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Background: Advanced clinical applications, such as dose accumulation and adaptive radiation therapy, require deformable image registration (DIR) algorithms capable of voxel-wise accurate mapping of treatment dose or functional imaging. By utilizing a multistage deformable phantom, the authors investigated scenarios where biomechanical refinement method (BM-DIR) may be better than the pure image intensity based deformable registration (IM-DIR)., Methods: The authors developed a biomechanical-model based DIR refinement method (BM-DIR) to refine the deformable vector field (DVF) from any initial intensity-based DIR (IM-DIR). The BM-DIR method was quantitatively evaluated on a novel phantom capable of ten reproducible gradually-increasing deformation stages using the urethra tube as a surrogate. The internal DIR accuracy was inspected in term of the Dice similarity coefficient (DSC), Hausdorff and mean surface distance as defined in of the urethra structure inside the phantom and compared with that of the initial IM-DIR under various stages of deformation. Voxel-wise deformation vector discrepancy and Jacobian regularity were also inspected to evaluate the output DVFs. In addition to phantom, two pairs of Head&Neck patient MR images with expert-defined landmarks inside parotids were utilized to evaluate the BM-DIR accuracy with target registration error (TRE)., Results: The DSC and surface distance measures of the inner urethra tube indicated the BM-DIR method can improve the internal DVF accuracy on masked MR images for the phases of a large degree of deformation. The smoother Jacobian distribution from the BM-DIR suggests more physically-plausible internal deformation. For H&N cancer patients, the BM-DIR improved the TRE from 0.339 cm to 0.210 cm for the landmarks inside parotid on the masked MR images., Conclusions: We have quantitatively demonstrated on a multi-stage physical phantom and limited patient data that the proposed BM-DIR can improve the accuracy inside solid organs with large deformation where distinctive image features are absent.

Purpose: Interest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction., Methods and Materials: Patients treated with Pd-103 to either 125 Gy or 90-100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90-100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model., Results: One hundred ninety-one and 41 patients were treated with 125 Gy versus 90-100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS., Conclusion: Lower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity., Methods and Materials: Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance)., Results: On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V 100% ), dose to 1 cc of rectum (D 1cc ), and dose to 2 cc of rectum (D 2cc ) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V 100 and dose to 90% of gland (D 90 ) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D 20 , D 5cc , and D 1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity-6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding., Conclusions: Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer., Methods and Materials: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms., Results: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the <180, 180-220, and >220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (<30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT., Conclusions: NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess, in a nationwide multi-institutional cohort study begun in 2005 and in which 6927 subjects were enrolled by 2010, the urinary and rectal toxicity profiles of subjects who enrolled during the first 2 years, and evaluate the toxicity profiles for permanent seed implantation (PI) and a combination therapy with PI and external beam radiation therapy (EBRT)., Methods and Materials: Baseline data for 2339 subjects out of 2354 patients were available for the analyses. Toxicities were evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events, and the International Prostate Symptom Scores were recorded prospectively until 36 months after radiation therapy., Results: Grade 2+ acute urinary toxicities developed in 7.36% (172 of 2337) and grade 2+ acute rectal toxicities developed in 1.03% (24 of 2336) of the patients. Grade 2+ late urinary and rectal toxicities developed in 5.75% (133 of 2312) and 1.86% (43 of 2312) of the patients, respectively. A higher incidence of grade 2+ acute urinary toxicity occurred in the PI group than in the EBRT group (8.49% vs 3.66%; P<.01). Acute rectal toxicity outcomes were similar between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late urinary toxicities were 6.04% versus 4.82% for the PI and the EBRT groups, respectively, with no significant differences between the treatment groups. The 3-year cumulative incidence rates for grade 2+ late rectal toxicities were 0.90% versus 5.01% (P<.01) for the PI and the EBRT groups, respectively. The mean of the postimplant International Prostate Symptom Score peaked at 3 months, but it decreased to a range that was within 2 points of the baseline score, which was observed in 1625 subjects (69.47%) at the 1-year follow-up assessment., Conclusions: The acute urinary toxicities observed were acceptable given the frequency and retention, and the late rectal toxicities were more favorable than those of other studies., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA)., Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations., Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm(3) was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types., Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To use Monte Carlo (MC) simulation and sector analysis to assess interseed attenuation and scatter (ISA) and tissue effects in permanent seed implant prostate brachytherapy and to compare methods for modeling tissue., Methods and Materials: CT-based postimplant plan simulations for 40 patients were evaluated using dose-volume histogram (DVH) parameters and sector analysis. Simulations in water (to evaluate ISA alone) and tissue assigned from contours or CT data, with and without calcifications, were compared., Results: For patients without calcifications, mean combined ISA and tissue effect reduced prostate D90 by 4.2 Gy (2.9%), prostate V100 by 0.5 cm(3) (1.4%), urethra D10 by 8.6 Gy (3.5%), rectal [Formula: see text] by 11.6 Gy (10.5%), and the 100% isodose volume by 4.7 cm(3). Larger differences were observed comparing planned dose to postimplant, mean prostate D90 reduced from 185 to 149.8 Gy (-19%). For patients with calcifications, larger tissue effects were observed, prostate D90 reduced by up to 7.4%. Sector analysis showed dose reductions were larger in anterior and base sectors of the prostate. For patients without calcifications, contour- and CT-based tissue model results agreed within <0.5% for all DVH parameters, with up to 4% difference for patients with calcifications., Conclusions: Advanced brachytherapy dose calculation methods that take account of ISA and tissue effects show that clinical (125)I implant dose is different from TG-43U1 (AAPM Task Group No. 43 Report-Update 1) calculations, reducing DVH parameter values particularly for patients with calcifications. Peripheral dose and areas of the implant with relatively poorer coverage are particularly affected. However, dose reductions are small compared with other postimplant dose uncertainties., (Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate., Methods and Materials: Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%., Results: The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate., Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess the influence of dose in different prostate regions, and the influence of anatomic variation on the risk of acute urinary retention (AUR) after I-125 prostate brachytherapy., Methods and Materials: In this case-control study, dosimetry and anatomy were compared between 50 patients with AUR (cases) and 50 patients without AUR (controls). Cases and controls were randomly selected from our database. The following structures were delineated on magnetic resonance imaging: prostate, urethra, peripheral zone, transitional zone, apex, base, midprostate, lower sphincter, and bladder neck. The dosimetric parameters analyzed were D(10), D(50), D(90), V(100), V(150), and V(200). The anatomic parameters analyzed were prostate protrusion into the bladder, bladder overlap, urethra angle, and urethra-bladder angle. The delineator was blinded to the patient's AUR status. Logistic regression analysis was used to investigate the association of these factors with AUR., Results: The dose delivered to different regions of the prostate was not significantly associated with the risk of AUR. Only dose to the bladder neck was significantly associated with AUR (odds ratio 1.13 per 10 Gy; 95% CI 1.02;1.26; p = 0.023). Mean bladder neck D(90) was 65 Gy in AUR cases vs. 56 Gy in controls (p = 0.016), and mean bladder neck D(10) was 128 Gy vs. 107 Gy, respectively (p = 0.018). Furthermore, on univariate analysis, a larger extent of both bladder overlap and of prostate protrusion were associated with a higher risk of AUR (odds ratio 1.16; 95% CI 1.04-1.28; p = 0.005, and odds ratio 1.83; 95% CI 1.37-2.45; p < 0.001, respectively). The mean extent of prostate protrusion was 3.5 mm in AUR cases vs. 1.0 mm in controls (p < 0.001). Odds ratios did not change substantially after adjustment for potential confounders. On multivariate analysis, the extent of prostate protrusion seemed to be a stronger risk factor for AUR than bladder overlap., Conclusion: The risk of AUR is not associated with dose delivered to different regions of the prostate. However, a higher dose to the bladder neck and a larger extent of prostate protrusion into the bladder are risk factors for the development of AUR after I-125 prostate brachytherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To quantitatively evaluate the dose distributions of high-dose-rate (HDR) prostate implants regarding target coverage, dose homogeneity, and dose to organs at risk., Material and Methods: Treatment plans of 174 implants were evaluated using cumulative dose-volume histograms (DVHs). The planning was based on transrectal ultrasound (US) imaging, and the prescribed dose (100%) was 10 Gy. The tolerance doses to rectum and urethra were 80% and 120%, respectively. Dose-volume parameters for target (V90, V100, V150, V200, D90, D(min)) and quality indices (DNR [dose nonuniformity ratio], DHI [dose homogeneity index], CI [coverage index], COIN [conformal index]) were calculated. Maximum dose in reference points of rectum (D(r)) and urethra (D(u)), dose to volume of 2 cm(3) of the rectum (D(2ccm)), and 0.1 cm(3) and 1% of the urethra (D(0.1ccm) and D1) were determined. Nonparametric correlation analysis was performed between these parameters., Results: The median number of needles was 16, the mean prostate volume (V(p)) was 27.1 cm(3). The mean V90, V100, V150, and V200 were 99%, 97%, 39%, and 13%, respectively. The mean D90 was 109%, and the D(min) was 87%. The mean doses in rectum and urethra reference points were 75% and 119%, respectively. The mean volumetric doses were D(2ccm) = 49% for the rectum, D(0.1ccm) = 126%, and D1 = 140% for the urethra. The mean DNR was 0.37, while the DHI was 0.60. The mean COIN was 0.66. The Spearman rank order correlation coefficients for volume doses to rectum and urethra were R(D(r),D(2ccm)) = 0.69, R(D(u),D0.(1ccm)) = 0.64, R(D(u),D1) = 0.23., Conclusion: US-based treatment plans for HDR prostate implants based on the real positions of catheters provided acceptable dose distributions. In the majority of the cases, the doses to urethra and rectum were kept below the defined tolerance levels. For rectum, the dose in reference points correlated well with dose-volume parameters. For urethra dose characterization, the use of D1 volumetric parameter is recommended.

Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure., Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexual toxicities and dosimetric parameters were compared between groups., Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities., Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.

Purpose: To investigate the dosimetry, treatment-related morbidity, and biochemical outcomes for brachytherapy in patients with prostate glands <20 cm(3)., Methods and Materials: From November 1996 to October 2006, 104 patients with prostate glands <20 cm(3) underwent brachytherapy. Multiple prostate, urethral, and rectal dosimetric parameters were evaluated. Treatment-related urinary and rectal morbidity were assessed from patient questionnaires. Cause-specific survival, biochemical progression-free survival, and overall survival were recorded., Results: The median patient age, follow up, and pre-treatment ultrasound volume was 64 years, 5.0 years and 17.6cm(3), respectively. Median day 0 dosimetry was significant for the following: V100 98.5%, D90 126.1% and R100 <0.5% of prescription dose. The mean urethral and maximum urethral doses were 119.6% and 133.8% of prescription. The median time to International Prostate Symptom Score resolution was 4 months. There were no RTOG grade III or IV rectal complications. The cause-specific survival, biochemical progression-free survival, and overall survival rates were 100%, 92.5%, and 77.8% at 9 years. For biochemically disease-free patients, the median most recent postbrachytherapy PSA value was 0.02 ng/mL., Conclusion: Our results demonstrate that brachytherapy for small prostate glands is highly effective, with an acceptable morbidity profile, excellent postimplant dosimetry, acceptable treatment-related morbidity, and favorable biochemical outcomes.

Purpose: To compare the urethral and prostate absolute and biologic effective doses (BEDs) for 131 Cs and 125 I prostate permanent implant brachytherapy (PPI)., Methods and Materials: Eight previously implanted manually planned 125 I PPI patients were replanned manually with 131 Cs, and re-planned using Inverse Planning Simulated Annealing. 131 Cs activity and the prescribed dose (115 Gy) were determined from that recommended by IsoRay. The BED was calculated for the prostate and urethra using an alpha/beta ratio of 2 and was also calculated for the prostate using an alpha/beta ratio of 6 and a urethral alpha/beta ratio of 2. The primary endpoints of this study were the prostate D90 BED (pD90BED) and urethral D30 BED normalized to the maximal potential prostate D90 BED (nuD30BED)., Results: The manual plan comparison (alpha/beta = 2) yielded no significant difference in the prostate D90 BED (median, 192 Gy2 for both isotopes). No significant difference was observed for the nuD30BED (median, 199 Gy2 and 202 Gy2 for 125 I and 131 Cs, respectively). For the inverse planning simulated annealing plan comparisons (alpha/beta = 2), the prostate D90 BED was significantly lower with 131 Cs than with 125 I (median, 177 Gy2 vs. 187 Gy2, respectively; p = 0.01). However, the nuD30BED was significantly greater with 131 Cs than with 125 I (median, 192 Gy2 vs. 189 Gy2, respectively; p = 0.01). Both the manual and the inverse planning simulated annealing plans resulted in a significantly lower prostate D90 BED (p = 0.01) and significantly greater nuD30BED for 131 Cs (p = 0.01), compared with 125 I, when the prostate alpha/beta ratio was 6 and the urethral alpha/beta ratio was 2., Conclusion: This report highlights the controversy in comparing the dose to both the prostate and the organs at risk with different radionuclides.

Background and Purpose: To compare post-implant dosimetry between high density source implants (HDI) and low density source implants (LDI)., Materials and Method: Dosimetric analysis of the whole prostate (V200, V150, V100, D90, D80, contiguous V200 and V150, external index), prostate quadrants (V200, V150, V100, D90), rectum (V150, V120, V100, V80, V60) and deviated surrogate urethra (V200, V150, V120, V100, V80) was performed on 39 consecutive prostate brachytherapy LDI and 39 volume matched HDI over the same time period. The distinction between LDI and HDI was based on differing prescribed dose using 125-Iodine sources, with MPD of 115 and 144 Gy, respectively, using a fixed source strength of 0.424 U (0.334 mCi). Cases were contoured by two independent blinded observers. Repeated measures analysis of variance was used to look at the effects of treatment arm, observer and their interaction., Results: Whole prostate (WP) volume did not differ significantly between the treatment arms, mean of 25.4 cc for LDI and 26.6 cc for HDI. There was no significant difference in any of the measured post-implant dosimetric parameters for the WP or quadrants, surrogate urethra or rectum., Conclusions: No difference in post-implant dosimetric parameters was observed between Iodine 125 LDI and HDI. Neither dose homogeneity nor conformality is compromised with a lower source density. Higher strength sources have the potential for considerable cost saving and reduced morbidity.

Recent studies on transurethral-applied local hyperthermia in both the canine and human prostate have revealed significant effects of natural thermoregulation on the therapeutical results in the prostate. Using a thermal clearance method, blood perfusion rates were measured within different regions in the canine prostate under normal and hyperthermic conditions. It has been found that the canine-prostatic blood perfusion is strongly linked to the geometrical location within the gland, the local tissue temperature, and the imposed thermal dosage. Results from this research are expected to provide a better understanding of the thermoregulatory behaviour in the canine prostate, and thus lay an important foundation for predicting tissue temperature in the human prostate during transurethral microwave hyperthermia.

In this research, experiments were performed to study thermoregulation in the canine prostate during microwave hyperthermia. The transurethral thermal therapy (T3) system provided by Urologix, Inc. was used to impose microwave heating in the canine prostate. Five types of temperature responses to different microwave power levels as time varies, including both damped and sustained oscillatory temperature responses, have been observed. Decreases in prostatic tissue temperature during the microwave heating are believed to be caused by the increase in local blood flow stimulated by tissue temperature elevations. In this study, the characteristic temperatures and time associated with each response. This work will help to provide a better understanding of how tissue temperature is regulated within the canine prostate during transurethral microwave hyperthermia. Results of the present study offer an experimental foundation for a more detailed theoretical analysis on the temperature distribution based on the power input and local blood perfusion.

Microwave irradiation administered by transurethral transducer to the prostate permits focused hyperthermia with resultant tissue ablation; a coding system within the catheter allows urethral preservation. We evaluated the effect of microwave hyperthermia in 13 dogs receiving 48-79 min of focused irradiation (16-45 watts, intraprostatic temperature > 45 degrees C) delivered by a specially-designed transducer with an operator-controlled directional antenna (T3, Urologix Inc., Minneapolis, MN); one other dog had transducer placement without irradiation (sham control). After treatment, the dogs were in good health, voiding well without complications, and were sacrificed after 5-38 days. The prostate and vasa deferentia were removed, fixed in 10% formalin, grossly inspected, cut at 5 mm intervals, and serially sectioned with whole mount sections; representative sections of the adjacent rectum and distal bladder were also obtained. All cases were histologically evaluated with prostatic mapping without knowledge of treatment or time of sacrifice. In the acute phase (5-13 days), the prostate showed sharply circumscribed periurethral coagulative necrosis with hemorrhage; necrosis was also seen in the mucosa and bladder wall of those with transducers placed at the bladder neck. In the subacute phase (17 days), the hemorrhagic necrosis was resolving, often with cystically dilated urethra due to sloughed necrotic tissue; the urothelium was intact. By 24-38 days, the necrosis was in the late stages of resolution, with residual patchy acute and chronic inflammation at the periphery, and frequent persistence of megalourethra. In all cases, the prostatic capsule was intact, the urethral mucosa was preserved, and the vasa deferentia and rectum were normal except for two cases with mild fat necrosis. Microwave irradiation allows precisely localized thermal ablation of prostatic tissue and enlargement of the urethral bore without clinical complications in dogs, offering promise as a therapeutic alternative to surgery in select patients with symptomatic prostatic nodular hyperplasia.