Factors Affecting the Risk of Brain Metastasis in Small Cell Lung Cancer With Surgery: Is Prophylactic Cranial Irradiation Necessary for Stage I-III Disease?

Purpose

The use of prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC) with surgical resection has not been fully identified. This study undertook to assess the factors affecting the risk of brain metastases in patients with stage I-III SCLC after surgical resection. The implications of PCI treatment for these patients are discussed.

Methods and Materials

One hundred twenty-six patients treated with surgical resection for stage I-III SCLC from January 1998-December 2009 were retrospectively analyzed to elucidate the risk factors of brain metastases. Log-rank test and Cox regression model were used to determine the risk factors of brain metastases.

Results

The median survival time for this patient population was 34 months, and the 5-year overall survival rate was 34.9%. For the whole group, 23.0% (29/126) of the patients had evidence of metastases to brain. Pathologic stage not only correlated with overall survival but also significantly affected the risk of brain metastases. The 5-year survival rates for patients with pathologic stages I, II, and III were 54.8%, 35.6%, and 14.1%, respectively (P=.001). The frequency of brain metastases in patients with pathologic stages I, II, and III were 6.25% (2/32), 28.2% (11/39), and 29.1% (16/55) (P=.026), respectively. A significant difference in brain metastases between patients with complete resection and incomplete resection was also observed (20.5% vs 42.9%, P=.028). The frequency of brain metastases was not found to be correlated with age, sex, pathologic type, induction chemotherapy, adjuvant chemotherapy, or adjuvant radiation therapy.

Conclusions

Stage I SCLC patients with complete resection had a low incidence of brain metastases and a favorable survival rate. Stage II-III disease had a higher incidence of brain metastases. Thus, PCI might have a role for stage II-III disease but not for stage I disease.

Introduction

Small cell lung cancer (SCLC) is characterized by rapid tumor growth, early dissemination, and a poor prognosis. On the basis of the 2011 NCCN (National Comprehensive Cancer Network) guidelines, surgery is only a recommendation for clinical stage I (T1-2N0) SCLC patients. However, surgical treatment may be given to stage II/III SCLC patients under the following situations: some resectable patients with no definite histopathologic diagnosis after bronchoscopic biopsy and cytologic biopsy, patients with preoperative diagnoses of non-small cell lung cancer (NSCLC), and patients with combined small cell lung cancer because the NSCLC component is less sensitive to chemotherapy and radiation therapy. Additionally, recent studies have reported that multimodality treatment involving surgery achieved a good prognosis in SCLC patients with limited-stage disease.

Brain metastases are common in patients with SCLC. About 15%-20% of SCLC patients had detectable brain metastases at the time of initial diagnosis, and the incidence of brain metastases increased as high as 50%-65% at postmortem examination 1, 2. It has been shown 3, 4, 5, 6, 7 that prophylactic cranial irradiation (PCI) can decrease the incidence of brain metastases and even improve the survival of SCLC patients.

Is PCI necessary for all SCLC patients after surgical resection? Few results have been reported about the frequency of the incidence of brain metastases in surgically treated SCLC. This study retrospectively analyzed 126 SCLC patients with surgical resection in our hospital to assess the risk factors of brain metastases and to discuss the indications for PCI treatment for those patients.