Clinical Investigation
Stereotactic Body Radiation Therapy for Early-Stage Non–Small-Cell Lung Carcinoma: Four-Year Results of a Prospective Phase II Study

https://doi.org/10.1016/j.ijrobp.2008.11.042Get rights and content

Purpose

The 50-month results of a prospective Phase II trial of stereotactic body radiation therapy (SBRT) in medically inoperable patients are reported.

Methods and Materials

A total of 70 medically inoperable patients had clinically staged T1 (34 patients) or T2 (36 patients) (≤7 cm), N0, M0, biopsy-confirmed non–small-cell lung carcinoma (NSCLC) and received SBRT as per our previously published reports. The SBRT treatment dose of 60-66 Gy was prescribed to the 80% isodose volume in three fractions.

Results

Median follow-up was 50.2 months (range, 1.4–64.8 months). Kaplan-Meier local control at 3 years was 88.1%. Regional (nodal) and distant recurrence occurred in 6 (8.6%) and 9 (12.9%) patients, respectively. Median survival (MS) was 32.4 months and 3-year overall survival (OS) was 42.7% (95% confidence interval [95% CI], 31.1–54.3%). Cancer-specific survival at 3 years was 81.7% (95% CI, 70.0–93.4%). For patients with T1 tumors, MS was 38.7 months (95% CI, 25.3–50.2) and for T2 tumors MS was 24.5 months (95% CI, 18.5–37.4) (p = 0.194). Tumor volume (≤5 cc, 5–10 cc, 10–20 cc, >20 cc) did not significantly impact survival: MS was 36.9 months (95% CI, 18.1–42.9), 34.0 (95% CI, 16.9–57.1), 32.8 (95% CI, 21.3–57.8), and 21.4 months (95% CI, 17.8–41.6), respectively (p = 0.712). There was no significant survival difference between patients with peripheral vs. central tumors (MS 33.2 vs. 24.4 months, p = 0.697). Grade 3 to 5 toxicity occurred in 5 of 48 patients with peripheral lung tumors (10.4%) and in 6 of 22 patients (27.3%) with central tumors (Fisher's exact test, p = 0.088).

Conclusion

Based on our study results, use of SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC.

Introduction

Non–small-cell lung cancer (NSCLC) continues to be the leading cause of cancer death. An increasing proportion of patients are presenting with Stage I disease, with the increasing use of computed tomography (CT) scans. Surgical resection of Stage I (T1–2, N0) NSCLC has been the standard of care for patients able to tolerate it, resulting in 5-year overall survival (OS) rates of 60–70% 1, 2, 3. An alternative for patients deemed medically inoperable is primary radiation therapy; however, tumor control and survival rates with this approach have historically been poor. Local control rates with conventional radiotherapy have been less than 50%, with 5-year survival ranging from 10% to 30% 4, 5, 6, 7, 8, 9, 10.

Stereotactic body radiation therapy (SBRT) has emerged as a way to reduce treatment volumes and to facilitate hypofractionation with delivery of large daily tumor doses. The early data with this technique have shown impressive tumor control rates 11, 12, 13, 14, 15, 16, 17, 18. Previously we reported results of a Phase I dose escalation trial in patients with medically inoperable Stage I NSCLC 19, 20. This Phase II trial was designed to extend our results and to treat a larger population of uniformly selected patients using the 60-Gy total dose for T1 tumors (20 Gy × three fractions) and 66-Gy total dose for T2 tumors (22 Gy × three fractions) based on the Phase I trial (21). We now report a 50-month follow-up of patients treated on this protocol.

Section snippets

Eligibility

Patients with pathologically proven NSCLC (squamous cell carcinoma, adenocarcinoma, large-cell carcinoma, bronchoalveolar cell carcinoma, or NSCLC not otherwise specified) were included in this trial. Before study enrollment, patients underwent physical examination, computed tomography (CT) of the chest and upper abdomen, pulmonary function testing, and whole-body 18F-fluorodeoxyglucose positron emission tomography (PET)/CT fusion study. Patients were required to have American Joint Committee

Results

All 70 patients (34 patients with T1 tumors and 36 patients with T2 tumors) enrolled completed therapy as planned and median follow-up was 50.2 months (range, 1.4–64.8 months). Kaplan-Meier local control at 3 years was 88.1% based on four cases of local failure (5.7%). Regional (nodal) and distant recurrence occurred in 6 patients (8.6%) and 9 patients (12.9%), respectively. This included 2 patients who had both local and regional recurrence, 1 patient who had both local and distant recurrence,

Discussion

Surgical treatment of Stage I NSCLC with lobectomy and hilar/mediastinal lymph node removal has been the standard against which alternative treatments have been compared. For patients unable to tolerate this procedure because of medical comorbidities such as chronic obstructive pulmonary disease, cardiac disease, diabetes mellitus, and vascular disease, options include a less extensive surgery such as wedge resection, local radiotherapy, or observation. However, studies have shown that patients

Acknowledgments

Supported by National Institutes of Health Grant No. 5R21CA097721-02. The authors acknowledge the contributions of Marvene Ewing, Colleen DesRosiers, Kathy Tudor, and Jill DeLuca.

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Accepted for oral presentation at American Society of Therapeutic Radiation Oncology 2008.

Conflict of interest: none.

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