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Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

ABSTRACT: Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose.Data were taken from two Scandinavian studies (N=207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to-follow-up: 3.6-6.4y). Within and across cohorts, bladder dose-volume parameters were tested as predictors for GU symptom domains identified from two study-specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (Az).For the identified Incontinence (2-5 symptoms), Obstruction (3-5 symptoms), and Urgency (2-7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (Az: 0.53-0.57) and Urgency (Az: 0.60). For Obstruction, performance increased for the across cohort analysis (Az: 0.61-0.64).Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses.

SUBMITTER: Thor M

PROVIDER: S-EPMC5512537 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

Thor Maria M Olsson Caroline C Oh Jung Hun JH Petersen Stine Elleberg SE Alsadius David D Bentzen Lise L Pettersson Niclas N Muren Ludvig Paul LP Høyer Morten M Steineck Gunnar G Deasy Joseph O JO

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20160212 1

<h4>Background and purpose</h4>Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient-reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose.<h4>Materials and methods</h4>Data were taken from two Scandinavian studies (N=207/276) including men treated with exter ...[more]

PMID: 26879287

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Project description:Gastrointestinal (GI) morbidity after radiotherapy (RT) for prostate cancer is typically addressed by studying specific single symptoms. The aim of this study was to explore the interplay between domains of patient- reported outcomes (PROs) on GI morbidity, and to what extent these are explained by RT dose to the GI tract.The study included men from two Scandinavian studies (N = 211/277) who had undergone primary external beam radiotherapy (EBRT) for localized prostate cancer to 70-78 Gy (2 Gy/fraction). Factor analysis was applied to previously identified PRO-based symptom domains from two study-specific questionnaires. Number of questions: 43; median time to follow-up: 3.6-6.4 years) and dose-response outcome variables were defined from these domains. Dose/volume parameters of the anal sphincter (AS) or the rectum were tested as predictors for each outcome variable using logistic regression with 10-fold cross-validation. Performance was assessed using area under the receiver operating characteristic curve (Az) and model frequency.Outcome variables from Defecation urgency (number of symptoms: 2-3), Fecal leakage (4-6), Mucous (4), and Pain (3-6) were defined. In both cohorts, intermediate rectal doses predicted Defecation urgency (mean Az: 0.53-0.54; Frequency: 70-75%), and near minimum and low AS doses predicted Fecal leakage (mean Az: 0.63-0.67; Frequency: 83-99%). In one cohort, high AS doses predicted Mucous (mean Az: 0.54; Frequency: 96%), whereas in the other, low AS doses and intermediate rectal doses predicted Pain (mean Az: 0.69; Frequency: 28-82%).We have demonstrated that Defecation urgency, Fecal leakage, Mucous, and Pain following primary EBRT for localized prostate cancer primarily are predicted by intermediate rectal doses, low AS doses, high AS doses, or a combination of low AS and intermediate rectal doses, respectively. This suggests that there is a domain-specific dose-response for the GI tract. To reduce risk of GI morbidity, dose distributions of both the AS region and the rectum should, therefore, be considered when prescribing prostate cancer RT.

Project description:When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ?2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (?18%), whereas maximum and mean doses decreased (?0.8 and ?4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ?1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness variations within this range.

Project description:Objective: To investigate predictors of patient-reported urinary incontinence (PRUI) in the first 2 years after post-prostatectomy radiotherapy (PORT) with particular emphasis on possible dose-effect relationships. Patients and Methods: Two-hundred-thirteen patients, whose clinical and dosimetric data were prospectively collected within a registered multi-institutional cohort study, underwent PORT with adjuvant (n = 106) or salvage (n = 107) intent with conventional (n = 123, prescribed dose to the prostatic bed: 66.6-79.8Gy in 1.8-2.0Gy/fr) or moderately hypo- (n = 90, 65.8-76.8Gy in 2.1-2.7Gy/fr) fractionation during the period 2011-2017. PRUI was evaluated through the ICIQ-SF questionnaire filled in at baseline and every 6 months thereafter. The analysis focused on three ICIQ-based clinically relevant endpoints: (a) very frequent leakage (FREQUENCY, ICIQ3 score >3), (b) moderate to severe amount of urine loss (AMOUNT, ICIQ4>2) (c) objective severe symptoms (OBJECTIVE, ICIQ3+4>5). Predictors of the incidence within 2 years for the three endpoints were investigated focusing only on patients without endpoint symptoms at baseline. A uni-variable logistic regression analysis was performed in order to determine the best dose metrics describing PRUI risk in terms of 2-Gy equivalent dose (EQD2) calculated with different α/β values reported in the literature (0.8, 3, 5Gy), and to identify the most significant clinical variables. Variables showing p < 0.20 at uni-variable analysis were entered into a backward stepwise multi-variable logistic regression analysis. Lastly, the goodness of fit and model calibration were evaluated and internally validated. Results: Patients without symptoms at baseline experienced (a), (b), and/or (c) within 2 years in 41/130 (32%), 40/192 (21%), and 41/129 (32%) of the cases, respectively. EQD2 for α/β = 0.8Gy was the best dose metric associated with PRUI. Multi-variable analysis identified baseline incontinence levels as the strongest predictor for all endpoints (p < 0.006). Both FREQUENCY and OBJECTIVE were significantly influenced also by EQD2(α/β = 0.8Gy). The goodness of fit was excellent, as was the calibration; internal calibration confirmed apparent performance. Conclusion: Baseline mild urinary incontinence symptoms strongly modulate the 2-year risk of PRUI. In addition, FREQUENCY is characterized by a marked dose-effect relationship also influencing the trend of OBJECTIVE, with results more reliable than AMOUNT as an objective index. A strong impact of fractionation on severe PRUI after post-prostatectomy radiotherapy also emerged.

Dataset Information

Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

Publications

Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy.

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