Clinical Investigation
Stereotactic Body Radiation Therapy for Early-Stage Non–Small-Cell Lung Cancer: The Pattern of Failure Is Distant

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Background

Stereotactic body radiation therapy (SBRT) represents a substantial paradigm shift in the treatment of patients with medically inoperable Stage I/II non–small-cell lung cancer. We reviewed our experience using either three- or five-fraction SBRT for peripheral or central tumors, respectively.

Methods and Materials

A total of 91 patients signed an institutional review board–approved consent form, were treated with SBRT, and have had ≥6 months of follow-up. Patients were referred for SBRT because of underlying comorbidities (poor performance status in 31 or poor lung function in 52) or refusal of surgery (8 patients). Of the cancers, 83 were peripheral and eight were central. Peripheral cancers received a mean dose of 18 Gy × three fractions. Cancers within 2 cm of the bronchus, esophagus, or brachial plexus were treated with 9 Gy × five fractions.

Results

The median follow-up duration for these patients was 18 months (range, 6–42 months). TNM staging was as follows: 58 patients with T1N0M0, 22 with T2N0M0, 2 with T3N0M0 (chest wall), and 6 with T1N0M1 cancers. The median tumor diameter was 2 cm (range, 1–5 cm). The median forced expiratory volume in 1 s was 46% (range, 17–133%) and the median carbon monoxide diffusing capacity (DLCO) was 49% (range, 15–144%). Two-year local tumor control was achieved in 86% of patients. The predominant pattern of failure was the development of distant metastasis or second lung cancer. The development of distant metastasis was the only significant prognostic factor for overall survival on multivariate analysis.

Conclusions

Local tumor control was shown to be high using SBRT for non–small-cell lung cancer. Overall survival is highly coerrelated with the development of distant metastasis.

Introduction

Stereotactic body radiation therapy (SBRT) represents a substantial paradigm shift in radiation therapy for patients with Stage I non–small-cell lung cancer (NSCLC) who are not candidates for surgical resection. A number of centers have consistently reported high local control rates with minimal side effects. However, the applied dose fractionation schedules vary widely from center to center, ranging from one to 10 fractions and doses of 20 to 60 Gy 1, 2, 3, 4, 5, 6, 7. Since initiating SBRT at our center in 2004, we have used a consistent technique and dose fractionation for a fairly large number of patients. Here we report our results, including patterns of failure, from which to base subsequent treatment.

Section snippets

Methods and Materials

We registered 127 patients treated with SBRT for Stage I NSCLC into our prospective database between April 2004 and July 2008. Each patient signed an informed consent form that was approved by an Institutional Review Board before entry into the registry. A total of 91 patients had at least 6 months of clinical follow-up information and form the basis of this report. Of these patients, 27 also entered into prospective Phase I or II intramural or cooperative group protocols. A total of 83

Results

Patient characteristics are shown in Table 1. The median follow-up was 18 months (range, 6–42 months). TNM staging was as follows: 58 patients with T1N0M0, 22 with T2N0M0, 2 with T3N0M0 (chest wall), and 6 with T1N0M1 cancers. The median tumor diameter was 2 cm (range, 1–5 cm). Patient ages were 31 to 93 years with a median age of 71 years. The median forced expiratory volume in 1 s (FEV1) was 46% (range, 17–133%) and the median carbon monoxide diffusing capacity (DLCO) was 49% (range, 15–144%).

Discussion

The SBRT approach is a promising development in the management of patients with medically inoperable Stage I NSCLC. In general, reported local tumor control rates are 85% to 95% with minimal toxicity (1). Questions remain as to what dose and fractionation schedule to use for optimal results, especially for tumors that are centrally located. A four-fraction scheme is preferred in Japan. The Japanese Clinical Oncology Group (JCOG) recently completed accrual of JCOG 0403, a Phase II study using

Conclusion

Our patients with peripheral lung cancers treated to 18 Gy × three fractions had excellent local control rates with minimal toxicity. For central tumors, our dose fractionation scheme of 9 Gy × five fractions has been safe, but the number of patients treated with this scheme is limited thus far. We plan to determine the maximum tolerated dose to bronchial structures and to correlate this MTD with tumor control through our ongoing in-house Phase I/II protocol. The main determinant of overall

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Conflict of interest: none.

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