Clinical investigation: lung
Long-term changes in pulmonary function tests after definitive radiotherapy for lung cancer

Presented at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, New Orleans, LA, October 2002.
https://doi.org/10.1016/S0360-3016(03)00182-2Get rights and content

Abstract

Purpose

To evaluate the long-term changes in pulmonary function tests (PFTs) in patients surviving at least 2 years after definitive radiotherapy (RT) for unresectable lung cancer.

Methods and materials

Between 1992 and 2000, 277 patients were enrolled in a prospective clinical study to relate RT-induced changes in lung function with dosimetric and functional metrics. Of these, 128 received definitive RT for lung cancer, and 13 of these had follow-up PFTs for approximately ≥2 years without evidence of recurrent or progressive cancer. PFTs were obtained before RT and approximately every 6 months after RT. The results were evaluated on the basis of each study’s “percentage of predicted” of normal values (i.e., adjusted for age, gender, height), and a patient’s sequential examinations were compared with their initial study and a percentage of the baseline value was calculated. Follow-up PFTs were available for a median of 38 months (range 23–95). The median patient age was 65 years (range 40–74), 6 patients were men, and 10 were white. Most had Stage T2–T4 and N2–N3. The median RT dose was 71.4 Gy (range 60–73), 6 had twice-daily RT. Four patients received chemotherapy, one concurrent and three neoadjuvant. None of the patients continued to smoke after their treatment. The median pre-RT PFT results were (percentage of predicted) forced expiratory volume in 1 s, 67% (range 24–121); forced vital capacity, 72% (range 45–116); and diffusing capacity of lung for carbon monoxide, 70% (range 41–129).

Results

At 6 months, all PFT values had declined, with some stabilization by 1 year. However, after 1 year, a gradual reduction occurred in all three parameters. Ten patients (77%) developed RT-induced respiratory symptoms (2 cough only, 8 dyspnea) at 2–21 months (median 5) after treatment. Two patients required inhalers, another required long-term steroids and oxygen. Of the 8 patients with dyspnea, 7 had an increase in symptoms beyond 2 years. No patient died of RT-induced pulmonary insufficiency.

Conclusion

RT caused a decline in PFTs that was apparent at 6 months and continued well beyond 1 year. The continued decline in PFTs is suggestive of progressive/evolving RT-induced lung injury. “Late” pulmonary symptoms have also occurred in these patients. Because of the high mortality rate of unresectable lung cancer, few patients can be evaluated for long-term analysis. Additional studies and pooling of data from multiple institutions may help to clarify better the long-term impact of RT on pulmonary function in this subset of patients.

Introduction

Lung cancer is the most common cause of cancer death in the United States, frequently presenting with locally advanced disease 1, 2. Definitive thoracic radiotherapy (RT), typically combined with chemotherapy, is used to treat patients with unresectable disease. The usual doses of RT are often associated with changes in pulmonary function tests (PFTs) and, in some cases, clinical pneumonitis (3). Previously published studies have reported PFT changes 1 year after definitive RT 4, 5. Longer follow-up results are available only for patients treated postoperatively (6). We have prospectively followed a large cohort of patients with malignancies whose RT fields encompassed portions of the thorax to assess, and try to predict, lung function changes. We report the changes in PFTs after definitive RT for lung cancer in patients with approximately ≥2 years follow-up data.

Section snippets

Methods and materials

Since 1992, we have been conducting a prospective clinical study to relate RT-induced changes in lung function with dosimetric and functional metrics. The study was open to all patients receiving thoracic RT with an expected survival ≥12 months, willing to return for regular follow-up evaluations, and without a history of prior RT. The Duke University Medical Center Institutional Review Board approved the study, and all patients provided written informed consent. Between 1992 and 2000, 128

Results

At 6 months, a decline was recorded in the median FEV1, FVC, and DLCO (89%, 89%, and 92% of baseline, respectively; Fig. 1). By 1 year, the results were closer to baseline (FEV1was back to 100%, FVC was at 105%, and DLCO at 90%). Graphs of the entire data set show the median values having a greater recovery than the results for the individual patients, which demonstrate more of a plateau (Fig. 2, Fig. 3, Fig. 4). However, over time, the reduction in all three parameters continued. From 1

Discussion

RT caused a decline in PFTs 6 months after treatment with a partial recovery, or plateau, by 12 months. The recovery of the median values observed was likely due to the limited data points at 1 year. Beyond 1 year, a continued decline occurred in PFTs, suggestive of progressive/evolving RT-induced lung injury. Of the 7 patients with data ≥3 years, all had a progressive decline in PFTs. “Late” pulmonary symptoms also occurred in these patients.

That some patients had improvement in pulmonary

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Supported in part by NIH Grant CA 69579.

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