Clinical Impact of Contouring Variability for Prostate Cancer Tumor Boost.

Abstract

In the FLAME randomized phase III trial, adding a focal radiotherapy (RT) boost to tumors visible on MRI improved prostate cancer disease-free survival, local control, and regional/distant metastasis-free survival without increasing toxicity. In a prospective study (ReIGNITE RT Boost), we found substantial variability in radiation oncologists' attempts to contour prostate cancer tumors on MRI. Participants' accuracy and reliability improved when they used a quantitative MRI biomarker for cancer called the restriction spectrum imaging restriction score (RSIrs). Here, we measure the impact of radiation oncologists' tumor contour attempts on RT plans and predicted probability of biochemical failure. A total of 44 radiation oncologists (participants) from multiple institutions contoured prostate tumors on 30 patient cases, some with only conventional MRI and some with conventional MRI plus RSIrs maps. We developed a knowledge-based planning automated algorithm to generate RT plans with focal tumor boost per the FLAME trial protocol: 77 Gy in 35 fractions to prostate and integrated boost up to 95 Gy to the focal target, provided no normal tissue constraints were violated. We applied this algorithm to each participant's tumor contour and compared dosimetric parameters to those achieved when using the expert-defined tumor (consensus of two radiologists and a radiation oncologist). The primary metric was dose covering 98% of the expert-defined tumor (D98%), which was associated with probability of biochemical failure in a model published with the FLAME trial. In this preliminary analysis, 42 target volumes were analyzed from 20 participants and two patient cases: case 1 was contoured with conventional MRI alone and case 2 with RSIrs. All plans had adequate coverage of the prostate and met all key normal tissue constraints. For case 1 (without RSIrs), the expert's D98% was 87.1 Gy. By comparison, median D98% for participants was 82.2 Gy (IQR 77.8 - 84.6 Gy). Per the FLAME trial model, the predicted probability of biochemical failure at 7 years is 6% for the expert, but participants' plans yielded a median failure probability of 11% (IQR 18 - 9%). For case 2 (with RSIrs), the expert's D98% was 82.8 Gy, while median D98% for participants was 80.6 Gy (IQR 80.0 - 81.0 Gy). Predicted probability of biochemical failure is 12% for the expert-defined target and median 13% (IQR 14 - 13%) for participants. Variability in radiation oncologists' prostate tumor contours can lead to clinically meaningful changes to focal RT boost plans. The probability of biochemical failure for one patient case increased from 6% to a median of 11% when using conventional MRI alone. Use of RSIrs may mitigate this problem by increasing the accuracy and reliability of radiation oncologists' tumor contours.