Molecular Subtypes and Tumor Microenvironment Characteristics of Small-Cell Lung Cancer Associated with Platinum-Resistance.

Although molecular subtypes of small-cell lung cancer (SCLC) have been proposed, their clinical relevance and therapeutic implications are not fully understood. Thus, we aimed to refine molecular subtypes and to uncover therapeutic targets. We classified the subtypes based on gene expression ( = 81) and validated them in our samples ( = 87).

Dynamics of disease progression during treatment with Osimertinib in patients with EGFR T790M-positive non-small cell lung cancer.

Background: Patterns of treatment failure and subsequent treatment in non-small cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies.

Methods: We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records.

The Clinical Impact of Capmatinib in the Treatment of Advanced Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation or Gene Amplification.

Purpose: Capmatinib, an oral MET kinase inhibitor, has demonstrated its efficacy against non-small cell lung cancer (NSCLC) with MET dysregulation. We investigated its clinical impact in advanced NSCLC with MET exon 14 skipping mutation (METex14) or gene amplification.

Materials And Methods: Patients who participated in the screening of a phase II study of capmatinib for advanced NSCLC were enrolled in this study.

Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase-Low Squamous Cell Lung Cancer.

Purpose: Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.

Materials And Methods: In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.

Diagnostic Accuracy of Percutaneous Transthoracic Needle Lung Biopsies: A Multicenter Study.

Objective: To measure the diagnostic accuracy of percutaneous transthoracic needle lung biopsies (PTNBs) on the basis of the intention-to-diagnose principle and identify risk factors for diagnostic failure of PTNBs in a multi-institutional setting.

Materials And Methods: A total of 9384 initial PTNBs performed in 9239 patients (mean patient age, 65 years [range, 20-99 years]) from January 2010 to December 2014 were included. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PTNBs for diagnosis of malignancy were measured.

Erratum: Analysis of Complications of Percutaneous Transthoracic Needle Biopsy Using CT-Guidance Modalities In a Multicenter Cohort of 10568 Biopsies.

This corrects the article on p. 323 in vol. 20, PMID: 30672172.

Analysis of Complications of Percutaneous Transthoracic Needle Biopsy Using CT-Guidance Modalities In a Multicenter Cohort of 10568 Biopsies.

Objective: To analyze the complications of percutaneous transthoracic needle biopsy using CT-based imaging modalities for needle guidance in comparison with fluoroscopy in a large retrospective cohort.

Materials And Methods: This study was approved by multiple Institutional Review Boards and the requirement for informed consent was waived. We retrospectively included 10568 biopsies from eight referral hospitals from 2010 through 2014.

Nondiagnostic Percutaneous Transthoracic Needle Biopsy of Lung Lesions: A Multicenter Study of Malignancy Risk.

Purpose To evaluate the malignancy risk of lung lesions that show nondiagnostic results at transthoracic needle biopsy (PTNB) of the lung and to identify any malignancy-associated risk factors in each nondiagnostic category. Materials and Methods In this retrospective study, 9384 initial PTNBs (9239 patients [mean age, 65 years; age range, 20-99 years] consisting of 5729 men [mean age, 66 years; age range, 20-99 years] and 3510 women [mean age, 63 years; age range, 20-94 years]) were performed in eight institutions between January 2010 and December 2014. PTNB results were categorized as diagnostic (malignant or specifically benign) or nondiagnostic (nonspecific benign pathologic findings, atypical cells, or insufficient specimen), and the proportion of final malignant diagnoses per nondiagnostic category was obtained.

EGFR and HER3 signaling blockade in invasive mucinous lung adenocarcinoma harboring an NRG1 fusion.

Rearrangements of NRG1 have been identified in invasive mucinous adenocarcinoma of the lung (IMA), formerly referred to as mucinous bronchioloalveolar carcinoma. NRG1 ligand signals through induction of HER2-HER3 heterodimers, thus leading to PI3K-AKT pathway activation. Therefore, targeting HER2, HER3 and the downstream pathway may be a hypothesis-driven strategy for IMA with NRG1 fusion.

Development and Validation of Deep Learning-based Automatic Detection Algorithm for Malignant Pulmonary Nodules on Chest Radiographs.

Purpose To develop and validate a deep learning-based automatic detection algorithm (DLAD) for malignant pulmonary nodules on chest radiographs and to compare its performance with physicians including thoracic radiologists. Materials and Methods For this retrospective study, DLAD was developed by using 43 292 chest radiographs (normal radiograph-to-nodule radiograph ratio, 34 067:9225) in 34 676 patients (healthy-to-nodule ratio, 30 784:3892; 19 230 men [mean age, 52.8 years; age range, 18-99 years]; 15 446 women [mean age, 52.

Development and Validation of Segmentation Method for Lung Cancer Volumetry on Chest CT.

The set of criteria called Response Evaluation Criteria In Solid Tumors (RECIST) is used to evaluate the remedial effects of lung cancer, whereby the size of a lesion can be measured in one dimension (diameter). Volumetric evaluation is desirable for estimating the size of a lesion accurately, but there are several constraints and limitations to calculating the volume in clinical trials. In this study, we developed a method to detect lesions automatically, with minimal intervention by the user, and calculate their volume.

Lung Cancer Screening with Low-Dose CT in Female Never Smokers: Retrospective Cohort Study with Long-term National Data Follow-up.

Purpose: Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings.

Materials And Methods: This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007.

Incorporating Erlotinib or Irinotecan Plus Cisplatin into Chemoradiotherapy for Stage III Non-small Cell Lung Cancer According to EGFR Mutation Status.

Purpose: Concurrent chemoradiotherapy (CCRT) is the standard care for stage III non-small cell lung cancer (NSCLC) patients; however, a more effective regimen is needed to improve the outcome by better controlling occult metastases. We conducted two parallel randomized phase II studies to incorporate erlotinib or irinotecan-cisplatin (IP) into CCRT for stage III NSCLC depending on epidermal growth factor receptor (EGFR) mutation status.

Materials And Methods: Patients with EGFR-mutant tumors were randomized to receive three cycles of erlotinib first and then either CCRT with erlotinib followed by erlotinib (arm A) or CCRT with IP only (arm B).

Randomized Phase II Study of Afatinib Plus Simvastatin Versus Afatinib Alone in Previously Treated Patients with Advanced Nonadenocarcinomatous Non-small Cell Lung Cancer.

Purpose: This phase II study examined whether the addition of simvastatin to afatinib provides a clinical benefit compared with afatinib monotherapy in previously treated patients with nonadenocarcinomatous non-small cell lung cancer (NA-NSCLC).

Materials And Methods: Patients with advanced NA-NSCLC who progressed after one or two chemotherapy regimens were randomly assigned to a simvastatin (40 mg/day) plus afatinib (40 mg/day) (AS) arm or to an afatinib (A) arm. The primary endpoint was response rate (RR).

ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer.

Purpose: We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).

Materials And Methods: Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m on days 1 and 8, and cisplatin 75 mg/m on day 1 every 3 weeks) or IP (irinotecan 65 mg/m and cisplatin 30 mg/m on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level.

A phase II study of nintedanib in patients with relapsed small cell lung cancer.

Objectives: Nintedanib is an oral triple angiokinase inhibitor. This study was conducted to evaluate the efficacy and safety of nintedanib in patients (pts) with relapsed/refractory small cell lung cancer (SCLC).

Patients And Methods: Pts with an ECOG PS from 0 to 2 who exhibited progression after one or two prior chemotherapy or chemo/radiotherapy were enrolled.

A study of docetaxel and irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family of tumors.

Background: Patients with Ewing sarcoma family of tumors (ESFT) who are resistant even to salvage chemotherapy, have dismal prognoses and few therapeutic options. Because the docetaxel/irinotecan (DI) combination has not been previously evaluated in ESFT, we prospectively evaluated its use in patients with recurrent or refractory ESFT.

Methods: Patients aged <30 years with ESFT, who failed ≥ third-line therapy, were eligible.

Missed pulmonary embolism on abdominal CT.

Objective: The purpose of this study is to evaluate a series of missed pulmonary emboli (PE) identified on abdominal CT and to describe their characteristics and the clinical scenario.

Materials And Methods: All reports of chest CT scans performed during a 12-month period were searched for keywords indicative of PE. Among patients with PE, patients who also underwent an enhanced abdominal CT within 3 months were assessed for missed PE.

Clinical significance of heterogeneity in response to retreatment with epidermal growth factor receptor tyrosine kinase inhibitors in patients with lung cancer acquiring secondary resistance to the drug.

Background: In patients with lung cancer acquiring resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), an intrapatient heterogeneity in response to retreatment with EGFR-TKIs remains to be elucidated.

Patients And Methods: Records were retrospectively reviewed for 68 patients with advanced non-small-cell lung cancer who received second EGFR-TKIs after systemic progression that followed durable response to the first EGFR-TKIs. All tumor lesions identified on radiologic images before second EGFR-TKIs were categorized into organs.

A phase II study of sunitinib in patients with relapsed or refractory small cell lung cancer.

Purpose: This study was conducted to evaluate the efficacy and safety of sunitinib in patients with relapsed or refractory small cell lung cancer (SCLC).

Patients And Methods: Eligibility included histologic or cytologic diagnosis of SCLC, ECOG PS of 0-2, cancer progression following one or two prior chemotherapy or chemo-radiotherapy (CRT) and adequate organ functions. Treatment regimen consisted of a 6-week cycle of sunitinib given as 50mg p.

Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations.

Aims: Deletion of exon 19 of the epidermal growth factor receptor (EGFR) and mutation of exon 21 are the most common EGFR mutations and predict higher response to EGFR tyrosine kinase inhibitors (TKI). Accumulating data show clinical differences in both response and survival between these two EGFR mutations. This study investigated the clinical impact of EGFR exon 19 deletion and L858R mutation by retrospectively analysing the clinical outcome of patients with advanced non-small-cell lung cancer (NSCLC) treated with EGFR TKI.

A phase 2 study of irinotecan, cisplatin, and simvastatin for untreated extensive-disease small cell lung cancer.

Background: The objective of this study was to investigate the efficacy of simvastatin in combination with irinotecan and cisplatin in chemotherapy-naive patients with extensive-disease small-cell lung cancer (ED-SCLC).

Methods: In this phase 2 study, 61 patients received treatment with irinotecan (65 mg/m(2) ) and cisplatin (30 mg/m(2) ) on Days 1 and 8 every 3 weeks until either death or disease progression occurred. Patients also received oral simvastatin (40 mg daily) during the course of chemotherapy.

Transbronchial and transesophageal fine-needle aspiration using an ultrasound bronchoscope in mediastinal staging of potentially operable lung cancer.

Objective: We performed this study to evaluate the role of transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) following endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the mediastinal staging of lung cancer.

Methods: In this prospective study, we applied transbronchial and transesophageal ultrasonography using an ultrasound bronchoscope on patients with confirmed or strongly suspected potentially operable non-small cell lung cancer. Following EBUS-TBNA, EUS-B-FNA was used for mediastinal nodes that were inaccessible or difficult to access by EBUS-TBNA.