Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis.
BACKGROUND
Radiation pneumonitis is a dose-limiting toxicity for patients undergoing concurrent chemoradiation therapy (CCRT) for non-small cell lung cancer (NSCLC). We performed an individual patient data meta-analysis to determine factors predictive of clinically significant pneumonitis.


METHODS
After a systematic review of the literature, data were obtained on 836 patients who underwent CCRT in Europe, North America, and Asia. Patients were randomly divided into training and validation sets (two-thirds vs one-third of patients). Factors predictive of symptomatic pneumonitis (grade ≥2 by 1 of several scoring systems) or fatal pneumonitis were evaluated using logistic regression. Recursive partitioning analysis (RPA) was used to define risk groups.


RESULTS
The median radiation therapy dose was 60 Gy, and the median follow-up time was 2.3 years. Most patients received concurrent cisplatin/etoposide (38%) or carboplatin/paclitaxel (26%). The overall rate of symptomatic pneumonitis was 29.8% (n=249), with fatal pneumonitis in 1.9% (n=16). In the training set, factors predictive of symptomatic pneumonitis were lung volume receiving ≥20 Gy (V(20)) (odds ratio [OR] 1.03 per 1% increase, P=.008), and carboplatin/paclitaxel chemotherapy (OR 3.33, P<.001), with a trend for age (OR 1.24 per decade, P=.09); the model remained predictive in the validation set with good discrimination in both datasets (c-statistic >0.65). On RPA, the highest risk of pneumonitis (>50%) was in patients >65 years of age receiving carboplatin/paclitaxel. Predictors of fatal pneumonitis were daily dose >2 Gy, V(20), and lower-lobe tumor location.


CONCLUSIONS
Several treatment-related risk factors predict the development of symptomatic pneumonitis, and elderly patients who undergo CCRT with carboplatin-paclitaxel chemotherapy are at highest risk. Fatal pneumonitis, although uncommon, is related to dosimetric factors and tumor location.
Department of Radiation Oncology, London Regional Cancer Program, London, Canada. david.palma@uwo.ca
David A
DA
Palma
Suresh
S
Senan
Kayoko
K
Tsujino
Robert B
RB
Barriger
Ramesh
R
Rengan
Marta
M
Moreno
Jeffrey D
JD
Bradley
Tae Hyun
TH
Kim
Sara
S
Ramella
Lawrence B
LB
Marks
Luigi
L
De Petris
Larry
L
Stitt
George
G
Rodrigues
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001208:Asia; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D002945:Cisplatin; D003663:Decision Trees; D005047:Etoposide; D005060:Europe; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009656:North America; D017239:Paclitaxel / Q000008:administration & dosage; D017564:Radiation Pneumonitis / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality; D011879:Radiotherapy Dosage
D005047:Etoposide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin