Abstract
AimTo model acute rectal toxicity in Intensity Modulated Radiation Therapy (IMRT) for prostate cancer using dosimetry and patient specific characteristics.MethodsA database of 79 prostate cancer patients treated with image guided IMRT was used to fit parameters of Lyman-Kutcher-Burman (LKB) and logistic regression Normal Tissue Complications Probability (NTCP) models to acute grade ≥ 2 rectal toxicities. We used a univariate regression model to find the dosimetric index which was most correlated with toxicity and a multivariate logistic regression model with machine learning algorithm to integrate dosimetry with patient specific characteristics. We used Receiver Operating Characteristics (ROC) analysis and the area under the ROC curve (AUC) to quantify the predictive power of models.ResultsSixteen patients (20.3%) developed acute grade≥2 rectal toxicity. Our best estimate (95% confidence interval) of LKB model parameters for acute rectal toxicity are exponent n=0.13 (0.1–0.16), slope m=0.09 (0.08–0.11), and threshold dose TD50=56.8 (53.7–59.9) Gy. The best dosimetric indices in the univariate logistic regression NTCP model were D25% and V50Gy. The best AUC of dosimetry only modeling was 0.67 (0.54, 0.8). In the multivariate logistic regression two patient specific variables were particularly strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to IMRT, while two additional variables, age and diabetes were weakly correlated. The AUC of the logistic regression NTCP model improved to 0.88 (0.8, 0.96) when patient specific characteristics were included. In a group of 79 patients, 40 took Statins and 39 did not. Among patients who took statins, (4/40)=10% developed acute grade ≥2 rectal toxicity, compared to (12/39)=30.8% who did not take statins (p=0.03). The average and standard deviation of PSA distribution for patients with acute rectal toxicity was PSAtox = 5.77 ± 2.27 and it was PSAnotox = 9.5 ± 7.8 for the remainder (p=0.01).ConclusionsPatient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer.
Highlights
Accurate modeling of the likelihood of complications in radiation therapy is increasingly important due to recent trends to dose escalate and hypofractionate
In the multivariate logistic regression two patient specific variables were strongly correlated with acute rectal toxicity, the use of statin drugs and PSA level prior to Intensity Modulated Radiation Therapy (IMRT), while two additional variables, age and diabetes were weakly correlated
Patient specific characteristics strongly influence the likelihood of acute grade ≥ 2 rectal toxicity in radiation therapy for prostate cancer
Summary
Accurate modeling of the likelihood of complications in radiation therapy is increasingly important due to recent trends to dose escalate and hypofractionate. Because of low incidence of late toxicity in IMRT treatments [1] it is reasonable to expect that avoidance of acute toxicity will become more important in future clinical practice. Compared to late rectal toxicity, higher incidence of acute rectal toxicity means that relatively small databases of IMRT treatments can be used to obtain toxicity models. Our institution accumulated a database of 79 prostate patients who were treated exclusively with an IMRT technique and MRI directed boost dose to the region of the prostate with the greatest disease burden [4]. We observed 16 (20%) acute grade ≥ 2 rectal toxicity events. This number of acute toxicity events is sufficient to permit fitting of Normal Tissue Complications Probability (NTCP) models
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