1. Cardiac events after treatment with high dose radiation therapy +/- chemotherapy for non-small cell lung cancer Linglong Tang, Anwen Liu, Daniel Gomez, Quynh-Nhu Nguyen, Lawrence B. Levy,Ting Xu, Ritsuko Komaki, Zhongxing Liao ASTRO 56 th Annual Meeting San Francisco 2014-9-14

2. The incidence of new cardiac toxicity is 53.1% (n=160) of 301 NSCLC patients. The incidence of new-onset grade 2 or above cardiac toxicity were 47.8%. The median time of developing grade 2 or above cardiac toxicity was 8.1 month. Results Cardiac Events N (%)Median time(month) Cardiac Toxicity144(47.8)8.1 Pericardial effusion (PCE)118(39.2)8.7 Ischemia17(5.6)8.8 Arrhythmia25(8.3)7.8 Heart Failure12(4.0)4.8 Valve Abnormalities21(7.0)9.6

3. Distribution of patient characteristics, clinical, and disease factors and their association with PCE Characteristic N (% of column) HR95% CIP IMRT (% of row) PSPT (% of row) P Age 0.800.53-1.190.26 <0.01 <70195(64.8) 127(73.4)68(53.1) >=70106(35.2) 46(26.6)60(46.9) Gender 1.120.78-1.620.53 0.64 Male175(58.1) 103(59.5)72(56.3) Female126(41.9) 70(40.5)56(43.8) Smoking 0.700.40-1.220.21 0.33 Yes272(90.4) 159(91.9)113(88.3) No29(9.6) 14(8.1)15(11.7) Diabetes mellitus 0.610.33-1.140.12 1.0 Yes39(13.2) 22(12.7)17(13.3) No262(86.8) 151(87.3)111(86.7) Prior cardiac disease 0.760.53-1.090.14 0.12 Yes182(60.5) 98(56.6)84(65.6) No119(39.5) 75(43.4)44(34.4) Hypertension 0.800.56-1.150.23 0.30 Yes 151(50.2) 82(47.4)69(53.9) No 150(49.8) 91(52.6)59(46.1) Location of tumor 0.960.71-1.300.78 <0.01 Left 117(38.9) 59(34.1)58(45.3) Right 169(56.1) 111(64.2)58(45.3) others 15(5.0) 3(1.7)12(9.4) Stage 1.080.69-1.680.74 <0.01 I-II33(11.0) 15(8.7)18(14.1) III- IV248(82.4) 158(91.3)90(70.3) Recurrence20(6.6) 020(15.6) Chemotherapy 1.710.89-3.260.11 <0.01 Yes258(85.7) 160(92.5)98(76.6) No43(14.3) 13(7.5)30(23.4)

4. Dose-volume parameters Multiple heart V5-V75 had cut off values associated with risk of PCE Two important constraints were selected using the martingale residuals: –V5=7% – V75=1%. The 2-year incidence of PCE Group 1 patients 25.5% (n=55) Group 2 patients 41.6% (n=214) Group 3 patients 63.2% (n=32) Effect of DVH group on PCE

5. Effect of radiotherapy technique and adjuvant chemotherapy on PCE Effect of adjuvant chemotherapy on PCE Effect of Radiotherapy technique on PCE There was no difference in the incidence of PCE between IMRT and Proton therapy group The patients with pericarditis-free time more than 2.5 months were analyzed, it was found that adjuvant chemotherapy increase the risk of PCE by univariate analysis (P=0.024)

6. The incidence of developing cardiac events after high-dose RT for NSCLC is approximately 50%, with the most common events being pericardial effusion. Dose-volume parameter was the independent predictive factor for PCE. The risk of PCE varied significantly, depending on radiation dose-volume parameters. Conclusion