Eugen Hlasny

Real-time magnetic resonance imaging-guided focal laser therapy in patients with low-risk prostate cancer.

Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)-guided focal laser ablation. The tumor was identified on MRI. A laser fiber was delivered via a catheter inserted through a perineal template and guided to the target with MRI. The tissue temperature was monitored during laser ablation by MRI thermometry. Accumulated thermal damage was calculated in real time. Immediate post-treatment contrast-enhanced MRI confirmed devascularization of the target. No adverse events were noted. MRI-guided focal laser therapy of low-risk PCa is feasible and may offer a good balance between cancer control and side effects.

Focal Laser Ablation for Prostate Cancer Followed by Radical Prostatectomy: Validation of Focal Therapy and Imaging Accuracy

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

Real-Time MRI-Guided Focused Ultrasound for Focal Therapy of Locally Confined Low-Risk Prostate Cancer: Feasibility and Preliminary Outcomes

OBJECTIVE Focal therapy is an emerging approach to the treatment of localized prostate cancer. The purpose of this study was to report the 6-month follow-up oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound in North America. SUBJECTS AND METHODS Four patients with a prostate-specific antigen (PSA) level of 10 ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 + 3) were prospectively enrolled in the study and underwent multiparametric MRI and transrectal ultrasound-guided prostate systematic biopsy. Under MRI guidance and real-time monitoring with MR thermography, focused high-frequency ultrasound energy was delivered to ablate the target tissue. The incidence and severity of treatment-related adverse events were recorded along with responses to serial quality-of-life questionnaires for 6 months after treatment. Oncologic outcomes were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided biopsy 6 months after treatment. RESULTS Four patients with a total of six target lesions were treated and had complications graded Clavien-Dindo I or less. Quality-of-life parameters were similar between baseline and 6-months. All four patients had normal MRI findings in the treated regions (100%), biopsy showed that three patients (75%) were clear of disease in the treated regions, representing complete ablation of five target lesions (83%). All patients had at least one Gleason 6-positive core outside of the treated zone. CONCLUSION MRI-guided focused ultrasound is a feasible method of noninvasively ablating low-risk prostate cancers with low morbidity. Further investigation and follow-up are warranted in a larger patient series with appropriate statistical analysis of oncologic and functional outcome measures.

Focal magnetic resonance guided focused ultrasound for prostate cancer: Initial North American experience

The treatment of low-risk prostate cancer is a common clinical dilemma between standard curative whole gland therapy (and its associated quality of life diminishing side effects) and active surveillance (and its low, but real, risk of progression). The goal of focal therapy in low-risk prostate cancer is to achieve the best balance between cancer control and maintenance of quality of life. Magnetic resonance-guided focused ultrasound (MRgFUS) surgery is a non-invasive thermal ablation method that integrates magnetic resonance imaging for target identification, treatment planning and closed-loop control of thermal deposition and focused ultrasound for thermal ablation of the tumour target. This novel transrectal system allows for tumour localization, targeting and monitoring of tumour target ablation in real time, while simultaneously preserving adjacent normal tissue thereby minimizing the side effects of standard curative surgical or radiation therapy. We report the first North American clinical experience of treatment of localized prostate cancer with focal MR-guided transrectal focused ultrasound (clinicaltrial.gov identifier NCT01226576).

Construction and Evaluation of an Anatomically Correct Multi-Image Modality Compatible Phantom for Prostate Cancer Focal Ablation

PURPOSE Focal therapy using lasers is emerging as an alternative strategy for prostate cancer treatment. However, to our knowledge no anatomically correct models are available to test imaging and ablation techniques. Animal models present ethical, anatomical and cost challenges. We designed and validated an inexpensive but anatomically correct prostate phantom incorporating tumor, rectum and urethra that can be used for simulated and experimental magnetic resonance guided focal intervention. Our secondary aim was to asses the phantom using other imaging modalities. MATERIALS AND METHODS The phantom, which was constructed of ballistic gel, includes an 80 gm prostate with urethra, tumor, perineum and rectum. Gadolinium was added to make the gel visible to magnetic resonance imaging. To recreate a tumor an irregularly shaped 5 cc volume of coagulable gel was inserted into the prostate phantom. The phantom was evaluated using magnetic resonance, computerized tomography and transrectal ultrasound. Thermal ablation was delivered via interstitial placement of laser fibers. Magnetic resonance thermometry was done to record real-time tissue temperatures during thermal ablation. RESULTS With all modalities tested the phantom emulated human prostate anatomy. The coagulable gel tumor allowed us to generate focal thermal lesions. The phantom had magnetic resonance imaging properties comparable to in vivo properties, allowing ablative zones to be accurately assessed and magnetic resonance thermometry to be done. CONCLUSIONS The phantom is a useful tool to test different aspects of thermal focal ablation for prostate cancer using multiple imaging modalities, particularly magnetic resonance. It is inexpensive and easily constructed, and may be considered a valuable model to train on and teach focal therapy.

MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes

Objective: To report the 6-month single-blinded results of unilateral thalamotomy with MRI-guided focused ultrasound (MRgFUS) in patients with tremors other than essential tremor. Methods: Three patients with tremor due to Parkinson disease, 2 with dystonic tremor in the context of cervicobrachial dystonia and writers cramp, and 1 with dystonia gene–associated tremor underwent MRgFUS targeting the ventro-intermedius nucleus (Vim) of the dominant hemisphere. The primary endpoint was the reduction of lateralized items of the Tremor Rating Scale of contralateral hemibody assessed by a blinded rater. Results: All patients achieved a statistically significant, immediate, and sustained improvement of the contralateral tremor score by 42.2%, 52.0%, 55.9%, and 52.9% at 1 week and 1, 3, and 6 months after the procedure, respectively. All patients experienced transient side effects and 2 patients experienced persistent side effects at the time of last evaluation: hemitongue numbness and hemiparesis with hemihypoesthesia. Conclusions: Vim MRgFUS is a promising, incision-free, but nevertheless invasive technique to effectively treat tremors other than essential tremor. Future studies on larger samples and longer follow-up will further define its effectiveness and safety. Clinicaltrials.gov identifier: NCT02252380. Classification of evidence: This study provides Class IV evidence that for patients with tremor not caused by essential tremor, MRgFUS of the Vim improves the tremor of the contralateral hemibody at 6 months.

Mechatronic system for in-bore MRI-guided insertion of needles to the prostate: An in vivo needle guidance accuracy study.

To present our experiences in initial clinical evaluation of a novel mechatronic system for in‐bore guidance of needles to the prostate for MRI‐guided prostate interventions in 10 patients. We report accuracy of this device in the context of focal laser ablation therapy for localized prostate cancer.

Optimizing contrast agent concentration and spoiled gradient echo pulse sequence parameters for catheter visualization in MR-guided interventional procedures: an analytic solution.

A critical requirement of MR‐guided interventions is the visualization of an instrument (e.g., catheter, needle) during the procedure. One approach is to fill the instrument with a contrast agent. Previously, the optimization of contrast agent visualization was performed only empirically. In the present study, an analytic optimization of contrast agent SNR efficiency was performed for a spoiled gradient echo pulse sequence.

Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy in Parkinson Tremor: Reoperation After Benefit Decay: Repeated MRgFUS Thalamotomy for PD Tremor

MRI-guided focused ultrasound (MRgFUS) is a novel, incision-free invasive technique to ablate deep body targets, including brain. Open, single-blind, and sham-controlled double-blind studies have confirmed the safety and efficacy of MRgFUS targeting ventro-intermedius nucleus (Vim) in PD tremor. Tremor recurrence has been reported in up to a third of patients within the first 2 years, although others have reported a more sustained benefit, similar to that observed after radiofrequency thalamotomy. We report on a previously reported 76-year-old righthanded patient with tremor-dominant PD for 14 years. He participated in our Vim-MRgFUS for essential tremor (nonET) tremor trial (NCT02252380), targeting the dominant hemisphere (Fig. 1A). At baseline, total, right-hemibody and disability tremor rating scale (TRS) scores were 46, 26, and 12 (Supplementary Video Segment 1), respectively, and dropped by 80%, 96%, and 92% 1 week after the first Vim-MRgFUS procedure (Supplementary Video Segment 2). During the first week posttreatment, he had mild forehead discomfort and a droopy right eyelid related to the pins. No significant effects were noticed on ipsilateral and axial scores. However, the right-sided tremor slowly reoccurred, and 6 months later, these scores were reduced by only 35%, 42%, and 25% relative to baseline, respectively (Fig. 1B,C). Given the lack of enduring significant efficacy and the fading of the thalamotomy lesion on follow-up imaging (Fig. 1A), we offered retreatment. After discussing the options, including radiofrequency, gamma knife thalamotomy, and MRgFUS subthalamotomy, a second MRgFUS thalamotomy was performed 18 months after the first one (Fig. 1A). Total, right-hemibody, and disability TRS scores were 39, 14, and 9 (Supplementary Video Segment 3). The second procedure reduced the right-hemibody TRS by 42% (1 week), 23% (1 month), 4% (3 months, Supplementary Video Segment 4), and 8% (12 months) relative to second treatment baseline (corresponding to 88.5%, 69.2%, 50.0%, and 53.8% relative to initial pretreatment baseline). As a result of the overall progression of the PD symptoms and tremor on contralateral hemibody, total and disability TRS scores were not reduced (Fig. 1B). The second procedure induced a very mild hemiparetic gait and limited right-hemibody ataxia, still present 1 year later. Reintroducing levodopa up to 750 mg/day only resulted in partial additional improvement. In case of tremor recurrence, DBS has the advantage of adjustability. A revival of lesional procedures emerged recently with MRgFUS, which has nevertheless been associated with a relatively fast decay of benefit in a subset of patients. Some of these patients have been treated successfully with additional radiofrequency thalamotomy or Vim DBS (unpublished data). Another possible way to treat patients with reoccurring tremor after is repeating MRgFUS. In contrast to gamma knife thalamotomy, there is no restriction by risk of radiation necrosis. Ours is the first report on repeated focused ultrasound for a neurological indication and shows that this is a possible strategy that can result in additional benefit on tremor. However, our case also illustrates that a repeated procedure can be associated cumulative adverse effects. In addition, tremor reduction does not always translate into a functional improvement because of the progression of tremor in other body sites or the appearance of PD symptoms resistant to thalamic procedures, such as bradykinesia or rigidity.

MP70-16 SAFETY AND FEASIBILITY OF REAL-TIME MRI-GUIDED FOCUSED ULTRASOUND FOR FOCAL THERAPY OF LOCALIZED PROSTATE CANCER USING THE EXABLATE 2100 DEVICE: PHASE 1 STUDY

determine toxicity, side-effects and early efficacy as well as to determine optimum treatment delivery of MRI-ultrasound fusion-guided intraprostatic injection of PRX302. METHODS: 18 men with histologically proven, clinically significant, localized low-intermediate risk prostate cancer associated with an MRI lesion were recruited (PSA </1⁄415, T2aN0Mo, Gleason </1⁄44+3 with a maximum cancer core length [MCCL] </1⁄410mm, or Gleason 3+3 with MCCL >/1⁄44mm (May/2015-Nov/2015). Patients had a single lesion injected transperineally using MRI-ultrasound image-fusion software (SmartTarget ), under general anaesthetic with up to 5mL of a standard dosing solution (20ug/mL) of PRX302. Follow-up occurred at 2 days and at 2, 6, 12, 24 and 26 weeks. A mpMRI-targeted transperineal biopsy of the treated area was performed at 24 weeks. All men who enrolled completed the study. RESULTS: Median age and PSA were 66.50 years (IQR 13.00) and 6.25ng/ml (IQR 2.45). 4 patients (22%) had high volume Gleason 6 and 14 (78%) had Gleason 7 cancer with median lesion size 0.3mL (IQR 0.2-0.5). The administration of PRX302 was well tolerated with no serious adverse events and no new safety signals. At 24 weeks following treatment, 2 had complete tumour ablation (no histological evidence of cancer). These 2 showed reductions in PSA of 3.0 to 2.2ng/ mL (26.7%) and 5.7 to 4.8ng/mL (15.8%), respectively. Seven had partial response defined as reductions in MCCL or Gleason grade. 9 had no histological response, with some experiencing increases in MCCL or grade. CONCLUSIONS: Our proof-of-concept study shows that a single intraprostatic administration of PRX302 has a biological effect on prostate tumor cells when focally injected with low side-effect profile. Optimizing the dosing and delivery of PRX302 based on tumour size may increase response rates and will be tested in a multicenter phase 2 study.