Clinical investigation: Lung
Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer

Presented at the 1999 meeting of the American Society for Therapeutic Radiology and Oncology in San Antonio, TX.
https://doi.org/10.1016/S0360-3016(00)00648-9Get rights and content

Abstract

Purpose: To identify factors that may predict for severe radiation pneumonitis or pneumonopathy (RP), we reviewed a set of simple, commonly available characteristics.

Methods and Materials: Medical records of 148 lung cancer patients with good performance status (ECOG 0–1) treated definitively with chemoradiation from 6/92–6/98 at the University of Pennsylvania were reviewed. Actuarial survival and the crude rate of severe radiation pneumonitis were determined as a function of several variables. Potential predictive factors examined included age, gender, histology, stage, pulmonary function, performance status (0 vs. 1), weight loss, tumor location, radiation dose, initial radiation field size, chemotherapy regimen, and timing of chemotherapy. Univariate analysis (log-rank test) was performed for each variable. Multivariate analysis was performed using linear regression.

Results: Median survival for the entire cohort was 14.7 months. Four patients were inevaluable for pneumonitis due to early death from progressive disease. Of the remaining 144 evaluable patients, 12 (8.3%) experienced severe RP. The most significant factor predicting for severe RP was performance status (p < 0.003). The risk of severe RP was 16% for PS-1 patients vs. 2% for PS-0 patients. Women were significantly more likely to develop severe RP than men (p = 0.01). Among 67 patients for whom pre-radiation therapy pulmonary function data were available, forced expiratory volume of the lung in 1 second (FEV1) was also significant (p = 0.03). No patient suffering severe RP had a pretreatment FEV1 > 2.0 liters. The median radiation dose was 59.2 Gy and median initial radiation field size was 228 cm2. Neither radiotherapy factor predicted for RP. Other factors studied, including chemotherapy drugs, and schedule, also were not significant predictors of severe RP.

Conclusions: Pretreatment performance status, gender, and FEV1 are significant predictors of severe radiation pneumonopathy, at least when using conventional radiation fields and doses. Complex radiation dose–volume algorithms that attempt to predict lung complication probabilities should probably incorporate these simply obtained clinical parameters.

Introduction

Radiation therapy is a mainstay of treatment for patients with locally advanced lung cancer 1, 2. Unfortunately, in addition to the disappointing cure rates with definitive radiation therapy (XRT), treatment can cause toxicity which may threaten quality of life. Serious treatment-related side effects are potentially lethal. Radiation pneumonopathy or radiation pneumonitis (RP) is a term used to describe the constellation of clinical, radiographic, and histologic findings reflecting lung injury from radiation. Symptomatic RP can be classified as a continuum of clinical findings ranging from mild cough/exertional dyspnea to death caused by respiratory failure (Table 1). Because locally advanced, unresectable lung cancer is usually rapidly fatal without treatment, most patients and physicians will accept the risk of mild to moderate RP. A very high risk of severe RP, however, may require deviating one’s plan away from standard chemoradiotherapy. Our report thus focuses on the risk of severe RP and attempts to identify factors predicting for this event. We also focus exclusively on patients treated with combined modality treatment (chemoradiotherapy), which has now become the standard of care for good-performance status patients with Stage III lung cancer (3).

Section snippets

Methods and materials

The University of Pennsylvania radiation oncology electronic database (PROCLIPS) was queried for lung cancer patients treated with chemoradiation between 6/92 and 6/98. The starting date for this study was selected to correspond to the time period when chemoradiation replaced XRT alone in the management of most patients with Stage III non–small cell lung carcinoma (NSCLC) in our institution. Our definition of severe RP corresponds most closely to Radiation Therapy Oncology Group (RTOG) Grade ≥

Results

The median overall survival was 14.7 months. Of the 144 patients, 12 experienced severe RP (8.3%). Of these cases, 7 were Grade 3, 3 were Grade 4, and 2 were Grade 5 (fatal).

Discussion

The incidence of moderate-to-severe (RTOG Grade 2 or greater) radiation pneumonitis in patients receiving XRT alone for lung cancer has been estimated to be between 2% and 9% 8, 9, 10, 11. Preclinical data suggest that the combination of chemotherapy and irradiation enhances the risk of pulmonary injury 12, 13. This is supported by clinical data from the RTOG experience, studying a variety of chemoradiation regimens in a series of Phase I, II, and III clinical studies (14). However, not all

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