Predicting Radiation Pneumonitis After Chemoradiation Therapy for Lung Cancer: An International Individual Patient Data Meta-analysis

Abstract

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 was obtained on 836 patients who underwent CCRT in Europe, North America and Asia. Patients were randomly divided into training and validation sets (2/3 vs. 1/3 of patients). Factors predictive of symptomatic pneumonitis (grade ≥ 2 by one 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 radiotherapy dose was 60 Gy, and median follow-up 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 (V20) [OR:1.03 per 1% increase, p=0.008], and carboplatin/paclitaxel chemotherapy [OR:3.33, p<0.001], with a trend for age [OR: 1.24 per decade, p=0.09]; 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, V20, 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.

Validation and optimization of a predictive model for radiation pneumonitis in patients with lung cancer

“…Due to the lack of high-risk patients in our cohort, only the validation of the STRIPE score could be investigated to distinguish low-risk versus intermediate risk patients. A similar discriminatory power of the STRIPE score was observed as in the original study (AUC 0.68 in the current cohort vs. 0.66 in the original cohort) (12). The addition of smoking status to the model strengthened its discriminatory ability to predict RP (AUC 0.72 vs. 0.68 for STRIPE score only) (Table III).…”

“…Patient demographics, clinical and treatment characteristics, and STRIPE scores are indicated in Table I. No patients were at a high risk of developing RP according to the STRIPE score (12), as concurrent treatment with carboplatin-paclitaxel was not used in the present patient cohort. However, 16 patients (23%) developed grade ≥2 RP.…”

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers

“…Although concurrent chemotherapy improves survival by approximately 5% at 5 years, it also significantly increases the risk of toxicity (2). Among the potential toxicities, pneumonitis and esophagitis are the best understood and for these reliable dose-volume constraints are routinely considered during radiotherapy planning (3,4).…”

CT ventilation functional image-based IMRT treatment plans are comparable to SPECT ventilation functional image-based plans

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Radiation-induced lung injury has detrimental effects on lung function and is associated with radiation pneumonitis, which is a potentially fatal toxicity and occurs in up to 30% of lung cancer patients treated with radiotherapy [1,2]. Radiotherapy that selectively avoids irradiating highly-functional lung regions may reduce pulmonary toxicity [3][4][5].

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