Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis

Int J Radiat Oncol Biol Phys. 2013 Feb 1;85(2):444-50. doi: 10.1016/j.ijrobp.2012.04.043. Epub 2012 Jun 9.

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 and materials: 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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Asia
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods
  • Cisplatin
  • Decision Trees
  • Etoposide
  • Europe
  • Female
  • Humans
  • Logistic Models
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • North America
  • Paclitaxel / administration & dosage
  • Radiation Pneumonitis / diagnosis*
  • Radiation Pneumonitis / etiology
  • Radiation Pneumonitis / mortality
  • Radiotherapy Dosage

Substances

  • Etoposide
  • Carboplatin
  • Paclitaxel
  • Cisplatin

Supplementary concepts

  • VP-P protocol