Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile

Hurwitz, Mark; Kaplan, Irving; Hansen, Jorgen L.; Prokopios-Davos, Savina; Topulos, George P.; Wishnow, Kenneth I.; Manola, Judith; Bornstein, Bruce A.; Hynynen, Kullervo

doi:10.1080/02656730500331967

Cited by 31 publications

(29 citation statements)

References 13 publications

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“…Both bDFS and OS improve in intermediate-and high-risk prostate cancer using RT combined with AST as compared with the use of RT alone or deferred AST until relapse [24]. Considering that long-term AST may increase the risk of fatal myocardial infarction, induce a metabolic syndrome with possible fractures and reduce QoL, some authors [10] thought that a short term AST (no more than 6 months) could be preferable in order to decrease side effects.…”

Section: The Rationale For Using Hyperthermia In Prostate Cancermentioning

confidence: 96%

Treatment for intermediate and high-risk prostate cancer: Controversial issues and the role of hyperthermia

Maluta

Dall’Oglio

Nadalini

2010

International Journal of Hyperthermia

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For patients affected by intermediate- and high-risk prostate cancer, a single local therapy is not enough, and a more aggressive treatment, such as androgen suppression therapy (AST) and pelvic irradiation, is indicated. Biochemical disease-free survival (bDFS) and overall survival (OS) improve in intermediate- and high-risk prostate cancer using radiotherapy (RT) combined with AST as compared with the RT alone. Hyperthermia (HT), combined with RT for the treatment of prostate cancer with intermediate- and high-risk, has been defined as "promising". In the development of new strategies, the reduction of short and long-term treatment related toxicity is of primary importance. Quality of Life (QoL) has been previously investigated and the authors concluded that HT does not negatively impact QoL in patients treated with radiation and HT. The use of HT in treating advanced prostate cancer has been reported by many centres; several studies suggest the feasibility of HT added to conventional RT. In intermediate- and high-risk prostate cancer, the combination of RT plus a long-term androgen suppression provides good results in terms of OS and QoL. HT, improving the anti-cancer effects of irradiation, as demonstrated by experimental in vitro and in vivo studies, could increase the outcome in the treatment of locally advanced prostate tumours without adding toxicity. A randomised phase III trial comparing RT-AST combined treatment plus/minus HT is needed to demonstrate the efficacy of HT.

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Section: The Rationale For Using Hyperthermia In Prostate Cancermentioning

confidence: 96%

Treatment for intermediate and high-risk prostate cancer: Controversial issues and the role of hyperthermia

Maluta

Dall’Oglio

Nadalini

2010

International Journal of Hyperthermia

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“…[21][22][23][24][25][26][27][28][29][30] Whole gland hyperthermia may not be possible simply through beamforming alone. However, the ExAblate 2100 has a rotational and translational positioning module that affords accurate positioning and orientation of the applicator within the patient.…”

Section: Discussionmentioning

confidence: 99%

“…Feasibility of safe hyperthermia delivery to the prostate using transrectal ultrasound arrays (∼1.5 MHz, 4-16 elements) has been reported in the past. [28][29][30] Diverging sonications with ExAblate array can be used to deliver diffuse hyperthermia similar to cylindrical-element applicators described in the aforementioned studies. Greater control of heating may be possible due to greater array beamforming possibilities arising from larger number of elements, mechanical rotation and translation capabilities, and volumetric thermal dosimetry through MR temperature monitoring.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies about hyperthermia to the prostate using endorectal ultrasound utilize a bolus of temperature-controlled water for applicator coupling and rectal wall protection. 21,22,27,29,30 The InSightec system can regulate bolus temperature over a large range (as low as 10…”

Section: C2 Boundary Conditionsmentioning

confidence: 99%

“…[21][22][23][24][25][26] Clinical studies have demonstrated feasibility of safe, reliable, and effective application of prostate hyperthermia with ERUS applicators. [27][28][29][30] Currently, MR guided high intensity focused ultrasound (MRgHIFU) systems are being increasingly utilized for noninvasive or minimally invasive thermal ablation of soft tissue tumors in multiple organ sites. 31,32 Typically, these are multielement phased array applicators capable of delivering ultrasound energy with precise spatial control.…”

Section: Introductionmentioning

confidence: 99%

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Model‐based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR‐guided endorectal HIFU ablation array

et al. 2014

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Purpose: Feasibility of targeted and volumetric hyperthermia (40-45• C) delivery to the prostate with a commercial MR-guided endorectal ultrasound phased array system, designed specifically for thermal ablation and approved for ablation trials (ExAblate 2100, Insightec Ltd.), was assessed through computer simulations and tissue-equivalent phantom experiments with the intention of fast clinical translation for targeted hyperthermia in conjunction with radiotherapy and chemotherapy. Methods: The simulations included a 3D finite element method based biothermal model, and acoustic field calculations for the ExAblate ERUS phased array (2.3 MHz, 2.3 × 4.0 cm 2 , ∼1000 channels) using the rectangular radiator method. Array beamforming strategies were investigated to deliver protracted, continuous-wave hyperthermia to focal prostate cancer targets identified from representative patient cases. Constraints on power densities, sonication durations and switching speeds imposed by ExAblate hardware and software were incorporated in the models. Preliminary experiments included beamformed sonications in tissue mimicking phantoms under MR temperature monitoring at 3 T (GE Discovery MR750W). Results: Acoustic intensities considered during simulation were limited to ensure mild hyperthermia (T max < 45• C) and fail-safe operation of the ExAblate array (spatial and time averaged acoustic intensity I SATA < 3.4 W/cm 2 ). Tissue volumes with therapeutic temperature levels (T > 41 • C) were estimated. Numerical simulations indicated that T > 41• C was calculated in 13-23 cm 3 volumes for sonications with planar or diverging beam patterns at 0.9-1.2 W/cm 2 , in 4.5-5.8 cm 3 volumes for simultaneous multipoint focus beam patterns at ∼0.7 W/cm 2 , and in ∼6.0 cm 3 for curvilinear (cylindrical) beam patterns at 0.75 W/cm 2 . Focused heating patterns may be practical for treating focal disease in a single posterior quadrant of the prostate and diffused heating patterns may be useful for heating quadrants, hemigland volumes or even bilateral targets. Treatable volumes may be limited by pubic bone heating. Therapeutic temperatures were estimated for a range of physiological parameters, sonication duty cycles and rectal cooling. Hyperthermia specific phasing patterns were implemented on the ExAblate prostate array and continuous-wave sonications (∼0.88 W/cm 2 , 15 min) were performed in tissue-mimicking material with real-time MR-based temperature imaging (PRFS imaging at 3.0 T). Shapes of heating patterns observed during experiments were consistent with simulations. Conclusions: The ExAblate 2100, designed specifically for thermal ablation, can be controlled for delivering continuous hyperthermia in prostate while working within operational constraints.

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Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer

Hurwitz

Hansen

Prokopios-Davos

et al. 2010

Cancer

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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) T 90 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 prostatespecific 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 þ 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. Cancer 2011;117:510-6.

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Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile

Abstract: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer is safe and well tolerated.

Cited by 31 publications

References 13 publications

Treatment for intermediate and high-risk prostate cancer: Controversial issues and the role of hyperthermia

Treatment for intermediate and high-risk prostate cancer: Controversial issues and the role of hyperthermia

Model‐based feasibility assessment and evaluation of prostate hyperthermia with a commercial MR‐guided endorectal HIFU ablation array

Hyperthermia combined with radiation for the treatment of locally advanced prostate cancer

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