Vaginal stenosis treatment using computed tomography and fluoroscopy guidance.

INTRODUCTION: Vaginal stenosis is a common complication following construction of a neovagina with vascularized myocutaneous flaps. This is primarily because of inconsistent or inappropriate vaginal dilator use. Image-guided recanalization, especially for obstructed genitourinary tracts, is an emerging idea in interventional radiology. Although multiple surgical techniques have been reported to treat vaginal agenesis or obstruction, the idea of image-guided recanalization of vaginal stenosis is a relatively new management strategy for vaginal stenosis. CASE: We present a challenging case of a patient who initially presented with the complaint of increasing pelvic pressure after the creation of a neovagina via vaginoplasty. She had a distal neovagina created after extensive surgical resection for a large infiltrating pelvic rectal adenocarcinoma. A computed tomography scan revealed a fluid-filled neovaginal abscess. Examination under anesthesia revealed complete stenosis of the neovagina with no identifiable tract for dilation. INTERVENTION: A computed tomography scan and fluoroscopy-guided sharp recanalization of the stenosed neovagina was performed, followed by serial fluoroscopic balloon angioplasty to dilate the stenosed neovagina. Finally, the patient underwent a gynecologic surgery for the excision of remaining granulation tissue to produce a more permanent patent neovagina, followed by regular and proper use of vaginal dilators to ensure patency. CONCLUSION: This case report demonstrates that image-guided techniques can be used to aid in vaginal recanalization in the postoperative setting.

Nodular Fasciitis: False Positive on 18F-Piflufolastat and 11C-Choline PET/CT.

ABSTRACT: PET/CT plays a crucial role in the management of prostate cancer with several emerging and established radiopharmaceuticals, including 18 F-piflufolastat and 11 C-choline. These radiotracers are thought to be relatively specific to prostate cancer; however, uptake has also been demonstrated in other benign and malignant lesions. Nodular fasciitis is a rapidly growing benign soft tissue neoplasm that is typically self-limiting. Although a few case reports describe 68 Ga-PSMA uptake in nodular fasciitis, uptake of 11 C-choline and other PSMA-targeted PET probes, including 18 F-piflufolastat, have not previously been reported. We present a novel case of nodular fasciitis demonstrating both 18 F-piflufolastat and 11 C-choline avidity.

Percutaneous MR Imaging-Guided Laser Ablation for the Treatment of Symptomatic Cervicofacial Vascular Malformations.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation for the treatment of symptomatic soft tissue vascular malformations (VMs) in the face and neck. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all consecutive patients who underwent MR imaging-guided and monitored laser ablation for treatment of symptomatic, cervicofacial soft tissue VM. Preablation and postablation MR imaging findings were independently reviewed. Preablation and postablation VM sizes were documented. Preablation T2 signal characteristics and enhancement patterns as well as postablation change in both signal and enhancement were semiquantitatively assessed. Changes in VM size were compared using a paired t test. RESULTS: Thirteen patients (women, 9; age, 14.5-69.5 years) with 13 VMs were treated for moderate-to-severe pain (n = 4), swelling/mass effect (n = 8), or predominantly cosmesis (n = 1) with 22 total ablation sessions. The baseline maximum VM diameter was 5.7 cm ± 4.2. At baseline, all VMs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. For painful VM, the baseline pain score was 8 ± 1. Clinical follow-up was available for 10 patients. Of patients with available follow-up, 3 (100%) treated for moderate-to-severe pain and 7 (100%) treated for swelling/mass effect reported subjective complete or partial symptomatic relief. The patient treated predominantly for cosmetic reasons was lost to follow-up. Two patients (15.4%) experienced minor adverse events by the Society of Interventional Radiology standards. There were no major adverse events. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation is safe and effective for the treatment of symptomatic, cervicofacial VMs.

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.

PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga.

Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.

Uterine and Fibroid Imaging Analysis from the FIRSTT Study.

Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010-2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov.

Body Interventional MRI for Diagnostic and Interventional Radiologists: Current Practice and Future Prospects.

Clinical use of MRI for guidance during interventional procedures emerged shortly after the introduction of clinical diagnostic MRI in the late 1980s. However, early applications of interventional MRI (iMRI) were limited owing to the lack of dedicated iMRI magnets, pulse sequences, and equipment. During the 3 decades that followed, technologic advancements in iMRI magnets that balance bore access and field strength, combined with the development of rapid MRI pulse sequences, surface coils, and commercially available MR-conditional devices, led to the rapid expansion of clinical iMRI applications, particularly in the field of body iMRI. iMRI offers several advantages, including superior soft-tissue resolution, ease of multiplanar imaging, lack of ionizing radiation, and capability to re-image the same section. Disadvantages include longer examination times, lack of MR-conditional equipment, less operator familiarity, and increased cost. Nonetheless, MRI guidance is particularly advantageous when the disease is best visualized with MRI and/or when superior soft-tissue contrast is needed for treatment monitoring. Safety in the iMRI environment is paramount and requires close collaboration among interventional radiologists, MR physicists, and all other iMRI team members. The implementation of risk-limiting measures for personnel and equipment in MR zones III and IV is key. Various commercially available MR-conditional needles, wires, and biopsy and ablation devices are now available throughout the world, depending on the local regulatory status. As such, there has been tremendous growth in the clinical applications of body iMRI, including localization of difficult lesions, biopsy, sclerotherapy, and cryoablation and thermal ablation of malignant and nonmalignant soft-tissue neoplasms. Online supplemental material is available for this article. ©RSNA, 2021.

Percutaneous MR Imaging-Guided Laser Ablation and Cryoablation for the Treatment of Pediatric and Adult Symptomatic Peripheral Soft Tissue Vascular Anomalies.

PURPOSE: To evaluate the safety and effectiveness of percutaneous magnetic resonance (MR) imaging-guided laser ablation and cryoablation for the treatment of symptomatic soft tissue vascular anomalies (VAs) of the trunk and extremities. MATERIALS AND METHODS: An institutional review board-approved retrospective review was undertaken of all pediatric and adult patients who underwent MR imaging-guided and monitored laser ablation and/or cryoablation for the treatment of symptomatic peripheral soft tissue VA. Preablation and postablation MR imaging was independently reviewed. Pain scores on the visual analog scale (0 to 10) and self-reported subjective symptomatic improvement were assessed. Change in VA size and pain scores were compared using a paired t test. RESULTS: Thirty patients (24 females; age, 10-75 years) with 34 VAs were treated for moderate to severe pain (n = 27) or swelling/mass effect (n = 3) with 60 total ablation sessions. The baseline maximum VA diameter was 9.5 cm ± 8.6. At baseline, all VAs (100%) demonstrated variable T2-weighted signal hyperintensity and enhancement. The baseline pain score was 6.4 ± 1.6. Clinical follow-up was available for 23 patients. At a mean follow-up time of 12.2 months ± 10.1, 19 of 20 (95%) patients treated for pain and 2 of 3 (67%) patients treated for swelling/mass effect reported partial or complete symptomatic relief. There was a significant decrease in the postablation pain scores (-5.7 ± 1.0, P < .001) and maximum VA size (-2.3 cm ± 2.7, P = .004), with >50% reduction in VA T2 signal (59%) and enhancement (73%). Nine of 30 (30%) patients experienced minor complications. CONCLUSIONS: MR imaging-guided and monitored percutaneous laser ablation and cryoablation appear to be safe and effective for the treatment of symptomatic peripheral soft tissue VAs.

A Single-Institution Experience in Percutaneous Image-Guided Cryoablation of Lymph Node Metastases.

OBJECTIVE. The purpose of this study was to assess the feasibility, safety, and efficacy of percutaneous cryoablation for the treatment of lymph node metastases. MATERIALS AND METHODS. In this single-institution retrospective study 55 patients were identified who underwent CT-guided cryoablation of metastatic lymph nodes between November 2006 and September 2019. Patient demographics, disease characteristics, and procedural details were recorded. The primary endpoints were technical success and major complications. The secondary endpoints were time to local and time to distant progression. Complications were graded according to the Society of Interventional Radiology consensus guidelines. RESULTS. The study sample comprised 55 patients (42 men, 13 women; mean age 64 ± 12 years) who underwent 61 cryoablation procedures to treat 65 lymph node metastases. Targeted nodes measured 1.7 ± 1.2 cm in mean short-axis diameter. Technical success was achieved in 60 of 61 cryoablation procedures (98%). Adjunctive maneuvers performed to protect adjacent structures included hydrodissection (n = 40), ureteral stenting (n = 3), and neural monitoring (n = 3). There were two Society of Interventional Radiology major complications (3%): pneumothorax (n = 1) and bleeding (n = 1). Local tumor control was achieved in treatment of 53 of 65 (82%) nodal metastases within a median of 25 months (range, 1-121 months) of follow-up. Local progression occurred in 12 of 65 cases (18%); the median time to recurrence was 11 months. CONCLUSION. Percutaneous cryoablation of nodal metastases is feasible and safe. Further investigation is warranted to assess the long-term efficacy of this technique and to define its role in oncologic care.

Experimental Investigation of Cryoneedle Heating during MR-Guided Cryoablation in Ex Vivo Tissue Samples at 1.5-Tesla.

PURPOSE: To investigate cryoneedle heating risks during magnetic resonance (MR)-guided cryoablation and potential strategies to mitigate these risks. MATERIALS AND METHODS: Ex vivo experiments were performed on a 1.5-Tesla (T) MR scanner using an MR conditional cryoablation system on porcine tissue phantoms. Cryoneedles were placed inside the tissue phantom either with or without an angiocatheter. Typical cryoneedle geometric configurations (including gas supply line) encountered in clinical procedures with low to high expected heating risks were investigated. Up to 4 fiber optic temperature sensors were attached to the cryoneedle/angiocatheter to measure the MR-induced cryoneedle heating at different locations during MR with different estimated specific absorption rates (SARs). The impact of cryoneedle heating on cryoablation treatment was studied by comparing temperature changes during 10-min freeze-thaw cycles with and without MR. RESULTS: Rapid temperature increases of >100 °C in < 2 minutes were observed during MR with a SAR of 2.1 W/kg. The temperature changes during a typical freeze-thaw cycle were also affected by cryoneedle heating when MR was used to monitor the ice-ball evolution. The observed cryoneedle heating was affected by multiple factors; including cryoneedle geometric configurations, sequence SAR, whether an angiocatheter was used, and whether the cryoneedle was connected to the rest of the cryoablation system. CONCLUSIONS: The ex vivo experiments demonstrated that MR could induce significant cryoneedle heating risks. Furthermore, MR-induced cryoneedle heating can affect temperatures in the ice-ball evolution during the freeze-thaw cycle. Several practical strategies to reduce the cryoneedle heating have been proposed.

Salvage ablation for locally recurrent prostate cancer.

PURPOSE OF REVIEW: This review aims to summarize the latest evidence for the use of salvage ablation of localized prostate cancer recurrences after primary therapy radiotherapy or prostatectomy. RECENT FINDINGS: Savage ablation represents a treatment option in select patients with localized recurrences following primary therapy of prostate cancer. Following radiotherapy, salvage cryotherapy and high-intensity focused ultrasound (HIFU) demonstrate encouraging oncologic outcomes. Biochemical recurrence-free survival ranged from 71% at 2 years to 44.2% at 10 years for cryotherapy and from 51% at 5 years to 28.7% at 10 years for HIFU. Rates of adverse effects appear to be more favorable with ablation compared to salvage surgery. Focal salvage ablation may offer a further balance between oncologic control and adverse effects. Following radical prostatectomy, recent data on the use of salvage ablation of local recurrences are less robust with only a few small studies published in the last 2 years. SUMMARY: Salvage ablation is an option for localized disease recurrences following primary treatment. Its role is most established for postradiation recurrence. It can also be utilized in postprostatectomy recurrence, although published data is more limited. Future studies are needed to further explore the role of ablation in both cohorts.

Improved MR-thermometry during hepatic microwave ablation by correcting for intermittent electromagnetic interference artifacts.

MRI-guided microwave ablation (MWA) is a minimally invasive treatment for localized cancer. MR thermometry has been shown to be able to provide vital information for monitoring the procedure in real-time. However, MRI during active MWA can suffer from image quality degradation due to intermittent electromagnetic interference (EMI). A novel approach to correct for EMI-contaminated images is presented here to improve MR thermometry during clinical hepatic MWA. The method was applied to MR-thermometry images acquired during four MR-guided hepatic MWA treatments using a commercially available MRI-configured microwave generator system. During the treatments MR thermometry data acquisition was synchronized to respiratory cycle to minimize the impact of motion. EMI was detected and corrected using uncontaminated k-space data from nearby frames in k-space. Substantially improved temperature and thermal damage maps have been obtained and the treatment zone can be better visualized. Our ex vivo tissue sample study shows the correction introduced minimal errors to the temperature maps and thermal damage maps.

Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE).

OBJECTIVE: To assess the safety and local recurrence-free survival in patients after cryoablation for treatment of pulmonary metastases. METHODS: This multicenter, prospective, single-arm, phase 2 study included 128 patients with 224 lung metastases treated with percutaneous cryoablation, with 12 and 24 months of follow-up. The patients were enrolled on the basis of the outlined key inclusion criteria, which include one to six metastases from extrapulmonary cancers with a maximal diameter of 3.5 cm. Time to progression of the index tumor(s), metastatic disease, and overall survival rates were estimated using the Kaplan-Meier method. Complications were captured for 30 days after the procedure, and changes in performance status and quality of life were also evaluated. RESULTS: Median size of metastases was 1.0 plus or minus 0.6 cm (0.2-4.5) with a median number of tumors of 1.0 plus or minus 1.2 cm (one to six). Local recurrence-free response (local tumor efficacy) of the treated tumor was 172 of 202 (85.1%) at 12 months and 139 of 180 (77.2%) at 24 months after the initial treatment. After a second cryoablation treatment for recurrent tumor, secondary local recurrence-free response (local tumor efficacy) was 184 of 202 (91.1%) at 12 months and 152 of 180 (84.4%) at 24 months. Kaplan-Meier estimates of 12- and 24-month overall survival rates were 97.6% (95% confidence interval: 92.6-99.2) and 86.6% (95% confidence interval: 78.7-91.7), respectively. Rate of pneumothorax that required pleural catheter placement was 26% (44/169). There were eight grade 3 complication events in 169 procedures (4.7%) and one (0.6%) grade 4 event. CONCLUSION: Percutaneous cryoablation is a safe and effective treatment for pulmonary metastases.

Percutaneous cryoablation of abdominal wall endometriosis: the Mayo Clinic approach.

Abdominal wall endometriosis (AWE) is a rare form of endometriosis that often results in substantial pain and debility. The current treatment algorithm for AWE is not well established. The purpose of this review is to describe the Mayo Clinic experience with thermal ablation of symptomatic AWE as well as to review current imaging and interventional literature regarding the diagnosis and treatment of AWE.

Rectal wall saline displacement for improved margin during MRI-guided cryoablation of primary and recurrent prostate cancer.

PURPOSE: To describe safety, efficacy, and added oncologic margin of saline displacement of the rectal wall during MRI-guided cryoablation of primary and recurrent prostate cancer. METHODS: A retrospective review was conducted for patients who underwent MRI-guided cryoablation with saline displacement of the rectal wall for treatment of primary and recurrent prostate cancer over a 2-year period. Saline displacement was used when the distance from the edge of the ablation area to the rectal wall was insufficient to provide at least a 5-mm treatment margin. Pre- and post-ablation rectal wall displacement distances as well as ablative zone margins were assessed with MRI. Saline displacement distance was measured from the rectal wall to the edge of the lesion for focal lesion ablation and from the edge of the prostate for hemi-gland ablation. Immediate and intermediate-term complications were assessed. RESULTS: Saline displacement was used in 25 patients undergoing MRI-guided cryoablation. Twenty-one patients underwent salvage cryoablation, while four patients had it as primary treatment for prostate cancer. Median pre- and post- saline displacement rectal wall displacement distances were 6.0 and 11.2 mm, respectively (P < 0.0001). Median-added oncologic margin achieved by saline displacement was 4.6 mm (range 0.6-26.5). Median follow-up was 14 months (range 5-29). There were no intra-procedural complications and 3 patients experienced minor (Clavien-Dindo grade I) complications. One rectal complication occurred in a patient undergoing salvage cryotherapy with a history of extensive pelvic surgery and radiation. CONCLUSIONS: Saline infusion at the time of MRI- guided cryoablation for prostate cancer resulted in increased distances between the target lesion and rectum. This is a useful technique in providing an added oncologic margin when treating lesions close to the rectal wall.

Magnetic Resonance-Guided Prostate Ablation.

In 2019, the American Cancer Society (ACS) estimates that 174,650 new cases of prostate cancer will be diagnosed and 31,620 will die due to the prostate cancer in the United States. Prostate cancer is often managed with aggressive curative intent standard therapies including radiotherapy or surgery. Regardless of how expertly done, these standard therapies often bring significant risk and morbidity to the patient's quality of life with potential impact on sexual, urinary, and bowel functions. Additionally, improved screening programs, using prostatic-specific antigen and transrectal ultrasound-guided systematic biopsy, have identified increasing numbers of low-risk, low-grade "localized" prostate cancer. The potential, localized, and indolent nature of many prostate cancers presents a difficult decision of when to intervene, especially within the context of the possible comorbidities of aggressive standard treatments. Active surveillance has been increasingly instituted to balance cancer control versus treatment side effects; however, many patients are not comfortable with this option. Although active debate continues on the suitability of either focal or regional therapy for the low- or intermediate-risk prostate cancer patients, no large consensus has been achieved on the adequate management approach. Some of the largest unresolved issues are prostate cancer multifocality, limitations of current biopsy strategies, suboptimal staging by accepted imaging modalities, less than robust prediction models for indolent prostate cancers, and safety and efficiency of the established curative therapies following focal therapy for prostate cancer. In spite of these restrictions, focal therapy continues to confront the current paradigm of therapy for low- and even intermediate-risk disease. It has been proposed that early detection and proper characterization may play a role in preventing the development of metastatic disease. There is level-1 evidence supporting detection and subsequent aggressive treatment of intermediate- and high-risk prostate cancer. Therefore, accurate assessment of cancer risk (i.e., grade and stage) using imaging and targeted biopsy is critical. Advances in prostate imaging with MRI and PET are changing the workup for these patients, and advances in MR-guided biopsy and therapy are propelling prostate treatment solutions forward faster than ever.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Targeted Prostate Biopsy and MR-Guided Therapy for Prostate Cancer.

In 2018, the American Cancer Society (ACS) estimates that 164,690 new cases of prostate cancer will be diagnosed and 29,430 will die due to the prostate cancer in the United States (Siegel et al., CA Cancer J Clin 67:7-30, 2018). Many men with prostate cancer are often managed with aggressive therapy including radiotherapy or surgery. No matter how expertly done, these therapies carry significant risk and morbidity to the patient's health related quality of life with impact on sexual, urinary and bowel function (Potosky et al., J Natl Cancer Inst 96:1358-1367, 2004). A recent meta-analysis of 19 studies reviewing the use of surgery and radiation for prostate cancer demonstrated patients who received radiation were more likely to die from their disease as compared to surgery (Wallis et al., Eur Urol 70:21-30, 2016). Furthermore, screening programs using prostatic specific antigen (PSA) and transrectal ultrasound (TRUS) guided systematic biopsy have identified increasing numbers of low risk, low grade "localized" prostate cancer. This indolent nature of many prostate cancers presents a difficult decision of when to intervene given the possible comorbidities of aggressive treatment. Active surveillance has been increasingly instituted in order to balance cancer control versus treatment side effects (Jemal et al., CA Cancer J Clin 56:106-130, 2006). Although active debate continues on the suitability of focal or regional therapy for these low or intermediate risk prostate cancer patients, many unresolved issues remain which complicate this approach of management. Some of the largest unresolved issues are: prostate cancer multifocality, limitations of current biopsy strategies, suboptimal staging by accepted imaging modalities, less than robust prediction models for indolent prostate cancers and whether established curative therapies can be safely and effectively used following focal therapy for prostate cancer. In spite of these restrictions focal therapy continues to confront the current paradigm of therapy for low and even intermediate risk disease (Onik, Tech Vasc Interv Radiol 10:149-158, 2017). It has been proposed that early detection and proper characterization may play a role in preventing the development of metastatic disease (Vickers et al., BMJ 346:f2023, 2013). There is Level 1 evidence supporting detection and subsequent aggressive treatment of intermediate and high-risk prostate cancer (Bill-Axelson et al., N Engl J Med 370:932-942, 2014). Therefore accurate assessment of cancer risk (i.e. grade and stage) using imaging and targeted biopsy is critical. Advances in prostate imaging with MRI have been accompanied with advances in MR guided therapy propelling prostate treatment solutions forward faster than ever.