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 56th Annual Meeting San Francisco 2014-9-14

• 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 Toxicity 144(47.8) 8.1 Pericardial effusion (PCE) 118(39.2) 8.7 Ischemia 17(5.6) 8.8 Arrhythmia 25(8.3) 7.8 Heart Failure 12(4.0) 4.8 Valve Abnormalities 21(7.0) 9.6

Distribution of patient characteristics , clinical, and disease factors and their association with PCE

Characteristic N (% of column) HR 95% CI P IMRT

(% of row)PSPT

(% of row) P

Age   0.80 0.53-1.19 0.26     <0.01<70 195(64.8)       127(73.4) 68(53.1)  >=70 106(35.2)       46(26.6) 60(46.9)  

Gender   1.12 0.78-1.62 0.53     0.64Male 175(58.1)       103(59.5) 72(56.3)  Female 126(41.9)       70(40.5) 56(43.8)  

Smoking   0.70 0.40-1.22 0.21     0.33Yes 272(90.4)       159(91.9) 113(88.3)  No 29(9.6)       14(8.1) 15(11.7)  

Diabetes mellitus   0.61 0.33-1.14 0.12     1.0Yes 39(13.2)       22(12.7) 17(13.3)  No 262(86.8)       151(87.3) 111(86.7)  

Prior cardiac disease   0.76 0.53-1.09 0.14     0.12Yes 182(60.5)       98(56.6) 84(65.6)  No 119(39.5)       75(43.4) 44(34.4)  

Hypertension   0.80 0.56-1.15 0.23     0.30Yes 151(50.2)       82(47.4) 69(53.9)  No 150(49.8)       91(52.6) 59(46.1)  

Location of tumor   0.96 0.71-1.30 0.78     <0.01Left 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   1.08 0.69-1.68 0.74     <0.01I-II 33(11.0)       15(8.7) 18(14.1)  III- IV 248(82.4)       158(91.3) 90(70.3)  Recurrence 20(6.6)       0 20(15.6)  

Chemotherapy   1.71 0.89-3.26 0.11     <0.01Yes 258(85.7)       160(92.5) 98(76.6)  No 43(14.3)       13(7.5) 30(23.4)  

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

Effect of radiotherapy technique and adjuvant chemotherapy on PCE

Effect of  adjuvant chemotherapy on PCEEffect 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)

• 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