Clinical investigation: lung
Outcome and prognostic factors for patients with non-small-cell lung cancer and severe radiation pneumonitis

https://doi.org/10.1016/S0360-3016(02)02994-2Get rights and content

Abstract

Purpose: Radiation pneumonitis is a serious complication that develops after thoracic irradiation. The purpose of this study was to identify prognostic factors for severe radiation pneumonitis in patients with non-small-cell lung cancer.

Methods and Materials: The medical records of patients with non-small-cell lung cancer and severe radiation pneumonitis were reviewed. Variables were analyzed by univariate and stepwise multivariate analysis using the Cox regression model.

Results: Among the 31 patients, the mortality rate approached 50% in the first 2 months after the onset of radiation pneumonitis. The variables significantly associated with survival in the univariate analysis were tumor histologic feature, grade and extent (out-of-field or in-field) of radiation pneumonitis, oxygenation index, and serum albumin (<35 g/L or ≥35 g/L), and uric acid levels at the onset of radiation pneumonitis. Only the extent of radiation pneumonitis and serum albumin level were independently associated with survival in the multivariate analysis.

Conclusion: The mortality rate of non-small-cell lung cancer patients with severe radiation pneumonitis is extremely high, and survival is much shorter in patients with out-of-field radiation pneumonitis or a low serum albumin level at the onset. Additional studies to investigate the factors precipitating out-of-field radiation pneumonitis should improve the management of irradiation complications.

Introduction

Lung cancer is the cause of 12.8% of all cancer cases and 17.8% of cancer deaths worldwide (1). About two-thirds of lung cancer cases are histologically non-small-cell lung cancer (NSCLC) (1). Of those with NSCLC, 30–40% have locally advanced or inoperable disease, for which the mainstay of treatment remains thoracic irradiation (RT) (2). The use of RT is constrained by pulmonary complications, especially radiation pneumonitis (3). Usually, the manifestations of radiation pneumonitis are mild, such as dry cough, fever, and mild dyspnea 3, 4, 5. However, 8–13% of NSCLC patients develop severe respiratory distress 2, 3, 6, 7, 8, and about 1.6% die after thoracic RT (2). Because of these disastrous effects, treatment breaks or dose reductions are often required, limiting the success of the therapy.

Many factors have been demonstrated to increase the risk of pulmonary radiation damage, including chemotherapy with anthracycline antibiotics 9, 10, large fractional and total doses of radiation 11, 12, hypofractionation 11, 12, concurrent chemoradiotherapy 12, 13, preexisting lung disease 14, 15, low performance status (14), prior RT (16), and steroid withdrawal (17). However, few studies have explored the outcome and factors influencing the prognosis of NSCLC patients with radiation pneumonitis, thus precluding the development of preventive or interventional strategies. This study was conducted to analyze the survival of, and prognostic factors for, NSCLC patients with radiation pneumonitis.

Section snippets

Methods and materials

Between August 1995 and July 2001, patients with histologically or cytologically documented NSCLC, who were receiving thoracic RT at the National Taiwan University Hospital (a 1500-bed medical center), were identified and their medical records reviewed. The diagnosis of radiation pneumonitis was defined as the presence of clinical symptoms, such as nonproductive cough and dyspnea; radiographically evident infiltrate in the lung involving an irradiated area; and clinical exclusion of pneumonia,

Results

Between August 1995 and July 2001, 514 patients with NSCLC underwent thoracic RT. Follow-up data were available for 463 patients. Of these, 31 (6.7%) developed severe radiation pneumonitis. The patient characteristics are listed in Table 2. RT was delivered to all 31 patients using AP-PA fields. In 15 patients (48%), the fractions of RT were >2.67 Gy. Nine patients (29%) received total radiation doses >55 Gy, 7 patients (23%) received total doses <45 Gy, and the remaining 15 (48%), total doses

Discussion

In our study, the incidence of severe radiation pneumonitis was 6.7%, lower than in previous reports 2, 6. This was probably because of the smaller total radiation doses used in our patients. The median survival time of the 27 patients who died after developing severe radiation pneumonitis was 58 days, much shorter than the life expectancy of patients with any stage of NSCLC who do not have radiation pneumonitis (20). After the exclusion of biases introduced by patient characteristics, such as

Conclusion

In our study, the mortality rate associated with severe radiation pneumonitis was extremely high in NSCLC patients. Survival was much shorter for patients with out-of-field radiation pneumonitis or a low serum albumin level at the condition’s onset than for their counterparts. Additional large-scale studies to determine the risk factors for out-of-field radiation pneumonitis may help minimize the most harmful effects of RT and, thus, improve its therapeutic benefit.

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