Docetaxel plus ramucirumab with primary prophylactic pegylated-granulocyte-colony stimulating factor for pretreated non-small cell lung cancer.

Purpose: The aim of our study was to evaluate the efficacy and safety of docetaxel plus ramucirumab with primary prophylactic pegylated (PEG)-granulocyte-colony stimulating factor (G-CSF) for pretreated non-small cell lung cancer (NSCLC).

Results: Sixty-one pretreated NSCLC patients underwent docetaxel plus ramucirumab. Primary prophylactic PEG-G-CSF was performed in 52 (85%) patients (prophylactic group).

Assessment of exposure risk of irinotecan and its active metabolite, SN-38, through perspiration during chemotherapy.

Background: Irinotecan (CPT-11) is the key drug used in chemotherapy for many malignant tumors. CPT-11 has cholinergic activity and induces perspiration during intravenous administration. In this study, concentrations of CPT-11 and its active metabolite, SN-38, released during perspiration were measured and risk of exposure of these drugs was assessed.

Programmed death-ligand 1 expression according to epidermal growth factor receptor mutation status in pretreated non-small cell lung cancer.

Background: Current clinical trials have suggested poorer efficacies of anti-programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor () mutations, implying lower PD-L1 expression in -mutant NSCLC than in -wild type.

Methods: We retrospectively analyzed correlation between PD-L1 expression and status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane staining.

Validation of the digital PCR system in tyrosine kinase inhibitor-resistant EGFR mutant non-small-cell lung cancer.

The aim of this study was to compare the accuracy of the QuantStudio 3D Digital polymerase chain reaction (dPCR) system and a PCR-based next generation sequencing (NGS) system for detecting a secondary mutation in the epidermal growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC) patients previously diagnosed with EGFR-activating mutations. Twenty-five patients with NSCLC previously treated with EGFR-TKIs were examined. The patients were treated daily with either erlotinib or gefitinib.

Standard-dose osimertinib for refractory leptomeningeal metastases in T790M-positive EGFR-mutant non-small cell lung cancer.

Background: Osimertinib demonstrated promising efficacy for refractory leptomeningeal metastases (LM) in preclinical data and a clinical study at 160 mg, but there is limited data for the standard 80 mg dose.

Methods: T790M-positive patients with suspected LM after classical epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) failure were enroled.

Results: We investigated 13 patients (5 definitive and 8 possible LM cases).

Programmed death-ligand 1 expression and T790M status in EGFR-mutant non-small cell lung cancer.

Background: Differential biology and prognosis between T790M+ and T790M- populations imply immunological differences also.

Methods: We retrospectively analyzed programmed death-ligand 1 (PD-L1) expression and T790M status in rebiopsied samples of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). PD-L1 immunohistochemistry was performed using the SP142 antibody for tumour cell (TC) and tumour-infiltrating immune cell (IC) and the 28-8 antibody for TC.

Single nucleotide variant sequencing errors in whole exome sequencing using the Ion Proton System.

Errors in sequencing are a major obstacle in the interpretation of next-generation sequencing (NGS) results. In the present study, sequencing errors identified from analysis of single nucleotide variants (SNVs) identified during exome sequencing of human germline DNA were studied using the Thermo Fisher Ion Proton System. Two consanguineous cases were selected for sequencing using the AmpliSeq Exome capture kit, and SNVs found in both cases were validated using Sanger sequencing.

PD-L1 Expression in Patients with Non-small Cell Lung Cancer.

Aim: The aim of this study was to evaluate whether irradiation induces the expression of tumor programed cell death ligand 1 (PD-L1) in patients with non-small cell lung cancer (NSCLC).

Patients And Methods: Seventeen patients with NSCLC who received chemoradiotherapy and underwent tumor resection and six patients whose pre-treatment biopsy specimens were available, were analyzed by immunohistochemistry for PD-L1 expression between September 2011 and June 2016 at the Institute of Biomedical Research and Innovation Hospital.

Results: Among six patients for which pre-irradiation biopsy samples were available, the H-score for PD-L1 was reduced after irradiation following staining with two different antibody clones (SP28-8 and SP142).

Rebiopsy of Histological Samples in Pretreated Non-small Cell Lung Cancer: Comparison Among Rebiopsy Procedures.

Aim: The aim of the present study was to compare successful rate, failure reasons, and complications among procedures of histological rebiopsy.

Patients And Methods: We retrospectively reviewed medical records of histologically rebiopsied cases with non-small cell lung cancer.

Results: One hundred and eleven histological rebiopsies were performed in: 86 (77%) lung; 11 (10%) lymph node; 5 (5%) pleura; 4 (4%) liver; 2 (2%) muscle; 2 (2%) adrenal gland; and 1 (1%) rib.

Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations.

Background: The aim of this study was to detect the epidermal growth factor receptor (EGFR)-activating mutations and other oncogene alterations in patients with non-small-cell lung cancers (NSCLC) who experienced a treatment failure in response to EGFR-tyrosine kinase inhibitors (TKIs) with a next generation sequencer.

Methods: Fifteen patients with advanced NSCLC previously treated with EGFR-TKIs were examined between August 2005 and October 2014. For each case, new biopsies were performed, followed by DNA sequencing on an Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel version 2.

EGFR-TKI rechallenge with bevacizumab in EGFR-mutant non-small cell lung cancer.

Background: Efficacies of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) rechallenge have been demonstrated in EGFR-mutant non-small cell lung cancer (NSCLC). However, their efficacies were only moderate. Some preclinical studies suggested synergistic effects of bevacizumab to EGFR-TKI in TKI-resistant models.

A randomized phase II study of bevacizumab in combination with docetaxel or S-1 in patients with non-squamous non-small-cell lung cancer previously treated with platinum based chemotherapy (HANSHIN Oncology Group 0110).

Objectives: This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC).

Materials And Methods: Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression.

Results: Ninety patients were randomized.

Validation of an Ion Torrent Sequencing Platform for the Detection of Gene Mutations in Biopsy Specimens from Patients with Non-Small-Cell Lung Cancer.

Background: Treatment for patients with advanced non-small cell lung cancer (NSCLC) is often determined by the presence of biomarkers that predict the response to agents targeting specific molecular pathways. Demands for multiplex analysis of the genes involved in the pathogenesis of NSCLC are increasing.

Methods: We validated the Ion Torrent Personal Genome Machine (PGM) system using the Ion AmpliSeq Cancer Hotspot Panel and compared the results with those obtained using the gold standard methods, conventional PCR and Sanger sequencing.

A new strategy for metachronous primary lung cancer: stereotactic body radiation therapy with concurrent chemotherapy.

Background/aim: Patients with malignant lung cancer often develop a solitary pulmonary nodule after treatment of the initial cancer. In those cases, it is difficult to distinguish primary lung cancer (PLC) from lung metastasis. Therefore, both local therapy for a single lung lesions and systemic therapy for micrometastases are needed.

Response to bevacizumab combination chemotherapy of malignant pleural effusions associated with non-squamous non-small-cell lung cancer.

Malignant pleural effusion (MPE) is a common complication of lung cancer with devastating consequences. Since vascular endothelial growth factor (VEGF) has been implicated in MPE, we hypothesized that bevacizumab, an anti-VEGF antibody, may be effective against MPE in patients with non-small-cell lung cancer (NSCLC). We analysed the records of 21 patients treated for NSCLC-associated MPE between February, 2010 and August, 2013 who consequently underwent bevacizumab combination chemotherapy at the Institute of Biomedical Research and Innovation Hospital.

Clinicopathological factors affecting progression-free survival of patients with previously treated advanced non-small cell lung cancer after S-1 therapy with or without bevacizumab.

Objectives: The aim of the present study was to analyze factors that affect progression-free survival (PFS) of patients with previously treated advanced non-small cell lung cancer (NSCLC) after S-1 therapy, in particular epidermal growth factor receptor (EGFR) mutation status.

Patients And Methods: Between October 2009 and June 2013, 56 patients with advanced NSCLC were analyzed for EGFR somatic mutations and treated with S-1 with or without bevacizumab. Risk factors associated with PFS were evaluated using a Cox proportional hazards regression model with a step-down procedure.

Continuous morphine infusion for end-stage lung cancer patients.

End-stage cancer patients frequently receive continuous morphine infusion (CMI) to alleviate the various symptoms associated with cancer progression or adverse events; however, there have been a limited number of studies concerning such patients. We conducted a retrospective analysis of 79 end-stage lung cancer patients who received CMI at the Kyoto University Hospital, Kyoto, Japan between 2008 and 2010. Thirty-one patients (39%) received CMI intravenously and 48 (61%) received it subcutaneously.

Pneumocystis jiroveci pneumonia and colonization in patients with advanced lung cancer.

Pneumocystis jiroveci pneumonia (PCP) has long been recognized as a cause of mortality in immuno-compromised populations, including those with advanced lung cancer. Although Pneumocystis colonization has only recently been described due to the development of more sensitive molecular techniques, including polymerase chain reaction (PCR), it is unknown whether Pneumocystis colonization leads to the development of PCP. In the present study, we aimed to determine the prevalence of Pneumocystis colonization in advanced lung cancer patients.

Effect of the BCL2 gene polymorphism on survival in advanced-stage non-small cell lung cancer patients who received chemotherapy.

Introduction: This study aimed to evaluate the association between BCL2 single-nucleotide polymorphisms and survival outcome in advanced non-small cell lung cancer (NSCLC).

Methods: One hundred and sixty-eight patients with advanced NSCLC who were treated with anti-cancer drugs and could be evaluated for therapeutic response between April 2005 and March 2010 at Kyoto University Hospital were enrolled. DNA was extracted from peripheral blood samples.

Increase in circulating endothelial progenitor cells predicts response in patients with advanced non-small-cell lung cancer.

Previous reports have shown that circulating endothelial progenitor cells (CEPs) are released in response to cytotoxic chemotherapy. We investigate the relationship between the kinetics of CEPs during one cycle of chemotherapy and the response to cytotoxic chemotherapy and prognostic impacts. Previously untreated patients (n = 38) receiving cytotoxic chemotherapy for non-small-cell lung cancer were included.

Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer.

Background: The insulin-like growth factor (IGF) pathway plays an important role in cell proliferation, differentiation, and apoptosis, and IGF induces those effects mainly through IGF receptor-1 (IGF-1R). The activities of IGF are strictly regulated by a family of IGF binding proteins (IGFBP), especially IGFBP3, a major serum carrier protein for IGF.

Patients And Methods: Between January 2006 and February 2009, in our hospital, 191 patients were histologically diagnosed as having non-small-cell lung cancer (NSCLC), and 74 patients were treated by chemotherapy alone.

Prognostic significance of preexisting interstitial lung disease in Japanese patients with small-cell lung cancer.

Unlabelled: We retrospectively investigated patients with small-cell lung cancer with or without interstitial lung disease (ILD). Response rates and median progression-free survival of first-line chemotherapy in patients with or without preexisting ILD was not significantly different. However, pneumonitis associated with chemotherapy was significantly increased in patients with preexisting ILD, and preexisting ILD is an independent prognostic factor for poorer survival.

Clinical significance of serum hepatocyte growth factor and epidermal growth factor gene somatic mutations in patients with non-squamous non-small cell lung cancer receiving gefitinib or erlotinib.

A study of patients with advanced non-squamous non-small cell lung cancer (NSCLC) evaluated epidermal growth factor receptor (EGFR) mutation status and serum hepatocyte growth factor (HGF) for their associations with response to gefitinib therapy and prognostic impact. An enzyme-linked immunosorbent assay was used to determine levels of HGF in serum from 96 Japanese patients with advanced non-squamous NSCLC. The peptic nucleic acid-locked nucleic acid clamp method was used to determine their EGFR somatic mutation status.

Efficacy of increased-dose erlotinib for central nervous system metastases in non-small cell lung cancer patients with epidermal growth factor receptor mutation.

Purpose: Recent reports indicate that refractory central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) are improved by high-dose gefitinib or erlotinib administration. We describe a Japanese woman with NSCLC and CNS metastases who was resistant to 75 mg daily erlotinib, but the metastases were improved by 150 mg daily erlotinib. We investigated the plasma and CSF concentrations of erlotinib at each dose as well as the correlation between the plasma and CSF concentrations of erlotinib.

Clinical significance of pretreatment C-reactive protein in patients with advanced nonsquamous, non-small cell lung cancer who received gefitinib.

Purpose: We examined patients with advanced nonsquamous, non-small cell lung cancer (NSCLC) to evaluate epidermal growth factor receptor (EGFR) mutation status and serum C-reactive protein (CRP) for their associations with response to gefitinib therapy and for prognostic impacts.

Methods: Serum levels of CRP from 79 Japanese patients with advanced nonsquamous NSCLC were measured before the start of gefitinib. We used the peptic nucleic acid-locked nucleic acid clamp method to determine their EGFR somatic mutation status.