The role of smoking status on the progression-free survival of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor versus platinum doublet chemotherapy: A meta-analysis of prospective randomized trials
Hasegawa Y.,Izumi Municipal Hospital |
Ando M.,Nagoya University |
Maemondo M.,Miyagi Cancer Center |
Yamamoto S.,University of Kansas |
And 8 more authors.
Oncologist | Year: 2015
Background. Univariate analyses from several randomized phase III trials seemed to suggest ever-smokers with advanced mutated epidermal growth factor receptor (EGFRm) non-small cell lung cancer (NSCLC) did not seem to benefit from EGFR tyrosine kinase inhibitors (TKIs) as first-line treatment when compared with platinum-doublet chemotherapy as measured by progression-free survival (PFS). Methods. A literature-based meta-analysis of PFS outcomes as measured by log-transformed pooled hazard ratio (HR) was performed using a random-effect model. Pooled HRs for smoking status, age, gender, ethnicity, type of EGFR mutation, and EGFR TKI were obtained. Comparison of the pooled HRwas performed by metaregression analysis. Results. Among the 1,649 EGFRm NSCLC patients analyzed from 7 prospective randomized trials (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6, and ENSURE), 83.7% were Asians, and 30.0% were ever-smokers. An equal percentage of ever-smokers received doublet chemotherapy (30.2%) or EGFR TKI (30.0%). The pooled HRfor PFS was 0.29 (95% confidence interval [CI]: 0.21-0.39) for never-smokers and 0.54 (95% CI: 0.38-0.76) for ever-smokers (p <.007 by metaregression).The pooled PFS HRforexon 19 deletion was 0.25 (95% CI: 0.19-0.31) and 0.44 for exon 21 substitution (95% CI: 0.34-0.57) (p <.001 by metaregression analysis). The pooled PFS HR was 0.33 (95% CI: 0.24-0.46) for Asians and 0.48 for non-Asians (95% CI: 0.28-0.84) (p =.261 by metaregression analysis). Conclusion. EGFRm NSCLC patients derived significant PFS benefit from TKI over platinum-doublet chemotherapy as first-line treatment regardless of smoking status; however, PFS benefit is significantly better in never-smokers by metaregression analysis. © AlphaMed Press 2015.
Yamamoto M.,Katsuta Hospital Mito Gamma House |
Serizawa T.,Tokyo Gamma Unit Center |
Shuto T.,Yokohama Rosai Hospital |
Akabane A.,Nippon Telegraph and Telephone |
And 29 more authors.
The Lancet Oncology | Year: 2014
Background: We aimed to examine whether stereotactic radiosurgery without whole-brain radiotherapy (WBRT) as the initial treatment for patients with five to ten brain metastases is non-inferior to that for patients with two to four brain metastases in terms of overall survival. Methods: This prospective observational study enrolled patients with one to ten newly diagnosed brain metastases (largest tumour <10 mL in volume and <3 cm in longest diameter; total cumulative volume ≤15 mL) and a Karnofsky performance status score of 70 or higher from 23 facilities in Japan. Standard stereotactic radiosurgery procedures were used in all patients; tumour volumes smaller than 4 mL were irradiated with 22 Gy at the lesion periphery and those that were 4-10 mL with 20 Gy. The primary endpoint was overall survival, for which the non-inferiority margin for the comparison of outcomes in patients with two to four brain metastases with those of patients with five to ten brain metastases was set as the value of the upper 95% CI for a hazard ratio (HR) of 1·30, and all data were analysed by intention to treat. The study was finalised on Dec 31, 2012, for analysis of the primary endpoint however, monitoring of stereotactic radiosurgery-induced complications and neurocognitive function assessment will continue for the censored subset until the end of 2014. This study is registered with the University Medical Information Network Clinical Trial Registry, number 000001812. Findings: We enrolled 1194 eligible patients between March 1, 2009, and Feb 15, 2012. Median overall survival after stereotactic radiosurgery was 13·9 months [95% CI 12·0-15·6] in the 455 patients with one tumour, 10·8 months [9·4-12·4] in the 531 patients with two to four tumours, and 10·8 months [9·1-12·7] in the 208 patients with five to ten tumours. Overall survival did not differ between the patients with two to four tumours and those with five to ten (HR 0·97, 95% CI 0·81-1·18 [less than non-inferiority margin], p=0·78; pnon-inferiority<0·0001). Stereotactic radiosurgery-induced adverse events occurred in 101 (8%) patients; nine (2%) patients with one tumour had one or more grade 3-4 event compared with 13 (2%) patients with two to four tumours and six (3%) patients with five to ten tumours. The proportion of patients who had one or more treatment-related adverse event of any grade did not differ significantly between the two groups of patients with multiple tumours (50 [9%] patients with two to four tumours vs 18 [9%] with five to ten; p=0·89). Four patients died, mainly of complications relating to stereotactic radiosurgery (two with one tumour and one each in the other two groups). Interpretation: Our results suggest that stereotactic radiosurgery without WBRT in patients with five to ten brain metastases is non-inferior to that in patients with two to four brain metastases. Considering the minimal invasiveness of stereotactic radiosurgery and the fewer side-effects than with WBRT, stereotactic radiosurgery might be a suitable alternative for patients with up to ten brain metastases. Funding: Japan Brain Foundation. © 2014 Elsevier Ltd.
Bunno M.,Koyo Hospital
Journal of the Wakayama Medical Society | Year: 2015
Objective We retrospectively elucidated the usefulness and problems of endoscopic submucosal dissection (ESD) for early gastric neoplasm in the very elderly patients( ≥ 85 years) in comparison with the non-elderly patients. Patients and methods 270 patients (273 lesions) treated with ESD from June 2005 to October 2014 were enrolled in our study. Subjects were classified into two groups very elderly (age ≥ 85 years) or non-elderly (age < 85 years). We investigated lesion characteristics, treatment outcomes and complications during the postoperative periods of ESD among two groups. Results No significant differences in clinical Characteristics, en bloc resection rate and operation time were observed. Pneumonia, but not post operative bleeding or perforation, developed in association with ESD were more frequently in the very elderly patients by 8.3 %. Conclusion Although pneumonia in association with ESD was more frequently observed in the very elderly patients in this study, ESD for early gastric neoplasm was managed appropriately even in the very elderly patients.
Hasegawa Y.,Izumi Municipal Hospital |
Ando M.,Nagoya University |
Kubo A.,Aichi Medical University |
Isa S.-I.,National Hospital Organization Kinki chuo Chest Medical Center |
And 6 more authors.
Lung Cancer | Year: 2014
Non-small cell lung cancer (NSCLC) in never smokers has emerged as a global public health issue. The cause is still unclear, and few studies have focused on the prevalence of human papillomavirus (HPV) in the never smokers. We performed a systematic search of PubMed for articles of HPV infection in human subjects with NSCLC up to September 2012. Although smoking status was not fully reported in all studies, we contacted the authors by e-mail to supplement this information. Differences in the distribution of patients with and without HPV infection were tested with the Chi squared test. We identified 46 eligible articles, including 23 from Asian countries (N= 2337 NSCLC cases), 19 from European countries (N= 1553) and 4 from North and South America (N= 160). The HPV prevalence was 28.1% (95% confidence interval (CI) 26.6-30.3%), 8.4% (95% CI 7.1-9.9%) and 21.3% (95% CI 15.2-28.4%), respectively. Eleven studies from East Asia (N= 1110) and 4 from Europe (N= 569) provided information on smoking status. The number of never smoker was 392 patients (33.9%) in East Asia and 54 patients (14.8%) in Europe. The HPV prevalence in East Asian countries was similar between never and ever smokers (33.9% vs 39.2%, P= 0.080). Based on the literature confirming the presence of HPV in lung cancer in never smokers, the virus plays a role in carcinogenesis in the disease. There were different patterns of HPV prevalence between Asian and European countries in the never smokers as well as in ever smokers. © 2013 Elsevier Ireland Ltd.
Yako R.,Wakayama Medical University |
Masuo O.,Wakayama Medical University |
Kubo K.,Koyo Hospital |
Nishimura Y.,Koyo Hospital |
Nakao N.,Wakayama Medical University
Journal of Neurosurgery | Year: 2016
The authors report an unusual case of a dural arteriovenous fistula (dAVF) draining only to the diploic vein and causing intracerebral hemorrhage. A 62-year-old woman presented with disturbance of consciousness and left hemiparesis. Brain CT scanning on admission showed a right frontal subcortical hemorrhage. Digital subtraction angiography revealed an arteriovenous shunt located in the region around the pterion, which connected the frontal branch of the right middle meningeal artery with the anterior temporal diploic vein and drained into cortical veins in a retrograde manner through the falcine vein. The dAVF was successfully obliterated by percutaneous transarterial embolization with N-butyl-2-cyanoacrylate. The mechanism of retrograde cortical venous reflux causing intracerebral hemorrhage is discussed. © AANS, 2016.
Tsujino K.,Kinki Central Hospital |
Tsujino K.,Osaka University |
Kurata T.,Kinki University |
Yamamoto S.,National Hospital Organization Kinki Chuo Chest Medical Center |
And 7 more authors.
Journal of Thoracic Oncology | Year: 2013
Introduction: The purpose of this study was to evaluate whether consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Methods: We systematically searched PubMed for phase II/III trials published before December 31, 2011, examining survival of LA-NSCLC treated with concurrent chemo-radiotherapy. Median overall survival and other study characteristics were collected from each study and pooled. We extracted log-transformed hazards and standard errors under the assumption that survival follows an exponential distribution, and computed a pooled median overall survival and a 95% confidence interval (CI) using random-effects model. Collected trial arms were categorized as having CCT or not having it, CCT+ and CCT-, respectively. Results: Forty-one studies were identified including seven phase III studies and 34 phase II studies with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical stage, performance status, cancer histology, sex, and median age between the two groups. There was no statistical difference in pooled mOS between CCT+ (19.0 month; 95% CI, 17.3-21.0) and CCT-(17.9 month; 95% CI, 16.1-19.9). Predicted hazard ratio of CCT+ to CCT-was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were no differences between the two groups with regard to grade 3-5 toxicities in pneumonitis, esophagitis, and neutropenia. These models estimated that addition of CCT could not lead to significant survival prolongation or risk reduction in death for LA-NSCLC patients. Conclusion: The pooled analysis based on a publication basis failed to provide evidence that CCT yields significant survival benefit for LA-NSCLC. © 2013 by the International Association for the Study of Lung Cancer.
Itakura T.,Koyo Hospital
Deep Brain Stimulation for Neurological Disorders: Theoretical Background and Clinical Application | Year: 2015
Chronic electrical stimulation of the brain has demonstrated excellent outcomes in patients with Parkinson’s disease and has recently also been applied to various other neurological diseases. This comprehensive, up-to-date textbook will meet the needs of all who wish to learn more about the application of deep brain stimulation and will provide a sound basis for safe and accurate surgery. The book comprises two main parts, the first of which presents relevant anatomical and functional background information on the basal ganglia, thalamus and other brain structures as well as on the mechanism of brain stimulation. The second part describes clinical studies on deep brain stimulation, covering results in a range of movement disorders and psychiatric diseases and also important aspects of instrumentation and technique. The authors are outstanding scientists and experts in the field from across the world. © Springer International Publishing Switzerland 2015.
PubMed | Koyo Hospital and Wakayama Medical University
Type: Case Reports | Journal: Journal of neurosurgery | Year: 2016
The authors report an unusual case of a dural arteriovenous fistula (dAVF) draining only to the diploic vein and causing intracerebral hemorrhage. A 62-year-old woman presented with disturbance of consciousness and left hemiparesis. Brain CT scanning on admission showed a right frontal subcortical hemorrhage. Digital subtraction angiography revealed an arteriovenous shunt located in the region around the pterion, which connected the frontal branch of the right middle meningeal artery with the anterior temporal diploic vein and drained into cortical veins in a retrograde manner through the falcine vein. The dAVF was successfully obliterated by percutaneous transarterial embolization with N-butyl-2-cyanoacrylate. The mechanism of retrograde cortical venous reflux causing intracerebral hemorrhage is discussed.
PubMed | Hyogo College of Medicine, Hanwa Daini Senboku Hospital, Koyo Hospital, Yokohama Municipal Citizens Hospital and 3 more.
Type: Comparative Study | Journal: Clinical lung cancer | Year: 2014
Early prediction of therapeutic outcome is important in determining whether the ongoing therapy is beneficial. In addition to anatomical response determined using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, recent studies have indicated that change in tumor glucose use on or after treatment correlates with histopathologic tumor regression and patient outcomes. This Perspective discusses the use of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for pharmacodynamic evaluation in a very early phase of treatment to predict clinical outcomes in patients with advanced non-small-cell lung cancer. We conducted a study to assess whether early metabolic response determined using FDG-PET correlated with clinical outcomes in patients treated with gefitinib or those treated with carboplatin plus paclitaxel (CP). Early metabolic response to gefitinib, but not CP, correlated with the late metabolic response, anatomical response, progression-free survival, and even overall survival. A rapid effect of molecular targeted agents might not be aptly evaluated using the conventional criteria, eg, RECIST, in a very early phase of treatment before volumetric shrinkage of the tumor. Based on the findings of several studies, and on the findings from our study, use of FDG-PET might enable prediction of clinical outcomes at a very early stage of treatment, especially in patients treated with molecular targeted agents with rapid clinical efficacy.
PubMed | Tokyo Women's Medical University, Shin Suma Hospital, Komaki City Hospital, Osaka City General Hospital and 8 more.
Type: | Journal: World neurosurgery | Year: 2016
Central neurocytoma (CN) is a rare benign neuronal tumor, and a limited number of reports have described the usefulness of radiosurgery for a relatively large group of patients. We evaluated the effectiveness and outcomes of Gamma Knife radiosurgery (GKS) for CN in a Japanese multi-institutional study.We performed retrospective analysis of 36 patients with CN who were treated with GKS in 12 institutes in Japan. All patients underwent surgery before GKS. The median tumor volume at GKS was 4.9 mL (range, 0.07-23.4 mL), and the median radiation dose prescribed to the tumor margin was 15 Gy (range, 10-20 Gy). The median follow-up period was 54.5 months (range, 3-180 months).The local tumor progression-free survival rates at 5 and 10 years were 94% and 86%, respectively. Three patients developed distant dissemination 16-90 months later. Overall progression-free survival was unrelated to the prescribed dose (<15 Gy vs. 15 Gy, P= 0.62), tumor size (<6 mL vs. 6 mL, P= 0.46), gender (P= 0.36), age (<30 vs. 30 years, P= 0.37), target of GKS (residual vs. recurrence, P= 0.90), and type of enhancement (homogeneous vs. inhomogeneous, P= 0.19). Two permanent complications occurred with 1 intratumoral hemorrhage and 1 radiation injury.GKS is effective for CN because of its high rate of long-term local tumor control. GKS may have a potential role as a primary treatment for asymptomatic, relatively small tumors in the absence of hydrocephalus without surgical resection.