Linear Tumor Regression of Rectal Cancer in Daily MRI during Preoperative Chemoradiotherapy: An Insight of Tumor Regression Velocity for Personalized Cancer Therapy

SIMPLE SUMMARY: We primarily assessed the pattern of tumor regression throughout the full course of CCRT using daily registration MRI (25 sets of MRI per patient) and, for the first time, observed in vivo linear tumor regression in daily MRI. Secondly, we investigated if the velocity of tumor regression had an effect on DFS of locally advanced rectal cancer and found its potential as a biomarker for real-time treatment response and further treatment decision. We believe this study makes a significant contribution to the literature compared to previous reports, especially by first demonstrating the linear pattern of daily tumor regression during neoadjuvant CCRT in an in vivo setting. We also suggested the potential value of tumor regression velocity as a marker for further treatment decisions in a disease with diverse treatment options, such as locally advanced rectal cancer. ABSTRACT: Objective: Neoadjuvant chemoradiotherapy (CCRT) is current standards of care for locally advanced rectal cancer. The precise and thorough investigation of a tumor during the full course of CCRT by means of daily MRI can provide an idea on real-time treatment sensitivity in addition to tumor biology. Tumor volumetry from daily MRI during CCRT may allow patient-driven treatment decisions. Material and Methods: Patients diagnosed with cT3-4 and/or cN+ rectal adenocarcinoma undergoing preoperative CCRT with capecitabine on the pelvis up to 50 Gy in 25 daily fractions from November 2018 to June 2019 were consecutively included. Rectal tumor volume was uniformly measured by a single physician (YKK) in daily 0.35T MRI obtained with MR-guided linear accelerator. Primary endpoint was to assess the pattern of tumor volume regression throughout the full course of CCRT using daily registration MRI. Secondary endpoint was to assess the effect of tumor regression velocity on disease-free survival (DFS). Tumor regression velocity (cc) per fraction of each patient was calculated using the simple regression analysis of tumor volumes from fraction 1 to fraction 25. Results: Twenty patients were included. Daily tumor volumetry demonstrated linear tumor regression during CCRT. The tumor regression velocity of all 20 patients was 2.40 cc per fraction (R(2) = 0.93; p < 0.001). The median tumor regression velocity was 1.52 cc per fraction. Patients with tumor regression velocity ≥ 1.52 cc per fraction were grouped as rapid regressors (N = 9), and those with tumor regression velocity < 1.52 cc per fraction were grouped as slow regressors (N = 11). Rapid regressors had greater tumor regression velocity (4.58 cc per fraction) compared to that of slow regressors (0.78 cc per fraction) with statistical significance (p < 0.001). The mean DFS of rapid regressors was 36.8 months, numerically longer than the 31.9 months of slow regressors (p = 0.400) without statistical significance. Rapid regressors had numerically superior DFS rate compared to slow regressors without statistical significance. The 2-year DFS was 88.9% for rapid regressors and 72.7% for slow regressors, respectively (p = 0.400). Conclusion: This study is the first observation of linear tumor regression in daily MRI during the preoperative CCRT of locally advanced rectal cancer. Daily tumor regression velocity discriminated DFS, although without statistical significance. This study with a phenomenal approach is hypothesis-generating. Nevertheless, the potential of CCRT from therapeutics to a newer level, the “theranostics”, has been inceptively suggested. Further validation studies for the value of daily tumor volumetry on treatment decisions are warranted.