Clinical Investigation
Stereotactic Ablative Radiation Therapy for Centrally Located Early Stage or Isolated Parenchymal Recurrences of Non-Small Cell Lung Cancer: How to Fly in a “No Fly Zone”

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Purpose

We extended our previous experience with stereotactic ablative radiation therapy (SABR; 50 Gy in 4 fractions) for centrally located non-small cell lung cancer (NSCLC); explored the use of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen; and suggested modified dose-volume constraints.

Methods and Materials

Four-dimensional computed tomography (4DCT)-based volumetric image-guided SABR was used for 100 patients with biopsy-proven, central T1-T2N0M0 (n=81) or isolated parenchymal recurrence of NSCLC (n=19). All disease was staged with positron emission tomography/CT; all tumors were within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Endpoints were toxicity, overall survival (OS), local and regional control, and distant metastasis.

Results

At a median follow-up time of 30.6 months, median OS time was 55.6 months, and the 3-year OS rate was 70.5%. Three-year cumulative actuarial local, regional, and distant control rates were 96.5%, 87.9%, and 77.2%, respectively. The most common toxicities were chest-wall pain (18% grade 1, 13% grade 2) and radiation pneumonitis (11% grade 2 and 1% grade 3). No patient experienced grade 4 or 5 toxicity. Among the 82 patients receiving 50 Gy in 4 fractions, multivariate analyses showed mean total lung dose >6 Gy, V20 >12%, or ipsilateral lung V30 >15% to independently predict radiation pneumonitis; and 3 of 9 patients with brachial plexus Dmax >35 Gy experienced brachial neuropathy versus none of 73 patients with brachial Dmax <35 Gy (P=.001). Other toxicities were analyzed and new dose-volume constraints are proposed.

Conclusions

SABR for centrally located lesions produces clinical outcomes similar to those for peripheral lesions when normal tissue constraints are respected.

Introduction

Image-guided stereotactic ablative radiation therapy (SABR; also called stereotactic body radiation therapy [SBRT]) is replacing conventional radiation therapy for the treatment of patients with medically inoperable, peripherally located stage I lung cancer 1, 2, 3, 4. A population-based study showed that SABR produced overall survival (OS) and disease-specific survival rates similar to those after lobectomy and better OS than conventional radiation (5). However, for lesions that are centrally located and thus close to critical structures, the use of SABR has been controversial 6, 7, 8, 9, 10, 11, 12, 13. The tumor within a 2-cm radius of the trachea and bronchial tree has been considered a “no fly zone” for high-dose radiation and was excluded from Radiation Therapy Oncology Group (RTOG) protocol 0236 (2) since early results of a phase 2 trial showed a low rate of freedom from grade 3 to 5 toxicity (54% at 2 years after treatment with 60-66 Gy in 3 fractions) (6). Severe bronchial stenosis, hemoptysis, or fistula after SABR for central tumors have been reported 6, 7, 9, 13. However, other hypofractionated regimens have been shown to be safe and well tolerated 8, 10, 11, 12.

We previously reported our preliminary result and proposed dose-volume constraints that used 50 Gy in 4 fractions to treat central lesions (8). We have continued to use SABR for centrally located lesions, and we report here updated information, with long-term follow-up, for 100 patients. We further sought to analyze our dose-volume constraints and modify them if necessary and to explore a new regimen of 70 Gy in 10 fractions for cases in which dose-volume constraints could not be met with the previous regimen.

Section snippets

Patients

From February 2005 to May 2011, 100 patients with centrally located primary stage I or isolated recurrent (T <6 cm, N0, M0), biopsy-confirmed non-small cell lung cancer (NSCLC) that had not been treated with thoracic radiation therapy were prospectively registered in our image-guided SABR program. The retrospective review reported here was approved by the appropriate institutional review board, and all patients provided written informed consent to participate. All tumors were within 2 cm of the

Patient characteristics, survival, and patterns of failure

From Feb 8, 2005, through May 9, 2011, 100 patients with centrally located tumors were treated with SABR; 82 patients (63 patients with primary stage I and 19 patients with isolated recurrent NSCLC after surgical resection) received 50 Gy in 4 fractions, and 18 patients received 70 Gy in 10 fractions (all with primary stage I disease). Patient characteristics are shown in Table 1. Treatment details and the distance between tumors and critical structures are listed in Table 2. At a median

Discussion

In the current study, we found that the use of SABR for 100 patients with tumors near the bronchial tree or other critical structures produced OS and local control rates comparable to those for peripheral lesions treated by us with SABR to 50 Gy in 4 fractions (3). Comparison of our result with those of published studies is listed in Table 3 6, 7, 8, 9, 10, 11, 12. Hence, we propose a reconsideration of the use of SABR for treating centrally located tumors with the use of appropriate

Acknowledgments

We thank the staff of the Thoracic Radiation Oncology section, Division of Radiation Oncology, for their help and Christine Wogan for editorial assistance.

References (25)

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Dr Xu's current address is Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin 150086, PR China.

Drs Li and Xu contributed equally to this manuscript.

This research was supported in part by National Cancer Institute (NCI) Cancer Center Support (core) grant CA016672 and NCI Clinical and Translational Science Award UL1 RR024148 to MD Anderson Cancer Center.

Conflict of interest: none.

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