ABSTRACT
<p><b>OBJECTIVE</b>To establish a diagnostic model of protein fingerprint pattern in the cerebrospinal fluid (CSF) for non-small-cell lung cancer (NSCLC) patients with brain metastases.</p><p><b>METHODS</b>The CSF samples were obtained from 29 NSCLC patients with brain metastasis, 23 non-tumor patients and 10 early-stage NSCLC patients without brain metastases for analysis of the protein expression profiles using surface-enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data were then analyzed by Biomarker Wizard software, and the tree analysis patterns were generated using the decision-tree model in Biomarker Patterns software. The diagnostic model was tested for its clinical application.</p><p><b>RESULTS</b>Five protein peaks were identified showing differential expression between patients with brain metastases and those without brain metastases. Combination of the 3 protein peaks (m/z: 8698.00, 1215.32 and 1245.70) could discriminate these two samples with a sensitivity of 100.00% (29/29) and a specificity of 100.00% (23/23). Five proteins were differentially expressed between the NSCLC patients with brain metastases and the non-tumor patients. With one protein peak (m/z: 6050.00), these two samples could be discriminated with a sensitivity of 90.00% (9/10) and a specificity of 78.26% (18/23).</p><p><b>CONCLUSION</b>The established diagnostic model of CSF protein fingerprint pattern provides high sensitivity and specificity in the diagnosis of NSCLC with brain metastasis.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Brain Neoplasms , Cerebrospinal Fluid , Diagnosis , Carcinoma, Non-Small-Cell Lung , Cerebrospinal Fluid , Diagnosis , Pathology , Cerebrospinal Fluid Proteins , Genetics , Decision Trees , Early Detection of Cancer , Gene Expression Profiling , Lung Neoplasms , Cerebrospinal Fluid , Diagnosis , Pathology , Peptide Mapping , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationABSTRACT
<p><b>BACKGROUND</b>Conventional treatment for non-small cell lung cancer (NSCLC) brain metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It might be increased by a potent radiosensitizer such as gemcitabine, which is believed to cross the disrupted blood-brain barrier. The primary objective of this study was to determine the maximum tolerated dose (MTD) of weekly gemcitabine given concurrently with WBRT.</p><p><b>METHODS</b>Patients with BM from NSCLC were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks). Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting dose was 400 mg/m(2), escalated by 100 mg/m(2) increments. At least three patients were included per level. Dose limiting toxicity (DLT) was defined as grade 4 hematological or grade 2 neurological toxicity. When two or more patients experience DLT, the MTD was reached.</p><p><b>RESULTS</b>A total of 16 patients were included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All had more than 3 BM. Up to 600 mg/m(2) (level 3) no neurology toxicity was observed. At 600 mg/m(2) two out of 9 patients developed grade 4 thrombocytopenia. One of the two patients' thrombocytopenia was confused with disseminated intravascular coagulation (DIC). At 700 mg/m(2) two out of 4 patients developed neurotoxicities. One developed grade 3 seizure and cognitive disorder. Another patient developed suspected grade 2 muscle weakness.</p><p><b>CONCLUSIONS</b>The MTD was reached at a dose of 700 mg/m(2). The dose of 600 mg/m(2) would be considered for further study.</p>