Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 455
Filtrar
1.
Ann Surg ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34596079

RESUMO

INTRODUCTION: Use of neoadjuvant immunotherapy agent in advanced stage NSCLC is controversial. Herein, we aim to report on a case series of successful conversion from initial unresectable stage cIIIB NSCLC to radical minimally invasive surgery through immunochemotherapy; with particular attention given to surgical outcomes and survival benefit of surgery. METHODS: Fifty-one patients with initial stage cIIIB NSCLC who received PD-1 agents plus platinum-based chemotherapy between May, 2018 to August, 2020 were retrospectively identified. Surgical and oncological outcomes of enrolled patients were collected. RESULTS: Of 31 patients who underwent subsequent resection, 23 (74.2%) patients underwent lobectomy, 1 (3.2%) underwent pneumonectomy, 5 (16.1%) underwent sleeve lobectomy, and 2 (6.5%) with bilobectomy. The median surgical time was 205 minutes (range, 100-520). The average blood loss was 185 (range: 10-1100) ml. Dense adhesions or fibrosis was noted in 15 cases. The median postoperative hospital stay was 6 (range: 3-13) days. No surgical-related mortality was recorded, only 5 patients (16.1%) experienced any postoperative morbidity (no grade 3 complications). Ten patients (32.3%) had major pathological response, with mediastinal down-staging been observed in 22/31 (71.0%) patients. With a median after up of 15.4 months, thirty-one patients that had surgery had relatively longer median DFS/PFS compared to that of either non-responders or responders that without surgery (27.5 vs. 4.7 vs. 16.7 months, respectively). CONCLUSIONS: Radical surgery after chemoimmunotherapy in initial unresectable stage IIIB NSCLC seems to be safe with low surgical-related mortality and morbidity, and was favorably associated with longer DFS/PFS compared to those without surgery.

2.
Thorac Cancer ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596367

RESUMO

BACKGROUND: The presence of pleural effusion is an independent predictor for poor survival in patients with small-cell lung cancer (SCLC). The aim of this study was to assess the efficacy and safety of anlotinib in patients with SCLC and pleural effusion. METHODS: This was a randomized, double-blind, multicenter, phase II trial. Patients histologically diagnosed with SCLC and pleural effusion and had received at least two lines of chemotherapy were enrolled into the study. The patients received anlotinib 12 mg/day or a placebo. RESULTS: The overall response rate (ORR) was 3.7% for anlotinib (n = 27) and 0% in the placebo group (n = 15) (p = 1.000). The disease control rate (DCR) of the anlotinib group (63.0%) was higher than that of the placebo group (0%, p < 0.0001). The median progression-free survival (PFS) increased in the anlotinib group (2.8 months) compared to the placebo group (0.7 months, HR = 0.10, 95% CI: 0.03-0.28, p < 0.001). The median overall survival of the anlotinib group (6.5 months) was higher than that of the placebo group (2.8 months, HR = 0.52, 95% CI: 0.22-1.23, p = 0.1285). The incidence of any grade adverse events was 100% in both groups. The percentage of grade 3-4 adverse events in the anlotinib group was 44.4% (12/27) compared to 40.0% (6/15) in the placebo group. Hypertension (37.0%), fatigue (29.6%), and loss of appetite (29.6%) typically appeared in the anlotinib group. CONCLUSIONS: In this post hoc analysis, anlotinib was associated with improved PFS in patients with SCLC and baseline pleural effusion. However, additional studies with a large sample size are necessary to substantiate the current findings.

3.
Signal Transduct Target Ther ; 6(1): 355, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

4.
Sleep Med ; 87: 183-190, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34627121

RESUMO

BACKGROUND: The relationship between insomnia and lung cancer is scanty. The Mendelian randomization approach provides the rationale for evaluating the potential causality between genetically-predicted insomnia and lung cancer risk. METHODS: We extracted 148 insomnia-related single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from published genome-wide association studies (GWASs). Summary data of individual-level genetic information of participants were obtained from the International Lung Cancer Consortium (ILCCO) (29,266 cases and 56,450 controls). MR analyses were performed using the inverse-variance-weighted approach, MR pleiotropy residual sum and outlier (MR-PRESSO) test, weighted median estimator, and MR-Egger regression. Sensitivity analyses were further performed using Egger intercept analysis, leave-one-out analysis, MR-PRESSO global test, and Cochran's Q test to verify the robustness of our findings. RESULTS: The results of the MR analysis indicated an increased risk of lung cancer in insomnia patients (OR = 1.1671; 95% CI 1.0754-1.2666, p = 0.0002). The subgroup analyses showed increased risks of lung adenocarcinoma (OR = 1.1878; 95% CI 1.0594-1.3317, p = 0.0032) and squamous cell lung cancer (OR = 1.1595; 95% CI 1.0248-1.3119, p = 0.0188). CONCLUSION: Our study indicated that insomnia is a causal risk factor in the development of lung cancer. Due to the lack of evidence on both the epidemiology and the mechanism level, more studies are needed to better elucidate the results of the study.

5.
J Magn Reson Imaging ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570394

RESUMO

BACKGROUND: The treatment efficacy of angiogenesis inhibitor could be underestimated at an early stage based on tumor volume changes. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can quantitatively assess tumors at the cellular level, but it is unclear whether it can provide useful information for assessing treatment response of anti-angiogenic treatment for lung adenocarcinoma. PURPOSE: To determine the use of IVIM-DWI for non-invasive monitoring of the early response to anti-angiogenic treatment in the orthotopic transplantation of lung adenocarcinoma model. STUDY TYPE: Prospective. POPULATION: Thirty-seven nude mice were randomized into two groups: treatment group (received bevacizumab + cisplatin, N = 20) and control group (received saline, N = 17). FIELD STRENGTH/SEQUENCE: Single-shot turbo spin-echo (TSE) IVIM-DWI, TSE T2-weighted imaging at 3.0 T. ASSESSMENT: Tumor volume, IVIM parameters (apparent diffusion coefficient [ADC], diffusivity [D], perfusion fraction [f], and pseudo-diffusion coefficient [D*]) were measured before and 2 hours, 3, 7, 10 and 14 days after treatment. Regions of interest were manually drawn along the inner edge of the tumor by two radiologists with 5 and 10-year experience in magnetic resonance imaging. Pathological examinations (hematoxylin and eosin stain, cluster of differentiation 34) were performed. STATISTICAL TESTS: Kolmogorov-Smirnov test, repeated-measure two-way analysis of variance test, Mann-Whitney U test, Pearson correlation analysis, receiver operating characteristic curve. P < 0.05 was considered statistically significant. RESULTS: The tumor volume of the two groups was significantly different only on day 14 (control group vs. treatment group, 43.15 ± 18.28 mm3 vs. 28.41 ± 1.71 mm3 ). ADC2h , ADC10d , D2h , D7d , D10d , and D14d were significantly higher, while f10d and f14d were significantly lower in the treatment group compared to those of the control group. Both the △ADC2h (r = -0.631) and △D2h (r = -0.700) showed moderate correlations with the relative tumor volume on day 14. DATA CONCLUSION: IVIM has the potential to predict and monitor the early response to anti-angiogenic treatment, earlier than size changes, for lung adenocarcinoma. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34419362

RESUMO

OBJECTIVES: The aim of the present study was to compare the short-term outcomes between spontaneous ventilation video-assisted thoracic surgery (SV-VATS) and mechanical ventilation video-assisted thoracic surgery (MV-VATS) in the elderly. All patients included in the present study underwent lobectomy, segmentectomy, or wedge resection and lymph node dissection. DESIGN: A retrospective cohor. SETTING: The first affiliated hospital of Guangzhou Medical University, Guangzhou, China. PARTICIPANTS: The present study included 799 elderly patients diagnosed with non-small-cell lung cancer undergoing SV-VATS or MV-VATS. After propensity score matching, 80 patients in the SV-VATS group and 80 patients in the MV-VATS group were analyzed. INTERVENTIONS: Patients in the SV-VATS group received spontaneous-ventilation anesthesia, which was administered as follows: intravenous anesthesia + laryngeal mask airway + thoracic paravertebral block + visceral pleural surface anesthesia + thoracic vagus nerve block. Patients in the MV-VATS group received general endotracheal anesthesia. SV-VATS or MV-VATS was performed according to the preference of the patients. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in anesthesia time (226.3 ± 79.8 v 238.5 ± 66.2 min; p = 0.44), surgery time (166.2 ± 102.6 v 170.1 ± 83.4 min; p = 0.66), and number of dissected lymph nodes (5.3 ± 7.5 v 4.4 ± 7.4; p = 0.23) between the two groups. There were significant differences in intraoperative bleeding (61.5 ± 165.1 v 82.2 ± 116.9 mL; p < 0.001). After surgery, the two groups were statistically comparable in terms of hospitalization (17.6 ± 7.6 v 17.2 ± 6.9 days; p = 0.95) and incidence of complications (7.5% v 13.8%; p = 0.20), while there were significant differences in chest tube duration (6.1 ± 3.3 v 4.5 ± 1.2 days; p < 0.001). CONCLUSIONS: SV-VATS is feasible and as safe as MV-VATS, and it could be considered as an alternative treatment for the elderly.

8.
Lancet Respir Med ; 9(9): 1021-1029, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34280355

RESUMO

BACKGROUND: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study. METHODS: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 of each cycle plus cisplatin 75 mg/m2 on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797. FINDINGS: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group. INTERPRETATION: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. FUNDING: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Éteres de Coroa/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , China , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Resultado do Tratamento
9.
J Cancer Res Clin Oncol ; 147(10): 2837-2849, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34318357

RESUMO

BACKGROUND: Since little consensus has been reached on whether milder reduction in forced expiratory volume in 1 s (FEV1) increases lung cancer incidence, we conducted a meta-analysis and performed Mendelian randomization (MR) analysis to explore the association and causal relationship between FEV1 and lung cancer incidence. METHODS: We conducted a comprehensive search from PubMed, Medline, EMBASE, and Cochrane Library databases as of February 2020. MR analysis was performed using summary data obtained from two large consortia [International Lung Cancer Consortium (ILCCO) and Neale Lab] to assess the possible causality between FEV1 and lung cancer risk. RESULTS: Eight studies involving 88,743 cases were included. The incidence of lung cancer increased with decreasing FEV1.The combined odds ratio (OR) of decreased FEV1 for lung cancer incidence was 1.91 [95% confidence interval (CI) 1.67-2.19; P < 0.001]. Compared with the highest quintile of FEV1 (quintile 5, > 100% of predicted), the OR was 3.06 (95% CI 2.20-4.24; P < 0.001) for quintile 1 (< 70% of predicted), 1.89 (95% CI 1.50-2.38; P < 0.001) for quintile 2 (70-80% of predicted), 1.53 (95% CI 1.31-1.79; P < 0.001) for quintile 3 (80-90% of predicted), and 1.64 (95% CI 1.18-2.28; P = 0.003) for quintile 4 (90-100% of predicted). In subgroup meta-analysis, the correlation between FEV1 and lung cancer risk was different among men (OR = 1.74; 95% CI 1.49-2.03; P < 0.001) and women (OR = 2.80; 95% CI 1.87-4.19; P < 0.001). However, MR analysis showed no causality between the FEV1 and lung cancer risk (OR = 1.199; 95% CI 0.958-1.500; P = 0.114). CONCLUSION: FEV1 is likely to be a predictor of lung cancer, especially for women. However, genetically decreased FEV1 is not causally correlated with lung cancer incidence.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Pulmão/fisiopatologia , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Estudo de Associação Genômica Ampla , Humanos , Incidência , Metanálise como Assunto , Fatores de Risco
10.
Ann Thorac Surg ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34214545

RESUMO

Carinal reconstruction and omental flap harvesting are traditionally performed via open approaches. We reported a case in which carinal reconstruction with bronchial flap and omental flap reinforcement was performed using minimally invasive approaches. The omental flap was harvested laparoscopically, and wrapped around the anastomosis, which reduced the risk of airway anastomosis complications. Non-circumferential resection and reconstruction used bronchial flap, which made it easier to perform under video-assisted thoracoscopic surgery conditions. Minimally invasive carinal reconstruction with bronchial flap and omental reinforcement after neoadjuvant treatment, can be safely performed.

11.
Future Oncol ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278827

RESUMO

Osimertinib is a third-generation, irreversible oral EGFR-tyrosine kinase inhibitor), that potently inhibits EGFR-tyrosine kinase inhibitor-sensitizing mutations and T790M resistance mutations together with efficacy in CNS metastases in patients with non-small-cell lung cancer (NSCLC). Here we describe the rationale and design for the Phase III NeoADAURA study (NCT04351555), which will evaluate neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone prior to surgery, in patients with resectable stage II-IIIB N2 EGFR mutation-positive NSCLC. The primary end point is centrally assessed major pathological response at the time of resection. Secondary end points include event-free survival, pathological complete response, nodal downstaging at the time of surgery, disease-free survival, overall survival and health-related quality of life. Safety and tolerability will also be assessed. Trial Registration number: NCT04351555 (ClinicalTrials.gov).

12.
Thorac Cancer ; 12(17): 2345-2351, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34273139

RESUMO

BACKGROUND: There is a lack of targeted therapeutic options for squamous cell lung cancer (SCC). Accelerated hypertension is an issue with many targeted therapies for lung cancer. This study aimed to analyze the efficacy of anlotinib, based on progression-free survival (PFS) and overall survival (OS) in patients with SCC, stratified by hypertension and Eastern Cooperative Oncology Group (ECOG) score. METHODS: This was a post hoc analysis of a multicenter, double-blind, phase III ALTER0303 randomized controlled trial. Only patients with SCC were included. The occurrence of hypertension during the study period was defined according to CTCAE 4.03. OS and PFS were the primary and secondary endpoints, respectively. The patients were stratified according to hypertension and ECOG score, respectively. RESULTS: The median PFS in the patients who developed hypertension was longer than in those who did not (7.2 (95% CI: 3.5-11.0) versus 3.2 (95% CI: 1.2-5.3) months, p = 0.001; HR (95% CI), 0.4 (0.2-0.8)). In the ECOG 0 patients, the median PFS in the patients who developed hypertension versus those who did not was 5.6 vs. 1.8 months, respectively (Figure 2(d)). In the ECOG 1 patients, the median PFS in the patients who developed hypertension versus those who did not was 7.0 (95% CI: 3.0-11.0) vs. 4.8 (95% CI: 1.2-8.5) months (p = 0.043). No statistically significant differences were found in OS in the stratified analyses. CONCLUSIONS: The occurrence of hypertension might be a clinical indicator predicting the efficacy of third-line anlotinib treatment in patients with SCC.

14.
Ann Thorac Surg ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34062123

RESUMO

BACKGROUND: The appropriate surgical approach of VATS for early-stage thymoma remains unclear. The present study aimed to explore the safety and feasibility of subxiphoid and subcostal arch thoracoscopic thymectomy in comparison with unilateral thoracoscopic thymectomy for treatment of early-stage thymoma. METHODS: The outcomes of 237 patients without myasthenia gravis who had undergone thoracoscopic thymectomy for Masaoka stage I and II thymoma from January 2015 to May 2019 at our center were retrospectively evaluated (subxiphoid and subcostal arch approach: 39; unilateral VATS approach: 198). A propensity score-matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner. RESULTS: There was no surgery-related mortality in included patients. Matching of patients according to propensity score resulted in a cohort that consisted of 39 patients in both groups. Patients had similar clinical characteristics in both groups. Compared with those in the unilateral group, patients in the subxiphoid group yielded lower pain scores at 24- and 72-hours post-operation, respectively (P<0.01). In addition, the operation time was longer in the subxiphoid group (147.5±43.6min vs. 93.2±33.8min, p<0.01). There were no significant differences in blood loss, total volume and time of drainage, complications or postoperative hospital stays between the two groups. CONCLUSIONS: Subxiphoid and subcostal arch thoracoscopic thymectomy for early-stage thymoma appears to be a safe and feasible procedure. It is considered to be less invasive as it may cause minimal postoperative pain compared to the unilateral VATS approach.

16.
Br J Cancer ; 125(3): 366-371, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34006926

RESUMO

BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC). METHODS: We conducted this Phase 2 trial at 11 institutions in China. Patients with pathologically confirmed SCLC who failed at least two lines of chemotherapy were enrolled. Subjects were randomly assigned in a 2:1 ratio to receive either anlotinib 12 mg orally once daily for 14 days every 3 weeks or placebo. The primary endpoint was progression-free survival (PFS). RESULTS: Between March 30, 2017 and June 8, 2018, a total of 82 and 38 patients were randomly assigned to receive anlotinib and placebo. The median PFS was significantly longer in the anlotinib group compared with the placebo group (4.1 months [95% confidence interval (CI), 2.8-4.2] vs 0.7 months [95% CI, 0.7-0.8]; hazard ratio (HR) 0.19 [95% CI, 0.12-0.32], p < 0.0001). Overall survival (OS) was significantly longer with anlotinib than placebo (7.3 months [95% CI, 6.1-10.3] vs 4.9 months [95% CI, 2.7-6.0]; HR 0.53 [95% CI, 0.34-0.81], p = 0.0029). CONCLUSIONS: Anlotinib as a third-line or subsequent treatment for Chinese patients with SCLC showed improved PFS and OS than placebo with favourable safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT03059797.

17.
Semin Arthritis Rheum ; 51(3): 565-575, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33932788

RESUMO

OBJECTIVE: Observational studies suggest that rheumatoid arthritis (RA) may be associated with lung cancer (LC) risk, while the evidence is inconsistent. We conducted a meta-analysis and a Mendelian randomization study to investigate the association and causality between RA and the LC risk. METHODS: We conducted a systematic search of cohort studies and performed a meta-analysis (PROSPERO ID CRD42020159082) to calculate the relative risks (RRs) and their 95% confidence intervals (95%CIs). Subgroup analyses based on sex and initiation year of follow-up were carried out. E-values of each study were calculated to evaluate if existing studies were sensitive to unmeasured confounding. Furthermore, we investigated the correlation between genetically predisposed RA and LC risk using summary statistics from the International Lung Cancer Consortium (11,348 cases and 15,861 controls) and 90 RA-related single nucleotide polymorphisms from European and East Asian descent as instrumental variables. A two-sample Mendelian randomization (MR) analysis was performed to detect the findings based on LC and histological subtypes. Sensitivity analyses were performed to test the robustness of our findings. RESULTS: In the meta-analysis of 11 cohort studies involving 183,888 patients, an increased risk of LC was observed among RA patients (RR = 1.44, 95%CI = 1.31-1.57). Subgroup analyses suggested that male patients have a relatively higher LC risk than female patients, and an increased incidence of LC in RA patients was found from 1950 to 2010. Conversely, in the MR analysis, we found that genetically predisposed RA was associated with a decreased risk of LC overall, while neither causally associated with the risk of lung adenocarcinoma nor squamous cell lung cancer. Nevertheless, genetically predisposed RA was associated with a decreased LC risk among the East Asian population, but not in Europeans. These results were robust against extensive sensitivity analyses. CONCLUSION: Our meta-analysis suggested that although RA was associated with a relatively higher LC risk, the causal relationship between genetically predisposed RA and LC risk was not supported by the MR study. Further studies are warranted to elucidate the possible association between RA and the risk of LC, as well as its underlying mechanisms.


Assuntos
Artrite Reumatoide , Neoplasias Pulmonares , Artrite Reumatoide/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único
18.
J Thorac Oncol ; 16(8): 1403-1414, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33915252

RESUMO

INTRODUCTION: ZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage SCLC (ES-SCLC). METHODS: Patients with complete response (CR) or partial response (PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥ 77 kg, platelet count ≥ 150,000/µL] or 200 mg) once daily until progression or unacceptable toxicity. Primary end points were progression-free survival (PFS) (blinded independent central review) and overall survival (sample size planned: 591 patients). Secondary end points included investigator-evaluated PFS and safety. RESULTS: ZL-2306-005 was terminated early owing to ES-SCLC treatment landscape changes (data cutoff: March 20, 2020). During July 2018-February 2020, a total of 185 of 272 patients screened were randomized (niraparib: n = 125 [CR = 1, PR = 124]; placebo: n = 60 [CR = 1, PR = 59]). Median (95% confidence interval [CI]) PFS (blinded independent central review) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio (HR) = 0.66 (95% CI: 0.46-0.95, p = 0.0242). Median overall survival was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR = 1.03 (95% CI: 0.62-1.73, p = 0.9052). Median investigator-evaluated PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR = 0.88 (95% CI: 0.61-1.26; p = 0.4653). Grade greater than or equal to 3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients. CONCLUSIONS: ZL-2306-005 did not reach primary end points. Nevertheless, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.


Assuntos
Neoplasias Pulmonares , Neoplasias Ovarianas , Protocolos de Quimioterapia Combinada Antineoplásica , Método Duplo-Cego , Feminino , Humanos , Indazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quimioterapia de Manutenção , Piperidinas/uso terapêutico
19.
Ann Thorac Surg ; 112(2): 661-664, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33901454

RESUMO

PURPOSE: Heart-lung transplantation (HLTx) is a life-saving treatment option for patients with advanced cardiopulmonary failure. However, posterior mediastinal bleeding and phrenic nerve damage are still intraoperative challenges for the traditional surgical method. This study reports an innovative non-in situ HLTx performed in our center, preventing posterior mediastinal bleeding and phrenic nerve damage effectively. DESCRIPTION: Between September 2015 and September 2020, 12 patients without previous heart surgery underwent a traditional HLTx and were deemed a control group, and 3 patients underwent an innovative non-in situ HLTx. The operative time, cold ischemic time, intraoperative bleeding, intraoperative transfusion, and the intensive care unit and hospital lengths of stay were assessed between traditional HLTx and non-in situ HLTx. EVALUATION: The innovative non-in situ HLTx was successfully performed in the 3 patients. We found that the intensive care unit and hospital lengths of stay, total surgical time, cold ischemic time, intraoperative bleeding, and intraoperative transfusion were decreased in the 3 patients compared with the traditional surgical method. CONCLUSION: Non-in situ HLTx may decrease posterior mediastinal bleeding and phrenic nerve damage effectively.


Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração-Pulmão/métodos , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
20.
Mult Scler Relat Disord ; 51: 102927, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33812221

RESUMO

BACKGROUND: The relationship of multiple sclerosis (MS) with lung cancer is under debate. Conventional observational studies have reported conflicting findings, but such studies are susceptible to confounding and reverse causation. With a Mendelian Randomization approach, we were able to evaluate the causality between MS and lung cancer. METHODS: According to published genome-wide association studies (GWASs), we obtained 35 MS-related single-nucleotide polymorphisms, which were used as instrumental variables in our study. Summary data of individual-level genetic information were obtained from the International Lung Cancer Consortium (ILCCO), with a total of 15,861 controls and 11,348 cases; the latter is composed of patients with lung adenocarcinoma and squamous cell lung cancer. The inverse variance-weighted method was applied to estimate the causation between MS and lung cancer. To further evaluate the pleiotropy, the MR-Egger and Weighted median methods were implemented. RESULTS: The results of MR analysis suggested a causal effect of MS on lung cancer incidence, with evidence of an increased risk for overall lung cancer [odds ratio (OR): 1.0648; 95% confidence interval (CI): 1.0163-1.1156; p = 0.0082]. However, subgroup analyses showed no significant causal relationships between MS and lung adenocarcinoma (OR = 1.0716; 95% CI 0.9840-1.1671, p = 0.1119) and squamous cell lung cancer (OR = 1.0284; 95% CI 0.9575-1.1045, p = 0.4424). In addition, no pleiotropy was found in our study. CONCLUSION: Our study indicated that MS is a causal risk factor in the development of lung cancer. Further work is needed to elucidate the potential mechanisms.


Assuntos
Neoplasias Pulmonares , Esclerose Múltipla , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Análise da Randomização Mendeliana , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...