ESTRO 38 Abstract book

S109 ESTRO 38

be a better indicator for RP for LA-NSCLC patients treated with proton therapy. Further statistical analysis with this data needs to be performed. However, this new dosimetric criteria could potentially help with the RP control in LA-NSCLC treated with proton therapy. PV-0208 Immune-related pneumonitis in NSCLC patients treated with ICI: impact of previous thoracic RT A. Botticella 1 , T. Ibrahim 2 , L. Mezquita 2 , L. Hendriks 2 , J. Le Pavec 3 , R. Ferrara 2 , C. Caramella 4 , S. Champiat 5 , J. Michot 5 , P. Lavaud 2 , P. Gustin 1 , D. Planchard 2 , A. Gazzah 2 , A. Marabelle 5 , E. Deutsch 1 , B. Besse 2 , C. Le Pechoux 1 1 Institut Gustave Roussy, Radiation Oncology Department, Villejuif, France ; 2 Institut Gustave Roussy, Oncology Department, Villejuif, France ; 3 Centre Chirurgical Marie Lannelongue, Laboratoire de Chirurgie Expérimentale-UPRES EA-2705, Plessis Robinson, France ; 4 Institut Gustave Roussy, Radiology Department, Villejuif, France; 5 Institut Gustave Roussy, Département D'Innovation Thérapeutique et des Essais Précoces DITEP, Villejuif, France Purpose or Objective Pneumonitis is a potentially lethal side effect of immune checkpoint inhibitors (ICI), occurring in 1–5% of patients enrolled in clinical trials. Little is known about the interactions between ICI and previous thoracic radiotherapy (RT). This is the aim of the present study. Material and Methods Between December 2012 and November 2017, 318 consecutive non-small cell lung cancer (NSCLC) patients received ICI in our Institution and their charts were retrospectively analyzed. Primary endpoint was to determine whether previous radiotherapy had an effect on pulmonary toxicity. Pulmonary toxicity was retrospectively assessed by Common Terminology Criteria for Adverse Events version 4.0. Results Median follow-up was 32.8 months [95%CI: 5-190]. Median age at the start of ICI was 63 years. 205 patients (64,5%) were males, 103 (32,4%) smokers and 250 (78,6%) with PS ≤1; 206 (64,8%) had adenocarcinoma and 76 (23,9%) squamous; 79 (24,8%) were KRAS mutated, 18 (5,5%) EGFR mutated and 5 (1,6%) ALK positive. PDL1 was ≥ 1% by immunohistochemistry in 86 (27%), negative in 37 (11,6%) and unknown in 196 (61,3%) patients. ICI treatment was median 3 rd line (range: 1-12), 89,4% monotherapy PD-(L)1 inhibition. 72 patients (22,6%) received a thoracic RT: 62 out of the 72 RT patients (87,5%) were irradiated with a curative intent. 53 patients (73,6% of the RT patients) received thoracic 3D-conformal RT or intensity modulated RT (normo- or mildly hypofractionated), whereas 9 received SBRT. 16,7% of the RT patients (12/72) showed a G1-4 immune- related pneumonitis (with a G=>3 of 11,1%), whereas for never-irradiated patients the G1-3 rate of immune-related pneumonitis was 2,4% (6/246), with only 1 G3 toxicity observed and no G>4 (t-test, p 0,001). Median interval between the onset of the immune-related pneumonitis and the end of the RT was 22,4 months. Conclusion NSCLC patients treated with ICI may be at higher risk of developing immune-related pneumonitis if previously treated with curative-intent thoracic RT.

≤ 30-35% and mean lung dose ≤ 20-23Gy; however, these parameters are based on photon therapy. The purpose of this study is to evaluate if such dosimetric predictors for RP still hold for LA-NSCLC patients treated with proton therapy. Material and Methods A total of 129 (46 photon, 83 proton) LA-NSCLC patients treated with concurrent CRT between 2011-2016 were used in the study. In this selected cohort, with a higher rate than clinically observed, 46 (20 photon, 26 proton) were patients that exhibited RP (all grades using CTCAE v4.0) after photon or proton therapy. Dose volume histograms for the uninvolved lung were generated for each patient. The percent lung volume receiving above various dose levels (e.g. V35Gy) were obtained in addition to the traditional V20Gy and mean lung dose. These dosimetric parameters for RP and non-RP patients in photon and proton groups were evaluated with a two- tailed student’s test and compared with the V20Gy and mean lung dose. Receiver Operating Characteristic (ROC) curves were generated for various dose levels. The volumetric constraint for the optimal dosimetric parameter was obtained through analyzing RP and non-RP sensitivity/specificity values. Results For proton patients, a greater separation between the RP and non-RP cohort was observed between V35Gy and V45Gy, when compared with the current clinical standard of V20Gy; however, the greatest difference between RP and non-RP photon patients remains around V20Gy. For proton patients, the maximum difference occurs at V37Gy, with 24.65±4.62% and 18.96±6.38% for RP and non- RP patients, respectively, while V20Gy was 31.63±4.99% and 26.26±7.74% for RP and non-RP patients, respectively. Mean lung dose values were consistent between proton and photon patients. A greater separation between RP and non-RP patients is observed when using V37Gy (p=0.0001) as compared to V20Gy (p=0.002) for proton patients. V20Gy (p=0.024) is significant for photon patients, but V37Gy (p=0.053) is not. V37Gy ROC curve had the highest Area Under the Curve (AUC) value compared with other dose levels for proton patients. Based on sensitivity/specificity, the optimal volume constraint of V37Gy is ≤ 23% for proton therapy and the constraint of V20Gy ≤ 30% is confirmed for photon patients.

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Conclusion While V20Gy is a strong predictor for RP in photon therapy, the volume receiving a higher dose, such as V37Gy, may

SP-0209 Multidisciplinary approaches as the keys to defeat lung cancer G.Scagliotti 1