Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study.

Purpose: Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.

Methods: We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).

A randomized phase II study of afatinib alone or combined with bevacizumab for treating chemo-naïve patients with non-small cell lung cancer harboring EGFR mutations.

Background: Adding bevacizumab to first-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) prolonged the progression-free survival (PFS), but limited data are available for second-generation EGFR-TKIs. AfaBev-CS is a randomized, phase II trial comparing afatinib plus bevacizumab and afatinib alone as first-line treatment.

Patients And Methods: Untreated patients with non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations (Del19 or L858R) were enrolled and randomly assigned to receive either afatinib (30 mg) plus bevacizumab (AfaBev group) or afatinib (40 mg) monotherapy (Afa group).

Clinicogenomic Features and Targetable Mutations in NSCLCs Harboring BRAF Non-V600E Mutations: A Multi-Institutional Genomic Screening Study (LC-SCRUM-Asia).

Introduction: BRAF non-V600E mutations occur in 1% to 2% of NSCLCs. Because of their rarity, the clinical backgrounds and outcomes of cytotoxic chemotherapy or immunotherapy remain unclear, and no targeted therapies are approved for BRAF non-V600E-mutant NSCLC.

Methods: In this multi-institutional prospective lung cancer genomic screening project (LC-SCRUM-Asia), we evaluated the clinicogenomic characteristics and therapeutic outcomes of BRAF non-V600E-mutant NSCLC.

Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data.

Introduction: Pembrolizumab is a programmed death-ligand 1 inhibitor that was initially indicated for monotherapy in patients with advanced lung cancer. The Japanese Lung Cancer Society conducted an observational study on pembrolizumab using confirmative data obtained through postmarketing all-case surveillance (PMACS), which was performed by a pharmaceutical company under the Japanese law in 2017.

Methods: This multicenter observational study was conducted by the Japanese Lung Cancer Society using PMACS data with the newly created central registration system regarding patients with NSCLC who received pembrolizumab monotherapy between February 1, 2017 and June 30, 2017; a new database was created by adding the clinical information regarding prognosis for 3 years after therapy to the existing data collected by PMACS.

Pembrolizumab-induced aseptic meningitis in a patient with non-small cell lung cancer: A case report and literature review of aseptic meningitis as an immune-related adverse event.

Aseptic meningitis is a rare immune-related adverse event (irAE), which occurs during treatment with immune checkpoint inhibitors (ICIs). This condition has non-specific symptoms and exhibits no clear signs on magnetic resonance imaging (MRI). There are only a few reports of aseptic meningitis caused by pembrolizumab treatment for non-small cell lung cancer (NSCLC).

First and repeat rebiopsy for detecting EGFR T790M mutation in non-small-cell lung cancer: CS-Lung-003 prospective observational registry study.

Purpose: Osimertinib is still essential for the treatment of epidermal growth factor receptor (EGFR)-T790M-positive non-small-cell lung cancer (NSCLC) even in a relapsed setting, which suggests the importance of rebiopsy. The clinical value of repeat rebiopsy in patients with NSCLC who are T790M-negative on a first rebiopsy remains unclear. In this study, we examined the status of the first rebiopsy and evaluated the frequency of repeat rebiopsy of T790M-negative tumors detected by the first rebiopsy.

The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer.

Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC). However, such oncogenic drivers are not found in 25-40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC.

Novel prospective umbrella-type lung cancer registry study for clarifying clinical practice patterns: CS-Lung-003 study protocol.

Introduction: Conventional cancer registries are suitable for simple surveillance of cancer patients, including disease frequency and distribution, demographics, and prognosis; however, the collected data are inadequate to clarify comprehensively diverse clinical questions in daily practice.

Methods: We constructed an umbrella-type lung cancer patient registry (CS-Lung-003) integrating multiple related prospective observational studies (linked studies) that reflect clinical questions about lung cancer treatment. The primary endpoint of this registry is to clarify daily clinical practice patterns in lung cancer treatment; a key inclusion criterion is pathologically diagnosed lung cancer.

Nivolumab-induced cholangitis in patients with non-small cell lung cancer: Case series and a review of literature.

Immune checkpoint inhibitors (ICIs), including nivolumab, have exhibited substantial benefits in the treatment of several types of cancers. However, treatment with ICIs is often accompanied by immune-related adverse events (irAEs), and a clear understanding of the precise indications and management of irAEs is important for harnessing the full potential of these agents. While skin- or gastrointestinal-associated irAEs have been relatively well studied, there are few reports regarding nivolumab-induced cholangitis.

Early Intensive Nutrition Intervention with Dietary Counseling and Oral Nutrition Supplement Prevents Weight Loss in Patients with Advanced Lung Cancer Receiving Chemotherapy: A Clinical Prospective Study.

Background: Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting (CINV). Recent developments in antiemetic drugs have substantially improved CINV, but nutritional intervention did not improve body weight. This study aimed to investigate the effects of nutrition intervention with appropriate antiemetic treatment in patients with non-small-cell lung cancer during chemotherapy.

Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol.

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has demonstrated a significant survival benefit over platinum-based chemotherapy in a first-line setting in advanced non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion. In addition, we and other groups have shown there to be favorable progression-free survival (PFS) outcomes, with acceptable toxicity profiles, with bevacizumab and first-generation EGFR-TKI combination therapy. On the basis of the above, we hypothesized that a combination of bevacizumab and afatinib could potentially improve efficacy.

Acute-phase reaction induced by zoledronate and its effect on prognosis of patients with advanced non-small cell lung cancer.

Objectives: Zoledronate (ZOL) is usually used for prevention of skeletal-related events in cancer patients with bone metastases. The first administration of ZOL is occasionally associated with development of acute-phase reaction (APR), which is due to activation of γδ T cells. ZOL-related APR was associated with better overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in our previous retrospective study.

Development of fever following first administration of zoledronate as a prognostic factor in advanced non-small cell lung cancer patients with bone metastases.

Nitrogen-containing bisphosphonates (N-BPs), which are usually used for the treatment of advanced cancer with bone metastasis, occasionally cause fever following the first administration. However, it is unclear as to how the development of fever following the first administration of N-BP is associated with clinical outcome. The aim of the present study was to determine the prognostic value of the development of fever following the first administration of N-BP in advanced non-small cell lung cancer patients with bone metastases.

An onion farmer with a case of hypersensitivity pneumonitis caused by .

A 62-year old man was admitted to our hospital with a 2-week complaint of a dry cough, general fatigue, and dyspnea on effort. He has been an onion farmer for several years and developed these symptoms after cleaning up onion peels with air compressors. A chest roentgenogram and computed tomography showed a ground glass shadow in the bilateral upper lung field.

A case of lung abscess successfully treated by transbronchial drainage using a guide sheath.

A 51-year-old man was diagnosed with colon cancer in September 2011, and a solitary pulmonary nodule was detected by computed tomography (CT) scan. We performed a transbronchial biopsy with endobronchial ultrasonography using a guide sheath (GS) and diagnosed lung metastasis of colon cancer. The patient experienced remittent fever after the biopsy in spite of intravenous antibiotic therapies.

DNA-PK Inhibition by NU7441 Enhances Chemosensitivity to Topoisomerase Inhibitor in Non-Small Cell Lung Carcinoma Cells by Blocking DNA Damage Repair.

Background: DNA double-strand breaks (DSBs) are the most cytotoxic form of DNA damage and are induced by ionizing radiation and specific chemotherapeutic agents, such as topoisomerase inhibitors. Cancer cells acquire resistance to such therapies by repairing DNA DSBs. A major pathway for the repair of DNA DSBs is non-homologous end-joining (NHEJ), which requires DNA-dependent protein kinase (DNA-PK) activity.

Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

Background: Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma.

Patients And Methods: The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed.

A novel mutation in a patient with pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease caused by mutations in and characterized by intra-alveolar accumulation of microliths. We diagnosed a case of PAM in a 27-year-old Japanese female and identified a novel mutation in (c.1390 G>C [G464R] in exon 12).

Causes of death in patients with asthma and asthma-chronic obstructive pulmonary disease overlap syndrome.

Background: The administration of inhaled corticosteroids and worldwide usage of several asthma guidelines have improved asthma mortality. Elderly patients with asthma show high mortality rates, and may have several comorbidities, including overlap with chronic obstructive pulmonary disease (COPD). Among patients showing asthma overlapped with COPD (asthma-COPD overlap syndrome; ACOS), mortality is worse than for asthma alone.

A novel point-of-care system for high-speed real-time polymerase chain reaction testing for epidermal growth factor receptor mutations in bronchial lavage fluids after transbronchial biopsy in patients with non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) gene mutation testing is essential for choosing appropriate treatment options in patients with advanced non-small cell lung cancer (NSCLC). However, a time delay occurs between histological diagnosis and molecular diagnosis in clinical situations. To minimize this delay, we developed a novel point-of-care test for EGFR mutations, based on a high-speed real-time polymerase chain reaction (PCR) system designated here as ultrarapid PCR combined with highly accurate bronchoscopic sampling.

A new rapid method for detecting epidermal growth factor receptor mutations in non-small cell lung cancer.

Mutations in the epidermal growth factor receptor (EGFR) gene are associated with a favorable clinical response to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib in non-small cell lung cancer (NSCLC). We present here, a new method for the rapid detection of the two most common EGFR mutations (delE746-A750 and L858R) from clinical samples. The methodology involves the combination of newly designed mutation-specific primers and a novel real-time PCR machine with an innovative thermo-control mechanism that enables ultrarapid PCR.

Favorable effect of the combination of vinorelbine and dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine in EGFR‑mutated lung adenocarcinoma: retrospective and in vitro studies.

Although cytotoxic chemotherapy is essential in epidermal growth factor receptor (EGFR)‑mutated non‑small cell lung cancer (NSCLC), it is unclear which regimen is most effective. We retrospectively compared the efficacy of standard platinum‑based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine (DIF) in EGFR‑mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR‑mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response rate and disease control rate afforded by the VNR + DIF treatment tended to be better than those by platinum‑based chemotherapy, and the progression‑free survival of the 24 VNR + DIF‑treated patients was significantly longer than that of the 15 platinum‑based chemotherapy patients.

Synergistic cell growth inhibition by the combination of amrubicin and Akt-suppressing agents in K-ras mutation-harboring lung adenocarcinoma cells: implication of EGFR tyrosine kinase inhibitors.

Previously we showed that Akt-suppressing agents, combined with amrubicin, synergistically inhibited the growth of small cell lung cancer cells. The combined effects of chemotherapeutic agents and Akt-suppressing agents, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, were evaluated in A549 lung adenocarcinoma cells harboring K-ras mutation and wild-type EGFR. Only amrubicin and not other chemotherapeutics (cisplatin, pemetrexed and paclitaxel) synergistically inhibited cell growth when combined with an Akt inhibitor, LY294002.

Cough and asthma diagnosis: physicians' diagnosis and treatment of patients complaining of acute, subacute and chronic cough in rural areas of Japan.

Background: Cough is one of the most common reasons for visiting a clinic. The causes of cough differ according to the duration of cough. Infectious disease is commonly observed in acute cough while noninfectious disease is commonly observed in chronic cough.