Genetic polymorphisms in the endothelial nitric oxide synthase gene correlate with overall survival in advanced non-small-cell lung cancer patients treated with platinum-based doublet chemotherapy.

BACKGROUND: Nitric oxide (NO) is a free radical that is involved in carcinogenesis. Endothelial NO, synthesized from L-arginine by endothelial NO synthase (eNOS), inhibits apoptosis and promotes angiogenesis, tumor cell proliferation and metastasis. The aim of this study was to evaluate the influence of polymorphisms in the eNOS gene on prognosis of patients with advanced stage non-small-cell lung cancer (NSCLC). METHODS: Unresectable, chemotherapy naïve stage III or IV NSCLC patients who were treated with standard platinum-containing doublet regimens were analyzed. All individuals were genotyped for the single-nucleotide polymorphism G894T in exon 7 of the eNOS gene and for a variable number of tandem repeats (VNTR) polymorphism in intron 4 that results in a rare smaller allele (a) and a common larger allele (b), to investigate the association between these polymorphisms and clinical outcomes. The primary endpoint was correlation with overall survival. RESULTS: From October 2004 to December 2007, 108 patients (male/female, 66/42; Stage IIIA/IIIB/IV, 6/30/72) aged 29-77 years (median 63) with good performance status were consecutively enrolled in this study. Using Kaplan-Meier estimates, we showed that 5-year overall survival was significantly increased in patients carrying the VNTR a-allele compared with VNTR b/b patients (P = 0.015). In multivariate Cox proportional hazard analysis, the VNTR polymorphism was an independent prognostic factor for survival. CONCLUSIONS: The results support the role of the VNTR polymorphism in intron 4 as a marker for survival in patients with advanced stage NSCLC who are candidates for standard chemotherapy.

Clinical significance of pretreatment C-reactive protein in patients with advanced nonsquamous, non-small cell lung cancer who received gefitinib.

PURPOSE: We examined patients with advanced nonsquamous, non-small cell lung cancer (NSCLC) to evaluate epidermal growth factor receptor (EGFR) mutation status and serum C-reactive protein (CRP) for their associations with response to gefitinib therapy and for prognostic impacts. METHODS: Serum levels of CRP from 79 Japanese patients with advanced nonsquamous NSCLC were measured before the start of gefitinib. We used the peptic nucleic acid-locked nucleic acid clamp method to determine their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. RESULTS: Having CRP-positive serum and having wild-type EGFR were both independent negative predictive factors for the response to gefitinib treatment by multivariate logistic regression model analysis. Having CRP-positive serum and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. CONCLUSIONS: Having CRP-positive serum predicted a lack of response to gefitinib therapy independent of EGFR mutational status. Both CRP-positive serum and wild-type EGFR were independent poor prognostic factors in patients with nonsquamous NSCLC who received gefitinib therapy.

Effect of vascular endothelial growth factor polymorphisms on survival in advanced-stage non-small-cell lung cancer.

Polymorphisms have been identified in the vascular endothelial growth factor (VEGF) gene that may affect VEGF production. We hypothesized that such polymorphisms may correlate with survival outcomes among advanced-stage non-small-cell lung cancer (NSCLC) patients. We evaluated the association between VEGF polymorphisms and overall survival among patients with advanced NSCLC who were treated with at least one cytotoxic regimen at Kyoto University Hospital between 2003 and 2008. We investigated the following VEGF polymorphisms: -460T > C (rs833061), +405G > C (rs2010963), +936C > T (rs3025039), -1154G > A (rs1570360), and -2578C > A (rs699947). Analyses of genotype associations with survival outcomes were performed using Cox proportional models, Kaplan-Meier methods, and the log-rank test. There were 126 patients and 80 deaths. On a Cox regression analysis of a current and former smoker (hazards ratio [HR], 1.422; 95% confidence interval [CI], 1.111-1.859; P = 0.0046), poor performance status (PS) (HR, 2.524; 95% CI, 1.483-3.827; P = 0.0019), the VEGF -460CC genotype (HR, 1.719; 95% CI, 1.166-2.390; P = 0.0084), VEGF -1154AA and AG genotypes (HR, 1.482; 95% CI, 1.144-1.897; P = 0.0034), and VEGF -2578AA genotype (HR, 1.797; 95% CI, 1.219-2.495; P = 0.0047) had a significant prognostic effect on survival based on univariate analysis. Based on multivariate analysis of a current and former smoker (HR, 1.407; 95% CI, 1.095-1.840; P = 0.0070), poor PS (HR, 2.249; 95% CI, 1.309-3.468; P = 0.0058), and the VEGF -1154AA and AG genotypes (HR, 1.419; 95% CI, 1.033-1.901; P = 0.0316) were significant independent prognostic factors for survival. In this study, polymorphisms in VEGF may affect survival in advanced NSCLC.

Antioxidant action of sugar-pendant C60 fullerenes.

The action of C60 fullerene and its derivatives as a radical-scavenging antioxidant has received much attention, but their reactivity toward free radicals and antioxidant capacity have not been well elucidated yet. In the present study, the reactivity of the two types of water-soluble, sugar-pendant C60 fullerenes, C60-1S and C60-2S, toward peroxyl radical and their effect against human plasma lipid peroxidation were measured. The rate constants for the reaction of C60-1S and C60-2S with peroxyl radicals were obtained from their effect on the bleaching of beta-carotene in lipid-SDS micelle system as 4.6 x 10(3) and 8.0 x 10(3) M(-1) s(-1) at 37 degrees C, respectively. They inhibited the free radical-induced lipid peroxidation in human plasma in a concentration-dependent manner. These results suggest that the sugar-pendant fullerenes C60-1S and C60-2S act as a radical-scavenging antioxidant with the activity similar to the phenolic antioxidants.

Clinical significance of pretreatment serum amphiregulin and transforming growth factor-alpha, and an epidermal growth factor receptor somatic mutation in patients with advanced non-squamous, non-small cell lung cancer.

Circulating amphiregulin and transforming growth factor-alpha (TGF-alpha) have been found to be correlated with an unfavorable response to gefitinib based on the identification of patients with a higher probability of resistance to the drug. However, the association between an epidermal growth factor receptor (EGFR) somatic mutation and the overexpression of its ligands has not been determined. To verify the clinical significance of the two serum markers and EGFR mutation status, we determined serum amphiregulin and TGF-alpha levels by enzyme-linked immunosorbent assay in 93 patients with advanced non-squamous, non-small cell lung cancer and EGFR somatic mutation status using the peptic nucleic acid-locked nucleic acid clamp method in 46 cases. The relationship between each independent clinicopathological variable and the response to gefitinib therapy was examined. We also evaluated the risk factors associated with prognosis. Fourteen (41.0%) of 34 progressive disease cases were positive for amphiregulin (P = 0.007). Eleven (32.4%) of 34 progressive disease cases were positive for TGF-alpha (P = 0.005). The median survival time of patients with the EGFR somatic mutation was significantly longer (P = 0.01). The same was true of amphiregulin- (P = 0.046) and TGF-alpha-negative patients (P < 0.01). In multivariate analysis, serum TGF-alpha positivity (hazard ratio, 2.558; P = 0.005) and the wild type EGFR gene (hazard ratio, 1.894; P = 0.003) were significant independent prognostic factors. Our study demonstrates that the status of the serum EGFR ligand, in addition to EGFR activating mutation, is a predictive factor for response to gefitinib therapy.

Antioxidant capacity of BO-653, 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran, and uric acid as evaluated by ORAC method and inhibition of lipid peroxidation.

The role of radical-scavenging antioxidant against oxidative stress has received much attention. The antioxidant capacity has been assessed by various methods. Above all, oxygen radical absorbance capacity (ORAC) has been frequently employed [Prior et.al., J. Agric. Food Chem.2005, 53, 4290]. In the present study, the antioxidant capacity of 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653) and uric acid was assessed by ORAC method using pyranine as a reference probe and compared with that against lipid peroxidation of human plasma. It was found that BO-653 was assessed to be much less potent than uric acid by ORAC method, whereas BO-653 exerted much higher antioxidant activity than uric acid against plasma lipid peroxidation. The reason for such discrepancy is discussed. The results suggest that ORAC method is suitable for the assessment of free radical scavenging capacity, but not for the assessment of antioxidant capacity against lipid peroxidation in plasma.

Characterization of novel furan compounds on the basis of their radical scavenging activity and cytoprotective effects against glutamate- and lipopolysaccharide-induced insults.

There is increasing evidence indicating that free radicals and oxygenases such as cyclooxygenase (COX) and lipoxygenase (LOX) are related to the onset and development of neurodegenerative diseases. In order to prevent and/or delay these diseases, the use of radical-scavenging antioxidants and inhibitors against oxygenases has received much attention. In the present study, we examined the radical-scavenging activity and cytoprotective effects of some novel furan compounds with potent inhibitory activity against oxygenases such as COX-1, COX-2, and 5-LOX. The radical-scavenging activity was assessed by studying the bleaching of beta-carotene by free radicals generated from an azo initiator. In this assay system, the rate constants for scavenging peroxyl radicals by furan S and furan L was estimated to be 2 x 10(4) and 3 x 10(4) M(-1) s(-1), respectively. We also investigated the cytoprotective effects of these compounds against cell death induced by several toxins. We found that the furan compounds exhibited cytoprotective effects against PC12 cell death induced by linoleic acid hydroperoxide, primary neuronal cell death induced by glutamate, and cell death induced by lipopolysaccharide. These results suggest the beneficial effects of the furan compounds against disorders related to glutamate and lipopolysaccharide.

[A case of severe adult-onset Still' s disease presenting with pleuropericarditis].

Adult-onset Still' s disease (AOSD) is an uncommon rheumatic disease characterized by high spiking fever, arthritis, an evanescent skin rash and variety of systemic symptoms, though initial onset of pleuropulmonary manifestation is relatively rare and could be responsible for a delay in diagnosis. We report a case of AOSD presenting with pleuritis with concomitant pericardial effusion. A 42-year-old Japanese man was admitted with a spiking fever of 40 degrees C, hyperleucocytosis (21.6 x 10(9)/l), and a high titer of C-reactive protein (16.84mg/dl). Chest X-ray film and computed tomography showed bilateral pleural effusion and massive pericardial effusion which both required tube drainage. Analyses of fluids revealed that both were exudative and sterile, and pleural biopsy showed nonspecific inflammation with mild fibrosis. Neither antibiotics nor antituberculosis drugs were effective. Rash, hepatosplenomegaly, polyarthritis, pharyngitis and right hypochondralgia were accompanied by serum hyperferritinemia. After exclusion of the possibility of infection, other connective tissue disease and malignancy, a diagnosis of AOSD was made. Improvement was not observed with nonsteroidal anti-inflammatory drug and corticosteroid therapy. Double filtration plasmapheresis (DFPP) following steroid pulse therapy alleviated the symptoms and the laboratory data immediately and corticosteroids could be tapered. DFPP is a safe therapeutic procedure and can be an alternative for refractory AOSD.

Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer.

Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients. Furthermore, the association between PCP and Pneumocystis colonization was also investigated. Advanced lung cancer patients with no indication of PCP were evaluated to determine the prevalence of Pneumocystis colonization. We analyzed their oral wash (OW) samples and retrospectively evaluated advanced lung cancer patients with PCP by analyzing their sections of formalin-fixed, paraffin-embedded lung tissues obtained following a diagnosis of lung cancer. Pneumocystis colonization was determined by a PCR test for Pneumocystis jiroveci (P. jiroveci). No P. jiroveci was detected by PCR in the OW samples of 47 advanced lung cancer patients with no indication of PCP, or in the lung tissues of four advanced lung cancer patients with PCP. These results indicate that PCP is not associated with Pneumocystis colonization in advanced lung cancer patients, although this study is limited since this was a cross-sectional and retrospective study.

Significance of pretreatment comorbidities in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor.

A standard, valid assay of comorbidities for elderly patients with advanced non-small-cell lung cancer (NSCLC) who have received antitumor therapy is needed to provide useful prognostic information. The aim of this study was to analyze prognostic factors and validate classic Charlson comorbidity index (CCI) and comorbidity scores in elderly patients with advanced NSCLC treated with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). A retrospective analysis was conducted on 162 patients with advanced NSCLC over 70 years old at diagnosis, who were treated with cytotoxic chemotherapy or with EGFR-TKIs between April 2003 and April 2009 at Kyoto University Hospital. Collected data included clinical assessments, treatments, toxicities, and outcomes. Survival was estimated using the Kaplan-Meier method. Prognostic factors were evaluated with log-rank and Cox regression tests. Based on multivariate analysis, unspecified NSCLC histology [Hazard ratio (HR), 1.631; 95% Confidence interval (CI), 1.184-2.263; P = 0.0016], more than 3 comorbidities (HR, 1.317; 95% CI, 1.020-2.675; P = 0.0350), and a CCI of more than 3 (HR, 1.321; 95% CI, 1.031-1.664; P = 0.0285) were significant independent negative prognostic factors for survival. Our results indicate that CCI and the number of comorbidities are independent predictors of survival in elderly patients undergoing systemic chemotherapy including EGFR-TKIs for advanced NSCLC. These factors should be taken into consideration in the pretreatment assessment as important factors predicting survival outcome.

Should Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Be Continued beyond Progressive Disease?

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is almost exclusively effective in patients with activating EGFR mutations, and median time to progression in such patients is generally up to 12 months. Usually, treatment with EGFR-TKI is terminated when disease progression is confirmed; however, acute exacerbation after the withdrawal of EGFR-TKI has been reported. In this paper, we report a case of a 35-year-old patient whose disease rapidly progressed after discontinuation of gefitinib and then rapidly regressed after reintroduction of gefitinib. In addition, we summarize the cases of 3 other patients who could be safely treated with continued erlotinib in combination with pemetrexed after disease progression. Currently, the mechanism of acquired resistance is intensively investigated and a number of new agents, such as irreversible EGFR inhibitors or MET inhibitors, are under development; however, they are still unavailable in clinical setting. We believe that continuing EGFR-TKI treatment after disease progression should be an option in patients who previously responded to EGFR-TKI under the present circumstances.

Association of diffuse, random pulmonary metastases, including miliary metastases, with epidermal growth factor receptor mutations in lung adenocarcinoma.

BACKGROUND: Although the association of multiple pulmonary metastases, and particularly miliary metastases, with response to gefitinib treatment in patients with nonsmall cell lung cancer has been reported, the association of miliary pulmonary metastases with epidermal growth factor receptor gene (EGFR) mutations remains unclear. METHODS: The authors retrospectively investigated the association of diffuse, random pulmonary metastases in patients with lung adenocarcinoma. The study included 163 Japanese patients who had unresectable, advanced lung adenocarcinoma diagnosed between April 2003 and March 2010. Computed tomography scans that were obtained at the time of diagnosis were analyzed by 2 investigators. For the purposes of this study, diffuse, random pulmonary metastases were defined as multiple nodules (n = 50; ≤ 3 cm in greatest dimension) distributed diffusely and randomly throughout the lungs. RESULTS: Of 163 patients, 55 had pulmonary metastases, and EGFR mutations were detected in 22 of those 55 patients. The mutations were identified preferentially among women (P = .15) and were identified significantly among patients who had a smoking history of < 10 pack-years (P = .0057). Diffuse, random pulmonary metastases were identified in 11 of 22 patients who had EGFR mutations and in 4 of 33 patients who had the wild-type EGFR (P = .0043). On the basis of multivariate analyses, EGFR mutations were associated independently with a smoking history of < 10 pack-years (P = .026) and with diffuse, random pulmonary metastases (P = .012). CONCLUSIONS: When patients with lung adenocarcinomas who had EGFR mutations developed pulmonary metastases, they tended to be diffuse and random, including military metastases. However, such metastases were much less common in patients who had lung adenocarcinomas with wild-type EGFR.

Clinical significance of the ratio between the alpha 2 plasmin inhibitor-plasmin complex and the thrombin-antithrombin complex in advanced non-small cell lung cancer.

The aims of this study are to: (a) confirm the prognostic significance of the procoagulant molecules D dimer, thrombin-antithrombin complex (TAT), and plasmin-α2-plasmin inhibitor complex (PIC); (b) to evaluate hemostatic activation in patients with advanced non-small cell lung cancer (NSCLC); and (c) to delineate the relationships between markers of hemostasis and other clinical characteristics. In this study, a low PIC/TAT ratio and poor PS were significant independent negative prognostic factors for survival in patients with advanced NSCLC. The PIC/TAT ratio may become a surrogate marker for treatment with anticoagulants in the future.

Differences in adverse events between 250 mg daily gefitinib and 150 mg daily erlotinib in Japanese patients with non-small cell lung cancer.

PURPOSE: The maximum tolerated dose (MTD) of erlotinib (150 mg) is the approved daily dose. In contrast, the approved daily dose of gefitinib (250 mg) is only one-third of its MTD. Significantly different adverse events have been associated with gefitinib and erlotinib. EXPERIMENTAL DESIGN: A retrospective investigation examining the adverse events and tolerances of 250 mg daily gefitinib and 150 mg daily erlotinib in Japanese patients with non-small cell lung cancer (NSCLC) was performed. Adverse events were assessed according to Common Terminology Criteria for Adverse Events version 3.0. To determine tolerance for each agent, failure was defined as dose reduction or discontinuation of the drug due to adverse events, and early failure as dose reduction or discontinuation due to adverse events before the first evaluation of response. RESULTS: More adverse events including skin disorders, diarrhea, oral mucositis, asthenic conditions, anorexia, nausea, vomiting, and gastrointestinal bleeding were observed in the erlotinib group. Liver function test abnormalities and pneumonitis did not differ between the two groups. Based on multivariate analysis, failure, early failure, and discontinuation due to adverse events were independently associated with erlotinib use. CONCLUSION: Our data show that 150 mg daily erlotinib was associated with more toxicity and less tolerability than 250 mg daily gefitinib.

Clinicopathologic factors affecting the progression-free survival of patients with advanced non-small-cell lung cancer after gefitinib therapy.

BACKGROUND: The aim of this study was to analyze the factors independent of epidermal growth factor (EGFR) gene mutations that affect the progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) after gefitinib therapy. PATIENTS AND METHODS: Eighty patients with advanced NSCLC between January 2003 and April 2010 at Kyoto University Hospital were analyzed for EGFR somatic mutations and treated with gefitinib. We adopted the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method for determination of EGFR mutation status. To evaluate risk factors associated with PFS, Cox proportional hazards regression model with a step-down procedure was used. Proportional hazards assumptions were checked and satisfied; only those variables with statistically significant results in univariate analysis were included in a multivariate analysis. RESULTS: The median PFS of patients with EGFR mutations were significantly longer than in patients with wild-type EGFR. The median PFS of patients after first-line gefitinib therapy was significantly longer than those who received treatment as a second-line therapy. The median PFS of patients over 75 years of age was significantly longer than in younger patients. Based on multivariate analysis, wild-type EGFR status and age < 75 years were significant and independent negative factors that affect PFS after gefitinib therapy. CONCLUSION: In this study, we showed the EGFR mutants and age > 75 years were good predictive factors for PFS after gefitinib therapy, suggesting that first-line gefitinib treatment for older patients is efficacious regardless of EGFR mutational status.

Association of the transforming growth factor ß1 promoter polymorphism, C-509T, with smoking status and survival in advanced non-small cell lung cancer.

Transforming growth factor ß (TGF-ß) signaling can inhibit tumor growth in developing tumors. However, it promotes tumor invasiveness and metastasis in late-stage tumors. A number of TGF-ß gene polymorphisms have been identified that can affect the survival of patients with advanced non-small cell lung cancer (NSCLC). In this study, we investigated the association of the TGF-ß1 polymorphism, C-509T, with survival in patients with advanced NSCLC. Japanese patients who were treated for unresectable advanced NSCLC between April 2003 and March 2008 at Kyoto University Hospital, were enrolled in this study. Analyses of genotype associations with survival outcomes were performed using statistical tests. The median survival of patients with the TT genotype was shorter, although not significantly, than that of patients with either the CT or CC genotype. Based on both univariable and multivariable analyses, the TGF-ß1 polymorphism, C-509T, was not associated with prognosis. In patients with a smoking status of <40 pack-years, the median survival was significantly shorter with the TT genotype than with the CT or CC genotype. Based on univariable analysis, stage IV cancer and the TT genotype had a significant prognostic effect on survival. Based on multivariable analysis, the TT genotype was a significantly independent prognostic factor for survival. There was no association between the TGF-ß1 polymorphism, C-509T, and survival in patients with advanced NSCLC. In patients with a smoking status of <40 pack-years, however, the TGF-ß1 polymorphism, C-509T, was significantly associated with the prognosis of advanced NSCLC, and the TT genotype was an independent prognostic factor for poor survival.

Phase I study of the combination of nedaplatin and gemcitabine in previously untreated advanced squamous cell lung cancer.

PURPOSE: The objectives of this phase I trial were to evaluate the toxicity of the nedaplatin/gemcitabine regimen, determine the maximum tolerated doses (MTDs) of these agents, and observe the anti-tumor effects of this regimen on advanced squamous cell lung cancer. METHODS: Patients with previously untreated advanced squamous cell lung cancer were eligible if they had a performance status of 0 or 1 with adequate organ function. The doses of gemcitabine (days 1 and 8) and nedaplatin (day 8) studied were 800/70, 1,000/80, 1,000/90, and 1,000/100 (mg/m(2)), repeated every 3 weeks. RESULTS: Toxicity and response could be assessed in all 13 patients enrolled. The patients included 12 men and one woman with a median age of 69 years (range 57-81 years). Three patients had stage IIIB disease and 10 patients had stage IV disease. The MTDs were reached at 1,000 mg/m(2) gemcitabine and 80 mg/m(2) nedaplatin. The most frequent toxic effects were thrombocytopenia and neutropenia; grade 3 or 4 thrombocytopenia was observed in 23% of patients, and grade 3 or 4 neutropenia was seen in 46% of patients. Non-hematologic toxicities were mild. Grade 3 fatigue, nausea/vomiting, and appetite loss occurred in two patients. The overall response rate was 62%. CONCLUSIONS: We recommend doses of 800 mg/m(2) gemcitabine and 70 mg/m(2) nedaplatin for phase II study. This combination chemotherapeutic regimen is active and well tolerated.

Clinical significance of epidermal growth factor receptor mutations and insulin-like growth factor 1 and its binding protein 3 in advanced non-squamous non-small cell lung cancer.

This study of patients with advanced non-squamous non-small cell lung cancer (NSCLC) evaluated epidermal growth factor receptor (EGFR) mutation status and two serum markers, serum insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3), for their associations to response to gefitinib therapy and for their prognostic impact. An immunoradiometric assay determined levels of IGF1 and IGFBP3 in serum from 68 patients with advanced non-squamous NSCLC. The peptic nucleic acid locked nucleic acid clamp method determined their EGFR somatic mutation status. We evaluated the relationship between each independent clinicopathological variable and the response to gefitinib therapy and the risk factors associated with prognosis. Having IGF1-positive serum as determined by the 75th percentile and having wild-type EGFR were both independent negative predictive factors for geftinib treatment by multivariate logistic regression model analysis. Both having serum positive for IGF1 as determined by the 25th percentile and having wild-type EGFR were significant independent negative prognostic factors for survival based on multivariate analysis. We demonstrated that having IGF1-positive serum predicts a negative response to gefitinib therapy independent of EGFR mutational status. We also demonstrated that both IGF1-positive serum and wild-type EGFR were independent poor prognostic factors in patients with non-squamous NSCLC who received gefitinib therapy.

Association between brain natriuretic peptide and distant metastases in advanced non-small cell lung cancer patients.

This study aimed to investigate the relationship between clinicopathological factors and plasma brain natriuretic peptide (BNP) levels in non-small cell lung cancer (NSCLC) patients. A total of 133 patients with advanced NSCLC were included in this study. The level of BNP was determined at the time of diagnosis. The BNP plasma concentration was measured using a chemiluminescent enzyme immunoassay kit. The univariate relationship between each independent clinicopathological variable and plasma BNP was examined using the Chi-square test. The survival curves were determined using the Kaplan-Meier method. According to the cut-off value of plasma BNP levels (11.5 and 22.4 pg/ml), plasma BNP negatively correlated with the presence of metastases (Chi-square test, p=0.0374 and p=0.0098, respectively). However, no significant association between patient survival time and plasma BNP levels was found. Reduced plasma BNP levels in advanced NSCLC patients with metastases were noted and the possibility was raised that BNP decreases distant metastases of advanced NSCLC patients.

Outcome of Surgical Treatment for Metastatic Vertebra Bone Tumor in Advanced Lung Cancer.

BACKGROUND: Spinal metastases of patients with advanced stage lung cancer are an important target for palliative therapy, because their incidence is high, and they often cause severe symptoms and worsen the quality of life. Surgery is one of the most effective treatment options, but the indication of surgery is unclear as the procedure is invasive and patients with spinal metastasis have a rather short life expectancy. Furthermore, there have been few studies that have focused on lung cancer with poor prognosis. METHODS: We reviewed all of the cases of lung cancer from January 1999 to July 2007 in the Department of Respiratory Medicine, Kyoto University Hospital, Japan. Thirteen patients with metastatic spinal tumor of lung cancer underwent surgery, and all of them had a poor performance status score (3 or 4). RESULTS: Neurological improvement by at least 1 Frankel grade was seen in 10 of 14 cases (71%). Improvement of the movement capacity was noted in 9 of 14 cases (64%), and pain improvement was noted in 12 of 14 (86%). Median postoperative survival was 5 months (1-25 months). In particular, the group with a good postoperative performance status score (0-2) was shown to have a better median postoperative survival of 13 months. CONCLUSIONS: Surgical treatment for symptomatic metastatic spinal tumor of lung cancer can improve quality of life in a substantially high percentage of patients. Surgery should be considered even if preoperative performance status is poor.