Predicting Radiotherapy Impact on Late Bladder Toxicity in Prostate Cancer Patients: An Observational Study

Abstract

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 value of dose to a specific volume of organ at risk (OAR), impact was analyzed through the Mann–Whitney rank-sum test. Logistic regression was used as the final model. The model performance was estimated by taking 1000 samples with replacement from the original dataset and calculating the AUC average. In addition, the calibration plot (Hosmer–Lemeshow goodness-of-fit test) was used to evaluate the performance of internal validation. RStudio Software version 3.3.1 and an in house developed software package “Moddicom” were used. Results: Data from 175 patients were collected. The median follow-up was 39 months (min–max 3.00–113.00). We performed Mann–Whitney rank-sum test with continuity correction in the subset of patients with late bladder toxicity grade ≥ 2: a statistically significant p-value with a Vdose of 51.43 Gy by applying a logistic regression model (coefficient 4.3, p value 0.025) for the prediction of the development of late G ≥ 2 GU toxicity was observed. The performance for the model’s internal validation was evaluated, with an AUC equal to 0.626. Accuracy was estimated through the elaboration of a calibration plot. Conclusions: Our preliminary results could help to optimize treatment planning procedures and customize treatments.

New dosimetric parameters to predict ano-rectal toxicity during radiotherapy treatment

“…In the era of personalized medicine, it is increasingly important to be able to predict toxicity and response to radiation treatment through radiomics and dosimetric parameters [30][31][32][33][34][35].…”

Dose-volume analysis of planned versus accumulated dose as a predictor for late gastrointestinal toxicity in men receiving radiotherapy for high-risk prostate cancer

“…Achieving an AUC of ≥ 0.6 and having a minimum 95 % CI ≥ 0.5 were considered statistically significant by Gulliford et al [23] . Internal validation was accomplished using bootstrapping techniques to obtain the best fit predictors with associated 95 % CI as described in published studies [24] , [25] . Lastly, subgroup analysis was conducted on MVA predictors using the AUC curve to determine the most relevant threshold differentiating the defined toxicity [26] .…”

Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose

“…This could be caused by data imbalance due to fewer toxicity events or LKB-NTCP as the dosimetric variable might not be the only driver of late GU toxicity. Studies have suggested that the inclusion of clinical predictors have improved the overall model performance for the defined GU toxicity (24,38).…”

“…Additionally, different rectal and bladder complications might be the results of various rectal/bladder pathogenic mechanisms as the existing constructed biological models were based on some assumptions and do not consider all involved biological mechanisms (42). Moreover, risk and severity of GI and GU toxicities have been reported to be associated with other factors such as patient's characteristics, hormonal therapy and the intake of medications (38,43,44). Thus, applications of the recommended LKB-NTCP parameters should include similar scenarios to those which the parameters were derived to have a more reliable toxicity estimation (45).…”