Accumulation of rectum dose-volume metrics for prostate external beam radiotherapy combined with brachytherapy: Evaluating deformably registered dose distribution addition using parameter-based addition.

INTRODUCTION: To investigate the accuracy of deriving dose-volume histogram (DVH) parameters from deformably registered data by comparing values with the simple addition of DVHs from each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR-BT) brachytherapy prostate treatment. METHODS: Eighty-two patients received EBRT in 23 fractions of 2 Gy and HDR-BT TG43 in three fractions of 6.5 Gy. The HDR-BT CT was deformably registered to the EBRT CT. The rectum D0.1cc , D1cc , D2cc and D10cc were calculated in two ways. (i) Parameter-adding: the EBRT DVH parameters (or the EBRT prescription dose) were added to the unregistered HDR-BT DVH parameters. (ii) Distribution-adding: the parameters were extracted after the EBRT doses were 3D-summed with the registered HDR-BT doses. Resulting differences between the parameters were investigated. RESULTS: The D0.1cc , D1cc and D2cc from parameter-adding were 21.3% (P < 0.001), 6.3% (P < 0.001) and 3.5% (P < 0.001) smaller than those from distribution-adding. The D10cc was 2.2% (P = 0.015) larger for distribution-adding. CONCLUSION: Distribution-adding was confounded by unsystematic inter/intra-observer rectum-contouring errors and registration accuracy near the anterior rectal wall. Consequently, clinical use of distribution-adding to assess rectal doses requires careful contour and registration evaluation.

Spatial features of dose-surface maps from deformably-registered plans correlate with late gastrointestinal complications.

This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1-80 Gy (increment = 1) and extracting inferior-superior extent, left-right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.

Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications.

BACKGROUND: Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment. METHODS: One hundred and eighteen patients received EBRT in 23 fractions of 2 Gy and HDR (TG43 algorithm) in 3 fractions of 6.5 Gy. Results for the Late Effects of Normal Tissues - Subjective, Objective, Management and Analytic toxicity assessments were available with a median follow-up of 72 months. The HDR CT was deformably-registered to the EBRT CT. Doses were corrected for dose fractionation. Rectum dose-volume histogram (DVH) parameters were calculated in two ways. (1) Distribution-adding: parameters were calculated after the EBRT dose distribution was 3D-summed with the registered HDR dose distribution. (2) Parameter-adding: the EBRT DVH parameters were added to HDR DVH parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate parameters with late peak toxicity (dichotomised at grade 1 or 2). RESULTS: The 48-80, 40-63 and 49-55 Gy dose regions from distribution-adding were significantly correlated with rectal bleeding, urgency/tenesmus and stool frequency respectively. Additionally, urgency/tenesmus and anorectal pain were associated with the 25-26 Gy and 44-48 Gy dose regions from distribution-adding respectively. Parameter-adding also indicated the low-mid dose region was significantly correlated with stool frequency and proctitis. CONCLUSIONS: This study confirms significant dose-histogram effects for gastrointestinal toxicities after including deformable registration to combine phases of EBRT/HDR prostate cancer treatment. The findings from distribution-adding were in most cases consistent with those from parameter-adding. The mid-high dose range and near maximum doses were important for rectal bleeding. The distribution-adding mid-high dose range was also important for stool frequency and urgency/tenesmus. We encourage additional studies in a variety of institutions using a variety of dose accumulation methods with appropriate inter-fraction motion management. TRIAL REGISTRATION: NCT NCT00193856 . Retrospectively registered 12 September 2005.

Registering prostate external beam radiotherapy with a boost from high-dose-rate brachytherapy: a comparative evaluation of deformable registration algorithms.

BACKGROUND: Registering CTs for patients receiving external beam radiotherapy (EBRT) with a boost dose from high-dose-rate brachytherapy (HDR) can be challenging due to considerable image discrepancies (e.g. rectal fillings, HDR needles, HDR artefacts and HDR rectal packing materials). This study is the first to comparatively evaluate image processing and registration methods used to register the rectums in EBRT and HDR CTs of prostate cancer patients. The focus is on the rectum due to planned future analysis of rectal dose-volume response. METHODS: For 64 patients, the EBRT CT was retrospectively registered to the HDR CT with rigid registration and non-rigid registration methods in VelocityAI. Image processing was undertaken on the HDR CT and the rigidly-registered EBRT CT to reduce the impact of discriminating features on alternative non-rigid registration methods applied in the software suite for Deformable Image Registration and Adaptive Radiotherapy Research (DIRART) using the Horn-Schunck optical flow and Demons algorithms. The propagated EBRT-rectum structures were compared with the HDR structure using the Dice similarity coefficient (DSC), Hausdorff distance (HD) and average surface distance (ASD). The image similarity was compared using mutual information (MI) and root mean squared error (MSE). The displacement vector field was assessed via the Jacobian determinant (JAC). The post-registration alignments of rectums for 21 patients were visually assessed. RESULTS: The greatest improvement in the median DSC relative to the rigid registration result was 35 % for the Horn-Schunck algorithm with image processing. This algorithm also provided the best ASD results. The VelocityAI algorithms provided superior HD, MI, MSE and JAC results. The visual assessment indicated that the rigid plus deformable multi-pass method within VelocityAI resulted in the best rectum alignment. CONCLUSIONS: The DSC, ASD and HD improved significantly relative to the rigid registration result if image processing was applied prior to DIRART non-rigid registrations, whereas VelocityAI without image processing provided significant improvements. Reliance on a single rectum structure-correspondence metric would have been misleading as the metrics were inconsistent with one another and visual assessments. It was important to calculate metrics for a restricted region covering the organ of interest. Overall, VelocityAI generated the best registrations for the rectum according to the visual assessment, HD, MI, MSE and JAC results.