Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints (original) (raw)
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Brachytherapy, 2011
PURPOSE: To describe biochemical relapse-free survival (BRFS) and late toxicity after combined highedose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate-and high-risk prostate cancer patients. METHODS AND MATERIALS: From March 2003 to September 2005, 64 men were treated by 3 Â 7 Gy HDR-B using one implant followed by 50 Gy IMRT. Median age was 66.1 years; risk of recurrence was intermediate in 30 (47%) or high in 34 (53%) patients. Forty-four (69%) patients received hormonal therapy. Patients were treated with a median of 13 HDR-B applicators (range, 8e17). Biochemical relapse was defined according to Phoenix criteria. Toxicity was scored according to the Common Toxicity Criteria scale version 3.0. RESULTS: Median followup was 5.1 years. The 3-year BRFS was 100% and 91% for intermediate-and high-risk patients. Late Grade 2 gastrointestinal (GI) toxicity occurred in 3 (4.7%) patients, late Grade 3 GI toxicity was absent. Late Grade 3 and 4 genitourinary (GU) toxicity was observed in 7 (10.9%) and 2 (3.1%) patients. The 5-year Grade 3 or higher late GU toxicity-free survival was associated with a higher number of HDR-B applicators (p 5 0.049). CONCLUSIONS: The 3-year BRFS was excellent and late GI toxicity was negligible. However, the late Grade 3 and 4 GU toxicity was unacceptably high.
Radiotherapy and Oncology, 2009
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 V 120 (urethral volume receiving P120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late P 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 V 120 on GU toxicity should be validated in further studies.
International Journal of Radiation Oncology*Biology*Physics, 2008
Purpose: To determine whether segmental urethral dosimetry is predictive for the degree of urinary morbidity after prostate brachytherapy in patients with no urinary symptoms before prostate brachytherapy. Methods and Materials: Between May 2000 and November 2005, 1,107 patients underwent iodine-125 monotherapy with urethral sparing techniques. A total of 166 patients fulfilled the selection criteria: baseline (International Prostate Symptom Score) IPSS #5, no androgen deprivation therapy, and prostate ultrasound planning volumes (PUTV) <45 mL. The median follow-up was 44 months. Urinary morbidity was defined by maximum increase in IPSS, time to IPSS resolution, maximum Radiation Therapy Oncology Group (RTOG) score, time to RTOG resolution, and urinary retention. Surrogate deviated urethra was contoured and doses calculated at the base, mid-prostate, apex, and urogenital diaphragm. Univariate and multivariate analysis was used to evaluate urethral and prostate dosimetry, age, PUTV, and number of needles for their association with urinary morbidity. Results: Urethral dose was fairly constant in all urethra segments except prostate base, where the variation in does was large. On multivariate analysis, higher urethral base D50, V100, and larger PUTV were predictive for higher maximum increase in IPSS. Higher urethral base V100 and larger PUTV predicted for prolonged IPSS resolution. Higher urethral base D50 and larger needle number predicted for longer RTOG resolution. Higher urethral base V100 predicted for RTOG $2 toxicity. Conclusions: Radiation dose to the urethral base, larger PUTV, and needle number, predicted for increased urinary toxicity after prostate brachytherapy. Correlation between urinary morbidity and urethral base dosimetry may reflect a large variation in urethral dose observed at the prostate base.
International Journal of Radiation Oncology*Biology*Physics, 2010
Purpose: Iodine-125 ( 125 I) prostate brachytherapy is planned with a prescribed dose of 145 Gy and minimal dose received by 90% of the prostate (D 90 ) of 120-125% (174-181 Gy). We examined the clinical outcomes and toxicity profile of men receiving a D 90 (isodose enclosing 90% of the prostate) of 180Gy.MethodsandMaterials:BetweenMarch1999andMay2006,129men(17180 Gy. Methods and Materials: Between March 1999 and May 2006, 129 men (17% of our total brachytherapy population) treated with 125 I monotherapy for Stage T1-T2 prostate cancer received a D 90 180Gy.MethodsandMaterials:BetweenMarch1999andMay2006,129men(17180 Gy. Implants were performed using transrectal ultrasonography and fluoroscopic guidance. The 1-month postplan dosimetry used magnetic resonance imaging-computed tomography fusion. The minimal follow-up was 2 years. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events toxicity scale, version 3. Results: The median patient age was 63 years (range, 50-76), and the pretreatment prostate-specific antigen level was 5.5 ng/mL (range, 0.6-13.5). The Gleason score was #6 in 125 patients and was 7 in 4 patients. The median follow-up period was 40 months (range, 24-111), and the median D 90 was 186 Gy. The median minimal dose received by 30% of the urethra was 203 Gy, and the median rectal volume receiving a minimum of 100% of the prescribed dose was 0.81 cm 3 . Acute Grade 2 genitourinary toxicity was seen in 5.4% and late Grade 2 in 7%. Late urinary retention (Grade 3) was seen in 2 patients (1.5%). Grade 1 rectal bleeding occurred in 9.3% and Grade 2 in 2.3%. On univariate logistic regression analysis, none of the clinical and dosimetric parameters predicted for rectal bleeding. Of 110 men who were potent before treatment, 81% remained potent 5 years after treatment. Three biochemical failures and only one local failure developed. The 5-year biochemical no evidence of disease rate using the ''nadir plus 2'' definition was 96.8%. Conclusion: A D 90 of $180 Gy is associated with excellent biochemical disease-free survival and acceptable toxicity. Ó 2010 Elsevier Inc.
Dosimetric analysis of radiation therapy oncology group 0321: The importance of urethral dose
Practical Radiation Oncology, 2014
Purpose: Radiation Therapy Oncology Group 0321 is the first multi-institutional cooperative group high-dose-rate (HDR) prostate brachytherapy trial with complete digital brachytherapy dosimetry data. This is a descriptive report of the data and an analysis of toxicity. Methods and Materials: Patients are treated with external beam radiation therapy at 45 Gy and 1 HDR implant with 19 Gy in 2 fractions. Implants are done with transrectal ultrasound guidance, and computed tomography (CT)-compatible nonmetallic catheters. HDR planning is done on ≤ 3mm-thick CT slices. The "mean DVH" (dose-volume histogram) of the planning target volume (PTV), implanted volume (IP), and organs at risk are calculated. This includes the mean and standard deviation (SD) of the volume at 10-percentage-point intervals from 10% to 200% of the prescribed dose. The conformal index (COIN), homogeneity index (HI), catheters per implant, and patients per institution are calculated. Multivariate analysis and hazard ratios calculation of all the variables against reported grade ≥ 2 (G2 +) genitourinary (GU) adverse events (Common Terminology Criteria for Adverse Events, version 3) are performed. Results: Dosimetry data are based on 122 eligible patients from 14 institutions. The mean of PTV, IP, catheters per implant, and patients per institution are 54 cc, 63 cc, 19 and 9, respectively. The mean of %V100 PTV , V80 Bladder , V80 Rectum , and V120 Urethra were 94%, 0.40 cc, 0.15 cc, and 0.25 cc, respectively. There are too few G2 + gastrointestinal adverse event (GI AE) for correlative analysis; thus, the analysis has been performed on the more common G2 + GU AE. There are positive correlations noted between both acute and late G2 + GU AE and urethral dose at multiple levels. Positive correlations with late AE are seen with PTV and IP at high-dose levels. A negative Note-Earn CME credit by taking a brief online assessment at https://www.astro.org/JournalCME. Practical Radiation Oncology (2014) 4, 27-34 correlation is seen between HI and acute AE. A higher patient accrual rate is associated with a lower rate of G2 + acute and late AE. Conclusions: Higher urethral dose, larger high-dose volumes, and lower dose homogeneity are associated with greater toxicities. A mean dose-volume histogram comparison at all dose levels should be used for quality control and future research comparison.
International journal of radiation oncology, biology, physics, 2014
To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area unde...
Journal of Clinical Oncology, 2018
The ASCO/Cancer Care Ontario (CCO) joint guidelines recommend that patients with unfavorable intermediate-to high-risk prostate cancer should be offered combined brachytherapy when receiving external-beam radiation therapy (EBRT) and that there may be increased genitourinary (GU) toxicity compared with EBRTalone. 1 The recommendation was based on three phase III trials demonstrating clinical improvement. 2-5 Spratt and Carroll, 6 in a recent Comments and Controversies article, criticized this recommendation. On behalf of the American Brachytherapy Society and the American Radium Society Appropriate Use Criteria Genitourinary Committee, we endorse the ASCO/CCO joint guidelines and wish to address the arguments presented in the article. With dose escalation provided by the addition of brachytherapy to EBRT, increased urinary toxicity may be expected but not to the extent that Spratt and Carroll 6 suggest. Regarding toxicity from the ASCENDRE-RT (Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy) trial, their commentary elided the difference between cumulative and point prevalence of late toxicity. The authors overstated the increased 5-year cumulative late grade $ 3 GU toxicity in the combination brachytherapy arm versus the EBRTalone arm, which was mostly composed of urethral strictures. These strictures were attributed to overestimating the inferior extent of the prostatic apex, resulting in treatment of the GU diaphragm, which is not commonly practiced in the current era of treatment planning with high-quality magnetic resonance imaging. Because many complications resolved, the prevalence (proportion of patients still experiencing toxicity) of grade $ 3 GU toxicity in ASCENDE-RT was much diminished, at , 10% in both arms (P 5 .06). 7 This prevalence rate is markedly less than the reported grade $ 3 incontinence rate (17% to 70%), impotence rate (80%), and stricture rate (10%) after radical prostatectomy in phase III studies including the PROTECT (Prostate Testing for Cancer and Treatment), PIVOT (Prostate Cancer Intervention Versus Observation Trial), and SPCG4 (Scandinavian Prostate Cancer Group Study Number 4) trials and in the Cancer of the Prostate Strategic Urologic Research Endeavor database. Despite these facts, the authors concluded that the "adverse effects in the ASCENDE-RT trial [combination arm] were of much greater concern than that between EBRT and surgery." 6 In analyzing the phase III trial by Hoskin et al, 4 the article omitted data demonstrating no difference in cumulative late
Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related urinary morbidity
International Journal of Radiation Oncology*Biology*Physics, 2005
and § Ohio University Eastern, St. Clairsville, OH Purpose: To evaluate the relationship between urinary morbidity after prostate brachytherapy and urethral doses calculated at the base, midprostate, apex, and urogenital diaphragm. Methods and Materials: From February 1998 through July 2002, 186 consecutive patients without a prior history of a transurethral resection underwent monotherapeutic brachytherapy (no supplemental external beam radiation therapy or androgen deprivation therapy) with urethral-sparing techniques (average urethral dose 100%-140% minimum peripheral dose) for clinical T1c-T2b (2002 AJCC) prostate cancer. The median follow-up was 45.5 months. Urinary morbidity was defined by time to International Prostate Symptom Score (IPSS) resolution, maximum increase in IPSS, catheter dependency, and the need for postimplant surgical intervention. An alpha blocker was initiated approximately 2 weeks before implantation and continued at least until the IPSS returned to baseline. Evaluated parameters included overall urethral dose (average and maximum), doses to the base, midprostate, apex, and urogenital diaphragm, patient age, clinical T stage, preimplant IPSS, ultrasound volume, isotope, and D90 and V100/150/200. Results: Of the 186 patients, 176 (94.6%) had the urinary catheter permanently removed on the day of implantation with only 1 patient requiring a urinary catheter >5 days. No patient had a urethral stricture and only 2 patients (1.1%) required a postbrachytherapy transurethral resection of the prostate (TURP). For the entire cohort, IPSS on average peaked 2 weeks after implantation with a mean and median time to IPSS resolution of 14 and 3 weeks, respectively. For the entire cohort, only isotope predicted for IPSS resolution, while neither overall average prostatic urethra nor segmental urethral dose predicted for IPSS resolution. The maximum postimplant IPSS increase was best predicted by preimplant IPSS and the maximum apical urethral dose. Conclusions: With the routine use of prophylactic alpha blockers and strict adherence to urethral-sparing techniques, detailed urethral dosimetry did not substantially improve the ability to predict urinary morbidity. Neither the average dose to the prostatic urethra nor urethral doses stratified into base, midprostate, apex, or urogenital diaphragm segments predicted for IPSS normalization. Radiation doses of 100%-140% minimum peripheral dose are well tolerated by all segments of the prostatic urethra with resultant tumorcidal doses to foci of periurethral cancer. © 2005 Elsevier Inc. Prostate, Brachytherapy, Urinary morbidity, Quality of life.
Physics and Imaging in Radiation Oncology
Background and purpose: Significant deviations between bladder dose planned (D P) and dose accumulated (D A) have been reported in patients receiving radiotherapy for prostate cancer. This study aimed to construct multivariate analysis (MVA) models to predict the risk of late genitourinary (GU) toxicity with clinical and D P or D A as dose-volume (DV) variables. Materials and methods: Bladder D A obtained from 150 patients were compared with D P. MVA models were built from significant clinical and DV variables (p < 0.05) at univariate analysis. Previously developed dose-basedregion-of-interest (DB-ROI) metrics using expanded ring structures from the prostate were included. Goodness-of-fit test and calibration plots were generated to determine model performance. Internal validation was accomplished using Bootstrapping. Results: Intermediate-high D A (V 30-65 Gy and DB-ROI-20-50 mm) for bladder increased compared to D P. However, at the very high dose region, D A (D 0.003 cc , V 75 Gy, and DB-ROI-5-10 mm) were significantly lower. In MVA, single variable models were generated with odds ratio (OR) < 1. DB-ROI-50 mm was predictive of Grade ≥ 1 GU toxicity for D A and D P (D A and D P ; OR: 0.96, p: 0.04) and achieved an area under the receiver operating curve (AUC) of > 0.6. Prostate volume (OR: 0.87, p: 0.01) was significant in predicting Grade 2 GU toxicity with a high AUC of 0.81. Conclusions: Higher D A (V 30-65 Gy) received by the bladder were not translated to higher late GU toxicity. DB-ROIs demonstrated higher predictive power than standard DV metrics in associating Grade ≥ 1 toxicity. Smaller prostate volumes have a minor protective effect on late Grade 2 GU toxicity.