Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

AIM: To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). MATERIALS AND METHODS: Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). RESULTS: Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p < 0.012; risk ratio: 1.15, 95% CI: 1.03-1.29) and the tumour extension anterior to the urethra, as assessed by MRI (p = 0.046, risk ratio: 2.51, 95% CI: 1.02-6.16). CONCLUSION: The location of cancer recurrence anterior to the urethra on MRI is an independent significant predictor of salvage HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation.

[Outcomes of HIFU for localised prostate cancer using the Ablatherm Integrate Imaging® device]. / Traitement du cancer localisé de la prostate avec l'appareil Ablatherm Imagerie Intégrée® : résultats carcinologiques et fonctionnels.

OBJECTIVES: To report the functional and oncological outcomes of HIFU for prostate cancer using the Ablatherm Integrate Imaging(®) device. METHODS: Between January 2005 and June 2009, all patients treated with HIFU as a primary care option for localized prostate cancer and fulfilling the French Urological Association (AFU) guideline were included in this study. Validated questionnaires were used to assess continence, potencies and quality of life. RESULTS: A total of 297 patients met the inclusion criteria: 149 were low risk and 148 were intermediate risk according to d'Amico's risk group. The median prostate specific antigen (PSA) nadir was 0.12ng/ml with 65% of patients reaching a nadir less than 0.3 ng/ml. Systematic control biopsies were performed on 175 patients with 89% of negative biopsies. The disease free survival rate at 40 months was 79% for low risk group and 62% for intermediate risk group. The pre and post-HIFU treatment International Prostate Symptoms Score (IPSS) score and quality of life questionnaire were not statistically different. In the opposite, the pre and post-HIFU erection function and continence status were significantly different. CONCLUSION: Local control and Biochemical Free Survival Rate achieved with HIFU were similar to those expected with conformal external radiation beam therapy. Among the functional outcomes, potency was the most impacted by the treatment.

New integrated imaging high intensity focused ultrasound probe for transrectal prostate cancer treatment.

The present study proposes a new integrated imaging (II) high-intensity focused ultrasound (HIFU) probe intended as an improvement to the Ablatherm prostate cancer treatment. Because of a perforation in the center of the II probe, the expected lesion differs from the one obtained for the original Ablatherm probe. In this paper, the new geometry and the strategy followed to establish the treatment parameters are presented. The original probe has a 40-mm focal length, a 50-mm aperture and is truncated at 31 mm. The II probe has a 45-mm focal length, a 61-mm aperture, a central perforation of 25 mm and is truncated at 31 mm. Both probes operate at 3 MHz. A mathematical model for lesion prediction was used for setting the treatment parameters for the II probe. These parameters should ensure equivalence between the lesions obtained with the original and II probes. Simulation-obtained parameters were validated by in-vitro and in-vivo (on liver of 70 New Zealand rabbits) experiments. The new II probe was used clinically to treat 30 patients. The mean age was 70.9 +/- 5.3 years (SD), the mean prostate volume 26.9 +/- 7.7 mL and the mean serum prostate specific antigen (PSA) concentration before treatment was 9.2 +/- 5.5 ng/mL. Simulations showed that for the II probe acoustical power and duration when the transducer is inactive should be reduced of 14% and 1s. In-vitro and in-vivo experiments confirmed the equivalence between the lesions obtained with the two probes. The lesion volume obtained under in-vitro conditions (for a traversed tissue depth of 16 mm to the focus) was 5 +/- 0.4 cm(3) and 5.1 +/- 0.5 cm(3) for the original and II probes, respectively. Under in-vivo conditions, the lesion volume (for a traversed tissue depth of 18 mm) was 5.3 +/- 1.1 cm(3) and 5.1 +/- 1.1 cm(3) for the original and II probes, respectively. During the clinical trial, a correction of + 1s in the exposure time was required to recreate the same degree of efficacy observed with the original probe (p = 0.97): 66.7 % of negative biopsies and 75% of patients with PSA at 3 mo < or =1 ng/mL. The morbidity observed was minimal and identical to that observed with the original probe.

[Locally recurrent prostatic adenocarcinoma after exclusive radiotherapy: results of high intensity focused ultrasound]. / Adénocarcinome prostatique en récidive locale après radiothérapie exclusive: résultats du traitement par ultrasons focalisés.

OBJECTIVES: To determine the efficacy and adverse effects of high intensity focused ultrasound (HIFU) for the treatment of local recurrence of prostate cancer after exclusive external beam radiotherapy. MATERIAL AND METHODS: Seventy-two patients with histologically and biologically documented local recurrence after radiotherapy were treated by HIFU. The mean age was 68.27+/-5.93 years, and mean PSA was 6.64+/-7.26ng/ml. Thirty patients were treated according to standard parameters and 42 according to specific parameters. ASTRO 2005 criteria, specific for salvage therapy (Phoenix consensus), were used to define recurrence. Progression-free survival was calculated by the Kaplan-Meier method. RESULTS: Mean follow-up was 39+/-28 months. The negative biopsy rate was 80% and the median nadir PSA was 0.10ng/ml. Specific survival was 94% at three years and 90% at five years, and progression-free survival was 50% at three years and 44% at five years. The urinary incontinence rate was 44% (grade 1 : 12%, grade 2/3 : 32%) and the urethral stricture or bladder neck stenosis rate was 30%. The use of specific parameters reduced the incidence of severe incontinence (19% versus 50, P=0.005) and stenosis (24% versus 40). CONCLUSIONS: Treatment with HIFU achieved a five-year progression-free survival of 44%, but patients must be clearly informed about the high rate of adverse effects.

[Ultrasound interstitial mini invasive probes for thermal ablation in liver: feasibility study in vivo]. / Sondes ultrasonores interstitielles mini-invasives pour l'ablation thermique dans le foie: étude de faisabilité in vivo.

High intensity ultrasounds are routinely used for thermal ablation of some cancers. However, for treating hepatic tumours with physical agents, RF applicators and cryoprobes are still preferred. The goal of the present study was to demonstrate the feasibility of using interstitial ultrasound probes in liver following two approaches: percutaneous and intra-tissular or endo vascular. In vivo trials on a porcine model demonstrated the minimally invasive nature of both procedures. Homogeneous and reproducible thermal lesions, up to 20 mm deep, were obtained. The work on these two original approaches deserves to be completed with more extended prospective studies. The association with an imaging method will have to be studied before proceeding to clinical trials.

[A tumour-mimic pig liver model for guiding focused ultrasound thermal ablation]. / Modèle de pseudotumeur pour guider l'ablation thermique par ultrasons focalisés: étude sur le porc.

There is no established liver tumour model in pigs to study the efficacy of ablative treatment options available for the treatment of liver tumours by physical agents. A tumour-mimic model visible with high contrast on sonograms and on gross pathology has been studied at mid-term on 20 pigs. The aim was to determine if these tumour-mimics are well tolerated and can be used to validate the use of thermal therapies at a preclinical stage. The dimensions of the tumour-mimics measured on sonograms were reproducible (diameter: 9.6 +/- 1.9 mm) and correlated with those performed in gross pathology (R(2)=0.73). The accuracy of focused ultrasound thermal therapy can be evaluated preclinically using these tumour-mimics.

Modeling of high-intensity focused ultrasound-induced lesions in the presence of cavitation bubbles

The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into account the effects of oscillating microbubbles that occur naturally in the tissue during high-intensity focused ultrasound (HIFU) treatment. First, the Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by microbubbles submitted to HIFU. Because this scattered pressure is not monochromatic, the concept of harmonic attenuation is introduced and a global attenuation coefficient is estimated for bubble-filled tissues. The first results show that this global attenuation coefficient varies significantly with respect to several parameters such as the frequency and the density of microbubbles in the medium, but also with respect to the incident acoustic pressure which thus becomes a transcendental function. Under these conditions, a layer-by-layer modeling, in the direction of propagation, is proposed to calculate the ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are estimated by the calculation of the thermal dose. Using this model, it can be observed first that, when the firing power increases, the lesion develops clearly in the direction of the transducer, with a shape agreeing with in vivo experimentation. Next, it is observed that the lesion can be significantly modified in size and position, if an interface (skin or inner wall) is simulated as a zone with multiple cavitation nuclei. With a firing power increase, it is also shown how a secondary lesion can appear at the interface and how, beyond a certain threshold, this lesion develops at the main lesion expense. Finally, a better in-depth homogeneity of lesions is observed when the acoustic frequency of HIFU is increased.

Visualisation of liver tumours using hand-held real-time strain imaging: results of animal experiments.

OBJECTIVE: Surgical resection is the only curative option for colorectal hepatic metastases. Intra-operative localisation of these metastases during hepatic resection is performed by intra-operative B-mode imaging and palpation. Because liver metastases are stiffer than normal tissues, elastography may be a useful complement to B-mode imaging. This paper reports quantitative measures of the image quality attained during intra-operative real-time elastographic visualisation of liver metastasis. METHODS: VX2 tumours were implanted in the liver of eight rabbits and were scanned in vivo. Measurements of the tumour dimensions obtained via elastography were compared with those obtained using B-mode imaging and with gross pathology. RESULTS: Measurements of tumour diameters were similar when obtained by intra-operative elastography and pathological measurement methods (mean difference±standard deviation, 0.1±0.9 mm). The contrast between tumours and normal tissues was significantly higher (p<0.05) in elastograms (26±10 dB contrast) than in sonograms (1±1 dB contrast). Sensitivity and specificity for detecting tumours using intra-operative elastography were 100% and 88%, respectively, and positive and negative predictive values were 89% and 100%, respectively. In two cases elastograms were able to detect a tumour that was ambiguous in B-mode images. CONCLUSION: Combined hand-held B-mode/strain imaging may provide additional information that is relevant for detection of liver metastases that may be missed by standard B-mode imaging alone, such as small and/or isoechoic tumours.