Clinical Investigation
Stereotactic Radiosurgery for Patients With Brain Metastases From Small Cell Lung Cancer

https://doi.org/10.1016/j.ijrobp.2011.01.001Get rights and content

Background

Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients.

Methods

We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival.

Results

The median follow-up from SRS in this patient population was 9 months (1–49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT.

Conclusions

Stereotactic radiosurgery for small-cell lung carcinoma brain metastases provided safe and effective local tumor control in the majority of patients.

Introduction

Lung cancer is the most common cause of cancer mortality worldwide in both men and women (1). Furthermore, lung cancer is the most common source of brain metastasis (2). Small-cell lung cancer (SCLC) accounts for about 10–15% of all lung cancers and occurs predominantly in smokers (3). Although only 10% of patients with SCLC will have brain metastases at diagnosis, the cumulative incidence at 2 years is approximately 50% 4, 5, 6. For this reason, many patients with SCLC receive prophylactic cranial irradiation (PCI), which appears to reduce the incidence of delayed brain metastases and lengthen overall survival (OS) 7, 8. Treatment options for brain metastases include surgical resection, whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), or a combination of these options 9, 10, 11, 12, 13, 14. There are few data in the literature on the experience and efficacy of SRS in the management of brain metastases from SCLC (15). This study updates our institution’s experience using radiosurgery as a treatment option for brain metastases from SCLC.

Section snippets

Methods and Materials

Forty-four patients with brain metastases from a histologically proven primary SCLC underwent SRS between July 1991 and June 2008. Thirty patients were female and 14 were male. The median patient age was 63 years (range, 38–84 years). The median Karnofsky performance status (KPS) at time of treatment was 80 (range, 50–100). Twenty-four patients (55%) had active systemic disease at the time of SRS. The median time to development of brain metastases was 8.5 months from initial diagnosis (range,

Results

The median follow-up from gamma knife SRS in this patient population was 9 months (range, 1–49 months). Thirty-nine (89%) of the 44 patients had died by time of analysis. Five patients died from their systemic disease and 2 had their deaths attributed to intracranial disease. The remaining 32 patients died from unknown or undocumented causes. The median OS in this series was 9 months from time of SRS (Fig. 1).

Multivariate testing using the Cox proportional hazards model revealed two factors

Discussion

Brain metastases are the most common type of intracranial tumor (21). They frequently occur in patients with SCLC and are found in approximately 10% of patients at the time of cancer diagnosis. More than 50% of patients will develop brain spread at 2 years 4, 5, 6. Because of such a high incidence, PCI has been advocated to reduce the development of brain metastases and to lengthen overall survival in patients 5, 7, 22. After brain spread is confirmed, with supportive care and steroids alone

Conclusions

This study represents the largest series of patients with brain metastases from SCLC treated with SRS. The results presented indicate that SRS provided safe and effective local tumor control in patients with metastatic brain lesions from SCLC. Despite aggressive treatment with SRS, these patients still remain at a high risk of distant brain failure. This study does not address the potential role of SRS with or without salvage SRS compared to the role of PCI or WBRT, a possible area for future

References (44)

  • D.M. Parkin et al.

    Global Cancer Statistics

    CA Cancer J Clin

    (2002)
  • J.S. Barnholtz-Sloan et al.

    Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System

    J Clin Oncol

    (2004)
  • R. Govindan et al.

    Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: Analysis of the surveillance, epidemiologic, and end results database

    J Clin Oncol

    (2006)
  • Komaki R. Prophylactic cranial irradiation for small cell carcinoma of the lung. Cancer Treat Symp...
  • R. Arriagada et al.

    Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission

    J Natl Cancer Inst

    (1995)
  • F.R. Hirsch et al.

    Intracranial metastases in small cell carcinoma of the lung: Correlation of clinical and autopsy findings

    Cancer

    (1982)
  • A. Auperin et al.

    Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group

    N Engl J Med

    (1999)
  • B. Slotman et al.

    Prophylactic cranial irradiation in extensive small-cell lung cancer

    N Engl J Med

    (2007)
  • J.S. Loeffler et al.

    Metastatic brain cancer

  • R.A. Patchell et al.

    A randomized trial of surgery in the treatment of single metastases to the brain

    N Engl J Med

    (1990)
  • C.J. Vecht et al.

    Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery?

    Ann Neurol

    (1993)
  • R.A. Patchell et al.

    Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial

    JAMA

    (1998)
  • Cited by (82)

    • Should Stereotactic Radiosurgery Be Considered for Salvage of Intracranial Recurrence after Prophylactic Cranial Irradiation or Whole Brain Radiotherapy in Small Cell Lung Cancer? A Population-Based Analysis and Literature Review

      2020, Journal of Medical Imaging and Radiation Sciences
      Citation Excerpt :

      10% cannot complete the full prescribed course of ReRT [13,14]. One-third do not report ReRT side effects [13]; however, the irreversible neurocognitive decline risked with one course of WBRT is likely to be exaggerated after ReRT [28,32]. Overall, repeat WBRT is unlikely to offer durable control [17].

    View all citing articles on Scopus

    Conflict of interest: Drs. Lunsford and Kondziolka are consultants for Elekta; however, no funds from Elekta were used to perform this study. Dr. Lunsford is also a stockholder in Elekta.

    View full text