Bladder Dosimetry Research Articles

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial

PurposeThe POP-RT phase III randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiotherapy (WPRT) versus prostate-only radiotherapy (PORT) for high/very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. Materials/MethodsLate urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65Gy, V68Gy) in the approved radiotherapy plans was compared for urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. ResultsComplete combined data for late urinary symptoms and dosimetry was available for 193/224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for WPRT and PORT (5.2% vs 4.1%, p=0.49), while grade 2 toxicity was 31.3% vs 22.7% respectively (p=0.12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior TURP, grade 2+ acute urinary toxicity, low bladder dose (V10Gy) and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. ConclusionOver long term follow up, whole pelvic radiotherapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiotherapy. The long term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Impact of Interfractional Bladder and Trigone Displacement and Deformation on Radiation Exposure and Subsequent Acute Genitourinary Toxicity: A Post Hoc Analysis of Patients Treated with Magnetic Resonance Imaging–Guided Prostate Stereotactic Body Radiation Therapy in a Phase 3 Randomized Trial

PurposeEmerging data suggest that trigone dosimetry may be more associated with post-stereotactic body radiotherapy (SBRT) urinary toxicity than whole bladder dosimetry. Herein, we quantify the dosimetric impact of interfractional displacement and deformation of the whole bladder and trigone during prostate SBRT using on-board, pre-treatment 0.35T MRI images. MethodsSeventy-seven patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase III single-center randomized trial were included. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and five on-board pre-treatment MRIs. Dice Similarity Coefficient (DSC) scores and changes in volume between simulation and daily treatments were calculated. Dosimetric parameters including Dmax, D0.03cc, Dmean, V40Gy, V39Gy, V38Gy, and V20Gy for the bladder and trigone for the simulation and daily treatments were collected. Both physician-scored (CTCAE v4.03 scale) as well as patient-reported (IPSS and EPIC-26 scores) acute genitourinary (GU) toxicity outcomes were collected and analyzed. ResultsThe average treatment bladder volume was about 30% smaller than the simulation bladder volume; however, the trigone volume remained fairly consistent despite being positively correlated with total bladder volume. Overall, the trigone accounted for less than 2% of the bladder volume. Median DSC for the bladder was 0.79 while the median DSC of the trigone was only 0.33. No statistically significant associations between our selected bladder and trigonal dosimetric parameters and grade 2 or greater GU toxicity were identified, though numerically, patients with GU toxicity (grade ≥ 2) had higher intermediate doses to the bladder (V20Gy and Dmean) and larger volumes exposed to higher doses in the trigone (V40Gy, V39Gy, and V38Gy). ConclusionsThe trigone exhibits little volume change, but considerable interfractional displacement/deformation. As a result, the relative volume of the trigone receiving high doses during prostate SBRT varies substantially between fractions, which could influence GU toxicity and may not be predicted by radiation planning dosimetry.

Dosimetric Predictors of Toxicities and Quality of Life Following Two-Fraction Stereotactic Body Radiotherapy for Prostate Cancer.

There is emerging interest in two-fraction stereotactic body radiotherapy (2#SBRT) for localized prostate cancer. However, there is limited data to guide organs at risk (OAR) dose constraints in 2#SBRT. We aim to identify dosimetric predictors of toxicities and quality of life (QoL) using real life patient data from two prospective 2#SBRT trials. We included 60 patients who had 2#SBRT in the 2STAR (NCT02031328) and 2SMART (NCT03588819) phase 2 trials. The prescribed dose was 26Gy to the prostate +/- focal boost of 32Gy to the dominant intraprostatic lesions. Toxicities and QoL data were prospectively collected using CTCAEv4 and EPIC26 questionnaires. For QoL, we reported the minimal clinical important changes (MCIC), defined as changes in QoL score of >0.5 standard deviation from baseline QoL score. We evaluated the bladder, urethra, rectum, and penile bulb dosimetry (urethra dosimetry only available in 30 patients in 2SMART trial). Some of the dosimetric parameters were log-transformed to normalize the distribution. Cox regression was used to identify dosimetric predictors for acute and late grade ≥2 GU toxicities. Logistic regression was used to identify dosimetric predictors for late MCIC in urinary, bowel and sexual QoL domains. Backward stepwise selection was used to identify significant dosimetric parameters. For GU toxicities and urinary QoL, three additional clinical factors (age, prostate volume and IPSS) were included in the final model as confounding factors. Receiver operating characteristics curve was used to identify cut-off for significant dosimetric parameters. The median follow-up for the cohort was 56 months (range: 39-78 months). The cumulative acute and late grade ³2 GU toxicities were 62% (37/60) and 57% (34/60) respectively. No bladder or urethra dosimetric parameter was associated with acute grade ≥2 GU toxicities. Bladder D0.5cc was significant predictor of late grade ≥2 GU toxicities in univariate model (P = 0.05), but not in multivariate model. Baseline IPSS score was the single strongest predictor for late grade ≥2 GU toxicities (HR = 1.9; 95% CI = 1.1-3.4; P = 0.03). For late QoL outcomes, there were 36% (21/58), 28% (16/58), and 29% (17/58) of patients with MCIC in urinary, bowel and sexual QoL domains respectively. Bladder V10Gy was associated with late urinary MCIC in multivariate model after adjusting for clinical confounders (HR = 2.6, 95% CI = 1.1-6.6; P = 0.04). 48% (14/29) and 24% (7/29) of patients with bladder V10Gy>13.9% and V10Gy≤13.9% respectively had late urinary MCIC. No rectum and penile bulb dosimetry parameters was identified to be associated with late bowel or sexual QoL. Using real life patient data from prospective clinical trials with medium term follow-up, we identified statistically significant bladder dosimetry parameter predictive of late urinary QoL. This finding could be useful to guide OAR dose constraints in prostate 2#SBRT trials.

Late Urinary Toxicity and QoL with Curative Radiotherapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase III Trial

Whole pelvic radiotherapy (WPRT) showed better biochemical failure-free survival and metastasis-free survival than prostate-only radiotherapy (PORT) in the phase III randomized POP-RT trial for high and very high-risk prostate cancer, albeit with higher RTOG grade 2 late urinary toxicity. We report updated long term, symptom-wise comparison and dose-effect relations from this trial. Late urinary toxicity, and cumulative severity of each symptom over the follow-up period was graded using CTCAE v5.0. Grade 2+ toxicities were compared between the trial arms by chi square test. Bladder dosimetry in 5-Gy increments (V5, V10, V15...V65 Gy, V68 Gy) from the trial database of approved radiotherapy plans, was compared for each urinary symptom and overall late gr2+ toxicity by student t-test. Observed differences in dosimetric parameters were tested using multivariable logistic regression analysis, including age at diagnosis, known diabetes, tumor stage, trial arm, and prior transurethral resection of prostate (TURP). Urinary QOL scores were compared between arms using generalised linear mixed model. Combined late symptom-wise toxicity and dose-volume data were available for analysis for 193/224 patients. At a median follow-up of 75 months, cumulative CTCAE gr2+ late urinary toxicity remained higher with WPRT than PORT, though not statistically significant (36.5% vs 26.8%, p = 0.15). Grade 3 toxicity was low and similar in both arms. Symptom-wise cumulative rates showed no significant difference between arms (Table 1). Dosimetric comparison showed significantly higher bladder V5-V15 in patients with gr2+ toxicity over those with <gr2 urinary toxicity. On symptom-wise analysis, V5-V40 range was significantly higher for presence of dysuria, hematuria, and urgency. No significant differences were observed over higher dose range for any urinary symptom. On multivariable analysis, no significant association was identifiable between bladder dosimetry and urinary symptoms. Urinary QOL scores was similar between both the arms for all the symptoms. Compared to prostate-only radiotherapy, whole pelvic radiotherapy resulted similar Grade 3 urinary toxicity of about 5% with about 10% higher cumulative grade 2+ urinary toxicity over long term follow up. This difference was not reflected in patient-reported QOL. WPRT particularly increased urgency and hematuria. Larger bladder volume being irradiated with 5Gy to 15Gy dose range could contribute to increase in urinary symptoms.

Dosimetric Impact of Interfractional Bladder and Trigone Deformations: A Post-Hoc Analysis of a Phase III Randomized Trial of MRI-Guided vs. CT-Guided Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> Emerging data suggest that dosimetry of the trigone may be more associated with post-SBRT urinary toxicity than whole bladder dosimetry. Herein, we quantify the dosimetric impact of interfractional deformations during SBRT for the whole bladder and trigone using on-board 0.35T MRI images. <h3>Materials/Methods</h3> Twenty consecutive patients treated with MRI-guided prostate SBRT (40 Gy/5 fractions) on the MRI arm of a phase III single-center randomized trial were included. All patients were encouraged to have a full bladder for treatment. Bladder and trigone structures were contoured on images obtained from a 0.35T simulation MRI and five on-board pre-treatment MRIs. Dice Similarity Coefficients (DSCs) and changes in volume, Dmax, and Dmean for the bladder and trigone were calculated. <h3>Results</h3> Overall, the trigone accounted for only 2% of the bladder volume. Median DSC for bladder was 0.83 (0.60-0.97) while the median DSC of trigone was only 0.39 (0-0.84) (p<0.001). No statistically significant changes in bladder or trigone volume were seen, though the trigone volume was significantly associated with bladder volume (p<0.0001). Quantitatively, the Dmax values for the bladder and trigone were relatively consistent, with only 2% relative change. In contrast, the Dmean values for the bladder and the trigone exhibited more variability (p<0.0001). <h3>Conclusion</h3> The trigone is an extremely small urinary substructure (∼2% of the bladder volume) that exhibits significant interfractional deformation. Minimal changes in Dmax for both structures are consistent with expectations given their high proximity to the target volume and the use of bladder preparation. However, constraints for the trigone are unexplored, and the very low DSC suggests that the relative volume of this substructure receiving higher doses (∼75-100% of the prescription dose) could vary substantially. A rigorous exploration of this concept for the full cohort of trial patients who completed MRI-guided SBRT is planned.

Radiation Dose to the Intraprostatic Urethra Correlates Strongly With Urinary Toxicity After Prostate Stereotactic Body Radiation Therapy: A Combined Analysis of 23 Prospective Clinical Trials

Clinical trials assessing evaluation prostate stereotactic body radiation therapy (SBRT) have used a wide range of allowed doses to the intraprostatic urethra, but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. The goal of this study was to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. The MEDLINE (PubMed) database was searched for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Logistic regression and weighted Pearson correlation models were used to assess associations between urinary toxicity rates and MUDM. Twenty-three unique studies (n=2232 patients) met the inclusion criteria and included a wide range of MUDMs (equivalent dose in 2 Gy fractions [EQD2]: 69-141.75 Gy; α/β=3 Gy). The median follow-up ranged from 3 to 67 months (median, 32 months). On logistic regression analysis, the MUDM EQD2 was significantly associated with multiple urinary toxicity endpoints, including acute grade (G) 2+ (odds ratio [OR], 1.02; P < .001), late G2+ (OR, 1.03; P < .0001), and late G3+ (OR, 1.04; P=.003) urinary toxicity. On weighted Pearson correlation analysis, the MUDM was more closely associated with all evaluated urinary toxicity endpoints than prescription dose, including acute G2+ (r=0.51; P=.02), late G2+ (r=0.9; P < .0001), and late G3+ toxicity (r=0.7; P=.003). Multivariate analysis accounting for age, prostate size, bladder dosimetry, and baseline urinary function confirmed associations between urinary outcomes and MUDM. Within the studied dose range, each increase of 1 Gy to the MUDM corresponded to a 0.8% and 1.0% increase in acute G2+ and late G2+ toxicity, respectively. Radiation dose to the urethra correlates closely with urinary toxicity in patients with prostate cancer treated with SBRT. Attention should be paid to the urethral dose when delivering prostate SBRT to high doses, and approaches for urethral dose reduction warrant further investigation.

Omission of MRI For Treatment Planning Does Not Affect Long-Term Outcomes after Prostate SBRT.

Stereotactic Body Radiation Therapy (SBRT) is increasingly being used to treat men with localized prostate cancer. Diagnostic MRI imaging as well as MRI-guided treatment for these patients have become widely utilized. A minority of patients are not candidates for MRI imaging due to pre-existing conditions or patient intolerance. To our knowledge, this is the largest series to investigate long-term outcomes in men for whom MRI imaging is not employed as a component of their prostate SBRT treatment. A total of 2775 patients with localized prostate cancer were treated with inhomogeneous-dosed SBRT at an academic institution between April 11, 2006 and November 23, 2019. By NCCN categorization, patients were treated for low (29.6%), favorable intermediate (26.0%), unfavorable intermediate (34.9%), and high risk (9.6%) disease. The majority (84.0%) of patients were treated with a median dose of 3500cGy (3500-3625) over 5 fractions. Androgen deprivation Therapy (ADT) was prescribed in 17.1% of cases. Disease Free Survival (DFS) was scored using the “nadir + 2” definition and long-term urinary and rectal toxicity was characterized as occurring ≥6 months post radiation. Correlation analyses were performed using the Pearson Chi-Square test. Estimates for DFS and toxicity were determined using the Kaplan-Meier method. 132 (4.8%) patients in this series received treatment without a planning MRI, with the most common reason being a history of implanted defibrillator (46.2%). Those treated without an MRI were slightly older (69.8 vs. 67.2 years, p<.001), and were more likely to have Gleason 8-10 histology (14.4% vs. 7.5%, p = .01) and high-risk disease (15.9% vs. 8.7%, p = .02). There was no difference in pre-treatment PSA. Those treated with MR imaging were more likely to be prescribed 3625cGy (12.1% vs. 4.6%, p = .004). The CTV was larger in men for whom an MRI was not utilized (84.3cc’s vs. 77.8cc’s, p = .029) as was maximum penile bulb dose (3061cGy vs. 2181cGy, p = .002). There was no difference in the use of ADT or in rectal or bladder dosimetry between these groups. Patients treated without MR imaging had no difference in 6-year freedom from grade 2+ rectal (96.6% vs. 97.1%, p = 0.42) and genitourinary toxicity (97.7% vs. 97.2%, p = 0.76). Similarly, there was no difference between these groups in 6-year DFS for low (97.7% vs. 97.2%, p = 0.60), favorable intermediate (100% vs. 83.1%, p = 0.61), unfavorable intermediate (84.3% vs. 84.5%, p = 0.19), or high-risk disease (64% vs. 67.5%, p = .06). This is the largest study to explore long-term outcomes in men treated with SBRT without MR imaging for localized prostate cancer. These patients are at risk for treatment with larger CTV size and penile bulb dose. Despite this, along with slight differences in baseline clinicopathologic features, the omission of MR imaging is safe and does not appear to affect long-term DFS or toxicity profiles.

Low Body Mass Index As a Risk Factor for Long-Term Proctitis after Prostate SBRT: Assessing the Dosimetric and Clinical Implications

Body Mass Index (BMI) is a parameter used by the World Health Organization and American Cancer Society (ACS) to categorize patient health. Stereotactic Body Radiation Therapy (SBRT) is a standard treatment option for men with localized prostate cancer. Previous studies have described a lower volume of anterior perirectal and mesorectal fat in individuals with lower BMI’s. This study assesses the incidence, dosimetric impact, and clinical implications of low BMI on patients treated with prostate SBRT. 2421 patients with prostate cancer and for whom BMI’s were available were treated at an academic institution with non-coplanar SBRT. Intrarectal amifostine was administered prior to each fraction. The mean age was 67.5 (41-93) years and the mean pre-treatment PSA was 7.55ng/ml (0.33-82.49). Patients were treated for low (23.4%), favorable intermediate (26.7%), unfavorable intermediate (41.3%), and high risk (8.6%) disease. Most (89.1%) patients were treated with a dose of 3500cGy (3500-3625) over 5 fractions. Androgen deprivation Therapy (ADT) was prescribed in 17.2% of cases. Proctitis was scored by RTOG late toxicity scale. The Pearson chi-square test was used to compare patient groupings. Freedom from grade 2+ proctitis was assessed using the Kaplan-Meier method and analyzed using Cox regression. The mean BMI in this series was 28.7 kg/m2 (15.2-58.8). Per ACS stratification, 19.6% of patients were normal weight, while 46.1% and 34.0% of patients were overweight and obese, respectively. 24 (1.0%) patients registered a BMI of ≤20 kg/m2. These patients were more likely to have T2b/T2c stage disease (30.4% vs. 12.7%, p = .039), but were without any difference in initial PSA, Gleason score, or NCCN risk grouping. They were more likely to have a pre-existing diagnosis of HIV (9.5% vs. 0.9%, p<.0001), with similar utilization of blood thinners. There was no difference in ADT use. Patients with a BMI ≤20 kg/m2 had smaller CTV sizes (55.9cc’s vs. 79.0cc’s, p = .002), with a higher Rectal V3600 (1.13cc’s vs. 0.69cc’s, p = .018). There was no difference in bladder dosimetry. They had a higher 6-year cumulative risk of grade 2+ (11.9% vs. 3.0%, p = .002) and grade 3+ (5.6% vs. 0.9%, p = .011) proctitis. There was no difference in bladder outcomes. On multivariate analysis, receiving treatment with a BMI ≤20 kg/m2 (OR 7.68, CI 1.53-38.50, p = .013) and using anti-coagulation use during SBRT (OR 4.16, CI 1.89-9.19, p<.0001) were the lone predictors for grade 2+ proctitis. Long-term rates of proctitis are low in patients receiving prostate SBRT. In a large institutional series, those with BMI ≤20 kg/m2 had an increased risk of grade 2+ and grade 3+ rectal toxicity. The association of lower BMI with higher rectal dosimetry might be a function of decreased perirectal fat. This data is thought provoking and might suggest patient groupings which may derive the greatest benefit to hydrogel placement prior to prostate SBRT.

Dosimetric Predictive Models for Urinary and Rectal Toxicities after Prostate Stereotactic Body Radiotherapy Assessed from the Expanded Prostate Cancer Index Composite Patient-reported Quality of Life

The underlying correlations between treatment planning parameters and treatment toxicities are greatly needed for prostate SBRT. We aimed to assess dosimetric quantities and their associations with patient-reported quality of life (QOL) using advanced machine learning techniques. One hundred one prostate SBRT patients were pooled and analyzed. Patients received 40 Gy in 5 fractions on a LINAC using an IMRT arc therapy delivery technique. Patient-specific differential dose-volume histograms (dDVHs, in 1 Gy dose bins from 0 to maximum doses) for rectum and bladder were extracted from the treatment planning system. Other pre-selected quantities, such as planning target volume (PTV) /rectal/bladder volumes and maximum doses, conformality index, etc. were also considered as potential predictors. Patient-reported QOL scores from the Expanded Prostate Cancer Index Composite (EPIC-26) were collected at consultation (baseline) and at 3- and 12- months post-SBRT. Patients were grouped by their score changes (decrement/no change/increment) according to minimally important difference score thresholds of 4, 5, and 6 in bowel, urinary irritative and urinary incontinence domains, respectively. Ensemble machine learning methods including Gradient Boosting Decision Tree (GBDT) were applied to interrogate each dose bin of the dDVHs and the other potential predictors to evaluate their relationships with QOL changes. The most plausible dosimetric features and their importance were derived from the reduction of square loss after tree node splitting using the GBDT. The Pearson correlation tests were performed on final selected dosimetric features. Multivariable linear logistic regression models were then constructed using the selected top features. The performance of predictive models was evaluated using area under the curve (AUC) using 5-fold cross validation. An independent cohort of 15 patients were used to validate the predictive models. At 12 months, bladder dosimetry demonstrated predictive ability for urinary irritation and incontinence symptoms with AUCs of 0.72 and 0.81, respectively. AUC = 0.65 was observed for rectal toxicities. Predictive models, constructed using top 5, 10 and 20 most plausible dosimetric parameters, yielded AUCs of 0.72, 0.76, 0.75; 0.62, 0.8 and 0.8; and 0.73, 0.76, 0.73 for urinary irritation, incontinence and bowel toxicity, respectively. We demonstrated the correlations between dosimetric quantities and patient-reported outcomes for bladder toxicities, dosimetric metrics had less predictive ability for rectal toxicity at 12 months after prostate SBRT. The linear models built on top 10 dosimetric parameters achieved great performances to predict toxicities. The identified dosimetric metrics and the multivariable linear models can be used to refine planning guidelines towards personalized treatment.

Real-world dosimetric comparison between CyberKnife SBRT and HDR brachytherapy for the treatment of prostate cancer

PurposeHigh-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) are currently the two treatment options for definitive radiotherapy of prostate cancer, employing extreme hypofractionation. There are only very few studies comparing their dosimetry, all using computed tomography for treatment planning. We present here a real-word dosimetric comparison between SBRT and ultrasound-based virtual HDR-BRT, with both imaging modalities coming from the same patient. Methods and MaterialsPatients with prostate cancer on a prospective trial evaluating the toxicity of robotic-based SBRT were treated to a total dose of 35 Gy in 5 fractions. Fifteen patients were included in this analysis. During ultrasound-based fiducial implantation, a three-dimensional data set as in real HDR-BRT procedure was acquired. Virtual HDR-BRT plans were generated and various organs at risk and prostate dosimetric parameters were evaluated. ResultsConcerning prostate, SBRT achieved significant higher D98, V35 Gy, and V37.5 Gy coverage, whereas virtual HDR-BRT achieved significant higher intratumoral doses reflected in the V42 Gy and V52.5 Gy. Rectal Dmax, V36 Gy, and V29 Gy were significantly lower for HDR-BRT with no difference as for V18 Gy. SBRT was significantly inferior regarding bladder dosimetry (Dmax, V36 Gy, V18 Gy), whereas urethra Dmax and V44 Gy where significantly higher at the expense of HDR-BRT. ConclusionsHDR-BRT is superior regarding rectum and bladder dosimetry, with SBRT being superior relative to urethra dosimetry. A randomized study is warranted to define the best extreme hypofractionated modality.

Dosimetric correlations with urinary quality of life in patients receiving post-prostatectomy radiation therapy

Acute urinary toxicity is well-documented in individuals receiving post-prostatectomy radiation. However, dosimetric correlations between bladder dose and acute urinary symptoms in the post-prostatectomy setting have not been well-studied. We examined the relationship between bladder dosimetry and acute changes in individual urinary symptoms among men receiving post-prostatectomy radiation therapy. Patient-reported urinary symptoms were prospectively collected for 90 consecutive prostate cancer patients receiving post-prostatectomy radiation using the validated quality of life instrument Prostate Cancer Symptom Indices. Data were collected prior to treatment and weekly during treatment. Individual symptom scores were examined and a change in severity of an individual symptom (from baseline) of ≥ 2 points was considered clinically significant. DVHs were generated for all the patients. Receiver operating characteristic curves were generated to evaluate the ability of different dose-volume metrics to identify patients who developed individual urinary symptoms during radiation treatment from those who did not. Logistic regression was used to examine the relationship between dose-volume parameters and worsening of individual urinary symptoms. Worsening of individual urinary symptoms during radiation treatment was reported by 7% (urinary flow) to 29% (urgency) of patients. The relative bladder volume receiving moderate doses of radiation was associated with urgency (AUC 0.67 for V30 Gy). Dose-volume parameters were not significantly associated with flow, frequency, nocturia, or dysuria. There is an acute worsening of urinary symptoms among men receiving modern post-prostatectomy radiation. Worsening of urgency is associated with bladder dosimetry while flow, frequency, nocturia, and dysuria are not. This data can be used during treatment planning to reduce acute urinary toxicity during post-prostatectomy radiation.

Dosimetric Analysis of Standard vs. IMRT Pelvic Radiation for Post-Operative Treatment of Endometrial and Cervical Cancer in NRG Oncology’s RTOG 1203

NRG Oncology’s RTOG 1203 demonstrated improved acute toxicity with post-operative intensity modulated radiation therapy (IMRT) for treatment of cervical and endometrial cancer compared to 3D-conformal (3DCRT) techniques. We aimed to correlate dosimetric parameters with patient reported outcomes from RTOG 1203, in hopes to establish dose constraints for patients receiving IMRT for cervical and endometrial cancers. Two different patient reported outcome assessment tools were used in this study, the PRO-CTCAE and the EPIC questionnaires. These assessments were evaluated in the bowel (GI) and urinary (GU) domains including subdomains of bowel bother, bowel function, urinary bother, urinary function, urinary incontinence, and urinary irritation. These assessments were completed at baseline, 5 weeks, 1 year and 3 years after the start of radiotherapy. Pearson and spearman correlation coefficients were used to correlate the radiation doses and volumes with these EPIC and PRO-CTCAE scores, and receiver operator curve (ROC) analyses were used to identify optimal dosimetric cut points for toxicity prediction. The initial radiation doses considered were mean bowel dose, rectum V40, rectum V45, and bladder mean dose, as they have shown to be significant predictors of toxicity in other retrospective analyses. Out of the 279, 129 patients on the IMRT arm had radiation dose data. Of the 129 IMRT patients, 72%, 69%, and 46% completed the PRO-CTCAE assessment at 5 weeks, 1 year and 3 years respectively, while 85%, 75%, and 53% of patients completed the EPIC assessment at 5 weeks, 1 year and 3 years. The median bowel dose, rectal V40, and rectal V45 were not statistically different between patients with and without GI symptoms including abdominal pain, diarrhea, and fecal incontinence at any time point (p>0.055). Similarly, median bladder dose was not associated with worsening GU symptoms, such as urinary function, bother or irritation, at any time point (p>0.13). Preliminary analysis of patient reported outcomes demonstrated no significant association with mean dose to bowel, rectal and bladder dosimetry in the IMRT cohort of RTOG 1203. Ongoing analysis will include investigating lower dose thresholds and their association with acute and late GI and GU patient reported outcomes, and to include patients from the 3DCRT cohort.

Correlation Between Bladder Dosimetry and Patient-Reported Acute Urinary Quality of Life During Modern Post-prostatectomy Image-Guided IMRT

Radical prostatectomy causes urinary symptoms including frequency and urgency, and post-prostatectomy (adjuvant or salvage) RT can further add to these symptoms during the RT treatment course. However, dosimetric correlations between bladder dose and acute urinary symptoms in the post-prostatectomy setting are understudied. The correlation between patient-reported urinary symptoms during RT and bladder dosimetry are the focus of this analysis. 90 consecutive patients treated from 2010-2015 with post-prostatectomy image-guided IMRT at a single institution were included. Patient-reported urinary symptoms using the validated Prostate Cancer Symptom Indices (PCSI) were collected pre-RT and weekly during treatment. PCSI assessed urinary frequency, urgency, flow, dysuria, incontinence, and nocturia graded on a Likert scale of 1 to 4 or 5. For this analysis, a ≥2 point increase in a symptom at any time during treatment compared to baseline was considered a clinically significant toxicity. Doses to the bladder and bladder wall were compared for patients who developed each urinary symptom vs those who did not. Receiver-operator curves were generated for each of those comparisons and the area under the curve (AUC) was used to assess the strength of the correlation. Patients were treated to a median dose of 66.6 Gy and 56% received concurrent ADT. Median time from surgery to RT was 1.6 years. Whole bladder doses (V10-V50) were correlated with worsening of urinary frequency, nocturia, incontinence, and urgency (Table) with AUC of 0.58-0.67. Higher bladder doses (≥V60) had a less strong association with AUC 0.55-0.67. There was no clear association between bladder dosimetry and urinary flow or dysuria. Results were similar with whole bladder and bladder wall dosimetry. In the setting of post-prostatectomy IMRT, low and medium doses to the bladder are correlated with acute worsening of urinary frequency, nocturia and urgency. These findings add to the understanding of bladder dose constraints and can help minimize acute urinary toxicity.Abstract 2619; TableWhole bladder dosimetry correlations with urinary symptomsSymptomVxAUCNo Toxicity (mean ± standard deviation)Toxicity (mean ± standard deviation)FrequencyV10 (cc)0.65106 ± 45144 ± 71V50 (cc)0.6266 ± 2677 ± 27NocturiaV10 (cc)0.64107 ± 50132 ± 56V50 (cc)0.6365 ± 2578 ± 32UrgencyV10 (%)0.6490 ± 1695 ± 13V50 (%)0.6556 ± 1968 ± 22IncontinenceV10 (%)0.5891 ± 1695 ± 9V50 (%)0.5959 ± 2165 ± 20 Open table in a new tab

A dosimetric dnalysis of flattening-filter-free mode linear accelerator-based stereotactic body radiation therapy and HDR brachytherapy for prostate cancer

Purpose: Prior studies have reported that linear accelerator (LINAC)-based stereotactic body radiation therapy (SBRT) plans for prostate cancer are unable to achieve comparable intraprostatic doses to high-dose-rate brachytherapy (HDR). However, the utilization of flattening-filter-free (FFF) beams provides superior dose distributions compared with flattened beams. The purpose of this study was to test the feasibility of achieving the high intraprostatic doses observed in HDR by utilizing LINAC - based SBRT with FFF beams. Methods: We randomly selected 10 patients with localized prostate cancer previously treated at our institution in 2013. FFF-mode LINAC-based SBRT and simulated HDR (using virtual HDR catheters) plans were generated for each patient. The planning target volume (PTV) V100, V125, V150 and V200 values were compared between the two plans using the two-sided paired samples t-test. Results: Regarding the PTV coverage, the mean V100 was slightly higher for SBRT at 96.47% compared with 94.68% for HDR (p = 0.003). The V125 (61.69% versus 66.51%, p = 0.004) and V200 (15.06% versus 19.66%, p < 0.001) were slightly lower for SBRT. There were no significant differences in V150 between the two plans (47.59% versus 49.8%, p = 0.375). Rectal and bladder dosimetry were also comparable between the two modalities, though the rectal maximum dose was lower in the SBRT plan (99.6% versus 103.66%, p = 0.006) and the dose to 15cc of bladder was lower in the HDR plan (96.34% versus 78.18%, p = 0.005). Conclusion: Utilization of FFF mode LINAC-based SBRT allows for achievable dosimetry that is very similar to high dose rate brachytherapy. Further studies are warranted regarding the safety and efficacy of this modality.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identify anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.

Urethral and bladder dosimetry of total and focal salvage Iodine-125 prostate brachytherapy: Late toxicity and dose constraints

IntroductionSalvage Iodine-125 brachytherapy (I-125-BT) constitutes a curative treatment approach for patients with organ-confined recurrent prostate cancer after primary radiotherapy. Currently, focal salvage (FS) instead of whole-gland or total salvage (TS) is being investigated, to reduce severe toxicity associated with cumulative radiation dose. Differences in urethral and bladder dosimetry and constraints to reduce late (>90days) genitourinary (GU) toxicity are presented here. Materials and methodsDosimetry on intraoperative ultrasound (US) of 20 FS and 28 TS patients was compared. The prostate, bladder, urethra and bulbomembranous (BM) urethra were delineated. Toxicity was assessed using the CTCAE version 4.0. Dose constraints to reduce toxicity in TS patients were evaluated with receiver operating characteristic (ROC) analysis. ResultsFS I-125 BT significantly reduces bladder and urethral dose compared to TS. Grade 3 GU toxicity occurred once in the FS group. For TS patients late severe (⩾grade 3) GU toxicity was frequent (38% in the total 61 patients and 56% in the 27 analyzed patients). TS patients with ⩾grade 3 GU toxicity showed higher bladder D2cc than TS patients without toxicity (median 43Gy) (p=0.02). The urethral V100 was significantly higher in TS patients with several toxicity profiles: ⩾grade 3 urethral strictures, ⩾grade 2 urinary retention and multiple ⩾grade 2 GU toxicity events. Dose to the BM urethra did not show a relation with stricture formation. ROC-analysis indicated a bladder D2cc <70Gy to prevent ⩾grade 3 GU toxicity (AUC 0.76, 95%CI: 0.56–0.96, p=0.02). A urethral V100 <0.40cc (AUC from 0.73–0.91, p=0.003–0.05) could prevent other late GU toxicity. ConclusionFS I-125 BT reduces urethral and bladder dose significantly compared to TS. With TS, there is an increased risk of cumulative dose and severe GU toxicity. Based on these findings, bladder D2cc should be below 70Gy and urethral V100 below 0.40cc.

Dosimetry, clinical factors and medication intake influencing urinary symptoms after prostate radiotherapy: An analysis of data from the RADAR prostate radiotherapy trial

Purpose/objectiveTo identify dosimetry, clinical factors and medication intake impacting urinary symptoms after prostate radiotherapy. Material and methodsData describing clinical factors and bladder dosimetry (reduced with principal component (PC) analysis) for 754 patients treated with external beam radiotherapy accrued by TROG 03.04 RADAR prostate radiotherapy trial were available for analysis. Urinary symptoms (frequency, incontinence, dysuria and haematuria) were prospectively assessed using LENT-SOMA to a median of 72months. The endpoints assessed were prevalence (grade ⩾1) at the end of radiotherapy (representing acute symptoms), at 18-, 36- and 54-month follow-ups (representing late symptoms) and peak late incidence including only grade ⩾2. Impact of factors was assessed using multivariate logistic regression models with correction for over-optimism. ResultsBaseline symptoms, non-insulin dependent diabetes mellitus, age and PC1 (correlated to the mean dose) impact symptoms at >1 timepoints. Associations at a single timepoint were found for cerebrovascular condition, ECOG status and non-steroidal anti-inflammatory drug intake. Peak incidence analysis shows the impact of baseline, bowel and cerebrovascular condition and smoking status. ConclusionsThe prevalence and incidence analysis provide a complementary view for urinary symptom prediction. Sustained impacts across time points were found for several factors while some associations were not repeated at different time points suggesting poorer or transient impact.

Anthropomorphic phantom to investigate the bladder dose in gynecological high-dose-rate brachytherapy.

This study presents a prototype of a phantom appropriate for experimental bladder dosimetry. This work presents details of the phantom construction and dosimetric results obtained using radiochromic film and optically stimulated luminescence dosimeters (OSLDs). The phantom was constructed of polymethyl methacrylate. Two artificial bladders were three-dimensional printed using previous computed tomography images. Radiochromic films and OSLDs were positioned on the artificial bladder walls, and the applicators were placed according to the original computed tomography image. The prototype phantom simulated the behavior of the dose on the bladder surface, enabling bladder movement in all directions. The dosimetric study that was performed using radiochromic film and OSLDs exhibited concordance, in most cases, with the results obtained from the planning system. The methodology presented offers conditions for researchers to investigate more accurately the behavior of the dose on the bladder surface during intracavitary brachytherapy procedures.

Impact of the radiotherapy technique on the correlation between dose–volume histograms of the bladder wall defined on MRI imaging and dose–volume/surface histograms in prostate cancer patients

The aim of this study was to evaluate the correlation between the ‘true’ absolute and relative dose–volume histograms (DVHs) of the bladder wall, dose–wall histogram (DWH) defined on MRI imaging and other surrogates of bladder dosimetry in prostate cancer patients, planned both with 3D-conformal and intensity-modulated radiation therapy (IMRT) techniques. For 17 prostate cancer patients, previously treated with radical intent, CT and MRI scans were acquired and matched. The contours of bladder walls were drawn by using MRI images. External bladder surfaces were then used to generate artificial bladder walls by performing automatic contractions of 5, 7 and 10 mm. For each patient a 3D conformal radiotherapy (3DCRT) and an IMRT treatment plan was generated with a prescription dose of 77.4 Gy (1.8 Gy/fr) and DVH of the whole bladder of the artificial walls (DVH-5/10) and dose–surface histograms (DSHs) were calculated and compared against the DWH in absolute and relative value, for both treatment planning techniques. A specific software (VODCA v. 4.4.0, MSS Inc.) was used for calculating the dose–volume/surface histogram. Correlation was quantified for selected dose–volume/surface parameters by the Spearman correlation coefficient. The agreement between %DWH and DVH5, DVH7 and DVH10 was found to be very good (maximum average deviations below 2%, SD < 5%): DVH5 showed the best agreement. The correlation was slightly better for absolute (R = 0.80–0.94) compared to relative (R = 0.66–0.92) histograms. The DSH was also found to be highly correlated with the DWH, although slightly higher deviations were generally found. The DVH was not a good surrogate of the DWH (R < 0.7 for most of parameters). When comparing the two treatment techniques, more pronounced differences between relative histograms were seen for IMRT with respect to 3DCRT (p < 0.0001).

Correlation between surrogates of bladder dosimetry and dose–volume histograms of the bladder wall defined on MRI in prostate cancer radiotherapy

The correlation between bladder dose–wall-histogram (DWH) and dose–volume-histogram (DVH), dose–surface-histogram (DSH), and DVH-5/10 was investigated in a group of 28 patients; bladder walls were drawn on T2-MRI. DVH showed the poorest correlation with DWH; DSH or DVH-5/10 should be preferred in planning; absolute DVH may be used for radical patients, although less robust.