Normal tissue complication models for clinically relevant acute esophagitis (>= grade 2) in patients treated with dose differentiated accelerated radiotherapy (DART-bid)

Background: One of the primary dose-limiting toxicities during thoracic irradiation is acute esophagitis (AE). The aim of this study is to investigate dosimetric and clinical predictors for AE grade >= 2 in patients treated with accelerated radiotherapy for locally advanced non-small cell lung cancer (NSCLC). Patients and methods: 66 NSCLC patients were included in the present analysis: 4 stage II, 44 stage IIIA and 18 stage IIIB. All patients received induction chemotherapy followed by dose differentiated accelerated radiotherapy (DART-bid). Depending on size (mean of three perpendicular diameters) tumors were binned in four dose groups: 6 cm 90 Gy. Patients were treated in 3D target splitting technique. In order to estimate the normal tissue complication probability (NTCP),two Lyman models and the cutoff-logistic regression model were fitted to the data with AE >= grade 2 as statistical endpoint. Inter-model comparison was performed with the corrected Akaike information criterion (AIC(c)),which calculates the model's quality of fit (likelihood value) in relation to its complexity (i.e. number of variables in the model) corrected by the number of patients in the dataset. Toxicity was documented prospectively according to RTOG. Results: The median follow up was 686 days (range 84-2921 days), 23/66 patients (35 %) experienced AE >= grade 2. The actuarial local control rates were 72.6 % and 59.4 % at 2 and 3 years, regional control was 91 % at both time points. The Lyman-MED model (D50 = 32.8 Gy, m = 0.48) and the cutoff dose model (D-c = 38 Gy) provide the most efficient fit to the current dataset. On multivariate analysis V38 (volume of the esophagus that receives 38 Gy or above, 95 %-CI 28.2-57.3) was the most significant predictor of AE >= grade 2 (HR = 1.05, CI 1.01-1.09, p = 0.007). Conclusion: Following high-dose accelerated radiotherapy the rate of AE >= grade 2 is slightly lower than reported for concomitant radio-chemotherapy with the additional benefit of markedly increased loco-regional tumor control. In the current patient cohort the most significant predictor of AE was found to be V38. A second clinically useful parameter in treatment planning may be MED (mean esophageal dose)

Cerebral cortex dose sparing for glioblastoma patients: IMRT versus robust treatment planning

Abstract Background To date, patients with glioblastoma still have a bad median overall survival rate despite radiation dose-escalation and combined modality treatment. Neurocognitive decline is a crucial adverse event which may be linked to high doses to the cortex. In a planning study, we investigated the impact of dose constraints to the cerebral cortex and its relation to the organs at risk for glioblastoma patients. Methods Cortical sparing was implemented into the optimization process for two planning approaches: classical intensity-modulated radiotherapy (IMRT) and robust treatment planning. The plans with and without objectives for cortex sparing where compared based on dose-volume histograms (DVH) data of the main organs at risk. Additionally the cortex volume above a critical threshold of 28.6 Gy was elaborated. Furthermore, IMRT plans were compared with robust treatment plans regarding potential cortex sparing. Results Cortical dose constraints result in a statistically significant reduced cerebral cortex volume above 28.6 Gy without negative effects to the surrounding organs at risk independently of the optimization technique. For IMRT we found a mean volume reduction of doses beyond the threshold of 19%, and 16% for robust treatment planning, respectively. Robust plans delivered sharper dose gradients around the target volume in an order of 3 – 6%. Aside from that the integration of cortical sparing into the optimization process has the potential to reduce the dose around the target volume (4 – 8%). Conclusions We were able to show that dose to the cerebral cortex can be significantly reduced both with robust treatment planning and IMRT while maintaining clinically adequate target coverage and without corrupting any organ at risk. Robust treatment plans delivered more conformal plans compared to IMRT and were superior in regards to cortical sparing