ESTRO 36 Abstract Book

S69 ESTRO 36 _______________________________________________________________________________________________

Purpose or Objective Conflicting results have been reported for the combined effect of heart and lung irradiation on the development of radiation pneumonitis (RP). The reported studies based on 3D-conformal radiotherapy considered the whole heart as an organ-at-risk, thereby not distinguishing between dose to the cardiac ventricles and atria. We assessed whether inclusion of incidental dose to these cardiac subvolumes improved the prediction of Grade ≥3 RP. Material and Methods We retrospectively assessed 188 consecutive patients with stage III non-small cell lung cancer (NSCLC) having undergone (chemo-)radiotherapy (≥60 Gy) using intensity- modulated radiation therapy (until 2011) or volumetric- modulated arc therapy (starting in 2011). Most patients (n=182) received 66 Gy in 33 (once-daily) fractions to the primary tumour and involved hilar/mediastinal lymph nodes based on FDG-PET/CT. The lungs and heart (ventricles and atria separately in 156 patients that received a contrast enhanced planning CT) were re- contoured to generate accurate dose-volume histogram (DVH) data. RP was assessed using the Radiation Therapy Oncology Group scoring criteria for pulmonary toxicity. Since high multicollinearity was observed between the DVH parameters, those with the highest Spearman correlation coefficient (Rs) were selected for the modelling procedure. Using a bootstrap approach, clinical parameters [age, gender, performance, smoking status, forced expiratory volume in 1 second, and cardiac comorbidity (i.e., medical history of myocardial infarction, heart failure, valvular heart disease, cardiac arrhythmias and/or hypertension)] and DVH parameters of lungs and heart (assessing atria and ventricles separately and combined) were evaluated for RP prediction. Results Twenty-six patients (13.8%) developed RP (median follow- up 18.4 months). Only the median mean lung dose (MLD) differed between groups (15.3 Gy vs 13.7 Gy for the RP and non-RP group, respectively; p=0.004). Most Rs of the lung DVH parameters exceeded those of the heart DVH parameters and only some lung DVH parameters were significantly correlated with RP [See Figure 1; highest Rs for MLD (0.21; p<0.01)]. Only cardiac comorbidity was borderline associated with RP (p=0.066) on univariate logistic regression analysis. After bootstrap modelling, heart DVH parameters were seldom included in the model predicting Grade ≥3 RP. The optimal model consisted of: MLD (Odds ratio (OR) 1.28 per Gy increase; p=0.03) and cardiac comorbidity (OR 2.45 in case of cardiac comorbidity; p=0.04). The area under the receiver operator characteristic curve was 0.71, with good calibration of the model.

were deformable registered to a reference patient, focusing on the lungs with bone masked. Mean dose distributions were created for patients alive or dead at a set time-point, censored for follow-up. Dose differences were tested for significance with permutation testing. The most significant area defined an anatomical region of interest and individual patient doses collected. A multivariate analysis investigated the importance of this region in patient survival, including tumour size. Cox- regression survival curves were plotted with patients split to those receiving less than or more than the same biologically equivalent dose that optimally split survival in the 20 fraction patients (α/β = 2). Results For 20 fraction patients, from 6 months, a significant difference was seen in the dose difference between patients alive and dead (p<<0.001). The most significant area was in the base of the heart near the origin of the coronary arteries, median dose of 16.3Gy (BED 10.3Gy). Multivariate analysis showed that tumour size was highly significant for patient survival (p<0.001) as was dose received by the anatomical region (p=0.029), HR 1.21 (1.02–1.44), highlighting the importance of dose received by this region. Cox-regression survival curves were plotted with patients split by those receiving more than or less than 8.5Gy, log-rank p<0.001, figure 1A, controlled for tumour size (p<0.001) and age (p=0.11). A cox-regression with the SABR patients split at 6.3Gy (translated BED from the 20 fraction patients) was plotted, figure 1B. A highly significant difference in survival (log-rank p=0.016) was seen where patients receiving more than 6.3Gy showed worse survival. Tumour size was not significant in the SABR group.

Conclusion Dose to a specific region in the base of the base heart predicts for early death in lung cancer patients treated with 55Gy in 20 fractions, as well as for SABR patients treated to 60Gy in 5 fractions. The effect was seen for the same BED (a/b = 2Gy). In the future, we will extend the SABR group and initialise cardiac imaging studies to identify a clinical cause for this effect. OC-0142 Incidental dose to cardiac subvolumes does not improve prediction of radiation pneumonitis in NSCLC R. Wijsman 1 , F. Dankers 1 , E. Troost 2 , A. Hoffmann 2 , J. Bussink 1 1 Radboud University Medical Center, Radiation oncology, Nijmegen, The Netherlands 2 Institute of radiooncology, Helmholtz-Zentrum Dresden- Rossendorf, Dresden, Germany