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ABSTRACT: The purpose of this work is to investigate the effects of pulsed focused ultrasound on the enhancement of 3H-Docetaxel delivery in prostate tumors in vivo. Human prostate cancer LNCaP cells (5 × 105) in 24 ml medium were injected into the prostates of male nude mice. When tumor reached the size of 160 ± 10 mm3 on MRI, HIFU treatment was performed using an InSightec ExAblate 2000 system with a 1.5 T GE MR scanner. The animals were
randomly divided into 3 groups (n=8 per group): Group 1, HIFU treatment + 3H-Docetaxel; Group 2, HIFU treatment only and Group 3, as control. For group 1, each mouse was treated with pulsed HIFU under
general anesthesia using MR guidance. Immediately after, HIFU treated animals received a single dose of i.v injection of Docetaxel
at 15 mg/kg mixed with 3H-Docetaxel at 50 uCi/kg in total volume of 150 μl. Animals in group 2 were treated the same as in group one with the exception
of HIFU treatment. Animals were sacrificed 30 minutes after i.v injections and tumors were removed and processed. The radioactivity
of 3Hdocetaxel in the tumor tissue was quantitatively measured by a liquid scintillation counter. Results showed that all animals
tolerated the MRgHIFU treatment well. There were no treatment-related adverse events including skin toxicity. Our data show
increased 3H-docetaxel concentration in tumor in the MRgHIFU treated group (1079 ± 132 cmp/75 mg) vs. those without MRgHIFU treatment
(524 ± 201 cmp/75 mg) with P = 0.037. We have demonstrated the enhancement of 3HDocetaxel uptake in implanted prostate tumors with MRgHIFU in vivo. Future studies will be carried out on the efficacy of Docetaxel combined with radiotherapy (RT) to inhibit prostate cancer
growth in vivo.
KeywordsMRgHIFU-Prostate Cancer-Mouse Model-In Vivo-Drug Delivery
05/2010: pages 341-344;
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ABSTRACT: Purpose: The purpose of this work is to develop an effective and efficient quality assurance (QA) program for the application of MR guided focused ultrasound (MRgFUS) as a multi‐modality platform for cancer therapy. Materials and Method: An MRgFUS system has been installed in our institution, which consists of an InSightec ExAblate 2000 high‐intensity focused ultrasound (HIFU) system and a 1.5T GE MR scanner. This system has been FDA approved for the treatment of uterine fibroids clinically and is being investigated under local IRB approval for treating bone metastases, prostate and breast cancers and the enhancement of drug delivery for gene therapy and chemotherapy. In addition to the daily, monthly and annual calibration and commissioning measurements for the MRI unit special QA procedures were developed for the HIFU system including the mechanical motion of the couch and transducer, the safety system and patient panic buttons, the functionality of the temperature mapping and treatment software, the acoustic power output and the localization of the treatment focal spot. Results: The MRgFUS system has been operational since the fall of 2006. Successful experiments have been performed on in vitro bio‐samples and in vivo animal models for pre‐clinical studies and for drug enhancement experiments. Patients with bone metastases have been treated successfully using the MRgFUS system for pain relief with a pre‐treatment QA procedure. Patients tolerated the HIFU treatment well. No skin damage was observed after treatment. The pain scale was significantly reduced within 24 hours and further reduced at later follow‐ups. Conclusions: Comprehensive QA procedures have been developed for the safe and successful operation of the MRgFUS system as a multi‐modality platform for breast surgery, bone palliation, and prostate boost in combination with radiotherapy clinically and for drug delivery enhancement investigations for gene therapy and chemotherapy using animal models.
Medical Physics 05/2009; 36(6):2631-2631. · 2.83 Impact Factor
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ABSTRACT: Purpose: The purpose of this work was to commission and to evaluate the role of MR guided high intensity focused ultrasound (MRgHIFU) in cancer therapy in ex vivo and in vivo. Method and Materials: An InSightec ExAblate 2000 HIFU system with a 1.5T GE MR scanner (MRgHIFU) is approved by FDA for the treatment of uterus fibroids clinically and being investigated in our department for treating bone metastases, prostate and breast cancers under local IRB approval. The phased array transducer is housed in a sealed bath and connected to a motion system. The focal region is cigar shaped, about 2mm in diameter and 10mm in focal length. Extensive experiments have been carried out on phantoms and excised tissues to determine optimal ultrasound parameters including the acoustic power output, frequency and exposure duration. We also performed in vivo studies on feasibility of enhancement of drug delivery for both chemotherapy and gene therapy using an animal model. Both MR T2‐weight MR image and proton resonance frequency shift MR images were used for treatment planning and monitoring the effect of the treatment in real time. Results: Phantom studies demonstrated that MRgHIFU could provide adequate temperature elevation for tissue ablation; acoustic power >10W leading to temperature elevation (ΔT) > 7 °C. At a lower acoustic power (5 W) we could keep ΔT < 4 °C, which is adequate for drug enhancement. The results were served for animal studies. Tissue damage was achieved at predetermined region in excised tissue through MR real‐time guidance. Our preliminary results showed increased drug concentrations in MRgHIFU treated mice than the control group. Conclusion: MRgHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy including tumor ablation, enhancement of drug livery and boost treatment for hypoxic tumors in combination with radiotherapy.
Medical Physics 05/2008; 35(6):2709-2709. · 2.83 Impact Factor
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ABSTRACT: Recent advances in laser technology have made proton (light ion) acceleration possible using laser-induced plasmas. In this
work, we report our work for the last few years on the investigation of a new proton therapy system for radiation oncology,
which employs laser-accelerated protons. If successfully developed, the new system will be compact, cost-effective, and capable
of delivering energy-and intensity-modulated proton therapy (EIMPT). We have focused our research on three major aspects:
(1) target design for laser-proton acceleration, (2) system design for particle/energy selection and beam collimation, and
(3) dosimetric studies on the use of laser-accelerated protons for cancer therapy. We have performed particle-in-cell (PIC)
simulations to investigate optimal target configurations for proton/ion acceleration. We also performed Monte Carlo simulations
to study the beam characteristics and the feasibility of using such beams for cancer treatment. Since laser-accelerated protons
have broad energy and angular distributions, which are not suitable for radiotherapy applications directly, we have designed
a compact particle selection and beam collimating system for EIMPT beam delivery. We also proposed a new gantry design to
make the whole system compact to retrofit existing linac vaults. We have compared Monte Carlo calculated dose distributions
using X-ray IMRT and laser-proton EIMPT. Our results show that EIMPT using laser protons produces superior target coverage
and much reduced critical structure dose and integral dose compared to X-ray IMRT.
Laser Physics 03/2006; 16(4):639-646. · 3.61 Impact Factor
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ABSTRACT: Purpose: Daily localization of post‐prostatectomy patients receiving radiation treatment to the surgical bed is a very challenging task. The anatomy bounding the prostate bed can significantly change from day to day due to rectal and bladder filling. Target localization based on bony anatomy may be inaccurate. Ultrasound (US) localization has potential, but since there is not a well‐defined target (i.e., prostate), reliability may be inadequate. In a previously presented study, we compared US alignments with CT alignments, and based on the results we developed a clinical procedure that incorporated the two imaging modalities. The results presented in this work are for the first 30 patients (183 alignments) that underwent IMRT treatment to the prostate bed after the initial study was completed. Method and Materials: Prior to the first treatment, each patient was aligned based on a pre‐treatment CT scan acquired with the Primatom CT‐on‐rails (Siemens). US images were then immediately acquired with the BAT system (Nomos) and these images were stored as templates. During subsequent treatments the US template images were used to assist the therapists when performing daily US alignment. The accuracy of the alignments was controlled by CT scans taken once every week. Results: The systematic differences between US and CT alignments were: 0.8 mm (lateral), 0.4 mm (AP) and 0.5 mm (longitudinal). Some of these values were statistically significant, but their clinical significance is low. The random differences between the two modalities (one standard deviation) were: 2.9 mm (lateral), 3.3 mm (AP) and 3.0 mm (longitudinal), and average absolute differences were: 2.3 mm (lateral), 2.6 mm (AP) and 2.5 mm (longitudinal). Conclusion: These results suggest that: (i) the systematic error of the every‐day US alignments is minimized; (ii) the target is fully covered by the PTV margin (8 mm) used at our institution in almost all cases.
Medical Physics 05/2005; 32(6):2106-2106. · 2.83 Impact Factor
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ABSTRACT: The purpose of this study is to evaluate the dosimetric accuracy of MRI-based treatment planning for prostate cancer using a commercial radiotherapy treatment planning system. Three-dimensional conformal plans for 15 prostate patients were generated using the AcQPlan system. For each patient, dose distributions were calculated using patient CT data with and without heterogeneity correction, and using patient MRI data without heterogeneity correction. MR images were post-processed using the gradient distortion correction (GDC) software. The distortion corrected MR images were fused to the corresponding CT for each patient for target and structure delineation. The femoral heads were delineated based on CT. Other anatomic structures relevant to the treatment (i.e., prostate, seminal vesicles, lymph notes, rectum and bladder) were delineated based on MRI. The external contours were drawn separately on CT and MRI. The same internal contours were used in the dose calculation using CT- and MRI-based geometries by directly transferring them between MRI and CT as needed. Treatment plans were evaluated based on maximum dose, isodose distributions and dose-volume histograms. The results confirm previous investigations that there is no clinically significant dose difference between CT-based prostate plans with and without heterogeneity correction. The difference in the target dose between CT- and MRI-based plans using homogeneous geometry was within 2.5%. Our results suggest that MRI-based treatment planning is suitable for radiotherapy of prostate cancer.
Physics in Medicine and Biology 12/2004; 49(22):5157-70. · 2.83 Impact Factor
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ABSTRACT: To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention.
Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables.
In all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk.
A significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.
BJU International 06/2004; 93(7):955-60. · 2.84 Impact Factor
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ABSTRACT: A Monte Carlo based intensity-modulated radiation therapy (IMRT) treatment planning system has been developed and used for breast treatment. An iterative method was used for optimization to generate IMRT plans and a step-and-shoot technique was used for beam delivery. The patient setup and incident beam directions were the same as those for conventional tangential photon treatment. The weights for the opposed beamlets in the two tangential beams were determined first by the doses at the depths of the maximum dose at both sides to minimize hot spots. The intensity of an individual beamlet pair was then optimized based on the dose at the midplane. Fine tuning was made to achieve optimal target dose uniformity and to reduce the dose to the heart when necessary. The final dose calculations were performed using the Monte Carlo method and the plans were verified by phantom measurements. The dose distributions and dose-volume-histograms of IMRT plans were compared with those of conventional plans that were generated using a commercial treatment planning system and recalculated using an in-house Monte Carlo system for the first 25 patients. The dose comparisons showed that the percentage volume receiving more than 95% of the prescription dose (V95) and the percentage volume receiving more than 100% of the prescription dose (V100) for the clinical target volume (CTV) of IMRT plans were about the same as those of conventional plans. The percentage volume receiving more than 105% of the prescription dose (V105) for the CTV was reduced from 23.1% to 7.9% on average. The percentage volume of the lung receiving more than 20 Gy dose (V20 Gy) during the entire treatment was reduced by about 10%. The percentage volume of the heart receiving more than 30 Gy dose (V30 Gy) is reduced from 3.3% to 0.3%. Further studies revealed that a less than 5 degrees change in couch angle and collimator angle at patient setup had no significant effect on the dose coverage of CTV but had significant effect on the dose to the lung and heart. The study on the effect of beam spoiler showed that it increased the dose at the buildup region by 0- 13% that varies with location. The machine output linearity and stability for small monitor unit delivery of Siemens accelerators used for this study was checked and found to be suitable for breast IMRT. The total effect of variations was calculated to be less than 1% for typical breast treatments. The beam delivery time was increased by about 2 min compared with conventional tangential treatments. The whole treatment including patient setup and beam delivery can be completed in a 15 min slot. The IMRT technique has been proven practical for breast treatment clinically. The results showed that tangential IMRT improved the dose homogeneity in the breast and reduced the dose to the lung and heart.
Medical Physics 06/2004; 31(5):1023-31. · 2.83 Impact Factor
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ABSTRACT: Authors from Philadelphia have studied the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer. They found that many patients at risk take measures to try and reduce this risk, even if the items that they take have not necessarily been shown to be effective.Another group of authors from Chicago evaluated the effect of seminal vesical invasion on survival in prostate cancer, and in particular attempted to validate Kattan's nomogram in this pathological subgroup. The authors from Vancouver attempted to identify sexual information resource preferences of patients before and after definitive treatment for early-stage prostate cancer with either radical prostatectomy or brachytherapy. They strongly advocate the need for physicians to offer patients access to such information.A group of authors from Brisbane investigated the effects of pharmacological treatments as apposed to clinical monitoring on quality of life in patients with non-localised prostate cancer, and found that the adverse effects on quality of life are important in deciding the timing of androgen suppression.OBJECTIVE
To define the prevalence and patterns of self-initiated herbal and vitamin supplementation among men at high risk of developing prostate cancer, as there is increasing public awareness of prostate cancer screening, risk-factor assessment and prevention, leading to increasing interest in the use and systematic study of nutritional therapies for prostate cancer prevention.SUBJECTS AND METHODS
Since 1996 our institution has prospectively maintained a prostate cancer-risk registry through its Prostate Cancer Risk Assessment Program (PRAP). Eligibility includes African-American men, any man with at least one first-degree relative or two or more second-degree relatives with prostate cancer, or men who tested positively for the BRCA1 gene mutation. A 420-item self-administered questionnaire was completed and included the use of nutritional supplements and complementary therapies. We divided men into groups who used supplements to lessen their cancer risk and those who did not. The prevalence and patterns of use were evaluated and the two groups then compared for differences in demographic, socio-economic and risk-perception variables.RESULTSIn all, 345 high-risk men were enrolled in the PRAP over a 5-year period. Data on the use of dietary or herbal supplements were available on 333 men (97%), of whom over half (170) reported taking one or more supplements to prevent prostate cancer. Supplement use was divided into eight categories, including vitamins, minerals, extracts from fruits/seeds, organic compounds, flowers/bulbs, leaves/bark, roots, or animal products. Most commonly used for self-initiated chemoprevention were vitamins (95%), minerals (28%), and fruit/seed extracts (18%). More than a quarter of men (27%) took three or more agents. Men taking proactive preventative measures were statistically more likely to be Caucasian and aged > 60 years (P < 0.05). African-Americans were less likely to self-initiate preventative steps. Men taking supplements tended to return more often for follow-up and participate in PRAP longer, while those not taking supplements tended to earn less and report less self-perceived risk.CONCLUSIONSA significant proportion of men at risk of developing prostate cancer initiate measures they perceive to reduce their risk. Although the chemopreventative efficacy of many of these supplements remains unsubstantiated, they are widely perceived by the public to reduce the risk of developing prostate cancer. These data provide an insight into patient perceptions and misconceptions of chemopreventative strategies, and may help to refine recruitment efforts in multi-institutional prostate cancer prevention trials.
BJU International 05/2004; 93(7):955 - 960. · 2.84 Impact Factor
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ABSTRACT: There are several localization techniques that have been used for prostate treatment. Recently, the potential use of a variety of CT-based equipment in the treatment room has been discussed. The goal of our study was to develop an automated procedure for daily treatment table shift calculation based on two CT data sets: simulation CT data and localization CT data. The method suggested in this study is a 3D image cross-correlation of small regions of interest (ROI) within the two data sets. The relative position of the two ROIs with respect to each other is determined by the maximum value of the normalized cross-correlation function, calculated for all possible relative locations of the two ROIs. After the best match is found the shifts are given by the vector connecting the treatment isocentre and the planning isocentre (both determined by the radio opaque fiducial markers on the patient's skin). The results have been compared with shifts calculated through manual fusion. The shift differences, averaged over 17 statistically independent shift calculations, are less then 1 mm in the lateral and longitudinal directions, and about 1 mm in the AP direction. The impact of image noise on the performance of the algorithm has been tested. The results show that the algorithm accurately adjusts for target positional changes even with Gaussian noise levels as high as 20% inserted.
Physics in Medicine and Biology 04/2004; 49(6):931-9. · 2.83 Impact Factor
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ABSTRACT: The focus of this work is the dosimetric impact of multileaf collimator (MLC) leaf width on the treatment of prostate cancer with intensity-modulated radiation therapy (IMRT). Ten patients with prostate cancer were planned for IMRT delivery using two different MLC leaf widths--4mm and 10mm--representing the Radionics micro-multileaf collimator (mMLC) and Siemens MLC, respectively. Treatment planning was performed on the XKnifeRT2 treatment-planning system (Radionics, Burlington, MA). All beams and optimization parameters were identical for the mMLC and MLC plans. All the plans were normalized to ensure that 95% of the planning target volume (PTV) received 100% of the prescribed dose. The differences in dose distribution between the two different plans were assessed by dose-volume histogram (DVH) analysis of the target and critical organs. We specifically compared the volume of rectum receiving 40 Gy (V40), 50 Gy (V50), 60 Gy (V60), the dose received by 17% and 35% of rectum (D17 and D35), and the maximum dose to 1 cm3 of the rectum for a prescription dose of 74 Gy. For the urinary bladder, the dose received by 25% of bladder (D25), V40, and the maximum dose to 1 cm3 of the organ were recorded. For PTV we compared the maximum dose to the "hottest" 1 cm3 (Dmax1 cm3) and the dose to 99% of the PTV (D99). The dose inhomogeneity in the target, defined as the ratio of the difference in Dmax1 cm3 and D99 to the prescribed dose, was also compared between the two plans. In all cases studied, significant reductions in the volume of rectum receiving doses less than 65 Gy were seen using the mMLC. The average decrease in the volume of the rectum receiving 40 Gy, 50 Gy, and 60 Gy using the mMLC plans was 40.2%, 33.4%, and 17.7%, respectively, with p < 0.0001 for V40 and V50 and p < 0.012 for V60. The mean dose reductions for D17 and D35 for the rectum using the mMLC were 20.4% (p < 0.0001) and 18.3% (p < 0.0002), respectively. There were consistent reductions in all dose indices studied for the bladder. The target dose inhomogeneity was improved in the mMLC plans by an average of 29%. In the high-dose range, there was no significant difference in the dose deposited in the "hottest" 1 cm3 of the rectum between the two plans for all cases (p > 0.78). In conclusion, the use of the mMLC for IMRT of the prostate resulted in significant improvement in the DVH parameters of the prostate and critical organs, which may improve the therapeutic ratio.
Journal of Applied Clinical Medical Physics 02/2004; 5(2):29-41. · 1.29 Impact Factor
