Stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer - Acute toxicity and patient-reported outcomes in the prospective, multicenter SMILE phase II trial.

Background: Due to superior image quality and daily adaptive planning, MR-guided stereotactic body radiation therapy (MRgSBRT) has the potential to further widen the therapeutic window in radiotherapy of localized prostate cancer. This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate cancer within the prospective, multicenter phase II SMILE trial. Materials and methods: A total of 69 patients with localized prostate cancer underwent MRgSBRT with daily online plan adaptation. Inclusion criteria comprised a tumor stage ≤ T3a, serum PSA value ≤ 20 ng/ml, ISUP Grade group ≤ 4. A dose of 37.5 Gy was prescribed to the PTV in five fractions on alternating days with an optional simultaneous boost of 40 Gy to the dominant intraprostatic lesion defined by multiparametric MRI. Acute genitourinary (GU-) and gastrointestinal (GI-) toxicity, as defined by CTCAE v. 5.0 and RTOG as well as patient-reported outcomes according to EORTC QLQ-C30 and -PR25 scores were analyzed at completion of radiotherapy, 6 and 12 weeks after radiotherapy and compared to baseline symptoms. Results: There were no toxicity-related treatment discontinuations. At the 12-week follow-up visit, no grade 3 + toxicities were reported according to CTCAE. Up until the 12-week visit, in total 16 patients (23 %) experienced a grade 2 GU or GI toxicity. Toxicity rates peaked at the end of radiation therapy and subsided within the 12-week follow-up period. At the 12-week follow-up visit, no residual grade 2 GU toxicities were reported and 1 patient (1 %) had residual grade 2 enteritic symptoms. With exception to a significant improvement in the emotional functioning score following MRgSBRT, no clinically meaningful changes in the global health status nor in relevant subscores were reported. Conclusion: Daily online-adaptive MRgSBRT for localized prostate cancer resulted in an excellent overall toxicity profile without any major negative impact on quality of life.

[Machine learning and multiparametric MRI for early diagnosis of prostate cancer]. / Maschinelles Lernen und multiparametrische MRT in der Früherkennung des Prostatakarzinoms.

In the last few years, the early diagnosis of prostate cancer has continued to shift from systematic biopsies to multiparametric MRI (mpMRI)-guided/MRI-transrectal ultrasound (TRUS) fusion biopsies and guidelines are already reflecting these changes. While MRI-TRUS fusion biopsies have already resulted in significant improvements in diagnostic sensitivity and, thus, correct diagnosis of clinically significant prostate cancer (sPC), its use to avoid biopsies in certain men is still controversial. Optimal use of mpMRI requires a high degree of reader expertise due to the difficulty of image interpretation and poses the problem of training sufficient numbers of radiologists while demand is increasing. Recently, artificial intelligence (AI) has been utilized to create fully automatic analysis tools for interpretation of mpMRI of the prostate, rivaling the performance of clinical radiologist interpretation in retrospective research studies, demonstrating the promising potential of AI for diagnostic prostate MRI in the future. This article will provide an overview of machine and deep learning and its application in mpMRI of the prostate for early diagnosis of prostate cancer.

Advanced diffusion weighted imaging of the prostate: Comparison of readout-segmented multi-shot, parallel-transmit and single-shot echo-planar imaging.

PURPOSE: This study evaluates objective and subjective image quality (IQ) of three different diffusion weighted imaging (DWI) sequences in prostate MRI at 3.0 Tesla within the same patients. METHOD: Thirty-six consecutive patients (70 ± 8 years) with multi-parametric prostate MRI (mp-MRI; 3 T) and subsequently verified prostate cancer (PCa) by targeted plus systematic MR/US-fusion biopsy from 03/2016 to 12/2017 were included. Readout-segmented (rs) multi shot echo-planar imaging (EPI), parallel transmit (ptx) EPI, and single-shot (ss) EPI with b-values of 0, (500,) 1,000 s/mm² and calculated b1,500 were prospectively acquired of every patient. Signal intensities (SI) of PCa and benign tissue (peripheral and transition zone; PZ and TZ) in ADC, b1,000, and calculated b1,500 images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective IQ on a 5-point scale by two blinded readers. RESULTS: For ss-EPI ADC, b-values of 1,000, and calculated 1,500 s/mm² images showed a higher SNR compared to rs-EPI and ptx-EPI (p < 0.01). CNR of PCa and benign tissue was significantly higher for rs-EPI in high b value images compared to ptx-EPI and ss-EPI (p < 0.01). Subjective IQ was significantly higher for rs-EPI (p < 0.01). Significantly higher ADC reduction combined with signal increase on high b value images for PCa compared to the surrounding healthy tissue in PZ and TZ (PCa contrast intensity) was detected for rs-EPI (p < 0.01). Single PCa lesions could only be recognized and correlated on rs-EPI. CONCLUSIONS: Rs-EPI and ptx-EPI were superior to ss-EPI regarding contrast intensity of PCA, but inferior regarding SNR. Subjective imaging parameters were superior for rs-EPI. Especially rs-EPI, but also ptx-EPI might improve and faciliate prostate cancer detection, rs-EPI at the expense of a longer acquisition time.

Magnetic resonance imaging-guided transurethral ultrasound ablation of prostate tissue in patients with localized prostate cancer: single-center evaluation of 6-month treatment safety and functional outcomes of intensified treatment parameters.

OBJECTIVES: To evaluate the effect of intensified treatment parameters on safety, functional outcomes, and PSA after MR-Guided Transurethral Ultrasound Ablation (TULSA) of prostatic tissue. PATIENTS AND METHODS: Baseline and 6-month follow-up data were collected for a single-center cohort of the multicenter Phase I (n = 14/30 at 3 sites) and Pivotal (n = 15/115 at 13 sites) trials of TULSA in men with localized prostate cancer. The Pivotal study used intensified treatment parameters (increased temperature and spatial extent of ablation coverage). The reporting site recruited the most patients to both trials, minimizing the influence of physician experience on this comparison of adverse events, urinary symptoms, continence, and erectile function between subgroups of both studies. RESULTS: For Phase I and TACT patients, median age was 71.0 and 67.0 years, prostate volume 41.0 and 44.5 ml, and PSA 6.7 and 6.7 ng/ml, respectively. All 14 Phase I patients had low-risk prostate cancer, whereas 7 of 15 TACT patients had intermediate-risk disease. Baseline IIEF, IPSS, quality of life, and pad use were similar between groups. Pad use at 1 month and quality of life at 3 months favored Phase I patients. At 6 months, there were no significant differences in functional outcomes or adverse events. CONCLUSION: TULSA demonstrated acceptable clinical safety in Phase I trial. Intensified treatment parameters in the TACT Pivotal trial increased ablation coverage from 90 to 98% of the prostate without affecting 6-month adverse events or functional outcomes. Long-term follow-up and 12-month biopsies are needed to evaluate oncological safety.

[Imaging for initial diagnosis of localized prostate cancer]. / Bildgebung im Rahmen der Primärdiagnostik beim lokal begrenzten Prostatakarzinom.

The initial diagnosis of prostate cancer has been traditionally performed using systematic core biopsies with the use of magnetic resonance imaging (MRI) reserved to problem-solving scenarios. There is currently an ongoing paradigm shift towards the use of MRI prior to targeted biopsy as the standard approach. Prostate cancer therefore does not remain the last solid tumor entity diagnosed by non-targeted techniques but joins other solid tumor entities for which targeted diagnostic approaches have existed for a while. However, the complexity of the background tissue signal in the prostate makes lesion detection challenging. This article will provide an overview of the components of multiparametric prostate MRI and their interpretation using structured interpretation according to the current PI-RADSv2 (Prostate Imaging Reporting and Data System version 2) guidelines and of novel ultrasound techniques for primary diagnosis.

Mutant KIT as imatinib-sensitive target in metastatic sinonasal carcinoma.

Background: Sinonasal carcinomas (SNCs) comprise various rare tumor types that are characterized by marked histologic diversity and largely unknown molecular profiles, yet share an overall poor prognosis owing to an aggressive clinical course and frequent late-stage diagnosis. The lack of effective systemic therapies for locally advanced or metastatic SNC poses a major challenge to therapeutic decision making for individual patients. We here aimed to identify actionable genetic alterations in a patient with metastatic SNC whose tumor, despite all diagnostic efforts, could not be assigned to any known SNC category and was refractory to multimodal therapy. Patients and methods: We used whole-exome and transcriptome sequencing to identify a KIT exon 11 mutation (c.1733_1735del, p.D579del) as potentially druggable target in this patient and carried out cancer hotspot panel sequencing to detect secondary resistance-conferring mutations in KIT. Furthermore, as a step towards clinical exploitation of the recently described signatures of mutational processes in cancer genomes, we established and applied a novel bioinformatics algorithm that enables supervised analysis of the mutational catalogs of individual tumors. Results: Molecularly guided treatment with imatinib in analogy to the management of gastrointestinal stromal tumor (GIST) resulted in a dramatic and durable response with remission of nearly all tumor manifestations, indicating a dominant driver function of mutant KIT in this tumor. KIT dependency was further validated by a secondary KIT exon 17 mutation (c.2459_2462delATTCinsG, p.D820_S821delinsG) that was detected upon tumor progression after 10 months of imatinib treatment and provided a rationale for salvage therapy with regorafenib, which has activity against KIT exon 11/17 mutant GIST. Conclusions: These observations highlight the potential of unbiased genomic profiling for uncovering the vulnerabilities of individual malignancies, particularly in rare and unclassifiable tumors, and underscore that KIT exon 11 mutations represent tractable therapeutic targets across different histologies.

Further reduction of disqualification rates by additional MRI-targeted biopsy with transperineal saturation biopsy compared with standard 12-core systematic biopsies for the selection of prostate cancer patients for active surveillance.

BACKGROUND: Active surveillance (AS) is commonly based on standard 10-12-core prostate biopsies, which misclassify ~50% of cases compared with radical prostatectomy. We assessed the value of multiparametric magnetic resonance imaging (mpMRI)-targeted transperineal fusion-biopsies in men under AS. METHODS: In all, 149 low-risk prostate cancer (PC) patients were included in AS between 2010 and 2015. Forty-five patients were initially diagnosed by combined 24-core systematic transperineal saturation biopsy (SB) and MRI/transurethral ultrasound (TRUS)-fusion targeted lesion biopsy (TB). A total of 104 patients first underwent 12-core TRUS-biopsy. All patients were followed-up by combined SB and TB for restratification after 1 and 2 years. All mpMRI examinations were analyzed using PIRADS. AS was performed according to PRIAS-criteria and a NIH-nomogram for AS-disqualification was investigated. AS-disqualification rates for men initially diagnosed by standard or fusion biopsy were compared using Kaplan-Meier estimates and log-rank tests. Differences in detection rates of the SB and TB components were evaluated with a paired-sample analysis. Regression analyses were performed to predict AS-disqualification. RESULTS: A total of, 48.1% of patients diagnosed by 12-core TRUS-biopsy were disqualified from AS based on the MRI/TRUS-fusion biopsy results. In the initial fusion-biopsy cohort, upgrading occurred significantly less frequently during 2-year follow-up (20%, P<0.001). TBs alone were significantly superior compared with SBs alone to detect Gleason-score-upgrading. NPV for Gleason-upgrading was 93.5% for PIRADS⩽2. PSA level, PSA density, NIH-nomogram, initial PIRADS score (P<0.001 each) and PIRADS-progression on consecutive MRI (P=0.007) were significant predictors of AS-disqualification. CONCLUSIONS: Standard TRUS-biopsies lead to significant underestimation of PC under AS. MRI/TRUS-fusion biopsies, and especially the TB component allow more reliable risk classification, leading to a significantly decreased chance of subsequent AS-disqualification. Cancer detection with mpMRI alone is not yet sensitive enough to omit SB on follow-up after initial 12-core TRUS-biopsy. After MRI/TRUS-fusion biopsy confirmed AS, it may be appropriate to biopsy only those men with suspected progression on MRI.

Imaging characteristics of oligodendrogliomas that predict grade.

BACKGROUND AND PURPOSE: Oligodendrogliomas are tumors that have variable WHO grades depending on anaplasia and astrocytic components and their treatment may differ accordingly. Our aim was to retrospectively evaluate imaging features of oligodendrogliomas that predict tumor grade. MATERIALS AND METHODS: The imaging studies of 75 patients with oligodendrogliomas were retrospectively reviewed and compared with the histologic grade. The presence and degree of enhancement and calcification were evaluated subjectively. rCBV and ADC maps were measured. Logistic linear regression models were used to determine the relationship between imaging factors and tumor grade. RESULTS: Thirty of 75 (40%) tumors enhanced, including 9 of 46 (19.6%) grade II and 21 of 29 (72.4%) grade III tumors (P < .001). Grade III tumors showed lower ADC values compared with grade II tumors (odds ratio of a tumor being grade III rather than grade II = 0.07; 95% CI, 0.02-0.25; P = .001). An optimal ADC cutoff of 925 10(-6) mm(2)/s was established, which yielded a specificity of 89.1%, sensitivity of 62.1%, and accuracy of 78.7%. There was no statistically significant association between tumor grade and the presence of calcification and perfusion values. Multivariable prediction rules were applied for ADC < 925 10(-6) mm(2)/s, the presence of enhancement, and the presence of calcification. If either ADC < 925 10(-6) mm(2)/s or enhancement was present, it yielded 93.1% sensitivity, 73.9% specificity, and 81.3% accuracy. The most accurate (82.2%) predictive rule was seen when either ADC < 925 10(-6) mm(2)/s or enhancement and calcification were present. CONCLUSIONS: Models based on contrast enhancement, calcification, and ADC values can assist in predicting the grade of oligodendrogliomas and help direct biopsy sites, raise suspicion of sampling error, and predict prognosis.