MRI-guided focused ultrasound focal therapy for patients with intermediate-risk prostate cancer: a phase 2b, multicentre study.

BACKGROUND: Men with grade group 2 or 3 prostate cancer are often considered ineligible for active surveillance; some patients with grade group 2 prostate cancer who are managed with active surveillance will have early disease progression requiring radical therapy. This study aimed to investigate whether MRI-guided focused ultrasound focal therapy can safely reduce treatment burden for patients with localised grade group 2 or 3 intermediate-risk prostate cancer. METHODS: In this single-arm, multicentre, phase 2b study conducted at eight health-care centres in the USA, we recruited men aged 50 years and older with unilateral, MRI-visible, primary, intermediate-risk, previously untreated prostate adenocarcinoma (prostate-specific antigen ≤20 ng/mL, grade group 2 or 3; tumour classification ≤T2) confirmed on combined biopsy (combining MRI-targeted and systematic biopsies). MRI-guided focused ultrasound energy, sequentially titrated to temperatures sufficient for tissue ablation (about 60-70°C), was delivered to the index lesion and a planned margin of 5 mm or more of normal tissue, using real-time magnetic resonance thermometry for intraoperative monitoring. Co-primary outcomes were oncological outcomes (absence of grade group 2 and higher cancer in the treated area at 6-month and 24-month combined biopsy; when 24-month biopsy data were not available and grade group 2 or higher cancer had occurred in the treated area at 6 months, the 6-month biopsy results were included in the final analysis) and safety (adverse events up to 24 months) in all patients enrolled in the study. This study is registered with ClinicalTrials.gov, NCT01657942, and is no longer recruiting. FINDINGS: Between May 4, 2017, and Dec 21, 2018, we assessed 194 patients for eligibility and treated 101 patients with MRI-guided focused ultrasound. Median age was 63 years (IQR 58-67) and median concentration of prostate-specific antigen was 5·7 ng/mL (IQR 4·2-7·5). Most cancers were grade group 2 (79 [78%] of 101). At 24 months, 78 (88% [95% CI 79-94]) of 89 men had no evidence of grade group 2 or higher prostate cancer in the treated area. No grade 4 or grade 5 treatment-related adverse events were reported, and only one grade 3 adverse event (urinary tract infection) was reported. There were no treatment-related deaths. INTERPRETATION: 24-month biopsy outcomes show that MRI-guided focused ultrasound focal therapy is safe and effectively treats grade group 2 or 3 prostate cancer. These results support focal therapy for select patients and its use in comparative trials to determine if a tissue-preserving approach is effective in delaying or eliminating the need for radical whole-gland treatment in the long term. FUNDING: Insightec and the National Cancer Institute.

Identifying Quantitative In Vivo Multi-Parametric MRI Features For Treatment Related Changes after Laser Interstitial Thermal Therapy of Prostate Cancer.

Laser interstitial thermal therapy (LITT) is a new therapeutic strategy being explored in prostate cancer (CaP), which involves focal ablation of organlocalized tumor via an interstitial laser fiber. While little is known about treatment-related changes following LITT, studying post-LITT changes via imaging is extremely significant for enabling early image-guided intervention and follow-up. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis via quantitative comparison of MRI features pre- and post-LITT, and hence identifying computerized MRI features that are highly sensitive as well as specific to post-LITT changes within the ablation zone in the prostate. A retrospective cohort of 5 patient datasets comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. Our scheme involved (1) inter-protocol registration of T2w and ADC MRI, as well as inter-acquisition registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissuespecific response, and (3) quantification of the information captured by T2w MRI and ADC maps via texture and intensity features. Correction of parameter drift resulted in visually discernible improvements in highlighting tissue-specific response in different MRI features. Quantitative, voxel-wise comparison of the changes in different MRI features indicated that steerable and non-steerable gradient texture features, rather than the original T2w intensity and ADC values, were highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. The highest ranked texture feature yielded a normalized percentage change of 186% within the ablation zone and 43% in a spatially distinct normal region, relative to its pre-LITT value. By comparison, both the original T2w intensity and ADC value demonstrated a markedly less sensitive and specific response to changes within the ablation zone. Qualitative as well as quantitative evaluation of co-occurrence texture features indicated the presence of LITT-related effects such as edema adjacent to the ablation zone, which were indiscernible on the original T2w and ADC images. Our preliminary results thus indicate great potential for non-invasive computerized MRI imaging features for determining focal treatment related changes, informing image-guided interventions, as well as predicting long- and short-term patient outcome.

Endometrioma presenting as a cavitary lung mass with intense 18F-FDG uptake on PET-CT.

[18F]-fluoro-2-deoxy-D-glucose positron emission tomography computed tomography is a useful tool to suggest the diagnosis of malignant processes. However, false positive results are known to occur in benign lesions that have a high metabolic activity. Here we describe the unusual diagnosis of a pulmonary endometrioma in a 47-year-old woman, presenting as a cavitary lung mass with intense (18)F-FDG uptake on PET-CT.

Quantifying Post- Laser Ablation Prostate Therapy Changes on MRI via a Domain-Specific Biomechanical Model: Preliminary Findings.

Focal laser ablation destroys cancerous cells via thermal destruction of tissue by a laser. Heat is absorbed, causing thermal necrosis of the target region. It combines the aggressive benefits of radiation treatment (destroying cancer cells) without the harmful side effects (due to its precise localization). MRI is typically used pre-treatment to determine the targeted area, and post-treatment to determine efficacy by detecting necrotic tissue, or tumor recurrence. However, no system exists to quantitatively evaluate the post-treatment effects on the morphology and structure via MRI. To quantify these changes, the pre- and post-treatment MR images must first be spatially aligned. The goal is to quantify (a) laser-induced shape-based changes, and (b) changes in MRI parameters post-treatment. The shape-based changes may be correlated with treatment efficacy, and the quantitative effects of laser treatment over time is currently poorly understood. This work attempts to model changes in gland morphology following laser treatment due to (1) patient alignment, (2) changes due to surrounding organs such as the bladder and rectum, and (3) changes due to the treatment itself. To isolate the treatment-induced shape-based changes, the changes from (1) and (2) are first modeled and removed using a finite element model (FEM). A FEM models the physical properties of tissue. The use of a physical biomechanical model is important since a stated goal of this work is to determine the physical shape-based changes to the prostate from the treatment, and therefore only physical real deformations are to be allowed. A second FEM is then used to isolate the physical, shape-based, treatment-induced changes. We applied and evaluated our model in capturing the laser induced changes to the prostate morphology on eight patients with 3.0 Tesla, T2-weighted MRI, acquired approximately six months following treatment. Our results suggest the laser treatment causes a decrease in prostate volume, which appears to manifest predominantly at the site of ablation. After spatially aligning the images, changes to MRI intensity values are clearly visible at the site of ablation. Our results suggest that our new methodology is able to capture and quantify the degree of laser-induced changes to the prostate. The quantitative measurements reflecting of the deformation changes can be used to track treatment response over time.

Focal laser ablation for localized prostate cancer: principles, clinical trials, and our initial experience.

Focal therapy of prostate cancer is an evolving treatment strategy that destroys a predefined region of the prostate gland that harbors clinically significant disease. Although long-term oncologic control has yet to be demonstrated, focal therapy is associated with a marked decrease in treatment-related morbidity. Focal laser ablation is an emerging modality that has several advantages, most notably real-time magnetic resonance imaging (MRI) compatibility. This review presents the principles of laser ablation, the role of multiparametric MRI for delineating the site of significant prostate cancer, a summary of published clinical studies, and our initial experience with 23 patients, criteria for selecting candidates for focal prostate ablation, and speculation regarding future directions.

Simultaneous Segmentation of Prostatic Zones Using Active Appearance Models With Multiple Coupled Levelsets.

In this work we present an improvement to the popular Active Appearance Model (AAM) algorithm, that we call the Multiple-Levelset AAM (MLA). The MLA can simultaneously segment multiple objects, and makes use of multiple levelsets, rather than anatomical landmarks, to define the shapes. AAMs traditionally define the shape of each object using a set of anatomical landmarks. However, landmarks can be difficult to identify, and AAMs traditionally only allow for segmentation of a single object of interest. The MLA, which is a landmark independent AAM, allows for levelsets of multiple objects to be determined and allows for them to be coupled with image intensities. This gives the MLA the flexibility to simulataneously segmentation multiple objects of interest in a new image. In this work we apply the MLA to segment the prostate capsule, the prostate peripheral zone (PZ), and the prostate central gland (CG), from a set of 40 endorectal, T2-weighted MRI images. The MLA system we employ in this work leverages a hierarchical segmentation framework, so constructed as to exploit domain specific attributes, by utilizing a given prostate segmentation to help drive the segmentations of the CG and PZ, which are embedded within the prostate. Our coupled MLA scheme yielded mean Dice accuracy values of .81, .79 and .68 for the prostate, CG, and PZ, respectively using a leave-one-out cross validation scheme over 40 patient studies. When only considering the midgland of the prostate, the mean DSC values were .89, .84, and .76 for the prostate, CG, and PZ respectively.

Quantitative Evaluation of Treatment Related Changes on Multi-Parametric MRI after Laser Interstitial Thermal Therapy of Prostate Cancer.

Laser interstitial thermal therapy (LITT) has recently shown great promise as a treatment strategy for localized, focal, low-grade, organ-confined prostate cancer (CaP). Additionally, LITT is compatible with multi-parametric magnetic resonance imaging (MP-MRI) which in turn enables (1) high resolution, accurate localization of ablation zones on in vivo MP-MRI prior to LITT, and (2) real-time monitoring of temperature changes in vivo via MR thermometry during LITT. In spite of rapidly increasing interest in the use of LITT for treating low grade, focal CaP, very little is known about treatment-related changes following LITT. There is thus a clear need for studying post-LITT changes via MP-MRI and consequently to attempt to (1) quantitatively identify MP-MRI markers predictive of favorable treatment response and longer term patient outcome, and (2) identify which MP-MRI markers are most sensitive to post-LITT changes in the prostate. In this work, we present the first attempt at examining focal treatment-related changes on a per-voxel basis (high resolution) via quantitative evaluation of MR parameters pre- and post-LITT. A retrospective cohort of MP-MRI data comprising both pre- and post-LITT T2-weighted (T2w) and diffusion-weighted (DWI) acquisitions was considered, where DWI MRI yielded an Apparent Diffusion Co-efficient (ADC) map. A spatially constrained affine registration scheme was implemented to first bring T2w and ADC images into alignment within each of the pre- and post-LITT acquisitions, following which the pre- and post-LITT acquisitions were aligned. Pre- and post-LITT MR parameters (T2w intensity, ADC value) were then standardized to a uniform scale (to correct for intensity drift) and then quantified via the raw intensity values as well as via texture features derived from T2w MRI. In order to quantify imaging changes as a result of LITT, absolute differences were calculated between the normalized pre- and post-LITT MRI parameters. Quantitatively combining the ADC and T2w MRI parameters enabled construction of an integrated MP-MRI difference map that was highly indicative of changes specific to the LITT ablation zone. Preliminary quantitative comparison of the changes in different MR parameters indicated that T2w texture may be highly sensitive as well as specific in identifying changes within the ablation zone pre- and post-LITT. Visual evaluation of the differences in T2w texture features pre- and post-LITT also appeared to provide an indication of LITT-related effects such as edema. Our preliminary results thus indicate great potential for non-invasive MP-MRI imaging markers for determining focal treatment related changes, and hence long- and short-term patient outcome.