Integrated models for the prediction of late genitourinary complaints after high-dose intensity modulated radiotherapy for prostate cancer: Making informed decisions
Abstract Background and purpose To develop predictive models for late radiation-induced hematuria and nocturia allowing a patient individualized estimation of pre-treatment risk. Materials and methods We studied 262 PCa patients treated with curative intensity modulated radiotherapy to the intact prostate or prostate bed. A total of 372 variables were used for prediction modeling, among which 343 genetic variations. Toxicity was scored using an in-house developed toxicity scale. Predictor selection is achieved by the EMLasso procedure, a penalized logistic regression method with an EM algorithm handling missing data and crossvalidation avoiding overfit. Model performance was expressed by the area under the curve (AUC) and by sensitivity and specificity. Results Variables of the model predicting late hematuria (36/262) are bladder volume receiving ⩾75Gy, prostatic transurethral resection and four polymorphisms. (AUC=0.80, sensitivity=83.3%, specificity=61.5%). The AUC drops to 0.67 when the genetic markers are left out. The model that predicts for late nocturia (29/262) contains the minimal clinical target volume (CTV) dose, the CTV volume and three polymorphisms (AUC=0.76, sensitivity=75.9%, specify=67.4%). This model is a better predictor for nocturia compared to the nongenetic model (AUC of 0.60). Conclusions We were able to develop models that predict for the occurrence of late radiation-induced hematuria and nocturia, including genetic factors which might improve the prediction of late urinary toxicity.
In clinical settings, missing data in the covariates occur frequently. For example, some markers are expensive or hard to measure. When this sort of data is used for model selection, the missingness is often resolved through a complete case analysis or a form of single imputation. An alternative sometimes comes in the form of leaving the most damaged covariates out. All these strategies jeopardise the goal of model selection. In earlier work, we have applied the logistic Lasso in combination wit...
Abstract Background and purpose Design a model for prediction of acute dysphagia following intensity-modulated radiotherapy (IMRT) for head and neck cancer. Illustrate the use of the EMLasso technique for model selection. Material and methods Radiation-induced dysphagia was scored using CTCAE v.3.0 in 189 head and neck cancer patients. Clinical data (gender, age, nicotine and alcohol use, diabetes, tumor location), treatment parameters (chemotherapy, surgery involving the primary tumor, lymph no...
The ability to predict individual risk of radiation-induced normal tissue complications is a long sought goal in radiobiology. The last decade saw increasing interest in identifying associations between single nucleotide polymorphisms (SNPs) and normal tissue complication risk. Nevertheless, it remains controversial whether SNPs will be useful predictors of normal tissue radiosensitivity. This paper provides a summary of a scientific debate held at the 31st ESTRO conference in which four scienti...
Purpose To investigate the clinical factors independently predictive of long-term severe urinary sequelae after postprostatectomy radiotherapy. Patients and Methods Between 1993 and 2005, 742 consecutive patients underwent postoperative radiotherapy with either adjuvant ( n = 556; median radiation dose, 70.2 Gy) or salvage ( n = 186; median radiation dose, 72 Gy) intent. Results After a median follow-up of 99 months, the 8-year risk of Grade 2 or greater and Grade 3 late urinary toxicity was alm...
CONTEXT: Prostate cancer (PCa) patients have many options within the realms of surgery or radiation therapy (RT). Technical advancements in RT planning and delivery have yielded different approache ...
Abstract Background Long-term results with salvage radiotherapy (SRT) for a biochemical recurrence after radical prostatectomy (RP) are poor. It has been suggested that radiotherapy doses >70Gy might result in improved outcome. Objective To report on the late toxicity profile and outcome of patients treated with high-dose salvage intensity-modulated radiotherapy (HD-SIMRT) with or without androgen deprivation (AD). Design, setting, and participants Between 1999 and 2008, 136 patients were referr...
Purpose To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical c...
#2Yoshiya Yamada(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 71
Last. Michael J. Zelefsky(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 117
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BACKGROUND. The authors investigated long-term tumor control and toxicity outcomes after high-dose, intensity-modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer. METHODS. Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5-field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse ...
Purpose To report on the interfraction total positioning error of the postoperative prostate bed and to quantify its components (bony misalignment [BM] and prostate bed motion [PBM]) using daily kilovoltage cone-beam computed tomography (CBCT). The role of an adaptive radiotherapy schedule (ART) was investigated. Methods and Materials A total of 547 daily CBCT images from 15 consecutive patients who had been treated with prostate bed radiotherapy were retrospectively analyzed. The positioning er...
Background and purpose: The aim of our study was to elaborate a suitable model on bladder late toxicity in prostate cancer (PC) patients treated by radiotherapy with volumetric technique. Materials and methods: PC patients treated between September 2010 and April 2017 were included in the analysis. An observational study was performed collecting late toxicity data of any grade, according to RTOG and CTCAE 4.03 scales, cumulative dose volumes histograms were exported for each patient. Vdose, the ...
Background: Acute skin toxicity is a common and usually transient side-effect of breast radiotherapy although, if sufficiently severe, it can affect breast cosmesis, aftercare costs and the patient's quality-of-life. The aim of this study was to develop predictive models for acute skin toxicity using published risk factors and externally validate the models in patients recruited into the prospective multi-center REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to red...
Despite the dramatic advancements in pelvic radiotherapy, urinary toxicity remains a significant side-effect. The assessment of clinico-dosimetric predictors of radiation cystitis (RC) based on clinical data has improved substantially over the last decade; however, a thorough understanding of the physiopathogenetic mechanisms underlying the onset of RC, with its variegated acute and late urinary symptoms, is still largely lacking, and data from pre-clinical research is still limited. The aim of ...
Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors....
Last. Martin A. Ebert(UWA: University of Western Australia)H-Index: 26
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Purpose: Dose information from organ sub-regions has been shown to be more predictive of genitourinary toxicity than whole organ dose volume histogram information. This study aimed to identify anatomically-localised regions where 3D dose is associated with genitourinary toxicities in healthy tissues throughout the pelvic anatomy. Methods and Materials: Dose distributions for up to 656 patients of the Trans-Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single...
Last. Renaud de Crevoisier(French Institute of Health and Medical Research)H-Index: 28
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Abstract Purpose To perform bladder dose-surface map (DSM) analysis for (1) identifying symptom-related sub-surfaces (Ssurf) and evaluating their prediction capability of urinary toxicity, (2) comparing DSM with dose-volume map (DVM) (method effect), and (3) assessing the reproducibility of DSM (cohort effect). Methods and materials Urinary toxicities were prospectively analyzed for 254 prostate cancer patients treated with IMRT/IGRT at 78/80 Gy. DSMs were generated by unfolding bladder surfaces...
Last. Klaus Reichardt(USP: University of São Paulo)H-Index: 23
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Abstract Woody biomass can be used for supplying energy as a strategy to mitigate climate change and increase energy security by reducing the dependency on fossil fuels. The aims of this study were: (i) to evaluate the biomass production for energy generation; and (ii) to determine the leaf area index, solar radiation interception and mean annual increment of three perennial woody crops Eucalyptus grandis, Mimosa scabrella and Ateleia glazioviana, grown under four planting spacings in Southern B...
Prostate cancer radiotherapy unavoidably involves the irradiation not only of the target volume, but also of healthy organs-at-risk, neighboring the prostate, likely causing adverse, toxicity-related side-effects. Specifically, in the case of urinary toxicity, these side effects might be associated with a variety of dosimetric, clinical and genetic factors, making its prediction particularly challenging. Given the inconsistency of available data concerning radiation-induced toxicity, it is cruci...
#1Eugenia Mylona(French Institute of Health and Medical Research)H-Index: 4
#2Oscar Acosta(French Institute of Health and Medical Research)H-Index: 21
Last. Renaud de Crevoisier(French Institute of Health and Medical Research)H-Index: 28
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Purpose To apply a voxel-based analysis to identify urethrovesical symptom-related subregions (SRSs) associated with acute and late urinary toxicity in prostate cancer radiation therapy. Methods and Materials Two hundred seventy-two patients with prostate cancer treated with intensity-modulated radiation therapy/image-guided radiation therapy were analyzed prospectively. Each patient's computed tomography imaging was spatially normalized to a common coordinate system via nonrigid registration. T...
#2Andrew Jackson(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 59
Last. Maria Thor(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 16
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Purpose The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thre...