External Validation of Early Regression Index (ERI_TCP) as Predictor of Pathologic Complete Response in Rectal Cancer Using Magnetic Resonance-Guided Radiation Therapy

Purpose: Tumor control probability (TCP)-based early regression index (ERI_TCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERI_TCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels.

Methods and materials: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERI_TCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERI_TCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index.

Results: Fourteen patients showed pCR. ERI_TCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERI_TCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99).

Conclusions: This study confirmed the validity and the robustness of ERI_TCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.