Shanghai Chest Hospital

Shanghai, China

Shanghai Chest Hospital

Shanghai, China
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Zhang L.,Sun Yat Sen University | Ma S.,Zhejiang Cancer Hospital | Song X.,Guangxi Zhuang Autonomous Region Tumour Hospital | Han B.,Shanghai Chest Hospital | And 11 more authors.
The Lancet Oncology | Year: 2012

Background: Maintenance treatment of patients with advanced non-small-cell lung cancer (NSCLC) without disease progression after first-line chemotherapy is a subject of ongoing research. The aim of the randomised, double-blind, placebo-controlled, INFORM study was to investigate the efficacy, safety, and tolerability of the EGFR-tyrosine-kinase inhibitor gefitinib in the maintenance setting. Methods: Patients were aged 18 years or older, were of east Asian ethnic origin, had a life expectancy of more than 12 weeks, histologically or cytologically confirmed stage IIIb or IV NSCLC, a WHO performance status of 0-2, and had completed four cycles of first-line platinum-based doublet chemotherapy without disease progression or unacceptable toxic effects. Between Sept 28, 2008 and Aug 11, 2009, 296 patients were randomly assigned 1:1 to receive either gefitinib (250 mg per day orally) or placebo (orally) within 3-6 weeks after chemotherapy until progression or unacceptable toxic effects. Randomisation was done via an interactive web response system with computer-generated randomisation codes. Our primary endpoint was progression-free survival assessed in the intention-to-treat population. This completed study is registered with, number NCT00770588. Findings: Progression-free survival was significantly longer with gefitinib (n=148) than with placebo (148) (median progression-free survival 4·8 months [95% CI 3·2-8·5] vs 2·6 months [1·6-2·8]; hazard ratio [HR] 0·42, 95% CI 0·33-0·55; p<0·0001). Adverse events occurred more frequently with gefitinib than with placebo; the most common adverse events of any grade were rash (73 [50%] of 147 in the gefitinib group vs 14 [9%] of 148 in the placebo group), diarrhoea (37 [25%] vs 13 [9%]), and alanine aminotransferase increase (31 [21%] vs 12 [8%]). The most commonly reported grade 3 or 4 adverse event was alanine aminotransferase increase (3 [2%] of 147 in the gefitinib group, none of 148 in the placebo group). Ten of 147 (7%) patients given gefitinib and five of 148 (3%) patients given placebo had serious adverse events. Three deaths were thought to be related to treatment with gefitinib: one from interstitial lung disease; one from lung infection; and one from pneumonia. Interpretation: Maintenance treatment with gefitinib significantly prolonged progression-free survival compared with placebo in patients from east Asia with advanced NSCLC who achieved disease control after first-line chemotherapy. Clinicians should consider these data when making decisions about maintenance treatment in such patients. Funding: AstraZeneca. © 2012 Elsevier Ltd.

Wu Y.-L.,Guangdong Academy of Medical science | Lee J.S.,National Cancer Center | Thongprasert S.,Maharaj Nakorn Chiang Mai Hospital | Yu C.-J.,National Taiwan University Hospital | And 28 more authors.
The Lancet Oncology | Year: 2013

Background: The results of FASTACT, a randomised, placebo-controlled, phase 2 study, showed that intercalated chemotherapy and erlotinib significantly prolonged progression-free survival (PFS) in patients with advanced non-small-cell lung cancer. We undertook FASTACT-2, a phase 3 study in a similar patient population. Methods: In this phase 3 trial, patients with untreated stage IIIB/IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio by use of an interactive internet response system with minimisation algorithm (stratified by disease stage, tumour histology, smoking status, and chemotherapy regimen) to receive six cycles of gemcitabine (1250 mg/m2 on days 1 and 8, intravenously) plus platinum (carboplatin 5 × area under the curve or cisplatin 75 mg/m2 on day 1, intravenously) with intercalated erlotinib (150 mg/day on days 15-28, orally; chemotherapy plus erlotinib) or placebo orally (chemotherapy plus placebo) every 4 weeks. With the exception of an independent group responsible for monitoring data and safety monitoring board, everyone outside the interactive internet response system company was masked to treatment allocation. Patients continued to receive erlotinib or placebo until progression or unacceptable toxicity or death, and all patients in the placebo group were offered second-line erlotinib at the time of progression. The primary endpoint was PFS in the intention-to-treat population. This trial is registered with, number NCT00883779. Findings: From April 29, 2009, to Sept 9, 2010, 451 patients were randomly assigned to chemotherapy plus erlotinib (n=226) or chemotherapy plus placebo (n=225). PFS was significantly prolonged with chemotherapy plus erlotinib versus chemotherapy plus placebo (median PFS 7·6 months [95% CI 7·2-8·3], vs 6·0 months [5·6-7·1], hazard ratio [HR] 0·57 [0·47-0·69]; p<0·0001). Median overall survival for patients in the chemotherapy plus erlotinib and chemotherapy plus placebo groups was 18·3 months (16·3-20·8) and 15·2 months (12·7-17·5), respectively (HR 0·79 [0·64-0·99]; p=0·0420). Treatment benefit was noted only in patients with an activating EGFR gene mutation (median PFS 16·8 months [12·9-20·4] vs 6·9 months [5·3-7·6], HR 0·25 [0·16-0·39]; p<0·0001; median overall survival 31·4 months [22·2-undefined], vs 20·6 months [14·2-26·9], HR 0·48 [0·27-0·84]; p=0·0092). Serious adverse events were reported by 76 (34%) of 222 patients in the chemotherapy plus placebo group and 69 (31%) of 226 in the chemotherapy plus erlotinib group. The most common grade 3 or greater adverse events were neutropenia (65 [29%] patients and 55 [25%], respectively), thrombocytopenia (32 [14%] and 31 [14%], respectively), and anaemia (26 [12%] and 21 [9%], respectively). Interpretation: Intercalated chemotherapy and erlotinib is a viable first-line option for patients with non-small-cell lung cancer with EGFR mutation-positive disease or selected patients with unknown EGFR mutation status. Funding: F Hoffmann-La Roche. © 2013 Elsevier Ltd.

Zhang J.,Shanghai Chest Hospital | Wu J.,Shanghai Chest Hospital | Tan Q.,Shanghai Chest Hospital | Zhu L.,Shanghai Chest Hospital | Gao W.,Shanghai Chest Hospital
Journal of Thoracic Oncology | Year: 2013

Background: Patients with pathological stage IA adenocarcinoma (AC) have a variable prognosis, even if treated in the same way. The postoperative treatment of pathological stage IA patients is also controversial. Methods: We identified 176 patients with pathological stage IA AC who had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China, between 2000 and 2006. No patient had preoperative treatment. The histologic subtypes of all patients were classified according to the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary lung AC classification. Patients' 5-year overall survival (OS) and 5-year disease-free survival (DFS) were calculated using Kaplan-Meier and Cox regression analyses. Results: One hundred seventy-six patients with pathological stage IA AC had an 86.6% 5-year OS and 74.6% 5-year DFS. The 10 patients with micropapillary predominant subtype had the lowest 5-year DFS (40.0%).The 12 patients with solid predominant with mucin production subtype had the lowest 5-year OS (66.7%). Univariate and multivariate analysis showed that sex and prognositic groups of the IASLC/ATS/ERS histologic classification were significantly associated with 5-year DFS of pathological stage IA AC. Conclusion: Our study revealed that sex was an independent prognostic factor of pathological stage IA AC. The IASLC/ATS/ERS classification of lung AC identifies histologic categories with prognostic differences that could be helpful in clinical therapy. © 2013 by the International Association for the Study of Lung Cancer.

Bai H.,Shanghai Chest Hospital | Han B.,Shanghai Chest Hospital
American Journal of Clinical Oncology: Cancer Clinical Trials | Year: 2013

BACKGROUND: Brain metastases commonly occur in non-small cell lung cancer (NSCLC), and patient prognosis is poor. Erlotinib, a specific inhibitor of epidermal growth factor receptor-associated tyrosine kinase, has shown antitumor activity in advanced NSCLC. This study evaluates erlotinib in the treatment for brain metastases from NSCLC. PATIENTS AND METHODS: We retrospectively reviewed 40 NSCLC patients with brain metastases. All were treated with oral erlotinib and followed until disease progression, death, or intolerable side effects. EGFR mutations within surgical specimens were retrospectively examined in 9 patients. RESULTS: For intracranial diseases, partial response (PR) was observed in 4 patients (10%), stable disease (SD) in 21 (52.5%), and progressive disease in 15 (37.5%), with an objective response rate of 10% and a disease control rate (DCR) of 62.5%. For extracranial diseases, DCR was observed in 17 patients (42.5%) (3 PRs+14 SDs) and progressive disease in 23 patients (57.5%). DCR within brain lesions in patients with activating EGFR mutations was 80% (1 PR+3 SDs), compared with 25% (1 SD) in patients with negative EGFR mutation. The median progression-free survival and median survival were 3.0 months and 9.2 months, respectively. There were no clinical factors associated with the response to erlotinib and survival as well (all P>0.05), whereas only the DCR in the brain was related to survival in multivariate analysis (P=0.000). CONCLUSIONS: Erlotinib is modestly active and well-tolerated by NSCLC patients with brain metastases. Erlotinib seems to be more effective in patients with activating EGFR mutations. Erlotinib may be an alternative to traditional treatments in this patient population. Copyright © 2012 by Lippincott Williams &Wilkins.

Xing Q.,Qingdao Childrens Hospital | Pan S.,Qingdao Childrens Hospital | An Q.,University of Sichuan | Zhang Z.,Zhejiang University | And 4 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2010

Objective: To summarize the clinical experiences and mid-term follow-up results of perventricular closure of perimembranous ventricular septal defect without cardiopulmonary bypass under transesophageal echocardiography guidance. Methods: A total of 408 patients with perimembranous ventricular septal defects, aged 5 months to 15 years (3.1 ± 1.7 years) with a body weight of 4.5 to 26 kg (13.6 ± 5.5 kg), underwent perventricular device closure. The procedure was performed via a small lower sternal incision. A guidewire was inserted through the ventricular septal defect to the left ventricle under transesophageal echocardiography guidance after a pursestring suture was placed on the right ventricular free wall. A modified delivery sheath was introduced over the guidewire to establish the delivery pathway. Proper devices were delivered and then deployed if no atrioventricular or aortic valvular disturbance, or residual shunt was detected by transesophageal echocardiography. Patients were followed up with a standard protocol, which is once every month in the first 3 postoperative months and then once every 3 months with echocardiography, electrocardiography, and chest radiography in each follow-up. Results: A total of 393 patients in this group underwent successful closure (96.3%), and the procedure was converted to conventional open repair in 15 patients (3.7%). A total of 213 symmetric devices (54.2%) and 180 asymmetric devices (45.8%) were implanted. Only 6 of the 393 patients (3.5%) received transfusion of blood products. New trivial or mild tricuspid regurgitation was found in 13 patients (3.3%), and there was no worsening of regurgitation in those patients with existing tricuspid regurgitation before operation. Eleven patients (2.8%) had incomplete right bundle branch block. Most of the patients were discharged 3 to 5 days after the operation. Follow-up in all patients ranged from 3 months to 2 years (14.6 ± 6.2 months) and revealed no residual shunt, new or aggravating aortic regurgitation, obstruction of left or right ventricular outflow tract, or device dislocation. Conclusion: Minimally invasive perventricular device closure of ventricular septal defect without cardiopulmonary bypass is a simple, effective, and relatively safe intervention under guidance of transesophageal echocardiography. This method should be considered for patients with ventricular septal defect. Long-term follow-up is necessary. © 2010 The American Association for Thoracic Surgery.

Zhong R.,Shanghai Chest Hospital | Teng J.,Shanghai Chest Hospital | Han B.,Shanghai Chest Hospital | Zhong H.,Shanghai Chest Hospital
Cancer Immunology, Immunotherapy | Year: 2011

Background: Lung cancer is the leading cause for cancer-related mortality and morbidity, and the survival of late-stage non-small cell lung cancer (NSCLC) remains poor. We hereby evaluate conventional chemotherapy followed by immunotherapy using dendritic cells and cytokine-induced killer cells in the treatment for late stage of NSCLC. Methods: Twenty-eight untreated patients suffered from IIIB to IV NSCLC were enrolled in the study between August 2004 and October 2005, and all received four courses of vinorelbine-platinum (NP) chemotherapy. Fourteen of them received conventional NP chemotherapy followed by vaccinated with CEA (605-613) peptide-pulsed autologous dendritic cells and CIK cells. Vaccination was repeated at 30-day intervals for 4 cycles. The adverse effects, time to progression (TTP), and overall survival (OS) in each group were evaluated. Results: The adverse effect as a result of chemoimmunotherapy was mild and tolerable. Rash, acne, and pruritus were more frequent in the chemoimmunotherapy group than in the chemotherapy group (64.2% vs. 7.1%, P = 0.004). Non-infectious fever was more frequent in the chemoimmunotherapy group than in the chemotherapy group (71.4% vs. 21.4% P = 0.02). Less grade 3/4 fatigue was observed in patients receiving chemoimmunotherapy: 7.1% versus 57.1% in chemotherapy group, P = 0.01. Compared with patients in chemotherapy group, time to progression in chemoimmunotherapy significantly prolonged, with the median improved from 5.2 months (95% CI: 3.3-6.0) to 6.9 months (95% CI: 5.0-8.8) (P = 0.03). The 1-, 2-, and 5-year survival rates were 64.3, 49, and 21.0%, respectively in chemoimmunotherapy group. Overall survival rate showed no statistically difference between two groups (P = 0.18). Conclusions: Chemoimmunotherapy could alleviate adverse effects of conventional chemotherapy and prolong survival for patients with late-stage NSCLC. © 2011 Springer-Verlag.

Shen S.,Shanghai Chest Hospital | Ai X.,Shanghai Chest Hospital | Lu S.,Shanghai Chest Hospital
Journal of Surgical Oncology | Year: 2013

Background: To evaluate long-term survival in thymic epithelial tumors (TETs), we present our experiences at a single institution in China. Methods: We performed a retrospective analysis including 115 patients with TETs from 2001 to 2006. Histological diagnosis was completed based on the new WHO classification system. A univariate and multivariate survival analysis was performed, which included myasthenia gravis (MG), WHO histological type, Masaoka stage, completeness of resection, and adjuvant radiotherapy (RT). Results: WHO histological subtype was closely correlated with that of Masaoka stage. The overall median survival time was 84.4 months and the 7-year survival rate was 78%. In the univariate analysis, three prognostic factors, including WHO histology type, Masaoka stage and complete resection, were statistically significant. In the analysis of the cases with complete resection, adjuvant RT did not show obvious survival benefit. In the multivariate analysis, Masaoka stage was the only independent factor that predicted long-time survival. Conclusions: Thymic carcinoma should be regarded as a different category of the disease due to its aggressive and poorer prognosis. Complete resection of the tumor and Masaoka stage I and II were found to contribute to a better survival. Adjuvant RT is not recommended for patients with complete resection in thymomas. © 2012 Wiley Periodicals, Inc.

Peng H.,Shanghai Chest Hospital | Ma M.,Shanghai Chest Hospital | Han B.,Shanghai Chest Hospital
Chinese Journal of Lung Cancer | Year: 2011

Background and objective: At present non-small cell lung cancer (NSCLC) is still the leading cause of death induced by cancer. The aim of this study is to investigate the prognostic factors of advanced NSCLC. Methods: Total 1,742 cases of stage IV NSCLC data from Jan 4, 2000 to Dec 25, 2008 in Shanghai Chest Hospital were collected, confirmed by pathological examinations. Analysis was made to observe the impact of treatment on prognosis in gender, age, smoking history, pathology, classification, clinical TNM stage. Survival rate, survival difference were evaluated by Kaplan-Meire method and Log-rank test respectively. The prognosis were analyzed by Cox multivariate regression. Results: The median survival time of 1,742 patients was 10.0 months (9.5 months-10.5 months). One, two, three, four, and five-year survival rates were 44%, 22%, 13%, 9%, 6% respectively. The median survivals of single or multiple metastasis were 11 months vs 7 months (P<0.001). Survival time were different in metastasic organs, with the median survival time as follows: lung for about 12 months (11.0 months-12.9 months), bone for 9 months (8.3 months-9.6 months), brain for 8 months (6.8 months-9.1 months), liver, adrenal gland, distannt lymph node metastasis for 5 months (3.8 months-6.1 months), and subcutaneous for 3 months (1.7 months-4.3 months). The median survival times of adenocarcinoma (n= 1,086, 62%) and squamous cell carcinoma cases (n=305, 17.5%) were 12 months vs 8 months (P<0.001). The median survival time of chemotherapy and best supportive care were 11 months vs 6 months (P<0.001); the median survival times ofwith and without radiotherapy were 11 months vs 9 months (P=0.017). Conclusion: Gender, age, gross type, pathological type, clinical T stage, N stage, numbers of metastatic organ, smoking history, treatment of advanced non-small cell lung cancer were independent prognostic factors.

FENG J.,Shanghai Chest Hospital
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2011

To evaluate the influence of the number, station and field of metastatic lymph node on the prognosis of thoracic esophageal cancer and to investigate an ideal nodal staging method. Clinicopathological and follow-up data of the 204 patients who underwent thoracic esophagectomy from June 2001 to December 2009 were analyzed retrospectively and all the patients were re-staged according to the 7th edition of the AJCC TNM staging system. Log-rank test was applied to perform survival analysis according to lymph node metastasis staging(number, station, and field), Cox proportional hazard model was used to screen risk factors. The follow-up rate was 93.1%(190/204). The median follow up time was 37.0(0-104) months. The overall and cancer-specific 5-year survival rates were 35.0% and 38.8%. When grouped according to the number of metastatic lymph node(0, 1-2, 3-6, ≥ 7), the 5-year survival rates of pN0, pN1, pN2 and pN3 were 47.8, 31.8%, 11.5% and 0 respectively(P=0.000). When grouped according to the number of stations of metastatic lymph node[N(0s), N(1s)(1 station LN metastasis), N(≥ 2s)(≥ 2 stations LN metastasis)], the 5-year survival rates of N(0s), N(1s), N(≥ 2s) were 47.8%, 31.5% and 11.3% respectively(P=0.000). When grouped according to the number of fields of metastatic lymph node, the 5-year survival rates of N0, 1 field, 2 fields and 3 fields involvement were 47.8%, 34.2%, 12.1% and 0 respectively(P=0.000). Cox regression showed that the number of stations [P=0.043, RR(95% CI)=1.540(1.013-2.342)], and the number of fields[P=0.010, RR(95%CI)=2.187(1.210-3.951)] of metastatic lymph node were the independent risk factors for survival. The extent of metastatic lymph node is an independent risk factor for the prognosis of esophageal cancer patients. Revision of the current N-classification of TNM staging system according to the number of stations of metastatic lymph node may be more reasonable.

Wang Z.X.,Shanghai Chest Hospital
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery | Year: 2013

Most patients with esophageal cancer have advanced disease at presentation. The efficacy of surgical resection alone is often unsatisfactory in patients with stage III or more advanced cancer according to the seventh edition of UICC staging system for esophageal cancer. The systematic multidisciplinary treatment is important. Mounting evidence indicates that preoperative concurrent chemoradiotherapy is the most effective induction therapy to down-stage tumor and increase radical resection rate. For the esophageal squamous cell carcinoma patients with multi-stations and multi-fields lymph node metastasis, preoperative induction chemotherapy would be a viable option. For locally advanced cancers which have been surgically resected, postoperative adjuvant radiotherapy maybe helpful to improve local control for the insufficient surgical dissection. The role of adjuvant chemotherapy also needs further studies. Thoracic esophageal squamous cell carcinoma and lower esophageal adenocarcinoma which is common in western countries are different. We need more prospective clinical studies to establish our treatment modalities for esophageal cancer.

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