Biologically effective dose for permanent prostate brachytherapy taking into account postimplant edema

PURPOSE: To study the influence of radiobiologic and physical parameters and parameters related to edema on the biologically effective dose (BED) for permanent prostate implants and to determine the optimal timing of seed reconstruction for BED calculation. METHODS AND MATERIALS: On the basis of the linear-quadratic model, an expression for the BED was derived, including the edema parameters. A set of parameter values was defined, and these parameter values were varied one at a time to examine the effect on the BED and the theoretically effective treatment time (t(eff)). A ratio epsilon was defined to investigate the optimal timing of seed reconstruction. RESULTS: The maximal BED decreases when the extent of lethal damage is smaller, the potential tumor doubling time is smaller, the half-life time of the seeds is shorter, and the magnitude of prostate volume increase is larger. For 125I, the optimal timing of seed reconstruction is 25 days after implantation. Seed reconstruction 1 day after the implantation results in an underestimation of the BED of at most 43%, depending on the magnitude and half-life of edema. An overestimation of the BED of at most 22% is calculated when seed reconstruction took place at the effective treatment time. CONCLUSION: The maximal BED depends strongly on the value of alpha, the potential tumor doubling time, and the choice of isotope. If prostate volume increase due to edema is not taken into account, the BED will be underestimated shortly after the implantation and overestimated if the calculations are based on images taken several months after implantation. The optimal timing of BED evaluation for 125I seed implants and typical prostate edema values is 25 days after implantation.     

Effect of post-implant edema on the rectal dose in prostate brachytherapy.

PURPOSE: To characterize the effect of prostate edema on the determination of the dose delivered to the rectum following the implantation of 125I or 103Pd seeds into the prostate. METHODS AND MATERIALS: From 3 to 5 post-implant computed tomography (CT) scans were obtained on 9 patients who received either 125I or 103Pd seed implants. None of the patients received hormone therapy. The outer surface of the rectum was outlined on each axial CT image from the base to the apex of the prostate. The D10 rectal surface dose, defined as the dose which encompasses only 10% of the surface area of the rectum, was determined from each CT scan by compiling a dose-surface histogram (DSH) of the rectal surface. The magnitude and half-life of the post-implant edema in each of these implants is known from the results of a previously published study based on the analysis of the serial CT scans. RESULTS: As the prostate edema resolved, the distance between the most posterior implanted seeds and the anterior surface of the rectum decreased. As a result, the D10 rectal surface dose increased with each successive post-implant CT scan until the edema resolved. The dose increased exponentially at approximately the same rate the prostate volume decreased. The D10 rectal surface dose at 30 days post-implant ranged from 16% to 190% (mean 68 +/- 50%) greater than on day 0. The dose on day 30 was at least 50% greater in 6 of 9 cases. CONCLUSION: The rectal surface dose determined by analysis of a post-implant CT scan of an 125I or 103Pd prostate seed implant depends upon the timing of the CT scan. The dose indicated by the CT scan on day 30 is typically at least 50% greater than that indicated by the CT scan on day 0. Because of this difference, it is important to keep the timing of the post-implant CT in mind when specifying dose thresholds for rectal morbidity.     

Comparison of dose length, area, and volume histograms as quantifiers of urethral dose in prostate brachytherapy

Purpose: To determine the magnitude of the differences between urethral dose-volume, dose-area, and dose-length histograms (DVH, DAH, and DLH, respectively, or DgH generically).

Methods and Materials: Six consecutive iodine-125 (¹²⁵I) patients and 6 consecutive palladium-103 (¹⁰³Pd) patients implanted via a modified uniform planning approach were evaluated with day 0 computed tomography (CT)-based dosimetry. The urethra was identified by the presence of a urinary catheter and was hand drawn on the CT images with a mean radius of 3.3 ± 0.7 mm. A 0.1-mm calculation matrix was employed for the urethral volume and surface analysis, and urethral dose points were placed at the centroid of the urethra on each 5-mm CT slice.

Results: Although individual patient DLHs were step-like, due to the sparseness of the data points, the composite urethral DLH, DAH, and DVHs were qualitatively similar. The DAH curve delivered more radiation than the other two curves at all doses greater than 90% of the prescribed minimum peripheral dose (mPD) to the prostate. In addition, the DVH curve was consistently higher than the DLH curve at most points throughout that range. Differences between the DgH curves were analyzed by integrating the difference curves between 0 and 200% of the mPD. The area-length, area-volume, and volume-length difference curves integrated in the ratio of 3:2:1. The differences were most pronounced near the inflection point of the DgH curves with mean A₁₂₅, V₁₂₅, and L₁₂₅ values of 36.6%, 31.4%, and 23.0%, respectively, of the urethra. Quantifiers of urethral hot spots such as D₁₀, defined as the minimal dose delivered to the hottest 10% of the urethra, followed the same ranking: area analysis indicated the highest dose and length analysis, the lowest dose. D₁₀ was 148% and 136% of mPD for area and length evaluations, respectively. Comparing the two isotopes in terms of the amount of urethra receiving a given dose, ¹⁰³Pd implants were significantly cooler than ¹²⁵I implants over most of the range of clinical interest, from 100% to 150% of mPD.

Conclusion: Dose gradients in prostate implants result in the observed ordering of DAH, DVH, and DLH from higher to lower doses. The three histogram approaches remain in close agreement up to 100% of the mPD but diverge at higher doses. Although urethral point doses are the most easily determined, they underestimate the amount of urethra at risk at higher doses compared to dose area analysis. Because dosimetric parameters detailing high-dose regions such as D₁₀ show only slight differences between calculation methods, they are recommended over the corresponding geometric entities G₁₅₀ or G₁₇₅. The differences between the D_gg entities are sufficiently small that they are unlikely to be of clinical significance or to confound analyses attempting to correlate urinary morbidity with urethral dosimetry.     

Effect of post-implant edema on prostate brachytherapy treatment margins

PURPOSE: To determine if postimplant prostate brachytherapy treatment margins calculated on Day 0 differ substantially from those calculated on Day 30. METHODS: Thirty patients with 1997 American Joint Commission on Cancer clinical stage T1-T2 prostatic carcinoma underwent prostate brachytherapy with I-125 prescribed to 144 Gy. Treatment planning methods included using loose seeds in a modified peripheral loading pattern and treatment margins (TMs) of 5-8 mm. Postimplant plain radiographs, computed tomography scans, and magnetic resonance scans were obtained 1-4 hours after implantation (Day 0). A second set of imaging studies was obtained at 30 days after implantation (Day 30) and similarly analyzed. Treatment margins were measured as the radial distance in millimeters from the prostate edge to the 100% isodose line. The TMs were measured and tabulated at 90 degrees intervals around the prostate periphery at 0.6-cm intervals. Each direction was averaged to obtain the mean anterior, posterior, left, and right margins. RESULTS: The mean overall TM increased from 2.6 mm (+/-2.3) on Day 0 to 3.5 mm (+/-2.4) on Day 30. The mean anterior margin increased from 1.2 mm on Day 0 to 1.8 mm on Day 30. The posterior margin increased from 1.2 mm on Day 0 to 2.8 mm on Day 30. The lateral treatment margins increased most over time, with mean right treatment margin increasing from 3.9 mm on Day 0 to 4.7 mm on Day 30. CONCLUSION: Treatment margins appear to be durable in the postimplant period, with a clinically insignificant increase from Day 0 to Day 30.     

Comparison of MRI-based and CT/MRI fusion-based postimplant dosimetric analysis of prostate brachytherapy

PURPOSE: The aim of this study was to compare the outcomes between magnetic resonance imaging (MRI)-based and computed tomography (CT)/MRI fusion-based postimplant dosimetry methods in permanent prostate brachytherapy. METHODS AND MATERIALS: Between October 2004 and March 2006, a total of 52 consecutive patients with prostate cancer were treated by brachytherapy, and postimplant dosimetry was performed using CT/MRI fusion. The accuracy and reproducibility were prospectively compared between MRI-based dosimetry and CT/MRI fusion-based dosimetry based on the dose-volume histogram (DVH) related parameters as recommended by the American Brachytherapy Society. RESULTS: The prostate volume was 15.97+/-6.17 cc (mean+/-SD) in MRI-based dosimetry, and 15.97+/-6.02 cc in CT/MRI fusion-based dosimetry without statistical difference. The prostate V100 was 94.5% and 93.0% in MRI-based and CT/MRI fusion-based dosimetry, respectively, and the difference was statistically significant (p=0.002). The prostate D90 was 119.4% and 114.4% in MRI-based and CT/MRI fusion-based dosimetry, respectively, and the difference was statistically significant (p=0.004). CONCLUSION: Our current results suggested that, as with fusion images, MR images allowed accurate contouring of the organs, but they tended to overestimate the analysis of postimplant dosimetry in comparison to CT/MRI fusion images. Although this MRI-based dosimetric discrepancy was negligible, MRI-based dosimetry was acceptable and reproducible in comparison to CT-based dosimetry, because the difference between MRI-based and CT/MRI fusion-based results was smaller than that between CT-based and CT/MRI fusion-based results as previously reported.     

Localization of linked 125I seeds in postimplant TRUS images for prostate brachytherapy dosimetry

PURPOSE: To demonstrate that (125)I seeds can be localized in transrectal ultrasound (TRUS) images obtained with a high-resolution probe when the implant is performed with linked seeds and spacers. Adequate seed localization is essential to the implementation of TRUS-based intraoperative dosimetry for prostate brachytherapy. METHODS AND MATERIALS: Thirteen preplanned peripherally loaded prostate implants were performed using (125)I seeds and spacers linked together in linear arrays that prevent seed migration and maintain precise seed spacing. A set of two-dimensional transverse images spaced at 0.50-cm intervals were obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. The image set extended from 1.0 cm superior to the base to 1.0 cm inferior to the apex. The visible echoes along each needle track were first localized and then compared with the known construction of the implanted array. The first step was to define the distal and proximal ends of each array. The visible echoes were then identified as seeds or spacers from the known sequence of the array. The locations of the seeds that did not produce a visible echo were interpolated from their known position in the array. A CT scan was obtained after implantation for comparison with the TRUS images. RESULTS: On average, 93% (range, 86-99%) of the seeds were visible in the TRUS images. However, it was possible to localize 100% of the seeds in each case, because the locations of the missing seeds could be determined from the known construction of the arrays. Two factors complicated the interpretation of the TRUS images. One was that the spacers also produced echoes. Although weak and diffuse, these echoes could be mistaken for seeds. The other was that the number of echoes along a needle track sometimes exceeded the number of seeds and spacers implanted. This was attributed to the overall length of the array, which was approximately 0.5 cm longer than the center-to-center distance between the first and last seed owing to the finite length of the seeds at the ends of the array. When this occurred, it was necessary to disregard either the most distal or most proximal echo, which produced a 0.5-cm uncertainty in the location of the array in the axial direction. For these reasons, simply localizing the visible echoes in the TRUS images did not guarantee the reliable identification of the seeds. CONCLUSION: Our results have demonstrated that a high percentage (>85%) of the implanted (125)I seeds can be directly visualized in postimplant TRUS images when the seeds and spacers are linked to preclude seed migration and rotation and when the images are obtained with a high-resolution TRUS probe. Moreover, it is possible to localize 100% of the seeds with the mechanism of linked seeds because the locations of the missing seeds can be determined from the known construction of the arrays.     

Dosimetric consequences of using a surrogate urethra to estimate urethral dose after brachytherapy for prostate cancer

PURPOSE: To assess the accuracy and dosimetric consequences of defining a surrogate urethra at the geometric center of the prostate in postimplant CT scans. METHODS AND MATERIALS: Eighty postimplant CT scans were obtained with a Foley catheter in place at Day 0 and at 1 month for 40 patients who had undergone (125)I prostate brachytherapy. The percentage of urethral volume receiving at least 275% of the prescribed dose (uV(275)), uV(250), uV(200), uV(150), maximal dose received by 90% of urethral volume (uD(90)), uD(70), uD(30), and uD(1) were measured for the Foley catheter and surrogate urethra. The distance between the Foley catheter and surrogate urethra was measured at the base, middle, and apex of the prostate. RESULTS: A statistically significant difference was found in all the above-listed dosimetric parameters between the Foley catheter and surrogate urethra at Day 0 (p 相似文献   

Intraoperative fluoroscopic dose assessment in prostate brachytherapy patients

PURPOSE: To evaluate a fluoroscopy-based intraoperative dosimetry system to guide placement of additional sources to underdosed areas, and perform computed tomography (CT) verification. METHODS AND MATERIALS: Twenty-six patients with prostate carcinoma treated with either I-125 or Pd-103 brachytherapy at the Puget Sound VA using intraoperative postimplant dosimetry were analyzed. Implants were performed by standard techniques. After completion of the initial planned brachytherapy procedure, the initial fluoroscopic intraoperative dose reconstruction analysis (I-FL) was performed with three fluoroscopic images acquired at 0 (AP), +15, and -15 degrees. Automatic seed identification was performed and the three-dimensional (3D) seed coordinates were computed and imported into VariSeed for dose visualization. Based on a 3D assessment of the isodose patterns additional seeds were implanted, and the final fluoroscopic intraoperative dose reconstruction was performed (FL). A postimplant computed tomography (CT) scan was obtained after the procedure and dosimetric parameters and isodose patterns were analyzed and compared. RESULTS: An average of 4.7 additional seeds were implanted after intraoperative analysis of the dose coverage (I-FL), and a median of 5 seeds. After implantation of additional seeds the mean V100 increased from 89% (I-FL) to 92% (FL) (p < 0.001). In I-125 patients an improvement from 91% to 94% (p = 0.01), and 87% to 93% (p = 0.001) was seen for Pd-103. The D90 increased from 105% (I-FL) to 122% (FL) (p < 0.001) for I-125, and 92% (I-FL) to 102% (FL) (p = 0.008) for Pd-103. A minimal change occurred in the R100 from a mean of 0.32 mL (I-FL) to 0.6 mL (FL) (p = 0.19). No statistical difference was noted in the R100 (rectal volume receiving 100% of the prescribed dose) between the two techniques. The rate of adverse isodose patterns decreased between I-FL and FL from 42% to 8%, respectively. The I-125 patients demonstrated a complete resolution of adverse isodose patterns after the initial isodose reconstruction (I-FL). The Pd-103 patients demonstrated a final rate of 8% gaps, 0% islands, and 0% holes on corrected isodose reconstruction. CONCLUSION: The use of intraoperative fluoroscopy-based dose assessment can accurately guide in the implantation of additional sources to supplement inadequately dosed areas within the prostate gland. Additionally, guided implantation of additional source, can significantly improve V100s and D90s, without significantly increasing rectal doses.     

High dose rate brachytherapy in the treatment of prostate cancer.

Because the HDR brachytherapy treatments are delivered within minutes and on an outpatient basis, HDR brachytherapy is very well tolerated by patients and offers complete radiation safety. Published studies2, 11, 12, 13, 16, 17, 18, 22, 24, 25 have shown high local clinical and biochemical control rates. Chronic complications have been acceptably low. Very low rates of urinary incontinence and high sexual potency rates have been reported. Gastrointestinal morbidity has been minimal. The development of Ir-192 HDR afterloading brachytherapy and refinements in the dosimetry have ushered in a new era in prostate brachytherapy. The control of the radiation dose and the ability to shape the radiation treatment envelope using a stepping source have allowed a giant step forward in radiation oncology technology. It is now possible to deliver tumoricidal doses of radiation conformally to the prostate while minimizing the dose to the bladder, urethra, and rectum. At present, HDR afterloaded brachytherapy is the optimal whole-organ and tumor-specific conformal radiation therapy for prostate cancer.     

Rectal-wall dose dependence on postplan timing after permanent-seed prostate brachytherapy

PURPOSE: Dose to rectal wall after permanent-seed prostate brachytherapy is dependent on distance between posterior prostatic seeds and anterior rectal wall and is influenced by postimplant periprostatic edema. We analyzed the effect of postplan timing on anterior rectal-wall dose. METHODS AND MATERIALS: Twenty patients received permanent seed 125I brachytherapy as monotherapy (145 Gy). Implants were preplanned by use of transrectal ultrasound (TRUS) and carried out by use of preloaded needles. Postimplant dosimetry was calculated by use of magnetic resonance imaging-computed tomography fusion on Days 1, 8, and 30. The anterior rectal-wall dose is reported as the isodose enclosing 1.0 or 2.0 cc of rectal wall and as the RV100 in cc. RESULTS: The dose to rectal wall increased progressively over time. The median increase in dose to 1.0 cc of rectal wall (RD [1 cc]) from Day 1 to 30 was 39.2 Gy (p < 0.001). RV100 increased from a median of 0.07 cc on Day 1 to 0.67 cc on Day 30. The most significant predictor of rectal-wall dose (RD [1 cc], RD [2 cc], or RV100) was the time of evaluation (p < 0.001). CONCLUSION: Although periprostatic edema cannot be quantified by postimplant imaging, the dose to the anterior rectal wall increases significantly over time as prostatic and periprostatic edema resolve. Critical-organ dose reporting and guidelines for minimizing toxicity must take into account the time of the assessment.     

Sequential evaluation of prostate edema after permanent seed prostate brachytherapy using CT-MRI fusion

PURPOSE: To analyze the extent and time course of prostate edema and its effect on dosimetry after permanent seed prostate brachytherapy. METHODS AND MATERIALS: Twenty patients scheduled for permanent seed (125)I prostate brachytherapy agreed to a prospective study on postimplant edema. Implants were preplanned using transrectal ultrasonography. Postimplant dosimetry was calculated using computed tomography-magnetic resonance imaging (CT-MRI) fusion on the day of the implant (Day 1) and Days 8 and 30. The prostate was contoured on MRI, and the seeds were located on CT. Factors investigated for an influence on edema were the number of seeds and needles, preimplant prostate volume, transitional zone index (transition zone volume divided by prostate volume), age, and prostate-specific antigen level. Prostate dosimetry was evaluated by the percentage of the prostate volume receiving 100% of the prescribed dose (V(100)) and percentage of prescribed dose received by 90% of the prostate volume (D(90)). RESULTS: Prostate edema was maximal on Day 1, with the median prostate volume 31% greater than preimplant transrectal ultrasound volume (range, 0.93-1.72; p < 0.001) and decreased with time. It was 21% greater than baseline at Day 8 (p = 0.013) and 5% greater on Day 30 (p < 0.001). Three patients still had a prostate volume greater than baseline by Day 30. The extent of edema depended on the transition zone volume (p = 0.016) and the preplan prostate volume (p = 0.003). The median V(100) on Day 1 was 93.6% (range, 86.0-98.2%) and was 96.3% (range, 85.7-99.5%) on Day 30 (p = 0.079). Patients with a Day 1 V(100) >93% were less affected by edema resolution, showing a median increase in V(100) of 0.67% on Day 30 compared with 2.77% for patients with a V(100) <93 % on Day 1. CONCLUSION: Despite the extreme range of postimplant edema, the effect on dosimetry was less than expected. Dose coverage of the prostate was good for all patients during Days 1-30. Our data indicate that postimplant dosimetry on the day of implant is sufficient for patients with good dose coverage (Day 1 V(100) >93%).     

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction

To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT).

Materials and methods

From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years.

Results

Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V₁₂₀ (urethral volume receiving ?120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late ? grade 2 GU toxicities (P = .049).

Conclusions

Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V₁₂₀ on GU toxicity should be validated in further studies.     

Role of high dose rate brachytherapy in the treatment of prostate cancer

High dose rate (HDR) brachytherapy in intermediate and high-risk prostate cancer patients has started in the late eighties in Europe and the United States, as a boost combined with external beam radiation therapy, as an attractive method for dose escalation. The results of the first dose-escalation study performed at William Beaumont Hospital has established the safety and efficacy of this combined treatment approach. Likewise, this landmark study enabled a paradigm shift in the radiobiology of prostate cancer, demonstrating that the alpha/beta of prostate cancer was much lower than previously believed to be and therefore the sensitivity of this tumor model to higher-than-conventional doses per fraction led to a dramatic increase of hypofractionated treatment regimens, the object of significant clinical research efforts, currently under way. The excellent toxicity profile and clinical outcome of HDR boost combined treatment prompted investigators to expand HDR brachytherapy indications to low/intermediate prostate cancer patients as the sole treatment modality. The results, toxicity and a brief review of the literature for both HDR boost and HDR monotherapy will be presented.