Prognostic Factors in Stereotactic Body Radiotherapy for Non–Small-Cell Lung Cancer

Purpose

To investigate the factors that influence clinical outcomes after stereotactic body radiotherapy (SBRT) for non–small-cell lung cancer (NSCLC).

Methods and Materials

A total of 101 consecutive patients who underwent SBRT with 48 Gy in 4 fractions for histologically confirmed Stage I NSCLC were enrolled in this study. Factors including age, maximal tumor diameter, sex, performance status, operability, histology, and overall treatment time were evaluated with regard to local progression (LP), disease progression (DP), and overall survival (OS) using the Cox proportional hazards model. Prognostic models were built with recursive partitioning analysis.

Results

Three-year OS was 58.6% with a median follow-up of 31.4 months. Cumulative incidence rates of LP and DP were 13.2% and 40.8% at 3 years, respectively. Multivariate analysis demonstrated that tumor diameter was a significant factor in all endpoints of LP, DP, and OS. Other significant factors were age in DP and sex in OS. Recursive partitioning analysis indicated a condition for good prognosis (Class I) as follows: female or T1a (tumor diameter ≤20 mm). When the remaining male patients with T1b–2a (>20 mm) were defined as Class II, 3-year LP, DP, and OS were 6.8%, 23.6%, and 69.9% in recursive partitioning analysis Class I, respectively, whereas these values were 19.9%, 58.3%, and 47.1% in Class II. The differences between the classes were statistically significant.

Conclusions

Tumor diameter and sex were the most significant factors in SBRT for NSCLC. T1a or female patients had good prognosis.

Introduction

Lung cancer is the leading cause of cancer death in Japan (1) and the United States (2). Surgery is accepted as the standard intervention for Stage I non–small-cell lung cancer (NSCLC) (3). Clinical outcomes of conventional radiotherapy for Stage I NSCLC are inferior to those of surgery. The overall survival rate of conventional radiotherapy for medically inoperable patients with Stage I NSCLC is approximately 15% (4).

Stereotactic body radiotherapy (SBRT) is a newly emerging method for treatment of extracranial lesions. Initial reports of SBRT were made by Blomgren et al. in 1995 (5) and by Uematsu et al. in 1998 (6). Initial experience and the results of Phase I trials of SBRT were reported by leading institutions in the early 2000s 7, 8, 9, 10. The results were very promising, with excellent rates of local control, and encouraged other institutions to begin using SBRT for lung cancer. According to a survey by the Japan 3-D Conformal External Beam Radiotherapy Group, 53 institutions had already begun using SBRT in Japan by November 2005, and more than 1000 patients with histologically confirmed NSCLC were treated with SBRT (11).

Local dose is thought to be a significant factor affecting the outcome after SBRT for NSCLC. Onishi et al. (12) reviewed 257 patients who received SBRT for Stage I NSCLC during the period 1995–2004 at 14 institutions in Japan. Significant differences were observed according to biologically effective dose (BED) at the isocenter. The local recurrence rate was 8.4% in patients who received BED of ≥100 Gy, whereas the rate was 42.9% in patients receiving <100 Gy in BED. The 5-year overall survival rate of medically operable patients was 70.8% among those who were treated with a BED of ≥100 Gy, compared with 30.2% among those treated with <100 Gy. Baumann et al. (13) retrospectively reviewed the results of SBRT for 138 patients with medically inoperable Stage I NSCLC treated during the period 1996–2003 at five centers in Sweden and Denmark. The group receiving a dose above 55.6 Gy in equivalent dose in 2-Gy fractions (EQD2) showed a significant survival advantage. According to the authors, 55.6 Gy in EQD2 at the planning target volume (PTV) periphery corresponded to BED 100 Gy at the isocenter, as in the Onishi study.

We started using SBRT for the lung in July 1998 and have performed SBRT in more than 100 patients with histologically confirmed NSCLC using a single-fractionation schedule of 48 Gy in 4 fractions at the isocenter, which corresponds to 105.6 Gy in BED. Although we have prescribed a dose of >100 Gy in BED, the disease progressed in several cases in our 10-year experience of SBRT. Prognostic factors other than local dose should be examined to improve SBRT outcomes for NSCLC.

The present study was performed to investigate the factors that influence clinical outcome after SBRT for lung cancer.