvironment, we investigated a less explored imaging marker assessing tumor BF for its potential to predict overall survival (OS).
Methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy (RT) underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for estimation of tumor BF before either 25x2 Gy (n=18) with concomitant chemotherapy or 5x5 Gy (n=6). 4-7 weeks post-RT the MRI was repeated. Baseline blood samples were analyzed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumor volumes were measured before and after RT. After the subsequent surgery, ypT scoring assessed tumor RT response. Cox regression for OS analysis and t-test for group comparisons were performed.
Results: 7 patients were non-survivors and the median follow-up for survivors was 55 months (range, 44-60). The change in tumor BF (ΔBF) during neoadjuvant RT was identified as a significant marker of OS (Table). Tumor stage and volume were not significant. All patients with more than 20% decline in BF were survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline levels of LDH (p = 0.032) and ANGPT-2 (p = 0.028).
Discussion: MRI-assessed tumor ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential biomarker for treatment stratification in a watch-and-wait strategy. Blood LDH and ANGPT-2 indicate that non-responding tumors may have a hypoxic microenvironment insusceptible to RT.
Parameter Hazard ratio for impaired OS p-value Tumor stage 1.08 [0.40-2.95] 0.88 ypT score of the surgical specimen 1.54 [0.76-3.12] 0.23 RT fractionation (25x2 Gy versus 5x5 Gy) 2.24 [0.50-9.90] 0.29 Baseline BF 0.96 [0.92-1.00] 0.05 Post-RT BF 1.02 [1.00-1.04] 0.11 ΔBF 1.03 [1.01-1.05] 0.01 Baseline tumor volume 1.01 [0.99-1.04] 0.43 Post-RT tumor volume 1.01 [0.98-1.05] 0.42 Δtumor volume 1.03 [0.99-1.07] 0.15
Citation Format: Kine M. Bakke, Sebastian Meltzer, Endre Grøvik, Anne Negård, Stein H. Holmedal, Lars G. Lyckander, Arne E. Færden, Atle Bjørnerud, Kjell-Inge Gjesdal, Anne H. Ree, Kathrine R. Redalen. Imaging the tumor microenvironment in rectal cancer: Decline in tumor blood flow (BF) during neoadjuvant treatment predicts excellent outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5269.