Stijn Heijmink

Prostate tumor delineation using multiparametric magnetic resonance imaging: Inter-observer variability and pathology validation

BACKGROUND AND PURPOSEnBoosting the dose to the largest (dominant) lesion in radiotherapy of prostate cancer may improve treatment outcome. The success of this approach relies on the detection and delineation of tumors. The agreement among teams of radiation oncologists and radiologists delineating lesions on multiparametric magnetic resonance imaging (mp-MRI) was assessed by measuring the distances between observer contours. The accuracy of detection and delineation was determined using whole-mount histopathology specimens as reference.nnnMATERIAL AND METHODSnSix observer teams delineated tumors on mp-MRI of 20 prostate cancer patients who underwent a prostatectomy. To assess the inter-observer agreement, the inter-observer standard deviation (SD) of the contours was calculated for tumor sites which were identified by all teams.nnnRESULTSnEighteen of 89 lesions were identified by all teams, all were dominant lesions. The median histological volume of these was 2.4cm(3). The median inter-observer SD of the delineations was 0.23cm. Sixty-six of 69 satellites were missed by all teams.nnnCONCLUSIONnSince all teams identify most dominant lesions, dose escalation to the dominant lesion is feasible. Sufficient dose to the whole prostate may need to be maintained to prevent under treatment of smaller lesions and undetected parts of larger lesions.

Magnetic resonance imaging for prostate cancer radiotherapy

For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with the wisdom of the crowd, and thus could serve as a reference for individual physicians in their decision making. With multi-parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted.

Quantitative assessment of fascia preservation improves the prediction of membranous urethral length and inner levator distance on continence outcome after robot-assisted radical prostatectomy

To determine whether preoperative prostate/pelvic anatomical structures and intraoperative fascia preservation (FP) predict continence recovery after robot‐assisted radical prostatectomy (RARP).

Seminal vesicle invasion on multi-parametric magnetic resonance imaging: Correlation with histopathology

OBJECTIVESnThe pre-treatment risk of seminal vesicle (SV) invasion (SVI) from prostate cancer is currently based on nomograms which include clinical stage (cT), Gleason score (GS) and prostate-specific antigen (PSA). The aim of our study was to evaluate the staging accuracy of 3T (3T) multi-parametric (mp) Magnetic Resonance Imaging (MRI) by comparing the imaging report of SVI with the tissue histopathology. The additional value in the existing prediction models and the role of radiologists experience were also examined.nnnMETHODSnAfter obtaining institutional review board approval, we retrospectively reviewed clinico-pathological data from 527 patients who underwent a robot-assisted radical prostatectomy (RARP) between January 2012 and March 2015. Preoperative prostate imaging with an endorectal 3T-mp-MRI was performed in all patients. Sequences consisted of an axial pre-contrast T1 sequence, three orthogonally-oriented T2 sequences, axial diffusion weighted and dynamic contrast-enhanced sequences. We considered SVI in case of low-signal intensity in the SV on T2-weighted sequences or apparent mass while diffusion-weighted and DCE sequences were used to confirm findings on T2. Whole-mount section pathology was performed in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI (index test) for the prediction of histological SVI (reference standard) were calculated. We developed logistic multivariable regression models including: clinical variables (PSA, cT, percentage of involved cores/total cores, primary GS 4-5) and Partin table estimates. MRI results (negative/positive exam) were then added in the models and the multivariate modeling was reassessed. In order to assess the extent of SVI and the reason for mismatch with pathology an MRI-review from an expert genitourinary radiologist was performed in a subgroup of 379 patients.nnnRESULTSnA total of 54 patients (10%) were found to have SVI on RARP-histopathology. In the overall cohort sensitivity, specificity, PPV and NPV for SVI detection on MRI were 75.9%, 94.7%, 62% and 97% respectively. Based on our sub-analysis, the radiologists expertise improved the accuracy demonstrating a sensitivity, specificity, PPV and NPV of 85.4%, 95.6%, 70.0% and 98.2%, respectively. In the multivariate analysis PSA (odds ratio [OR] 1.07, p=0.008), primary GS 4 or 5 (OR 3.671, p=0.007) and Partin estimates (OR 1.07, p=0.023) were significant predictors of SVI. When MRI results were added to the analysis, a highly significant prediction of SVI was observed (OR 45.9, p<0.0001). Comparing Partin, MRI and Partin with MRI predictive models, the areas under the curve were 0.837, 0.884 and 0.929, respectively.nnnCONCLUSIONSnMRI had high diagnostic accuracy for SVI on histopathology. It provided added diagnostic value to clinical/Partin based SVI-prediction models alone. A key factor is radiologists experience, though no inter-observer variability could be examined due to the availability of a single expert radiologist.

Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

Patterns of Benign Prostate Hyperplasia Based on Magnetic Resonance Imaging Are Correlated With Lower Urinary Tract Symptoms and Continence in Men Undergoing a Robot-assisted Radical Prostatectomy for Prostate Cancer

OBJECTIVEnTo investigate the association between benign prostatic hyperplasia (BPH) patterns, classified by magnetic resonance imaging (MRI), with lower urinary tract symptoms (LUTS) or continence, preoperatively and after robot-assisted laparoscopic radical prostatectomy (RARP).nnnMATERIALS AND METHODSnThis retrospective study included 49 prostate cancer patients, with prostate size >47u2009cm3, who underwent an endorectal MRI followed by RARP. Five BPH patterns were identified according to Wasserman, and additional prostate measurements were recorded. LUTS were assessed using the International Prostate Symptom Score and the PR25-LUTS-Questionnaire score. Continence was assessed using the International Consultation of Incontinence Questionnaire-Short Form.nnnRESULTSnBPH pattern 3 (44.9%) was identified most common, followed by pattern 5 (26.6%), 1 (24.5%), and 2 and 4 (both 2%). BPH patterns were significant predictors of preoperative LUTS, with pedunculated with bilateral transition zone (TZ) and retrourethral enlargement (pattern 5) causing more severe symptoms compared with bilateral TZ and retrourethral enlargement (pattern 3) and bilateral TZ enlargement (pattern 1), whereas pattern 3 was additionally associated with more voiding symptoms compared with pattern 1. None of the BPH patterns was predictive of postoperative LUTS and continence. Independent predictors of continence at 12 months were lower preoperative PR25-LUTS score (Pu2009=u2009.022) and longer membranous urethral length (Pu2009=u2009.025).nnnCONCLUSIONnMRI is useful for classifying patients in BPH patterns which are strongly associated with preoperative LUTS. However, BPH patterns did not predict remnant LUTS or postoperative incontinence. Postoperative continence status was only associated with preoperative LUTS and membranous urethra length.

The value of periprostatic fascia thickness and fascia preservation as prognostic factors of erectile function after nerve-sparing robot-assisted radical prostatectomy

PurposeTo determine the correlation of preoperative fascia thickness (FT) and intraoperative fascia preservation (FP) with erectile function (EF) after nerve-sparing robot-assisted radical prostatectomy (RARP).MethodsOur analysis included 106 patients, with localized prostate cancer and no erectile dysfunction (ED) before RARP, assessed with preoperative 3xa0Tesla (3xa0T) multiparametric magnetic resonance imaging (MRI). FP score was defined as the extent of FP from the base to the apex of the prostate, quantitatively assessed by the surgeon. Median fascia thickness (MFT) per patient was defined as the sum of the median FT of 12 MRI regions. Preserved MFT (pMFT) was the sum of the saved MFT. The percentage of pFMT (ppMFT) was also calculated. Fascia surface (FS) was measured on MRI and it was combined with FP score resulting in preserved FS (pFS) and percentage of pFS (ppFS).ResultsFP score, pMFT, ppMFT, pFS and ppFS were significantly lower (pu2009<u20090.0001) in patients with ED. In the multivariate regression analysis, lower FP score [odds ratio (OR) 0.721, pu2009=u20090.03] and lower ppMFT (OR 0.001, pu2009=u20090.027) were independent predictors of ED. ROC analysis showed the highest area under the curve for ppMFT (0.787) and FP score (0.767) followed by pMFT (0.755) and ppFS (0.743).ConclusionsMRI-determined periprostatic FT combined with intraoperative FP score are correlated to postprostatectomy EF. Based on the hypothesis that a thicker fascia forms a protective layer for the nerves, we recommend assessing FT preoperatively to counsel men for the odds of preserving EF after RARP.

Contouring of prostate tumors on multiparametric MRI: Evaluation of clinical delineations in a multicenter radiotherapy trial

PURPOSEnTo date no guidelines are available for contouring prostate cancer inside the gland, as visible on multiparametric (mp-) MRI. We assessed inter-institutional differences in interpretation of mp-MRI in the multicenter phase III FLAME trial.nnnMETHODSnWe analyzed clinical delineations on mp-MRI and clinical characteristics from 260 patients across three institutes. We performed a logistic regression analysis to examine each institutes weighting of T2w, ADC and Ktrans intensity maps in the delineation of the cancer. As reviewing of all delineations by an expert panel is not feasible, we made a selection based on discrepancies between a published tumor probability (TP) model and each institutes clinical delineations using Areas Under the ROC Curve (AUC) analysis.nnnRESULTSnRegression coefficients for the three institutes were -0.07, -0.27 and -0.11 for T2w, -1.96, -0.53 and -0.65 for ADC and 0.15, 0.20 and 0.62 for Ktrans, with significant differences between institutes for ADC and Ktrans. AUC analysis showed median AUC values of 0.92, 0.80 and 0.79. Five patients with lowest AUC values were reviewed by a uroradiologist.nnnCONCLUSIONnRegression coefficients revealed considerably different interpretations of mp-MRI in tumor contouring between institutes and demonstrated the need for contouring guidelines. Based on AUC values outlying delineations could efficiently be identified for review.

Biochemical recurrence prediction after radiotherapy for prostate cancer with T2w magnetic resonance imaging radiomic features

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68Ga PSMA PET/CT predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate and high‐risk prostate cancer

To determine the value of gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA)‐11 positron emission tomography (PET) /computed tomography (CT) in men with newly diagnosed prostate cancer.