Is There an Added Value of Quantitative DCE-MRI by Magnetic Resonance Dispersion Imaging for Prostate Cancer Diagnosis?

In this multicenter, retrospective study, we evaluated the added value of magnetic resonance dispersion imaging (MRDI) to standard multiparametric MRI (mpMRI) for PCa detection. The study included 76 patients, including 51 with clinically significant prostate cancer (csPCa), who underwent radical prostatectomy and had an mpMRI including dynamic contrast-enhanced MRI. Two radiologists performed three separate randomized scorings based on mpMRI, MRDI and mpMRI+MRDI. Radical prostatectomy histopathology was used as the reference standard. Imaging and histopathology were both scored according to the Prostate Imaging-Reporting and Data System V2.0 sector map. Sensitivity and specificity for PCa detection were evaluated for mpMRI, MRDI and mpMRI+MRDI. Inter- and intra-observer variability for both radiologists was evaluated using Cohen's Kappa. On a per-patient level, sensitivity for csPCa for radiologist 1 (R1) for mpMRI, MRDI and mpMRI+MRDI was 0.94, 0.82 and 0.94, respectively. For the second radiologist (R2), these were 0.78, 0.94 and 0.96. R1 detected 4% additional csPCa cases using MRDI compared to mpMRI, and R2 detected 20% extra csPCa cases using MRDI. Inter-observer agreement was significant only for MRDI (Cohen's Kappa = 0.4250, p = 0.004). The results of this study show the potential of MRDI to improve inter-observer variability and the detection of csPCa.

Membranous urethral length measurement on preoperative MRI to predict incontinence after radical prostatectomy: a literature review towards a proposal for measurement standardization.

OBJECTIVES: To investigate the membranous urethral length (MUL) measurement and its interobserver agreement, and propose literature-based recommendations to standardize MUL measurement for increasing interobserver agreement. MUL measurements based on prostate MRI scans, for urinary incontinence risk assessment before radical prostatectomy (RP), may influence treatment decision-making in men with localised prostate cancer. Before implementation in clinical practise, MRI-based MUL measurements need standardization to improve observer agreement. METHODS: Online libraries were searched up to August 5, 2022, on MUL measurements. Two reviewers performed article selection and critical appraisal. Papers reporting on preoperative MUL measurements and urinary continence correlation were selected. Extracted information included measuring procedures, MRI sequences, population mean/median values, and observer agreement. RESULTS: Fifty papers were included. Studies that specified the MRI sequence used T2-weighted images and used either coronal images (n = 13), sagittal images (n = 18), or both (n = 12) for MUL measurements. 'Prostatic apex' was the most common description of the proximal membranous urethra landmark and 'level/entry of the urethra into the penile bulb' was the most common description of the distal landmark. Population mean (median) MUL value range was 10.4-17.1 mm (7.3-17.3 mm), suggesting either population or measurement differences. Detailed measurement technique descriptions for reproducibility were lacking. Recommendations on MRI-based MUL measurement were formulated by using anatomical landmarks and detailed descriptions and illustrations. CONCLUSIONS: In order to improve on measurement variability, a literature-based measuring method of the MUL was proposed, supported by several illustrative case studies, in an attempt to standardize MRI-based MUL measurements for appropriate urinary incontinence risk preoperatively. CLINICAL RELEVANCE STATEMENT: Implementation of MUL measurements into clinical practise for personalized post-prostatectomy continence prediction is hampered by lack of standardization and suboptimal interobserver agreement. Our proposed standardized MUL measurement aims to facilitate standardization and to improve the interobserver agreement. KEY POINTS: • Variable approaches for membranous urethral length measurement are being used, without detailed description and with substantial differences in length of the membranous urethra, hampering standardization. • Limited interobserver agreement for membranous urethral length measurement was observed in several studies, while preoperative incontinence risk assessment necessitates high interobserver agreement. • Literature-based recommendations are proposed to standardize MRI-based membranous urethral length measurement for increasing interobserver agreement and improving preoperative incontinence risk assessment, using anatomical landmarks on sagittal T2-weighted images.

IMPemBra: a phase 2 study comparing pembrolizumab with intermittent/short-term dual MAPK pathway inhibition plus pembrolizumab in patients with melanoma harboring the BRAFV600 mutation.

BACKGROUND: Continuous combination of MAPK pathway inhibition (MAPKi) and anti-programmed death-(ligand) 1 (PD-(L)1) showed high response rates, but only limited improvement in progression-free survival (PFS) at the cost of a high frequency of treatment-related adverse events (TRAE) in patients with BRAFV600-mutated melanoma. Short-term MAPKi induces T-cell infiltration in patients and is synergistic with anti-programmed death-1 (PD-1) in a preclinical melanoma mouse model. The aim of this phase 2b trial was to identify an optimal regimen of short-term MAPKi with dabrafenib plus trametinib in combination with pembrolizumab. METHODS: Patients with treatment-naïve BRAFV600E/K-mutant advanced melanoma started pembrolizumab 200 mg every 3 weeks. In week 6, patients were randomized to continue pembrolizumab only (cohort 1), or to receive, in addition, intermittent dabrafenib 150 mg two times per day plus trametinib 2 mg one time per day for two cycles of 1 week (cohort 2), two cycles of 2 weeks (cohort 3), or continuously for 6 weeks (cohort 4). All cohorts continued pembrolizumab for up to 2 years. Primary endpoints were safety and treatment-adherence. Secondary endpoints were objective response rate (ORR) at week 6, 12, 18 and PFS. RESULTS: Between June 2016 and August 2018, 33 patients with advanced melanoma have been included and 32 were randomized. Grade 3-4 TRAE were observed in 12%, 12%, 50%, and 63% of patients in cohort 1, 2, 3, and 4, respectively. All planned targeted therapy was given in 88%, 63%, and 38% of patients in cohort 2, 3, and 4. ORR at week 6, 12, and 18 were 38%, 63%, and 63% in cohort 1; 25%, 63%, and 75% in cohort 2; 25%, 50%, and 75% in cohort 3; and 0%, 63%, and 50% in cohort 4. After a median follow-up of 43.5 months, median PFS was 10.6 months for pembrolizumab monotherapy and not reached for patients treated with pembrolizumab and intermittent dabrafenib and trametinib (p=0.17). The 2-year and 3-year landmark PFS were both 25% for cohort 1, both 63% for cohort 2, 50% and 38% for cohort 3 and 75% and 60% for cohort 4. CONCLUSIONS: The combination of pembrolizumab plus intermittent dabrafenib and trametinib seems more feasible and tolerable than continuous triple therapy. The efficacy is promising and appears to be favorable over pembrolizumab monotherapy. TRIAL REGISTRATION NUMBER: NCT02625337.

Prostate MRI for Improving Personalized Risk Prediction of Incontinence and Surgical Planning: The Role of Membranous Urethral Length Measurements and the Use of 3D Models.

Prostate MRI has an important role in prostate cancer diagnosis and treatment, including detection, the targeting of prostate biopsies, staging and guiding radiotherapy and active surveillance. However, there are other ''less well-known'' applications which are being studied and frequently used in our highly specialized medical center. In this review, we focus on two research topics that lie within the expertise of this study group: (1) anatomical parameters predicting the risk of urinary incontinence after radical prostatectomy, allowing more personalized shared decision-making, with special emphasis on the membranous urethral length (MUL); (2) the use of three-dimensional models to help the surgical planning. These models may be used for training, patient counselling, personalized estimation of nerve sparing and extracapsular extension and may help to achieve negative surgical margins and undetectable postoperative PSA values.

A standardized method to measure the membranous urethral length (MUL) on MRI of the prostate with high inter- and intra-observer agreement.

OBJECTIVES: The membranous urethral length (MUL), defined as the length between the apex and penile base as measured on preoperative prostate magnetic resonance imaging (MRI), is an important predictor for urinary incontinence after radical prostatectomy. Literature on inter- and intra - observer agreement of MUL measurement is limited. We studied the inter- and intra-observer agreement between radiologists using a well-defined method to measure the MUL on the prostate MRI. METHODS: Prostate cancer patients underwent a preoperative MRI and robot-assisted radical prostatectomy (RARP) at one high-volume RARP center. MUL measurement was based on well-defined landmarks on sagittal T2-weighted (anatomical) images. Three radiologists independently performed MUL measurements retrospectively in 106 patients blinded to themselves, to each other, and to clinical outcomes. The inter- and intra-observer agreement of MUL measurement between the radiologists were calculated, expressed as intra-class correlation coefficient (ICC). RESULTS: The initial inter-observer agreement was ICC 0.63; 95% confidence interval (CI) 0.28-0.81. Radiologist 3 measured the MUL mean 3.9 mm (SD 3.3) longer than the other readers, interpreting the caudal point of the MUL (penile base) differently. After discussion on the correct anatomical definition, radiologist 3 re-assessed all scans, which resulted in a high inter-observer agreement (ICC 0.84; 95% CI 0.66-0.91). After a subsequent reading by radiologists 1 and 2, the intra-observer agreements were ICC 0.93; 95% CI 0.89-0.96, and ICC 0.98; 95% CI 0.97-0.98, respectively. Limitation is the monocenter design. CONCLUSIONS: The MUL can be measured reliably with high agreement among radiologists. KEY POINTS: • After discussion on the correct anatomical definition, the inter- and intra - observer agreements of membranous urethral length (MUL) measurement on magnetic resonance imaging (MRI) were high. • A reproducible method to measure the MUL can improve the clinical usefulness of prediction models for urinary continence after RARP which may benefit patient counselling.

A Prospective Multicenter Comparison Study of Risk-adapted Ultrasound-directed and Magnetic Resonance Imaging-directed Diagnostic Pathways for Suspected Prostate Cancer in Biopsy-naïve Men.

BACKGROUND: European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice. OBJECTIVE: To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included. INTERVENTION: Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests. RESULTS AND LIMITATIONS: A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01). CONCLUSIONS: Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer. PATIENT SUMMARY: Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.

Value of Different Magnetic Resonance Imaging-based Measurements of Anatomical Structures on Preoperative Prostate Imaging in Predicting Urinary Continence After Radical Prostatectomy in Men with Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Measurements of anatomical structures on preoperative prostate magnetic resonance imaging (MRI) are used in risk models for treatment decisions to predict urinary continence (UC) following radical prostatectomy (RP). However, the association between these parameters and UC is unclear. OBJECTIVE: To systematically summarize the literature on prognostic preoperative prostate MRI measurements of (peri)prostatic structures in relation to time to recovery of postoperative UC in men with prostate cancer. EVIDENCE ACQUISITION: Online libraries were searched up to August 27, 2021. Article selection and critical appraisal were performed by two reviewers. All papers reporting on preoperative MRI measurements with UC correlation in univariable or multivariable analyses were included. EVIDENCE SYNTHESIS: In the 50 studies included (mostly retrospective), 57 MRI parameters were evaluated. The pooled analyses showed that greater membranous urethra length (MUL) was prognostic for regaining UC at 1 mo (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.10-1.21), 3 mo (OR 1.23, 95% CI 1.16-1.31), 6 mo (OR 1.16, 95% CI 1.08-1.25), and 12 mo (OR 1.19, 95% CI 1.10-1.29). Several other anatomical structures showed at least in one study a significant correlation with later return to UC: four prostate-related parameters (greater depth, apical protrusion, larger intravesical protrusion, small dorsal vascular complex), five urethra-related parameters (thicker wall, severe fibrosis, smaller volume, larger preoperative angle between the prostate axis and membranous urethra, shorter minimal residual MUL), and six musculoskeletal-related parameters (lower perfusion ratio, thinner levator ani muscle, larger inner or outer levator distance, shorter pelvic diaphragm length, and larger midpelvic area). CONCLUSIONS: Greater MUL as measured on preoperative MRI was an independent prognostic factor for return to UC within 1 mo after RP and remained prognostic at 12 mo. Other anatomical structures may potentially be predictive, but these would need to be substantiated in prospective trials before being adopted in postoperative UC risk models for treatment decisions in men with prostate cancer. PATIENT SUMMARY: We summarized study data on the relation between measurements of anatomical structures on preoperative magnetic resonance imaging scans and urinary continence after removal of the prostate. Greater length of one part of the urethra (membranous urethra) is associated with faster return to continence. Other anatomical structures have potential for predicting postoperative continence, but need further investigation.

Radiomic combination of spatial and temporal features extracted from DCE-MRI for prostate cancer detection.

Multi-parametric MRI is part of the standard prostate cancer (PCa) diagnostic protocol. Recent imaging guidelines (PI-RADS v2) downgraded the value of Dynamic Contrast-Enhanced (DCE)-MRI in the diagnosis of PCa. A purely qualitative analysis of the DCE-MRI time series, as it is generally done by radiologists, might indeed overlook information on the microvascular architecture and function. In this study, we investigate the discriminative power of quantitative imaging features derived from texture and pharmacokinetic analysis of DCE-MRI. In 605 regions of interest (benign and malignant tissue) delineated in 80 patients, we found through independent cross-validation that a subset of quantitative spatial and temporal features extracted from DCE-MRI and incorporated in machine learning classifiers obtains a good diagnostic performance (AUC = 0.80-0.86) in distinguishing malignant from benign regions.Clinical Relevance- These findings highlight the underlying potential of quantitative DCE-derived radiomic features in identifying PCa by MRI.

68Ga-PSMA-11 PET, 18F-PSMA-1007 PET, and MRI for Gross Tumor Volume Delineation in Primary Prostate Cancer: Intermodality and Intertracer Variability.

PURPOSE: To assess the intermodality and intertracer variability of gallium-68 (68Ga)- or fluorine-18 (18F)-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and biparametric magnetic resonance imaging (bpMRI)-based gross tumor volume (GTV) delineation for focal boosting in primary prostate cancer. METHODS: Nineteen prospectively enrolled patients with prostate cancer underwent a PSMA PET/MRI scan, divided into a 1:1 ratio between 68Ga-PSMA-11 and 18F-PSMA-1007, before radical prostatectomy (IWT140193). Four delineation teams performed manual contouring of the GTV based on bpMRI and PSMA PET imaging, separately. Index lesion coverage (overlap%) and interobserver variability were assessed. Furthermore, the distribution of the voxelwise normalized standardized uptake values (SUV%) was determined for the majority-voted (>50%) GTV (GTVmajority) and whole prostate gland to investigate intertracer variability. The median patientwise SUV% contrast ratio (SUV%-CR, calculated as median GTVmajority SUV% / median prostate gland without GTVmajority SUV%) was calculated according to the tracer used. RESULTS: A significant difference in overlap% favoring PSMA PET compared with bpMRI was found in the 18F subgroup (median, 63.0% vs 53.1%; P = .004) but was not present in the 68Ga subgroup (32.5% vs 50.6%; P = .100). Regarding interobserver variability, measured Sørensen-Dice coefficients (0.58 vs 0.72) and calculated mean distances to agreement (2.44 mm vs 1.22 mm) were statistically significantly lower and higher, respectively, for the 18F cohort compared with the 68Ga cohort. For the bpMRI-based delineations, the median Sørensen-Dice coefficient and mean distance to agreement were 0.63 and 1.76 mm, respectively. Median patientwise SUV%-CRs of 1.8 (interquartile range [IQR], 1.6-2.7) for 18F-PSMA and 3.3 (IQR, 2.7-5.9) for 68Ga-PSMA PET images were found. CONCLUSIONS: Both MRI and PSMA PET provided consistent intraprostatic GTV lesion detection. However, the PSMA tracer seems to have a major influence on the contour characteristics, owing to an apparent difference in SUV% distribution in the prostate gland.

Clinical impact of PSMA PET/CT in primary prostate cancer compared to conventional nodal and distant staging: a retrospective single center study.

BACKGROUND: To evaluate the impact of Gallium-68 [68Ga] labeled prostate specific membrane antigen (PSMA) positron emission tomography (PET)/X-ray computed tomography (CT) compared with conventional imaging on staging and clinical management of men evaluated for primary prostate cancer (PCa). METHODS: Men with newly diagnosed biopsy-proven PCa who had been staged with a conventional staging protocol including bone scintigraphy (BS) and additionally underwent [68Ga]PSMA PET/CT, were evaluated retrospectively. Imaging findings from BS, magnetic resonance imaging (MRI) and/or CT were categorized regarding locoregional nodal (N) and distant metastasis (M) status as negative, positive or equivocal before and after addition of the information of PET/CT. Also, the imaging-based level of confidence (LoC) in correct assessment of N and M status was scored. Impact of PET/CT on clinical management was evaluated by the percentage of treatment category changes after PET/CT as determined in the multidisciplinary tumour board. RESULTS: Sixty-four men with intermediate and high-risk PCa were evaluated. With additional information of PET/CT, N status was upstaged in 23%, and downstaged in 9%. M status was upstaged in 13%, and downstaged in 23%. A net increase in LoC of 20% was noted, mainly regarding M status. Treatment category changed from palliative to curative in 9%, and from curative to palliative in 3%. An undecided treatment plan changed to curative in 14%, as well as to palliative in another 9%. In total, a 36% treatment category change was noted. High negative predictive value of PET/CT for M status was indicated by 27 patients that underwent robot-assisted radical prostatectomy and reached postoperative biochemical disease-free status or had a likely other site of disease recurrence. CONCLUSIONS: PSMA PET/CT can cause considerable changes in N and M staging, as well as in management compared to conventional staging. Findings of this study support the replacement of BS and CT by PSMA PET/CT in staging primary PCa.

Oligometastatic Prostate Cancer: Results of a Dutch Multidisciplinary Consensus Meeting.

BACKGROUND: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. RESULTS AND LIMITATIONS: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. CONCLUSIONS: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. PATIENT SUMMARY: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation.

Histopathological Features of MRI-Invisible Regions of Prostate Cancer Lesions.

BACKGROUND: Previous studies have reported tumor volume underestimation with multiparametric (mp)MRI in prostate cancer diagnosis. PURPOSE: To investigate why some parts of lesions are not visible on mpMRI by comparing their histopathology features to those of visible regions. STUDY TYPE: Retrospective. POPULATION: Thirty-four patients with biopsy-proven prostate cancer scheduled for prostatectomy (median 68.7 years). FIELD STRENGTH/SEQUENCE: T2 -weighted, diffusion-weighted imaging, T2 mapping, and dynamic contrast-enhanced MRI on two 3T systems and one 1.5T system. ASSESSMENT: Two readers delineated suspicious lesions on mpMRI. A pathologist delineated the lesions on histopathology. A patient-customized mold enabled the registration of histopathology and MRI. On histopathology we identified mpMRI visible and invisible lesions. Subsequently, within the visible lesions we identified regions that were visible and regions that were invisible on mpMRI. For each lesion and region the following characteristics were determined: size, location, International Society of Urological Pathology (ISUP) grade, and Gleason subpatterns (density [dense/intermediate], tumor morphology [homogeneous/heterogeneous], cribriform growth [yes/no]). STATISTICAL TESTS: With generalized linear mixed-effect modeling we investigated which features explain why a lesion or a region was invisible on MRI. We compared imaging values (T2 , ADC, and Ktrans ) for these features with one-way analysis of variance (ANOVA). RESULTS: Small, anterior, and ISUP grade 1-2 lesions (n = 34) were missed more frequent than large, posterior, ISUP grade ≥ 3 lesions (n = 35). Invisible regions on mpMRI had lower tumor density, heterogeneous tumor morphology, and were located in the transition zone. Both T2 and ADC values were higher in "intermediate" compared with "dense" regions (P = 0.002 and < 0.001) and in regions with heterogeneous compared with homogeneous morphology (P < 0.001 and 0.03). Ktrans was not significantly different (P = 0.24 and 0.99). DATA CONCLUSION: Regions of prostate cancer lesions that are invisible on mpMRI have different histopathology features than visible regions. This may have implications for monitoring during active surveillance and focal treatment strategies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1235-1246.

Gross Tumor Delineation in Esophageal Cancer on MRI Compared With 18F-FDG-PET/CT.

PURPOSE: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). There is increasing interest in integrating magnetic resonance imaging (MRI) in radiation treatment, which can potentially obviate CT- or FDG-PET/CT-based delineation. The aim of this study is to evaluate the feasibility of target delineation on T2-weighted (T2W) MRI and T2W including diffusion-weighted MRI (T2W + DW-MRI) compared with current-practice FDG-PET/CT. METHODS: Ten observers delineated primary esophageal tumor GTVs of 6 patients on FDG-PET/CT, T2W-MRI, and T2W + DW-MRI. GTVs, generalized conformity indices, in-slice delineation variation (root mean square), and standard deviations in the position of the most cranial and caudal delineated slice were calculated. RESULTS: Delineations on MRI showed smaller GTVs compared with FDG-PET/CT-based delineations. The main variation was seen at the cranial and caudal border. No differences were observed in conformity indices (FDG-PET/CT, 0.68; T2W-MRI, 0.66; T2W + DW-MRI, 0.68) and in-slice variation (root mean square, 0.13 cm on FDG-PET/CT; 0.10 cm on T2W-MRI; 0.14 cm on T2W + DW-MRI). In the 2 tumors involving the gastroesophageal junction, addition of DW-MRI to T2W-MRI significantly decreased caudal border variation. CONCLUSIONS: MRI-based target delineation of the esophageal tumor is feasible with interobserver variability comparable to that with FDG-PET/CT, despite limited experience with delineation on MRI. Most variation was seen at cranial-caudal borders, and addition of DW-MRI to T2W-MRI may reduce caudal delineation variation of gastroesophageal junction tumors.

[Radiological assessment of lymph nodes in the inguinal region]. / Radiologische beoordeling van lymfeklieren in de lies.

In this commentary, the radiological aspects of ultrasonography of lymph nodes in the inguinal region and the various differential diagnoses are discussed.

Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.

BACKGROUND: The outcome of patients with macroscopic stage III melanoma is poor. Neoadjuvant treatment with ipilimumab plus nivolumab at the standard dosing schedule induced pathological responses in a high proportion of patients in two small independent early-phase trials, and no patients with a pathological response have relapsed after a median follow up of 32 months. However, toxicity of the standard ipilimumab plus nivolumab dosing schedule was high, preventing its broader clinical use. The aim of the OpACIN-neo trial was to identify a dosing schedule of ipilimumab plus nivolumab that is less toxic but equally effective. METHODS: OpACIN-neo is a multicentre, open-label, phase 2, randomised, controlled trial. Eligible patients were aged at least 18 years, had a WHO performance status of 0-1, had resectable stage III melanoma involving lymph nodes only, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1. Patients were enrolled from three medical centres in Australia, Sweden, and the Netherlands, and were randomly assigned (1:1:1), stratified by site, to one of three neoadjuvant dosing schedules: group A, two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg once every 3 weeks intravenously; group B, two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg once every 3 weeks intravenously; or group C, two cycles of ipilimumab 3 mg/kg once every 3 weeks directly followed by two cycles of nivolumab 3 mg/kg once every 2 weeks intravenously. The investigators, site staff, and patients were aware of the treatment assignment during the study participation. Pathologists were masked to treatment allocation and all other data. The primary endpoints were the proportion of patients with grade 3-4 immune-related toxicity within the first 12 weeks and the proportion of patients achieving a radiological objective response and pathological response at 6 weeks. Analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02977052, and is ongoing with an additional extension cohort and to complete survival analysis. FINDINGS: Between Nov 24, 2016 and June 28, 2018, 105 patients were screened for eligibility, of whom 89 (85%) eligible patients were enrolled and randomly assigned to one of the three groups. Three patients were excluded after randomisation because they were found to be ineligible, and 86 received at least one dose of study drug; 30 patients in group A, 30 in group B, and 26 in group C (accrual to this group was closed early upon advice of the Data Safety Monitoring Board on June 4, 2018 because of severe adverse events). Within the first 12 weeks, grade 3-4 immune-related adverse events were observed in 12 (40%) of 30 patients in group A, six (20%) of 30 in group B, and 13 (50%) of 26 in group C. The difference in grade 3-4 toxicity between group B and A was -20% (95% CI -46 to 6; p=0·158) and between group C and group A was 10% (-20 to 40; p=0·591). The most common grade 3-4 adverse events were elevated liver enzymes in group A (six [20%)]) and colitis in group C (five [19%]); in group B, none of the grade 3-4 adverse events were seen in more than one patient. One patient (in group A) died 9·5 months after the start of treatment due to the consequences of late-onset immune-related encephalitis, which was possibly treatment-related. 19 (63% [95% CI 44-80]) of 30 patients in group A, 17 (57% [37-75]) of 30 in group B, and nine (35% [17-56]) of 26 in group C achieved a radiological objective response, while pathological responses occurred in 24 (80% [61-92]) patients in group A, 23 (77% [58-90]) in group B, and 17 (65% [44-83]) in group C. INTERPRETATION: OpACIN-neo identified a tolerable neoadjuvant dosing schedule (group B: two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg) that induces a pathological response in a high proportion of patients and might be suitable for broader clinical use. When more mature data confirm these early observations, this schedule should be tested in randomised phase 3 studies versus adjuvant therapies, which are the current standard-of-care systemic therapy for patients with stage III melanoma. FUNDING: Bristol-Myers Squibb.

Multiparametric MRI Tumor Probability Model for the Detection of Locally Recurrent Prostate Cancer After Radiation Therapy: Pathologic Validation and Comparison With Manual Tumor Delineations.

PURPOSE: Focal salvage treatments of recurrent prostate cancer (PCa) after radiation therapy require accurate delineation of the target volume. Magnetic resonance imaging (MRI) is used for this purpose; however, radiation therapy-induced changes complicate image interpretation, and guidelines are lacking on the assessment and delineation of recurrent PCa. A tumor probability (TP) model was trained and independently tested using multiparametric magnetic resonance imaging (mp-MRI) of patients with radio-recurrent PCa. The resulting probability maps were used to derive target regions for radiation therapy treatment planning. METHODS AND MATERIALS: Two cohorts of patients with radio-recurrent PCa were used in this study. All patients underwent mp-MRI (T2 weighted, diffusion-weighted imaging, and dynamic contrast enhanced). A logistic regression model was trained using imaging features from 21 patients with biopsy-proven recurrence who qualified for salvage treatment. The test cohort consisted of 17 patients treated with salvage prostatectomy. The model was tested against histopathology-derived tumor delineations. The voxel-wise TP maps were clustered using k-means to generate a gross tumor volume (GTV) contour for voxel-level comparisons with manual tumor delineations performed by 2 radiologists and with histopathology-validated contours. Later, k-means was used with 3 clusters to define a clinical target volume (CTV), high-risk CTV, and GTV, with increasing tumor risk. RESULTS: In the test cohort, the model obtained a median (range) area under the curve of 0.77 (0.41-0.99) for the whole prostate. The GTV delineation resulted in a median sensitivity of 0.31 (0-0.87) and specificity of 0.97 (0.84-1.0) with no significant differences between model and manual delineations. The 3-level clustering GTV and high-risk CTV delineations had median sensitivities of 0.17 (0-0.59) and 0.49 (0-0.97) and specificities of 0.98 (0.84-1.00) and 0.94 (0.84-0.99), respectively. CONCLUSIONS: The TP model had a good performance in predicting voxel-wise presence of recurrent tumor. Model-derived tumor risk levels achieved sensitivity and specificity similar to manual delineations in localizing recurrent tumor. Voxel-wise TP derived from mp-MRI can in this way be incorporated for target definition in focal salvage of radio-recurrent PCa.

The role of MRI for detection and staging of radio- and focal therapy-recurrent prostate cancer.

Local recurrent prostate cancer after radical treatment is found in the majority of men with a rising PSA. Salvage treatment procedures for recurrent disease, such as radiation therapy and ablative procedures, can provide long-term responses in well-selected cases. Prostate magnetic resonance imaging (MRI) allows diagnosis and staging, and the value provides information on treatment selection, treatment planning and treatment guidance in local recurrent prostate cancer.

Improved repeatability of dynamic contrast-enhanced MRI using the complex MRI signal to derive arterial input functions: a test-retest study in prostate cancer patients.

PURPOSE: The arterial input function (AIF) is a major source of uncertainty in tracer kinetic (TK) analysis of dynamic contrast-enhanced (DCE)-MRI data. The aim of this study was to investigate the repeatability of AIFs extracted from the complex signal and of the resulting TK parameters in prostate cancer patients. METHODS: Twenty-two patients with biopsy-proven prostate cancer underwent a 3T MRI exam twice. DCE-MRI data were acquired with a 3D spoiled gradient echo sequence. AIFs were extracted from the magnitude of the signal (AIFMAGN ), phase (AIFPHASE ), and complex signal (AIFCOMPLEX ). The Tofts model was applied to extract Ktrans , kep and ve . Repeatability of AIF curve characteristics and TK parameters was assessed with the within-subject coefficient of variation (wCV). RESULTS: The wCV for peak height and full width at half maximum for AIFCOMPLEX (7% and 8%) indicated an improved repeatability compared to AIFMAGN (12% and 12%) and AIFPHASE (12% and 7%). This translated in lower wCV values for Ktrans (11%) with AIFCOMPLEX in comparison to AIFMAGN (24%) and AIFPHASE (15%). For kep , the wCV was 16% with AIFMAGN , 13% with AIFPHASE , and 13% with AIFCOMPLEX . CONCLUSION: Repeatability of AIFPHASE and AIFCOMPLEX is higher than for AIFMAGN , resulting in a better repeatability of TK parameters. Thus, use of either AIFPHASE or AIFCOMPLEX improves the robustness of quantitative analysis of DCE-MRI in prostate cancer.

Recent developments in penile cancer imaging.

PURPOSE OF REVIEW: This review discusses new findings in penile cancer imaging in relation to the European Association of Urology and National Comprehensive Cancer Network guidelines. RECENT FINDINGS: For imaging in penile cancer patients who are candidates for organ-sparing primary treatment, ultrasound with Doppler seems to be the method of choice in addition to physical examination. The sentinel node biopsy (SNB) procedure is used to detect small nodal metastases in clinically node-negative patients. In recent years, this procedure has been enhanced by 3D imaging using single photon emission computed tomography (SPECT) with computed tomography (CT) to improve preoperative localization and interpretation of sentinel nodes, as well as hybrid fluorescent and radioactive tracers to increase intraoperative localization of sentinel nodes. 18F-fluorodeoxyglucose PET (FDG-PET) with CT appears to be mainly useful for pelvic and distant staging in clinically node-positive patients. Other modalities with a potential future role in penile cancer are ultrasound with shear wave elastography, FDG-PET with MRI and ultrasmall paramagnetic iron oxide-enhanced MRI. SUMMARY: Imaging modalities in penile cancer have advanced throughout the years, assisting in treatment decision-making and during invasive procedures.