Tateaki Naito

Shizuoka Cancer Center, Sizuoka, Shizuoka, Japan

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Publications (82)202.29 Total impact

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    ABSTRACT: The effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). Given the lack of research in this area, we here examined whether progression-free survival (PFS) or post-progression survival (PPS) could serve as valid surrogate endpoints for OS after second-line chemotherapy in advanced NSCLC, using individual-level data. Between April 2009 and June 2011, 39 patients with advanced non-squamous NSCLC who had received second-line chemotherapy following first-line chemotherapy treatment with cisplatin and pemetrexed were analysed. The relationships of PFS and PPS with OS were analysed at the individual level. Spearman rank correlation analyses and linear regression analyses showed that PPS was strongly associated with OS (r = 0.90, p < 0.05, R (2) = 0.85), whereas PFS only moderately correlated with OS (r = 0.76, p < 0.05, R (2) = 0.50). Best response at third-line treatment and number of regimens employed after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Analysis of individual-level data of patients treated with second-line chemotherapy suggested that PPS may be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Moreover, our findings suggest that subsequent treatment after disease progression following second-line chemotherapy may greatly influence OS. However, these results should be validated in further large-scale studies.
    Medical oncology (Northwood, London, England). 08/2014; 31(8):88.
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    ABSTRACT: Whether the mutant allele frequency (MAF) may also have predictive implications for tyrosine kinase inhibitor (TKI) therapy in patients with advanced EGFR-mutated lung adenocarcinoma (AELAd) remains unknown.
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 07/2014;
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    ABSTRACT: Pleural effusion is frequently observed in patients with advanced lung cancer. Although effusion can be obtained less invasively and repeatedly, its use in multiplexed molecular profiling has not been fully investigated.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 07/2014; 9(7):1048-52. · 4.55 Impact Factor
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    ABSTRACT: Gefitinib and erlotinib are used to treat advanced non-small cell lung cancer (NSCLC). Gefitinib is a common first-line treatment, but most patients develop resistance. This phase II study evaluated the efficacy of erlotinib after acquired resistance to gefitinib. Between January 2008 and September 2009, we enrolled 50 patients with advanced NSCLC who had received one or more chemotherapy regimens, including gefitinib monotherapy to which they had partial responses (PR) or stable disease (SD). Erlotinib (150 mg) was administered until disease progression or unacceptable toxicity. Patients were 11 males, 39 females; median age 65 years (range=36-81 years); 46 with adenocarcinoma; performance status 0/1/2: 24/19/7; and smoking status, never/former/current: 33/15/2. Prior gefitinib response, PR/SD: 36/14. Median duration of prior gefitinib therapy was 419 days (range=63-1,540 days). Median interval after gefitinib therapy was 29 days (range=13-1,198 days). Of 47 patients on erlotinib, four showed PR and 29 showed SD [response rate, 8.5%; disease control rate (DCR), 70.2%]. DCR for patients who continued gefitinib treatment for more than one year was significantly higher (81.5%) than for patients who could not continue (57.1%; p=0.018); but was not affected by prior gefitinib response or treatment interval. Median tiMETo treatment failure: 100 days (95% confidence interval=90-110 days); median overall survival: 342 days (95% confidence interval=242-442 days). Rash (78%) and diarrhea (68%) were the most common adverse reactions; grade 5 pneumonitis occurred in one patient (2%). Erlotinib treatment after gefitinib failure may prolong the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors treatment.
    Anticancer research 04/2014; 34(4):1975-81. · 1.71 Impact Factor
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    ABSTRACT: Whether fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake within tumor cells differs between primary and recurrent lung cancers is unknown. The aim of this study was to investigate the prognostic significance of (18)F-FDG uptake by comparing that measured preoperatively at the primary site to that measured postoperatively at sites of non-small cell lung cancer (NSCLC) recurrence. Only patients with postoperative recurrences who received platinum-based chemotherapy as the initial treatment after recurrence were included in the study. Fifty-two patients underwent (18)F-FDG positron emission tomography (PET) examinations before thoracotomy and at the time of recurrence after curative surgery. All recurrences were treated with platinum-based chemotherapy. (18)F-FDG uptake in the preoperative primary tumors was significantly higher than that in the recurrent tumors (p=0.028), demonstrating a statistically significant correlation (Pearson's correlation coefficient γ=0.482, p<0.001), especially in adenocarcinoma (AC) patients. Low (18)F-FDG avidity within the primary tumor significantly correlated with the presence of epidermal growth receptor factor (EGFR) mutations. (18)F-FDG uptake in the primary tumors was an independent prognostic factor for predicting outcome in NSCLC patients receiving platinum-based chemotherapy for the treatment of postoperative recurrence. In NSCLC patients treated by chemotherapy for recurrence, preoperative measurements of (18)F-FDG uptake may be a more powerful surrogate marker for predicting outcome when measured preoperatively at the primary tumor site rather than postoperatively at sites of recurrence.
    Respiratory investigation. 03/2014; 52(2):121-8.
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    ABSTRACT: Cisplatin plus pemetrexed is a standard front-line chemotherapeutic regimen for inoperable malignant pleural mesothelioma (MPM). However, no clinical trials have compared the efficacy of cisplatin plus pemetrexed and cisplatin plus gemcitabine, which may be comparable based on previous phase II study results. This study aimed at evaluating the efficacy of cisplatin plus pemetrexed and comparing it with that of cisplatin plus gemcitabine in Japanese MPM patients. From July 2002 to December 2011, 13 and 17 consecutive patients with inoperable MPM were treated with cisplatin plus gemcitabine and cisplatin plus pemetrexed, respectively, at the Shizuoka Cancer Center. We reviewed the medical charts of these patients and evaluated their characteristics as well as data regarding drug toxicity and antitumor efficacy. The response rates were 15% and 35% in the cisplatin plus gemcitabine and cisplatin plus pemetrexed groups, respectively (P=0.4069), while disease control rates were 77%, and 82%, respectively (P=0.9999). Progression-free survival was significantly higher with cisplatin plus pemetrexed (median, 215.5 days) than with cisplatin plus gemcitabine (median, 142.5 days) (P=0.0146; hazard ratio [HR], 0.3552). Overall survival showed a tendency towards being superior with cisplatin plus pemetrexed (median, 597.5 days) compared with cisplatin plus gemcitabine (median, 306.5 days) (P=0.1725, HR, 0.5516). Hematological toxicities, especially thrombocytopenia and neutropenia, tended to be more frequent and severe in the cisplatin plus gemcitabine group. Cisplatin plus pemetrexed may be superior and should continue to be the standard front-line chemotherapeutic regimen for inoperable MPM.
    Respiratory investigation. 03/2014; 52(2):101-6.
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    ABSTRACT: Background: There is no standard therapy for relapsed patients who have received postoperative platinum-based adjuvant chemotherapy for resected non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of platinum combination chemotherapy re-challenge for such patients. Methods: Medical records from 3 institutes from April 2005 to July 2012 were retrospectively reviewed. Patients who underwent complete surgical resection were eligible if they received postoperative adjuvant chemotherapy consisting of cisplatin plus vinorelbine once and then re-challenge with platinum combination chemotherapy. Results: Sixteen patients were enrolled in this study. After re-challenge with platinum combination chemotherapy, we observed an overall response rate of 31.2% (5/16) and a disease control rate of 81.2% (13/16). Median progression-free survival and overall survival from the start of the re-administration of platinum combination chemotherapy were 6.5 and 28.0 months, respectively. Frequently observed severe adverse events (≥grade 3) included neutropenia (31.2%), thrombocytopenia (31.2%), leukopenia (12.5%) and hyponatremia (12.5%). Frequently observed non-hematological toxicities (≥grade 2) were anorexia (37.5%) and nausea (37.5%). Conclusion: Re-challenge with platinum combination chemotherapy was effective and safe; therefore, this therapy should be considered as a treatment option for relapsed patients after postoperative cisplatin-based adjuvant chemotherapy for resected NSCLC. © 2014 S. Karger AG, Basel.
    Chemotherapy 01/2014; 59(4):307-313. · 2.07 Impact Factor
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    ABSTRACT: In locally advanced Non-Small-Cell Lung Cancer (LA-NSCLC) patients treated with chemoradiotherapy (CRT), optimal surrogate endpoint for cure has not been fully investigated. The clinical records of LA-NSCLC patients treated with concurrent CRT at Shizuoka Cancer Center between Sep. 2002 and Dec. 2009 were reviewed. The primary outcome of this study was to evaluate the surrogacy of overall response rate (ORR) and progression-free survival (PFS) rate at 3-month intervals (from 9 to 30 months after the initiation of treatment) for the 5-year survival rate. Landmark analyses were performed to assess the association of these outcomes with the 5-year survival rate. One hundred and fifty-nine patients were eligible for this study. The median follow-up time for censored patients was 57 months. The ORR was 72%, median PFS was 12 months, and median survival time was 39 months.Kaplan-Meier curve of progression-free survival and hazard ratio of landmark analysis at each time point suggest that most progression occurred within 2 years. With regard to 5-year survival rate, patients with complete response, or partial response had a rate of 45%. Five-year survival rates of patients who were progression free at each time point (3-months intervals from 9 to 30 months) were 53%, 69%, 75%, 82%, 84%, 89%, 90%, and 90%, respectively. The rate gradually increased in accordance with progression-free interval extended, and finally reached a plateau at 24 months. Progression-free survival at 2 years could be a reliable surrogate marker for the 5-year survival rate in LA-NSCLC patients treated with concurrent CRT.
    BMC Cancer 01/2014; 14(1):18. · 3.33 Impact Factor
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    ABSTRACT: Background Concurrent chemoradiation in stage III non-small cell lung cancer (NSCLC) patients with cavitary lesions is reported to cause serious lung complications and is a predictor of poor survival. However, the efficacy and toxicity associated with chemotherapy for advanced NSCLC patients with cavitary lesions is not clear. We investigated the toxicities, particularly hemoptysis and cavity infection, and efficacy associated with chemotherapy for NSCLC patients with cavitary lesions. Methods We retrospectively reviewed consecutive patients who received first-line chemotherapy, including platinum-based chemotherapy, single-agent chemotherapy, or epidermal growth factor receptor-tyrosine kinase inhibitors, at our institution between January 2008 and December 2010. Results We found tumor cavitation prior to treatment in 23 of 415 NSCLC patients (5.5%). The response rate of all the patients was 30%, and the median survival time (MST) was 8.9 months. The MST of the 15 patients treated with platinum-based chemotherapy was 11 months. Grade 1 bronchopulmonary hemorrhage occurred in 2 patients. Grade 3 cavitary infection occurred in 2 patients, resulting in the discontinuation of chemotherapy. Conclusions This study indicates that the toxicity of chemotherapy for NSCLC patients with cavitary lesions is tolerable; however, the development of cavitary infection should be carefully considered. In addition, this study suggests that the efficacy of chemotherapy for NSCLC patients with cavitary lesions is similar to the response rates reported in the literature; however, the survival of these patients may be worse than that for general NSCLC patients.
    Respiratory Investigation. 01/2014;
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    ABSTRACT: We herein present the case of a 36-year-old woman who developed perianal metastasis of non-small cell lung cancer that was diagnosed based on the presence of symptoms mimicking a hemorrhoid. The patient initially underwent radiotherapy for a left superior sulcus tumor, then subsequently complained of a perianal mass that had prolapsed and bled. The tumor was removed via resection. Histologically, the mass was diagnosed as poorly differentiated carcinoma and considered to be a metastatic lesion arising from the primary lung cancer.
    Internal medicine (Tokyo, Japan). 01/2014; 53(11):1149-52.
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    ABSTRACT: Objectives Advances in the molecular profiling of lung adenocarcinoma over the past decade have led to a paradigm shift in its diagnosis and treatment. However, there are very few reports on the molecular profiles of small cell lung cancers (SCLCs). We therefore conducted the present Shizuoka Lung Cancer Mutation Study to analyze genomic aberrations in patients with thoracic malignancies. Materials and Methods We collected samples of SCLC from a biobank system and analyzed their molecular profiles. We assessed 23 mutations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2) using pyrosequencing plus capillary electrophoresis. We also amplified EGFR, MET, PIK3CA, FGFR1, and FGFR2 using quantitative real-time polymerase chain reaction (PCR) and the fusion genes ALK, ROS1, and RET using reverse transcription PCR. Results Between July 2011 and January 2013, 60 SCLC patients were enrolled in the study. Samples included eight surgically resected snap-frozen samples, 50 formalin-fixed paraffin-embedded samples, and seven pleural effusion samples. We detected 13 genomic aberrations in nine cases (15%), including an EGFR mutation (n = 1, G719A), a KRAS mutation (n = 1, G12D), PIK3CA mutations (n = 3, E542 K, E545 K, E545Q), an AKT1 mutation (n = 1, E17 K), a MET amplification (n = 1), and PIK3CA amplifications (n = 6). EGFR and KRAS mutations were found in patients with combined SCLC and adenocarcinoma. No significant differences were detected in the characteristics of patients with and without genomic aberrations. However, serum neuron-specific enolase and progastrin-releasing peptide levels were significantly higher in patients without genomic aberrations than in those with aberrations (p = 0.01 and 0.04, respectively). Conclusion Genomic aberrations were found in 15% SCLC patients, with PIK3CA amplifications most frequently observed. To further our understanding of the molecular profiles of SCLC, comprehensive mutational analyses should be conducted using massive parallel sequencing.
    Lung cancer (Amsterdam, Netherlands) 01/2014; · 3.14 Impact Factor
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    ABSTRACT: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations. Keywords: non-small cell lung cancer, overall survival, post-progression survival, progression-free survival, tumor response.
    Neoplasma 12/2013; · 1.57 Impact Factor
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    ABSTRACT: Pleural dissemination detected by computed tomography (CT) is considered to be unfavorable for patients with non-small-cell lung cancer (NSCLC). However, the prognosis of NSCLC patients who are diagnosed with pleural dissemination at the time of surgery has yet to be adequately elucidated. To assess the outcomes of platinum-based chemotherapy in NSCLC patients in whom pleural dissemination was detected during exploratory thoracotomy with or without a videoscope, the clinical records of NSCLC patients who were admitted to Shizuoka Cancer Center between September, 2002 and April, 2009 were reviewed. A total of 19 patients were included in this study, 12 males and 7 females, with a median age of 65 years. All patients were diagnosed with adenocarcinoma and 6 were epidermal growth factor receptor (EGFR) gene mutation-positive. The median number of treatment cycles of first-line platinum-based chemotherapy was 4 (range, 1-6 cycles) and the objective response rate was 21% [95% confidence interval (CI): 8.5-43]. The median progression-free and overall survival were 10.4 (95% CI: 6.3-18.4) and 50.5 months (95% CI: 32.5-98.0), respectively. Of the 18 patients with reported disease progression, 9 (50%) developed locoregional tumor progression. In conclusion, NSCLC patients in whom pleural dissemination is detected during surgery tend to have a favorable prognosis for survival. Systemic chemotherapy and additional local treatment may improve their clinical outcomes.
    Molecular and clinical oncology. 11/2013; 1(6):949-952.
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    ABSTRACT: The aim of this study was to investigate the relationship between the expression levels of thymidylate synthase (TS) and 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) uptake on positron emission tomography (PET) in various thoracic neoplasms. In total, 392 patients [non-small cell lung cancer (NSCLC) (n=140), malignant pleural mesothelioma (MPM) (n=21), pulmonary metastatic tumors (PMT) (n=148), thymic epithelial tumors (n=49) and pulmonary neuroendocrine (NE) tumor (n=34)] who underwent 18F-FDG PET before treatment were included in this study. Tumor sections were stained using immunohistochemistry for determination of TS, orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase (DPD), vascular endothelial growth factor (VEGF), microvessel density (MVD), CD34 and p53. The expression of TS in thoracic neoplasms had a positivity of 58% (230/392), and the positive rates of TS expression in NSCLC, PMT, thymic epithelial tumor, NE tumor and MPM samples were 56, 57, 57, 85 and 47%, respectively. The positivity of TS expression was significantly higher in NE tumors compared to that in other thoracic tumors. A statistically significant correlation between TS expression and 18F-FDG uptake was observed in thoracic neoplasms, in particular primary lung adenocarcinomas, high-grade NE tumors, thymomas and MPMs. Moreover, TS expression was closely associated with angiogenesis, DPD, OPRT and p53. Our results indicated that SUVmax by 18F-FDG uptake may be an alternative biomarker for predicting TS expression in patients with primary lung adenocarcinoma, high-grade NE tumor, thymoma and MPM.
    Oncology Reports 10/2013; · 2.30 Impact Factor
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    ABSTRACT: It is widely recognized that pulmonary neuroendocrine tumors (PNET) include a spectrum that ranges from low-grade typical carcinoid (TC) and atypical carcinoid (AC) to high-grade large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). However, little is known about the usefulness of 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron-emission tomography (PET) in such tumors. We therefore, conducted a study including the analysis of the underlying biology of (18)F-FDG uptake. Thirty-four patients with early-stage PNETs who underwent (18)F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter-1 (Glut1 and Glut3), hypoxia-inducible factor-1 alpha (HIF-1α), hexokinase-I, vascular endothelial growth factor (VEGF), microvessel density (MVD) determined by CD34 and (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. (18)F-FDG uptake correlated significantly with Glut1, HIF-1α, VEGF and CD34 expression. Uptake of (18)F-FDG tended to increase from low-grade to high-grade PNETs. Tumor metabolic activity was a useful marker for predicting postoperative prognosis in patients with early-stage PNETs. The amount of (18)F-FDG uptake is determined by the presence of glucose metabolism, hypoxia and angiogenesis.
    Anticancer research 10/2013; 33(10):4219-4228. · 1.71 Impact Factor
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    ABSTRACT: BackgroundS-1 is a novel antimetabolic agent that inhibits thymidylate synthase. The expression of thymidylate synthase is higher in squamous (Sq) non-small cell lung cancer (NSCLC) than in non-Sq NSCLC. The aim of this retrospective study was to assess the efficacy of S-1 monotherapy for advanced NSCLC according to the histological subtype. Methods We reviewed the clinical records of patients with advanced NSCLC treated with S-1 monotherapy as second- or third-line therapy between May 2005 and July 2012 at Shizuoka Cancer Center. ResultsA total of 71 patients were included in this retrospective study. Patient characteristics were similar in the Sq NSCLC (n = 15) and non-Sq NSCLC (n = 56) groups, except with regard to sex and smoking status. The overall response rates were 0% (95% confidence interval [CI] 0–17%) for Sq NSCLC and 11% (95% CI 3–19%) for non-Sq NSCLC (P = 0.33). For Sq NSCLC and non-Sq NSCLC, the median progression-free survival times were 2.1 and 2.8 months (P = 0.02), respectively, and the median overall survival times were 6.1 and 10.1 months (P = 0.01), respectively ConclusionS-1 monotherapy may be more effective in patients with non-Sq NSCLC than in those with Sq NSCLC.
    Thoracic Cancer. 08/2013;
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    ABSTRACT: Patients harboring sensitive epidermal growth factor receptor (EGFR) mutations show a dramatic response to treatment with EGFR tyrosine kinase inhibitors (TKIs). However, there have been no clinical reports in lung cancer patients that compare the time-to-response between radiotherapy and EGFR-TKIs. We reviewed 17 and 32 consecutive patients with inoperable stage III/IV NSCLC who harbored sensitive EGFR mutations and who were treated with thoracic radiotherapy with or without chemotherapy and EGFR-TKIs, respectively. There were statistically significant differences in time-to-partial response (PR) with regard to the treatment modalities (radiotherapy vs. EGFR-TKIs, median 57 days vs. 22 days, log-rank test, p=0.008). EGFR-TKIs elicit tumor shrinkage earlier than does radiotherapy in patients with a sensitive EGFR mutation, suggesting that EGFR-TKIs may be useful for early symptom improvement in these patients.
    Anticancer research 08/2013; 33(8):3279-84. · 1.71 Impact Factor
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    ABSTRACT: Serum CYFRA 21--1 is one of the most important serum markers in the diagnosis of non-small cell lung cancer (NSCLC), especially squamous-cell carcinoma. However, it remains unknown whether pretreatment serum CYFRA 21--1 values (PCV) may also have prognostic implications in patients with advanced lung adenocarcinoma. We retrospectively reviewed the data of 284 patients (pts) who were diagnosed as having advanced lung adenocarcinoma and had received initial therapy. Of the study subjects, 121 pts (43%) had activating epidermal growth factor receptor (EGFR) mutations (Mt+), while the remaining 163 pts (57%) had wild-type EGFR (Mt-). Univariate analysis identified gender (male/ female), ECOG performance status (PS) (0-1/ >=2), PCV (<2.2 ng/ml/ >=2.2 ng/ml), EGFR mutation status (Mt+/ Mt-), pretreatment serum CEA values (<5.0 ng/ml/ >=5.0 ng/ml), smoking history (yes/ no) and EGFR-TKI treatment (yes/ no) as prognostic factors (p = .008, p < .0001, p < .0001, p < .0001, p = .036, p = .0012, p < .0001 respectively). Cox's multivariate regression analysis identified PCV < 2.2ng/ml as the only factor significantly associated with prolonged survival (p < .0001, hazard ratio: 0.43, 95% CI 0.31-0.59), after adjustments for PS (p < .0001), EGFR mutation status (p = .0069), date of start of initial therapy (p = .07), gender (p = .75), serum CEA level (p = .63), smoking history (p = .39) and EGFR-TKI treatment (p = .20). Furthermore, pts with Mt+ and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt+ and PCV of >=2.2 ng/ml (MST: 67.0 vs. 21.0 months, p < .0001), and patients with Mt- and PCV of <2.2 ng/ml had a more favorable prognosis than those with Mt- and PCV of >=2.2 ng/ml (MST: 24.1 vs. 10.2 months, p < .0001). PCV may be a potential independent prognostic factor in both Mt+ and Mt- patients with advanced lung adenocarcinoma.
    BMC Cancer 07/2013; 13(1):354. · 3.33 Impact Factor
  • Journal of Clinical Oncology 07/2013; · 18.04 Impact Factor
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    ABSTRACT: In this study, we present a method for efficient enrichment of small-sized circulating tumor cells (CTCs) such as those found in the blood of small cell lung cancer (SCLC) patients using a microcavity array (MCA) system. To enrich CTCs from whole blood, a microfabricated nickel filter with a rectangular MCA (104 cavities/filter) was integrated with a miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and blood cells. The shape and porosity of the MCA were optimized to efficiently capture small tumor cells on the microcavities under low flow resistance conditions, while allowing other blood cells to effectively pass through. Under optimized conditions, approximately 80% of SCLC (NCI-H69 and NCI-H82) cells spiked in 1 mL of whole blood, were successfully recovered. In clinical samples, CTCs were detectable in 16 of 16 SCLC patients. In addition, the number of leukocytes captured on the rectangular MCA was significantly lower than that on the circular MCA (p < 0.001), suggesting that use of the rectangular MCA diminishes a considerable number of carryover leukocytes. Therefore, our system has potential as a tool for the detection of CTCs in small cell-type tumors and detailed molecular analyses of CTCs.
    Analytical Chemistry 05/2013; · 5.70 Impact Factor

Publication Stats

298 Citations
202.29 Total Impact Points

Institutions

  • 2009–2014
    • Shizuoka Cancer Center
      • Division of Drug Discovery and Development
      Sizuoka, Shizuoka, Japan
  • 2013
    • Gunma University
      Maebashi, Gunma Prefecture, Japan
    • Tokyo University of Agriculture and Technology
      • Division of Biotechnology and Life Science
      Edo, Tōkyō, Japan