Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial. METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported. RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported. CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

Echo-Focusing in Transcranial Focused Ultrasound Thalamotomy for Essential Tremor: A Feasibility Study.

BACKGROUND: Transcranial magnetic resonance-guided focused ultrasound (TcMRgFUS) systems currently employ computed tomography (CT)-based aberration corrections, which may provide suboptimal trans-skull focusing. OBJECTIVES: The objective of this study was to evaluate a contrast agent microbubble imaging-based transcranial focusing method, echo-focusing (EF), during TcMRgFUS for essential tremor. METHODS: A clinical trial of TcMRgFUS thalamotomy using EF for the treatment of essential tremor was conducted (NCT03935581; funded by InSightec [Tirat Carmel, Israel]). Patients (n = 12) were injected with Definity (Lantheus Medical Imaging, North Billerica, MA) microbubbles, and EF was performed using a research feature add-on to a commercial TcMRgFUS system (ExAblate Neuro, InSightec). Subablative thermal sonications carried out using (1) EF and (2) CT-based aberration corrections were compared via magnetic resonance thermometry, and the optimal focusing method for each patient was employed for TcMRgFUS thalamotomy. RESULTS: EF aberration corrections provided increased sonication efficiency, decreased focal size, and equivalent targeting accuracy relative to CT-based focusing. EF aberration corrections were employed successfully for lesion formation in all 12 patients, 3 of whom had previously undergone unsuccessful TcMRgFUS thalamotomy via CT-based focusing. There were no adverse events related directly to the EF procedure. CONCLUSIONS: EF is feasible and appears safe during TcMRgFUS thalamotomy for essential tremor and improves on the trans-skull focal quality provided by existing CT-based focusing methods. © 2020 International Parkinson and Movement Disorder Society.

Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor.

Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.

Magnetic resonance-guided focused ultrasound thalamotomy for treatment of essential tremor: A 2-year outcome study.

BACKGROUND: Magnetic resonance-guided focused ultrasound is an emerging, minimally invasive thermoablation technique for medically refractory essential tremor. Beyond the initial year, data regarding efficacy and potential predictors of efficacy are still preliminary. OBJECTIVES: The objective of this study was to assess the outcome at 2 years and the association between lesion volume and outcome 1 year after treatment. METHODS: We reviewed data from 37 patients who underwent unilateral magnetic resonance-guided focused ultrasound thalamotomy, with primary outcome being dominant tremor subscore of the Clinical Rating Scale for Tremor. We used multivariable linear regression to model initial lesion volume with 1-year outcome, adjusting for other clinically relevant variables. RESULTS: Although we detected a trend in loss of clinical benefit within the first year, the dominant tremor score at 2 years continued to be significantly improved (43.4%, 95% confidence interval 27.8%-59.0%) from baseline. Secondarily, initial lesion volume is significantly associated with 1-year outcome. CONCLUSION: Our findings show that magnetic resonance-guided focused ultrasound thalamotomy results in sustained tremor reduction for medically refractory essential tremor even in the long term, and we highlight areas for improvement.

Predicting lesion size by accumulated thermal dose in MR-guided focused ultrasound for essential tremor.

PURPOSE: To correlate the accumulated thermal dose (ATD) with lesion size in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy to help guide future clinical treatments. MATERIALS AND METHODS: Thirty-six patients with medication-refractory essential tremor were treated using a commercial MRgFUS brain system (ExAblate 4000, InSightec) in a 3T MR scanner (MR750, GE Healthcare). Intraoperative MR-thermometry was performed to measure the induced temperature and thermal dose distributions (thermal coefficient = -0.00909 ppm/°C). The ATD was calculated over multiple sonications with appropriate corrections for spatial-shifting artifacts. The ATD profile sizes obtained for dose values of 17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C (CEM) were correlated with the corresponding lesion sizes measured via axial T1- and T2-weighted MR images acquired 1 day post-treatment. RESULTS: Of a total of 232 included sonications, 83 required corrections for off-resonance-induced spatial-shifting artifacts (correction range = [1.1,2.2] mm). The mean lesion sizes measured on T2-weighted MR images (6.2 ± 1.3 mm, mean ± SD) were 15% larger than those measured on corresponding T1-weighted MR images (5.3 ± 1.2 mm, mean ± SD). The ATD values that provided the best correlations with the measured lesion sizes on T2- and T1-weighted MR images were 100 and 200 CEM, respectively. CONCLUSION: The ATD was correlated with lesion size measured 1 day following MRgFUS thalamotomy for essential tremor. These data provide useful information for predicting brain lesion size and determining treatment endpoints in future clinical MRgFUS procedures.

The reduction in treatment efficiency at high acoustic powers during MR-guided transcranial focused ultrasound thalamotomy for Essential Tremor.

PURPOSE: To analyze clinical data indicating a reduction in the induced energy-temperature efficiency relationship during transcranial focused ultrasound (FUS) Essential Tremor (ET) thalamotomy treatments at higher acoustic powers, establish its relationship with the spatial distribution of the focal temperature elevation, and explore its cause. METHODS: A retrospective observational study of patients (n = 19) treated between July 2015 and August 2016 for (ET) by FUS thalamotomy was performed. These data were analyzed to compare the relationships between the applied power, the applied energy, the resultant peak temperature achieved in the brain, and the dispersion of the focal volume. Full ethics approval was received and all patients provided signed informed consent forms before the initiation of the study. Computer simulations, animal experiments, and clinical system tests were performed to determine the effects of skull heating, changes in brain properties and transducer acoustic output, respectively. All animal procedures were approved by the Animal Care and Use Committee and conformed to the guidelines set out by the Canadian Council on Animal Care. MATLAB was used to perform statistical analysis. RESULTS: The reduction in the energy efficiency relationship during treatment correlates with the increase in size of the focal volume at higher sonication powers. A linear relationship exists showing that a decrease in treatment efficiency correlates positively with an increase in the focal size over the course of treatment (P < 0.01), supporting the hypothesis of transient skull and tissue heating causing acoustic aberrations leading to a decrease in efficiency. Changes in thermal conductivity, perfusion, absorption rates in the brain, as well as ultrasound transducer acoustic output levels were found to have minimal effects on the observed reduction in efficiency. CONCLUSIONS: The reduction in energy-temperature efficiency during high-power FUS treatments correlated with observed increases in the size of the focal volume and is likely caused by transient changes in the tissue and skull during heating.

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor.

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

Focused Ultrasound Hyperthermia Mediated Drug Delivery Using Thermosensitive Liposomes and Visualized With in vivo Two-Photon Microscopy.

The future of nanomedicines in oncology requires leveraging more than just the passive drug accumulation in tumors through the enhanced permeability and retention effect. Promising results combining mild hyperthermia (HT) with lyso-thermosensitive liposomal doxorubicin (LTSL-DOX) has led to improved drug delivery and potent antitumor effects in pre-clinical studies. The ultimate patient benefit from these treatments can only be realized when robust methods of HT can be achieved clinically. One of the most promising methods of non-invasive HT is the use of focused ultrasound (FUS) with MRI thermometry for anatomical targeting and feedback. MRI-guided focused ultrasound (MRgFUS) is limited by respiratory motion and large blood vessel cooling. In order to translate exciting pre-clinical results to the clinic, novel heating approaches capable of overcoming the limitations on clinical MRgFUS+HT must be tested and evaluated on their ability to locally release drug from LTSL-DOX. Methods: In this work, a new system is described to integrate focused ultrasound (FUS) into a two-photon microscopy (2PM) setting to image the release of drug from LTSL-DOX in real-time during FUS+HT in vivo. A candidate scheme for overcoming the limitations of respiratory motion and large blood vessel cooling during MRgFUS+HT involves applying FUS+HT to 42°C in short ~30s bursts. The spatiotemporal drug release pattern from LTSL-DOX as a result is quantified using 2PM and compared against continuous (3.5min and 20min at 42°C) FUS+HT schemes and unheated controls. Results: It was observed for the first time in vivo that these short duration temperature elevations could produce substantial drug release from LTSL-DOX. Ten 30s bursts of FUS+HT was able to achieve almost half of the interstitial drug concentration as 20min of continuous FUS+HT. There was no significant difference between the intravascular area under the concentration-time curve for ten 30s bursts of FUS+HT and 3.5min of continuous FUS+HT. Conclusion: We have successfully combined 2PM with FUS+HT for imaging the release of DOX from LTSL-DOX in vivo in real-time, which will permit the investigation of FUS+HT heating schemes to improve drug delivery from LTSL-DOX. We have evaluated the ability to release DOX in short 30s FUS+HT bursts to 42°C as a method to overcome limitations on clinical MRgFUS+HT and have found that such exposures are capable of releasing measurable amounts of drug. Such an exposure has the potential to overcome limitations that hamper conventional MRgFUS+HT treatments in targets that are associated with substantial tissue motion.

To heat or not to heat: Challenges with clinical translation of thermosensitive liposomes.

Thermosensitive liposomes have been put forward as a strategy to improve upon the limited tumor drug availability associated with conventional non-thermosensitive liposomes. ThermoDox® is the first and only thermosensitive liposome formulation to reach clinical development. The initial Phase III clinical trial on ThermoDox® (i.e. HEAT trial) evaluating the combination of ThermoDox® and radiofrequency ablation (RFA) in comparison to RFA alone for treatment of inoperable hepatocellular carcinoma (HCC) failed to reach its primary endpoint in progression-free survival (PFS). Nevertheless, a subgroup analysis demonstrated a marked improvement in PFS and a significant improvement in overall survival (OS) for patients who underwent RFA treatment for at least 45min. Potential reasons for failure of the HEAT trial have been summarized in this review and include issues with clinical trial design, lack of supporting preclinical data, and improvements in the control arm (i.e. RFA alone). In recent years, there have been many developments and improvements in heating infrastructure, thermometry and treatment planning of hyperthermia and ablation treatments. Still, there are many barriers to the clinical implementation and accessibility of heat treatment. This review provides an in-depth analysis of the current status, as well as potential challenges faced by continued clinical translation of thermosensitive liposomes.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: therapeutic effect in rabbit Vx2 tumours.

PURPOSE: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. MATERIALS AND METHODS: Rabbits bearing one Vx2 thigh tumour (n = 6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. RESULTS: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. CONCLUSIONS: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.

MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study.

BACKGROUND: Essential tremor is the most common movement disorder and is often refractory to medical treatment. Surgical therapies, using lesioning and deep brain stimulation in the thalamus, have been used to treat essential tremor that is disabling and resistant to medication. Although often effective, these treatments have risks associated with an open neurosurgical procedure. MR-guided focused ultrasound has been developed as a non-invasive means of generating precisely placed focal lesions. We examined its application to the management of essential tremor. METHODS: Our study was done in Toronto, Canada, between May, 2012, and January, 2013. Four patients with chronic and medication-resistant essential tremor were treated with MR-guided focused ultrasound to ablate tremor-mediating areas of the thalamus. Patients underwent tremor evaluation and neuroimaging at baseline and 1 month and 3 months after surgery. Outcome measures included tremor severity in the treated arm, as measured by the clinical rating scale for tremor, and treatment-related adverse events. FINDINGS: Patients showed immediate and sustained improvements in tremor in the dominant hand. Mean reduction in tremor score of the treated hand was 89·4% at 1 month and 81·3% at 3 months. This reduction was accompanied by functional benefits and improvements in writing and motor tasks. One patient had postoperative paraesthesias which persisted at 3 months. Another patient developed a deep vein thrombosis, potentially related to the length of the procedure. INTERPRETATION: MR-guided focused ultrasound might be a safe and effective approach to generation of focal intracranial lesions for the management of disabling, medication-resistant essential tremor. If larger trials validate the safety and ascertain the efficacy and durability of this new approach, it might change the way that patients with essential tremor and potentially other disorders are treated. FUNDING: Focused Ultrasound Foundation.

High-intensity focused ultrasound (HIFU) for dissolution of clots in a rabbit model of embolic stroke.

It is estimated that only 2-6% of patients receive thrombolytic therapy for acute ischemic stroke suggesting that alternative therapies are necessary. In this study, we investigate the potential for high intensity focused ultrasound (HIFU) to initiate thrombolysis in an embolic model of stroke. Iron-loaded blood clots were injected into the middle cerebral artery (MCA) of New Zealand White rabbits, through the internal carotid artery and blockages were confirmed by angiography. MRI was used to localize the iron-loaded clot and target the HIFU beam for treatment. HIFU pulses (1.5 MHz, 1 ms bursts, 1 Hz pulse repetition frequency, 20 s duration) were applied to initiate thrombolysis. Repeat angiograms and histology were used to assess reperfusion and vessel damage. Using 275 W of acoustic power, there was no evidence of reperfusion in post-treatment angiograms of 3 rabbits tested. In a separate group of animals, 415 W of acoustic power was applied and reperfusion was observed in 2 of the 4 (50%) animals treated. In the last group of animals, acoustic power was further increased to 550 W, which led to the reperfusion in 5 of 7 (∼70%) animals tested. Histological analysis confirmed that the sonicated vessels remained intact after HIFU treatment. Hemorrhage was detected outside of the sonication site, likely due to the proximity of the target vessel with the base of the rabbit skull. These results demonstrate the feasibility of using HIFU, as a stand-alone method, to cause effective thrombolysis without immediate damage to the targeted vessels. HIFU, combined with imaging modalities used to identify and assess stroke patients, could dramatically reduce the time to achieve flow restoration in patients thereby significantly increasing the number of patients which benefit from thrombolysis treatments.

Localised drug release using MRI-controlled focused ultrasound hyperthermia.

PURPOSE: Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. MATERIALS AND METHODS: Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. RESULTS: Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). CONCLUSIONS: The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.

Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer: long-term results from Dana-Farber Cancer Institute study 94-153.

BACKGROUND: The authors present long-term results from a phase 2 study that assessed the efficacy of transrectal ultrasound hyperthermia plus radiation with or without androgen suppression for the treatment of locally advanced prostate cancer. METHODS: Patients with clinical T2b-T3bN0M0 disease (according to 1992 American Joint Committee on Cancer [AJCC] criteria) received radiation plus 2 transrectal ultrasound hyperthermia treatments. After the first 4 patients, 6 months of androgen suppression were allowed. The study was designed to assess absolute improvement in the 2-year disease-free survival rate compared with the short-term androgen suppression arm in Radiation Therapy Oncology Group (RTOG) study 92-02. RESULTS: Thirty-seven patients received a total of 72 hyperthermia treatments. The mean cumulative equivalent minutes (CEM) T90 43°C was 8.4 minutes. According to the 1992 AJCC classification, there were 19 patients with T2b tumors, 8 patients with T2c tumors, 5 patients with T3a tumors, and 5 patients with T3b tumors. The median Gleason score was 7 (range, 6-9), and the median prostate-specific antigen (PSA) level was 13.3 ng/mL (range, 2-65 ng/mL). Thirty-three patients received androgen suppression. At a median follow-up of 70 months (range, 18-110 months), the 7-year overall survival rate was 94%, and 61% of patients remained failure free (according to the American Society for Therapeutic Radiology and Oncology definition for failure free survival). The absolute rate of disease-free survival at 2 years, which was the primary study endpoint, improved significantly (84%) compared with a rate of 64% for similar patients on the 4-month androgen suppression arm of RTOG 92-02. When Phoenix criteria (PSA nadir + 2 ng/mL) were used to define biochemical failure, 89% of patients were failure free at 2 years. CONCLUSIONS: Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer appeared to be promising. The current results indicated that further study of hyperthermia for the treatment of prostate cancer with optimal radiation and systemic therapy is warranted.

Driving circuitry for focused ultrasound noninvasive surgery and drug delivery applications.

Recent works on focused ultrasound (FUS) have shown great promise for cancer therapy. Researchers are continuously trying to improve system performance, which is resulting in an increased complexity that is more apparent when using multi-element phased array systems. This has led to significant efforts to reduce system size and cost by relying on system integration. Although ideas from other fields such as microwave antenna phased arrays can be adopted in FUS, the application requirements differ significantly since the frequency range used in FUS is much lower. In this paper, we review recent efforts to design efficient power monitoring, phase shifting and output driving techniques used specifically for high intensity focused ultrasound (HIFU).

Hyperthermia classic commentary: 'A scanned, focused, multiple transducer ultrasonic system for localised hyperthermia treatments', by K. Hynynen, R. Roemer, D. Anhalt, et al., International Journal of Hyperthermia 1987;3:21-35.

This commentary reviews the development of image-guided focused ultrasound treatments since the publication of the above paper. The impact of the research presented in the paper on the development of the current image-guided noninvasive surgery and treatments will also be discussed.

MRI-guided focused ultrasound treatments.

Focused ultrasound (FUS) allows noninvasive focal delivery of energy deep into soft tissues. The focused energy can be used to modify and eliminate tissue for therapeutic purposes while the energy delivery is targeted and monitored using magnetic resonance imaging (MRI). MRI compatible methods to deliver these exposures have undergone rapid development over the past 10 years such that clinical treatments are now routinely performed. This paper will review the current technical and clinical status of MRI-guided focused ultrasound therapy and discuss future research and development opportunities.