Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis
Introduction
The skeletal system is one of the most common distant sites of metastasis in non-small cell lung cancer (NSCLC). Approximately 30–40% of patients with advanced lung cancer develop skeletal metastases [1], [2], which may lead to skeletal complications such as pathological fractures, severe bone pain, spinal cord compression, and potentially life-threatening hypercalcemia of malignancy. In the past, the management of bone metastasis in patients with NSCLC seems to have been neglected due to the short life expectancy of patients (less than 6 months) [3], which does not allow for the manifestation of bone complications. However, recent treatment regimens for advanced NSCLC involving platinum-based chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib have prolonged the median survival time, especially in patients with adenocarcinoma [4], [5]. This has led to a high frequency of skeletal related events (SREs) in the remaining lifetime of these patients. Furthermore bone metastasis can reduced quality of life, and increased economic burden. Traditional therapies such as surgical stabilization or radiotherapy only achieve local control for palliation and unfortunately most patients receiving only local therapy die of progressive systemic disease. Currently, no specific agent reduces the tumor burden of skeletal metastases, although there is some data to support that bisphophates can reduce SREs in patients with NSCLC [1], [2], [6], [7]. It is not easy to select a systemic chemotherapy regimen in patients with NSCLC and bone metastasis because adverse prognostic factors such as poor performance status or old age can influence systemic chemotherapy. In breast cancer patients [7] with bone metastasis, coexisting nonosseous metastatic disease has been identified as an important prognostic factor, whereas in prostate cancer patients [8], [9], performance status, tumor grade, hemoglobin level, prostate-specific antigen, and alkaline phosphatase have been found to be prognostic factors.
However there are no studies evaluating prognostic factors in NSCLC with bone metastasis at the time of diagnosis. Therefore, we investigated the frequency of skeletal related events and prognostic factors in NSCLC patients presenting with bone metastasis at the time of diagnosis.
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Patients
We retrospectively investigated 220 NSCLC patients with skeletal metastases at the time of diagnosis at Seoul National University Hospital between January 2000 and August 2007. Among the 220 patients, 9 patients who had only rib metastases and 15 patients who had brain metastases and received radiotherapy were excluded from the SRE analysis.
This study was approved by the Institutional Review Board of Seoul National University Hospital.
Chemotherapy regimens
The first-line chemotherapy regimens administrated were: (1)
Patient characteristics
The baseline characteristics of patients are summarized in Table 1. Among the 196 patients, the median age was 60 years with a range of 25–95 years. The histology of the lung cancer included 128 patients with adenocarcinoma, 33 patients with squamous cell carcinoma, and 35 patients with NSCLC. One hundred seventy-eight patients had multiple skeletal metastases at more than two sites, and 18 patients had single bone lesions. One hundred twenty-six patients presented with initial bone pain at
Discussion
This study showed that progression of bone metastases resulting in SREs was common in patients presenting with initial bone metastases at the time of NSCLC diagnosis. Out of 196 patients with bone metastasis at the time of diagnosis with NSCLC, 86 had initial SRE and 28 (33%) of these had a second SRE during follow-up. Among 110 patients without initial SRE, 47 had one SRE and 16 (34%) had a second SRE during the follow up period. Our study also indicated that initial ECOG performance status,
Conflict of interest statement
The authors have no conflicts of interest to declare.
Author's contributions
HMB conceived and designed the study, led the drafting of the manuscript, did the analysis and interpretation, and approved the final manuscript. TMK and DWK interpreted and analyzed and approved the final manuscript. DSH led the co-drafting interpreted and analyzed and approved the final manuscript. SHY and DSH provided financial and administrative support and approved the final manuscript. YJK participated in the interpretation of the results and approved the final manuscript. DWK, DSH, SCY,
Acknowledgments
This study was supported by a grant of the Innovative Research Institute for Cell Therapy, Republic of Korea (A062260) and National Research Foundation of Korea (NRF) Grant funded by the Korean Government (2010–0009563).
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