3D-CRT
Effects of radiotherapy and chemotherapy on lung function in patients with non–small-cell lung cancer

Presented at the 3rd S. Takahashi Memorial International Workshop on 3-Dimensional Conformal Radiotherapy, December 8–10, 2001, Nagoya, Japan.
https://doi.org/10.1016/S0360-3016(03)00077-4Get rights and content

Abstract

Purpose

To evaluate the effects of chemoradiation on objective tests of pulmonary function.

Methods and materials

One hundred lung cancer patients treated in five protocols between 1992 and 2000 with combinations of thoracic radiotherapy (RT) and chemotherapy were evaluated with pre- and post-RT pulmonary function tests. The pulmonary function tests were analyzed for changes in measures of obstruction (forced expiratory volume in 1 s per unit of vital capacity [FEV1/VC]), restriction (total lung capacity [TLC]), and diffusing capacity (diffusing capacity for carbon monoxide [DLCO]). The use and timing of chemotherapy and RT, as well as patient, tumor, and treatment factors, were evaluated using univariate and multivariate analyses.

Results

No treatment or patient factors were significantly associated with changes in FEV1/VC. Chemotherapy with RT, compared with RT alone, was associated with a lower post-RT TLC (92% vs. 107%, p = 0.002). Nodal status (N2-N3 vs. N1),tumor location (central vs. peripheral), use of ≥6 treatment fields, and tumor volume ≥100 cm3 were also associated with a significantly lower post-RT TLC. On univariate analysis, the use of any chemotherapy (p = 0.029) and the use of concurrent vs. sequential chemotherapy (p = 0.028) were predictive of a lower post-RT DLCO. Patient age ≥60 years, nodal status (N2-N3 vs. N0-N1), tumor volume ≥100 cm3, tumor location (central vs. peripheral), and use of ≥6 treatment fields were also associated with a significantly lower post-RT DLCO. The fractional volume of irradiated normal lung correlated with the decrease in DLCO (p <0.001), with a 1.3% DLCO decline for each 1% of total lung volume that received >20 Gy.

Conclusion

The addition of chemotherapy to RT significantly exacerbates the post-RT decrease in TLC and DLCO. The greatest decrease in DLCO occurs in patients treated with concurrent chemoradiation.

Introduction

Thoracic radiotherapy (RT) is associated with significant alterations in lung function as assessed by objective pulmonary function tests (PFTs) 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. The extent of residual lung function is a major determinant of a patient’s functional status after treatment. This is particularly true of patients with lung cancer who frequently have pretreatment pulmonary compromise secondary to both malignancy and coexisting lung disease. It is increasingly important to understand the relationship between thoracic RT and the decline in lung function in the setting of aggressive concurrent chemoradiation regimens. After RT alone, the decline in diffusion capacity has been reported to range from 10% to 34% (1). Greater declines in PFTs have been reported after combined therapy with chemotherapy and RT compared with RT alone 2, 6, 11, 12. Among combined modality regimens, concurrent chemoradiation is expected to be more toxic than sequential treatment.

Patients treated with thoracic RT are usually a heterogeneous group that has received different combinations of RT and chemotherapy. However, all the patients in our study were treated in one of five multi-institutional or in-house protocols. All treatments, therefore, fell into a small number of well-defined groups, with all patients within a group receiving the same treatment. This allowed a meaningful comparison of the effects of different combinations of RT and chemotherapy on indexes of lung function.

Section snippets

Patients

One hundred patients with non–small-cell lung cancer were treated in five protocols between 1992 and 2000 with combinations of thoracic RT and chemotherapy and had pre- and posttreatment PFTs. Four of the protocols were the multi-institutional Radiation Therapy Oncology Group (RTOG) 91-06 (7 patients), RTOG 92-04 (23 patients), RTOG 93-11 (19 patients), and RTOG 94-10 (28 patients) trials that evaluated different combinations of chemotherapy and RT and the effects of radiation dose escalation.

Obstruction

Great variation in FEV1/VC after treatment was observed. FEV1/VC decreased in 45 of 93 patients, increased in 46 patients, and was unchanged in 2 patients. The time after treatment had no significant effect on FEV1/VC. Table 3 shows the posttreatment FEV1/VC as a percentage of the pretreatment value in each treatment group. The differences were not statistically significant. No treatment, patient, or tumor factors were significantly associated with FEV1/VC changes. The significance of the

Changes in FEV1

Most previous studies have evaluated the effects of RT on FEV1. FEV1 is highly dependent on the VC. Hence, a low VC can result in a low FEV1 without any airway obstruction. The American Thoracic Society recommends using FEV1/VC as a measure of airway obstruction to account for abnormal VC (16). This is particularly important in evaluating lung function after RT. Lung volumes change after treatment, both because of fibrosis associated with radiation damage and because of reexpansion of a

Conclusion

Thoracic RT is associated with a significant reduction in DLCO. The addition of chemotherapy and, particularly, concurrent chemotherapy to RT exacerbates the decline in diffusion capacity 13, 14, 15, 33, 34, 35, 36.

References (36)

  • J.C. Theuws et al.

    Dose-effect relations for early local pulmonary injury after irradiation for malignant lymphoma, and breast cancer

    Radiother Oncol

    (1998)
  • J.C. Theuws et al.

    Changes in local pulmonary injury up to 48 months after irradiation for lymphoma and breast cancer

    Int J Radiat Oncol Biol Phys

    (2000)
  • Y. Seppenwoolde et al.

    Radiation dose-effect relations and local recovery in perfusion for patients with non-small-cell lung cancer

    Int J Radiat Oncol Biol Phys

    (2000)
  • C. Gridelli et al.

    Thoracic radiotherapy and daily vinorelbine as radiosensitizer in locally advanced non small cell lung cancerA phase I study

    Lung Cancer

    (2000)
  • R. Komaki et al.

    Randomized phase III study of amifostine in patients treated with chemoradiation for inoperable stage II-III non-small cell lung cancer (NSCLC)

    Int J Radiat Oncol Biol Phys

    (2001)
  • L.B. Marks

    The pulmonary effects of thoracic irradiation

    Oncology (Huntingt)

    (1994)
  • J.C. Theuws et al.

    Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphomaA follow-up study

    J Clin Oncol

    (1999)
  • N.C. Choi et al.

    Physiologic changes in pulmonary function after thoracic radiotherapy for patients with lung cancer and role of regional pulmonary function studies in predicting postradiotherapy pulmonary function before radiotherapy

    Cancer Treat Symp

    (1985)
  • Cited by (0)

    Presented at the 3rd Annual Meeting of the American Society for Therapeutic Radiology and Oncology, San Francisco, CA, November 4–7, 2001.

    View full text