Clinical Investigation
Gamma Knife Stereotactic Radiosurgery as Salvage Therapy After Failure of Whole-Brain Radiotherapy in Patients With Small-Cell Lung Cancer

https://doi.org/10.1016/j.ijrobp.2011.11.059Get rights and content

Purpose

Radiosurgery has been successfully used in selected cases to avoid repeat whole-brain irradiation (WBI) in patients with multiple brain metastases of most solid tumor histological findings. Few data are available for the use of radiosurgery for small-cell lung cancer (SCLC).

Methods and Materials

Between November 1999 and June 2009, 51 patients with SCLC and previous WBI and new brain metastases were treated with GammaKnife stereotactic radiosurgery (GKSRS). A median dose of 18 Gy (range, 10–24 Gy) was prescribed to the margin of each metastasis. Patients were followed with serial imaging. Patient electronic records were reviewed to determine disease-related factors and clinical outcomes after GKSRS. Local and distant brain failure rates, overall survival, and likelihood of neurologic death were determined based on imaging results. The Kaplan-Meier method was used to determine survival and local and distant brain control. Cox proportional hazard regression was performed to determine strength of association between disease-related factors and survival.

Results

Median survival time for the entire cohort was 5.9 months. Local control rates at 1 and 2 years were 57% and 34%, respectively. Distant brain failure rates at 1 and 2 years were 58% and 75%, respectively. Fifty-three percent of patients ultimately died of neurologic death. On multivariate analysis, patients with stable (hazard ratio [HR] = 2.89) or progressive (HR = 6.98) extracranial disease (ECD) had worse overall survival than patients without evidence of ECD (p = 0.00002). Concurrent chemotherapy improved local control (HR = 89; p = 0.006).

Conclusions

GKSRS represents a feasible salvage option in patients with SCLC and brain metastases for whom previous WBI has failed. The status of patients’ ECD is a dominant factor predictive of overall survival. Local control may be inferior to that seen with other cancer histological results, although the use of concurrent chemotherapy may help to improve this.

Introduction

Whole-brain irradiation (WBI) is the standard therapy for treatment of the brain in small-cell lung cancer (SCLC), either in the prophylactic setting or with known brain metastases. The rationale for WBI is primarily due to the high incidence of brain metastases in SCLC and the increased likelihood of a diffuse failure pattern of brain metastases 1, 2, 3. Evidence suggests a modest survival benefit in the setting of both limited stage and extensive stage disease with the addition of prophylactic cranial irradiation (PCI) after complete or substantive partial response to treatment of the primary site 4, 5.

Despite the relative radio-responsive nature of SCLC, disease failure in the brain after previous WBI is not uncommon (4). Historically, salvage options in this setting are limited. Repeated WBI has been reported to be minimally effective in a limited number of patients with recurrent brain metastases of all histological results, and median survival time after reirradiation is short (6). Moreover, there is scant evidence regarding reirradiation of the whole brain for SCLC and few neurocognitive toxicity data for whole-brain reirradiation in general.

GammaKnife stereotactic radiosurgery (GKSRS) has been used successfully in the salvage setting for brain metastases in patients for whom WBI has failed (7). However, given the propensity of SCLC for multiple metastases, the benefit of focal reirradiation and the factors predictive of successful outcome are unknown. The potential to spare patients from high cumulative integral radiation doses of whole-brain reirradiation makes radiosurgical salvage a potentially attractive option to avoid the increased risk of neurocognitive decline. The possibility remains, however, for multiple brain failures outside the SRS-treated lesions, and the timing and pattern of such out of field failure are poorly defined.

At our institution, we have practiced a strategy of radiosurgical salvage of brain metastases in patients with SCLC for whom WBI has previously failed. Those with four or fewer brain metastases are offered radiosurgery for salvage; however, occasionally, patients with greater numbers of metastases have been treated. We report our single-institution series documenting the failure patterns of such an approach, as well as an analysis of the disease-related factors that may affect survival, to help determine which patients may warrant salvage radiosurgery with delay or avoidance of repeat WBI.

Section snippets

Data acquisition

This study was approved by the Wake Forest University Institutional Review Board. The Wake Forest University Medical Center GammaKnife Program Tumor Registry was searched for all patients who received GKSRS and had a diagnosis of SCLC. Two patients who did not previously receive WBI were excluded. Between November 1999 and June 2009, 51 GKSRS procedures were performed at Wake Forest University Baptist Medical Center in Winston-Salem, NC, on patients with SCLC with recurrent brain metastases for

Survival

Median survival time of the entire cohort was 5.9 months. One- and 2-year overall survival rates were 24% and 15%, respectively. Kaplan-Meier plot for overall survival is shown in Figure 1. Multivariate analysis assessing factors that predicted for survival is depicted in Table 2. Multivariate analysis revealed that the status of ECD (stable or progressive vs. absent) at time of salvage GKSRS predicted for overall survival (stable, hazard ratio [HR] = 2.89; progressive, HR = 6.98, p = 0.00002).

Discussion

The role of radiosurgery in patients with SCLC for whom prophylactic or therapeutic WBI has failed is controversial. Thus far, a single additional series has been published evaluating the efficacy of GKSRS in SCLC after WBI failure. In that series, the authors reported a median overall survival time of 18 months, with an overall local control rate of 81% (3). In our series, freedom from local failure was 57% at 1 year, which is substantially worse than that generally seen for brain metastases

Conclusions

GKSRS is a modestly effective salvage treatment option for patients with SCLC for whom previous prophylactic or therapeutic WBI has failed. Patients with absent or stable extracranial oligometastatic disease have improved survival times. Local control may be inferior to that seen with other cancer histological results.

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Conflict of interest: none.

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