Gefitinib, erlotinib and afatinib are approved for first‐line treatment of advanced non‐small cell lung cancer (NSCLC) bearing an activating epidermal growth factor receptor (EGFR) mutation. However, ...the clinical outcomes among the three EGFR tyrosine kinase inhibitors (TKIs) are still controversial. We aimed to evaluate clinical outcomes and secondary EGFR T790M mutation among the three EGFR TKIs. From May 2014 to January 2016, a total of 301 patients received treatment with gefitinib, erlotinib or afatinib, for first‐line treatment of advanced NSCLC with an activating EGFR mutation, based on their clinicians’ choice. The median overall survival (OS) was 37.0 months. Although the baseline characteristics of patients were unequal, progression‐free survival and OS did not differ among the 3 groups. Multivariate analysis found that gefitinib (adjusted odds ratio aOR 3.29, 95% confidence interval CI, 1.15–9.46, p = 0.027), EGFR TKI treatment duration more than 13 months (aOR 3.16, 95% CI, 1.20–8.33, p = 0.020), male (aOR 3.25, 95% CI, 1.10–9.66, p = 0.034), initial liver metastasis (aOR 4.97, 95% CI 1.18–20.96, p = 0.029) and uncommon EGFR mutation (aOR 0.14, 95% CI, 0.02–0.97, compared to EGFR deletion 19, p = 0.047) were independent factors for secondary T790M mutation. In real‐world practice, choosing first line EGFR TKI based on the patients’ clinical characteristics yielded good clinical outcomes. First‐line gefitinib, longer EGFR TKI treatment duration, male, initial liver metastasis and uncommon EGFR mutations may be independent factors for secondary EGFR T790M mutation.
What's new?
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) commonly are used as first‐line therapy for advanced non‐small cell lung cancer (NSCLC). However, the actual extent of their clinical performance, including impacts on secondary EGFR T790M mutation, the most frequent EGFR‐TKI resistance mechanism, remains uncertain. Here, analyses of first‐line EGFR‐TKIs afatinib, erlotinib, gefitinib in advanced EGFR‐mutant NSCLC, with TKIs chosen by clinicians’ discretion, shows median overall survival to be 37 months, which is longer than previously reported. Secondary EGFR T790M mutation was independently associated with multiple factors, including first‐line gefitinib therapy and EGFR TKI use for more than 13 months.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Objective Due to the limitations of the small single incision, an ideal preoperative localization technique is essential for surgical resection of small pulmonary nodules by uniportal ...video-assisted thoracoscopic surgery (VATS). The aim of this study is to evaluate the usefulness and safety of preoperative computed tomography (CT)-guided patent blue vital (PBV) dye localization in patients with small indeterminate pulmonary nodules who have undergone uniportal VATS for lung resection. Methods In this retrospective study, 177 consecutive patients (196 pulmonary nodules) who underwent preoperative CT-guided PBV dye localization and uniportal VATS from January 2013 to September 2015 were enrolled. Results The CT-dye localization procedure was performed successfully and correctly for 99.5% (195/196) of the nodules within a mean procedure time of 30 minutes. The mean size of the nodules was 7.8 mm, and their mean depth from the pleural surface was 18.3 mm. Most of the nodules (78.6%, 154/196) were pure ground-glass nodules (GGNs) and part-solid GGN with ground-glass opacity (GGO) of 50% or more. Asymptomatic pneumothorax occurred in 29.4% (52/177) of patients after the localization procedure, but none required invasive treatment. All nodules were successfully resected using uniportal VATS without any conversion to thoracotomy. The postoperative course was smooth, with a short mean hospital stay (3.3 ± 1.2 days) and a low morbidity rate (0.6%, 1/177). Conclusions Preoperative CT-guided PBV dye localization is a feasible, safe, and accurate procedure. It makes uniportal VATS easy for small, poorly located pulmonary nodules with GGO predominance and synchronous multiple nodules.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the feasibility and safety of thoracoscopic lobectomy without endotracheal intubation.
General anesthesia with single-lung ventilation is considered mandatory for thoracoscopic lobectomy ...for non-small cell lung cancer (NSCLC). Nonintubated thoracoscopic lobectomy has not been reported previously.
From August 2009 through June 2010, some 30 consecutive patients with clinical stage I or II NSCLC were treated by nonintubated thoracoscopic lobectomy using epidural anesthesia, intrathoracic vagal blockade, and sedation. To evaluate the feasibility and safety of this novel technique, they were compared with a control group consisting of 30 consecutive patients with clinical stage I or II NSCLC who underwent thoracoscopic lobectomy using intubated general anesthesia from August 2008 through July 2009.
Collapse of the operative lung and inhibition of coughing were satisfactory in the nonintubated patients, induced by spontaneous breathing, and vagal blockade. Three patients in the nonintubated group required conversion to intubated-single lung ventilation because of persistent hypoxemia, poor epidural anesthesia pain control, and bleeding. One patient in each group was converted to thoracotomy because of bleeding. The 2 groups had comparable anesthesia durations, surgical durations, blood loss, and numbers of dissected lymph nodes. Patients who underwent nonintubated surgery had lower rates of sore throat (6.7% vs 40.0%, P = 0.002) and earlier resumption of oral intake (mean, 4.7 hours vs 18.8 hours, P < 0.001). Patients undergoing nonintubated surgery also had a trend toward better noncomplication rates (90% vs 66.7%, P = 0.057) and shorter postoperative hospital stays (mean, 5.9 days vs 7.1 days, P = 0.078).
Nonintubated thoracoscopic lobectomy is technically feasible and is as safe as lobectomy performed with intubation in highly selected patients. It can be a valid alternative of single-lung-ventilated thoracoscopic surgery in managing early-stage NSCLC.
Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To ...probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58-0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport (
), de no serine synthesis (
,
, and
), folate cycle (
and
), and down-regulation in glutaminolysis (
,
,
, and
). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.
Reactivation of hepatitis B virus (HBV) is a documented risk during cytotoxic chemotherapy in patients with lung cancer. Cases of HBV reactivation in non–small-cell lung cancer (NSCLC) patients ...receiving epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment have been reported; however, the incidence of HBV reactivation in patients treated with EGFR TKIs has not yet been reported.
We enrolled 171 patients who were diagnosed as having NSCLC from 2011 through 2017 and who also had positive hepatitis B surface antigen (HBsAg). All patients had received EGFR TKIs as anticancer treatment for at least 2 weeks during their treatment course. Reactivation of HBV is defined as one of the following: an increase in HBV DNA by at least 10-fold compared to baseline or an absolute increase to >10ˆ5 IU/mL with abnormal liver function.
The median duration of EGFR TKI treatment was 10.5 months (95% confidence interval: 8.2–12.8). Sixteen (9.36%) patients met the criteria of HBV reactivation during EGFR TKI treatment, with an annual incidence of 7.86%. HBV reactivation occurred during erlotinib treatment in 6 patients, followed by 5 patients with gefitinib treatments, 3 patients with osimertinib treatment and 2 with afatinib treatment. No independent risk factor for HBV reactivation was identified.
NSCLC patients receiving EGFR TKI treatment may have a clinically meaningful risk of HBV reactivation during the treatment period. Thus, monitoring liver function, HBV viral load and serology of HBV (i.e., HBeAg and anti-HBc) during EGFR TKI therapy is recommended for NSCLC patients with positive HBsAg.
•NSCLC patients have a clinically meaningful risk of HBV reactivation during EGFR TKI treatment.•No independent risk factors were identified for HBV reactivation during EGFR TKI treatment.•HBV screening and monitoring liver function are recommended for NSCLC patients before and during EGFR TKI treatment.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
JAG1 is a Notch ligand that plays a critical role in multiple signaling pathways. However, the functionality of JAG1 in non-small cell lung cancer (NSCLC) has not been investigated thoroughly. By ...comparison of gene transcripted RNA profiles in the cell line pair with differential invasion ability, we identified JAG1 as a potential metastasis enhancer in lung cancer. Ectopic expression of JAG1 on lung cancer cells enhanced cell migration and invasion as well as metastasis in vitro and in vivo. Conversely, knockdown of JAG1 with siRNA in highly invasive cancer cells led to the reduction of migration and invasion. In clinical analysis, JAG1 mRNA expression was higher in tumors than in adjacent normal tissues in 14 of 20 patients with squamous cell carcinoma (SCC). SCC patients with higher JAG1 transcription had poor overall survival than those with low-transcripted JAG1. Microarray analysis indicated that the enforced JAG1 transcription was associated with an elevated HSPA2 RNA transcription, which played a role in promoting cancer cell migration and invasion. In conclusion, this is the first study that demonstrated that JAG1 might act as a potential prognostic marker and JAG1/HSPA2 axis mediates lung cancer malignancy at least partly.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It remains a challenge to preoperatively forecast whether lung pure ground-glass nodules (pGGNs) have invasive components. We aimed to construct a radiomic model using tumor characteristics to ...predict the histologic subtype associated with pGGNs. We retrospectively reviewed clinicopathologic features of pGGNs resected in 338 patients with lung adenocarcinoma between 2011-2016 at a single institution. A radiomic prediction model based on forward sequential selection and logistic regression was constructed to differentiate adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma. The study cohort included 133 (39.4%), 128 (37.9%), and 77 (22.8%) patients with AIS, MIA, and invasive adenocarcinoma (acinar 55.8%, lepidic 33.8%, papillary 10.4%), respectively. The majority (83.7%) underwent sublobar resection. There were no nodal metastases or tumor recurrence during a mean follow-up period of 78 months. Three radiomic features-cluster shade, homogeneity, and run-length variance-were identified as predictors of histologic subtype and were selected to construct a prediction model to classify the AIS/MIA and invasive adenocarcinoma groups. The model achieved accuracy, sensitivity, specificity, and AUC of 70.6%, 75.0%, 70.0%, and 0.7676, respectively. Applying the developed radiomic feature model to predict the histologic subtypes of pGGNs observed on CT scans can help clinically in the treatment selection process.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
