Contouring variation affects estimates of normal tissue complication probability for breast fibrosis after radiotherapy.

BACKGROUND: Normal tissue complication probability (NTCP) models can be useful to estimate the risk of fibrosis after breast-conserving surgery (BCS) and radiotherapy (RT) to the breast. However, they are subject to uncertainties. We present the impact of contouring variation on the prediction of fibrosis. MATERIALS AND METHODS: 280 breast cancer patients treated BCS-RT were included. Nine Clinical Target Volume (CTV) contours were created for each patient: i) CTV_crop (reference), cropped 5 mm from the skin and ii) CTV_skin, uncropped and including the skin, iii) segmenting the 95% isodose (Iso95%) and iv) 3 different auto-contouring atlases generating uncropped and cropped contours (Atlas_skin/Atlas_crop). To illustrate the impact of contour variation on NTCP estimates, we applied two equations predicting fibrosis grade ≥ 2 at 5 years, based on Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) models, respectively, to each contour. Differences were evaluated using repeated-measures ANOVA. For completeness, the association between observed fibrosis events and NTCP estimates was also evaluated using logistic regression. RESULTS: There were minimal differences between contours when the same contouring approach was followed (cropped and uncropped). CTV_skin and Atlas_skin contours had lower NTCP estimates (-3.92%, IQR 4.00, p < 0.05) compared to CTV_crop. No significant difference was observed for Atlas_crop and Iso95% contours compared to CTV_crop. For the whole cohort, NTCP estimates varied between 5.3% and 49.5% (LKB) or 2.2% and 49.6% (RS) depending on the choice of contours. NTCP estimates for individual patients varied by up to a factor of 4. Estimates from "skin" contours showed higher agreement with observed events. CONCLUSION: Contour variations can lead to significantly different NTCP estimates for breast fibrosis, highlighting the importance of standardising breast contours before developing and/or applying NTCP models.

A deep learning model (FociRad) for automated detection of γ-H2AX foci and radiation dose estimation.

DNA double-strand breaks (DSBs) are the most lethal form of damage to cells from irradiation. γ-H2AX (phosphorylated form of H2AX histone variant) has become one of the most reliable and sensitive biomarkers of DNA DSBs. However, the γ-H2AX foci assay still has limitations in the time consumed for manual scoring and possible variability between scorers. This study proposed a novel automated foci scoring method using a deep convolutional neural network based on a You-Only-Look-Once (YOLO) algorithm to quantify γ-H2AX foci in peripheral blood samples. FociRad, a two-stage deep learning approach, consisted of mononuclear cell (MNC) and γ-H2AX foci detections. Whole blood samples were irradiated with X-rays from a 6 MV linear accelerator at 1, 2, 4 or 6 Gy. Images were captured using confocal microscopy. Then, dose-response calibration curves were established and implemented with unseen dataset. The results of the FociRad model were comparable with manual scoring. MNC detection yielded 96.6% accuracy, 96.7% sensitivity and 96.5% specificity. γ-H2AX foci detection showed very good F1 scores (> 0.9). Implementation of calibration curve in the range of 0-4 Gy gave mean absolute difference of estimated doses less than 1 Gy compared to actual doses. In addition, the evaluation times of FociRad were very short (< 0.5 min per 100 images), while the time for manual scoring increased with the number of foci. In conclusion, FociRad was the first automated foci scoring method to use a YOLO algorithm with high detection performance and fast evaluation time, which opens the door for large-scale applications in radiation triage.

Relation between DIR recalculated dose based CBCT and GI and GU toxicity in postoperative prostate cancer patients treated with VMAT.

BACKGROUND AND PURPOSE: To investigate the relationship between deformable image registration (DIR) recalculated dose on cone beam computed tomography (CBCT) and gastrointestinal and genitourinary toxicity in postoperative prostate cancer patients treated with volumetric modulated arc therapy and its actual delivered dose. MATERIAL AND METHODS: A total of 114 patients were retrospectively studied. Delineation of rectum and bladder was performed on each CBCT image. Actual delivered dose on CBCT available fraction was recalculated using DIR. Dosimetric parameters of rectum and bladder were then evaluated by Quantitative Analyses of Normal Tissue Effects in the Clinic study. Differences in mean volume between patients with grade 0-1 and grade 2-5 CTCAEv5.0 toxicities were compared. Relationship between toxicity and radiation volume was analyzed using logit analysis. RESULTS: Significant differences between the actual and planned dose-volume were observed in nearly all doses of rectum. High-grade acute rectal toxicity was significantly associated with planned dose-volume in V50 and V75, and actual dose in all doses. High-grade chronic rectal toxicity was significantly associated with all planned and actual rectal dose-volume parameters. There was no significant association between all dose-volume parameters and acute or chronic bladder toxicity. CONCLUSION: Significant differences between actual and planned dose-volume, and significant association between actual dose-volume and acute rectal toxicity, but not planned dose-volume suggests that actual dose-volume may more precisely reflect toxicity due to daily variation in the rectum during the treatment course. Adaptive planning should be considered as a novel approach for reducing toxicity.

Multi-institutional evaluation using the end-to-end test for implementation of dynamic techniques of radiation therapy in Thailand.

AIM: In this study, an accuracy survey of intensity-modulated radiation therapy (IMRT) and volumetric arc radiation therapy (VMAT) implementation in radiotherapy centers in Thailand was conducted. BACKGROUND: It is well recognized that there is a need for radiotherapy centers to evaluate the accuracy levels of their current practices, and use the related information to identify opportunities for future development. MATERIALS AND METHODS: An end-to-end test using a CIRS thorax phantom was carried out at 8 participating centers. Based on each center's protocol for simulation and planning, linac-based IMRT or VMAT plans were generated following the IAEA (CRP E24017) guidelines. Point doses in the region of PTVs and OARs were obtained from 5 ionization chamber readings and the dose distribution from the radiochromic films. The global gamma indices of the measurement doses and the treatment planning system calculation doses were compared. RESULTS: The large majority of the RT centers (6/8) fulfilled the dosimetric goals, with the measured and calculated doses at the specification points agreeing within ±3% for PTV and ±5% for OARS. At 2 centers, TPS underestimated the lung doses by about 6% and spinal cord doses by 8%. The mean percentage gamma pass rates for the 8 centers were 98.29 ± 0.67% (for the 3%/3 mm criterion) and 96.72 ± 0.84% (for the 2%/2 mm criterion). CONCLUSIONS: The 8 participating RT centers achieved a satisfactory quality level of IMRT/VMAT clinical implementation.

Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

PURPOSE: To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. MATERIAL AND METHODS: The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD2) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD2 verification with pair t-test statistical analysis using IBM SPSS Statistics version 22 (64-bit). RESULTS: Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D90%, 0.56% in the bladder, 1.74% in the rectum when determined by D2cc, and less than 1% in Pinnacle. The difference in the EQD2 between the software calculation and the manual calculation was not significantly different with 0.00% at p-values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. CONCLUSIONS: The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.