Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer.

Purpose: The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).

Methods: Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m on day 8 plus oral S-1 at a dosage of 40 mg/m twice per day for two different treatment schedules for up to 4 cycles. Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions.

Efficacy of Cell-Free and Concentrated Ascites Reinfusion Therapy for Palliative Care in a Patient with Malignant Pleural Mesothelioma: A Case Report.

Cell-free and concentrated ascites reinfusion therapy (CART) is recognized as a useful treatment to improve the symptoms caused by refractory ascites. Recently, a few clinical studies have reported the effects of CART for malignant ascites, especially in gynecological and gastrointestinal cancers. We report the case of malignant ascites in a patient with malignant pleural mesothelioma (MPM) whose symptoms were relieved by CART.

Switch maintenance chemotherapy using S-1 with or without bevacizumab in patients with advanced non-small cell lung cancer: a phase II study.

Objectives: We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC).

Patients And Methods: Patients not showing disease progression after induction platinum-based chemotherapy received S-1 at the dose of 40mg/m twice daily for 14 consecutive days, every three weeks, with or without bevacizumab (Bev) at the dose of 15mg/kg. In cases where the induction chemotherapy regimen contained Bev, Bev was used as continuation maintenance chemotherapy where appropriate.

Prognostic Factor Analysis in Patients With Small-Cell Lung Cancer Treated With Third-Line Chemotherapy.

Background: There is little information on the clinical outcome of patients with small-cell lung cancer (SCLC) treated with third-line chemotherapy. The purpose of this study was to clarify the prognostic factors of SCLC patients receiving third-line chemotherapy.

Patients And Methods: Between November 2001 and October 2011, 202 of 648 consecutive SCLC patients at the National Cancer Center Hospital East received third-line chemotherapy.

Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma.

Metastasis and growth in neoplastic lesions requires the multistep regulation of microenvironmental factors. We aimed to elucidate the microenvironmental changes in the process of lymphatic metastasis of lung squamous cell carcinoma. We examined the morphological characteristics of 102 cases of primary tumor (PT), 50 of intralymphatic tumor (ILT), 51 of lymph node (LN) micrometastasis (LN-Mic; ≤2 mm in size), and 82 of LN macrometastasis (LN-Mac; ≥10 mm in size).

Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer.

Hepatotoxicity is a major cause of the withdrawal of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) when treating EGFR mutation-positive non-small cell lung cancer (NSCLC). We report a case in which gefitinib- and elrotinib-induced severe hepatotoxicity arose in a patient with the uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1) and cytochrome p450 3A5 (CYP3A5) poor metabolizer phenotypes. Afatinib is not significantly metabolized by cytochrome p450-mediated pathways.

Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung.

Purpose: Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC), little is known about its molecular features. We analyzed lung LCNECs to identify biologically relevant genomic alterations.

Experimental Design: We performed targeted capture sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC samples [65 surgically resected cases, including 10 LCNECs combined with non-small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13 advanced cases].

A phase I dose-escalation study of LY2875358, a bivalent MET antibody, given as monotherapy or in combination with erlotinib or gefitinib in Japanese patients with advanced malignancies.

Background MET is a tyrosine kinase receptor involved in the regulation of cell proliferation and migration. Reported here are the phase I dose-escalation results for LY2875358, a monoclonal antibody against MET, in Japanese patients with advanced malignancies. Methods The study comprised a 3 + 3 dose-escalation part for LY2875358 monotherapy in patients with advanced malignancies (Part A) followed by an assessment of LY2875358 in combination with erlotinib or gefitinib in patients with non-small cell lung cancer (Part B).

Natural History of Pulmonary Subsolid Nodules: A Prospective Multicenter Study.

Introduction: The purpose of this study was to evaluate the natural course of the progression of pulmonary subsolid nodules (SSNs).

Materials And Methods: Eight facilities participated in this study. A total of 795 patients with 1229 SSNs were assessed for the frequency of invasive adenocarcinomas.

Factors influencing the concordance of histological subtype diagnosis from biopsy and resected specimens of lung adenocarcinoma.

Objectives: Lung adenocarcinoma is heterogeneous, characterized by various histological subtypes. Determination of the predominant histological subtype (lepidic, papillary, acinar or solid-predominant) has been shown to correlate with genetic abnormalities and clinicopathological features. Although subtyping using small biopsy samples is important for tailored approaches to clinical management, limited data exist on the concordance of predominant subtype between resected specimens and biopsy specimens.

Clinical Impact of Gastric Acid-Suppressing Medication Use on the Efficacy of Erlotinib and Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations.

Background: Gastric acid-suppressing medications (AS), namely, proton pump inhibitors and histamine-2 receptor antagonists, increase gastric pH, which may reduce the absorption of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors-erlotinib and gefitinib.

Patients And Methods: From 2008 to 2011, 130 consecutive patients with advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations were treated with either erlotinib or gefitinib at our institution. The clinical characteristics of the patients were reviewed, and the efficacy and toxicity of erlotinib and gefitinib were compared for patients receiving and not receiving AS.

Aggressive tumor microenvironment of solid predominant lung adenocarcinoma subtype harboring with epidermal growth factor receptor mutations.

Introduction: Tumor microenvironment critically affects cancer progression. This study aimed to identify differences in microenvironments of lung adenocarcinomas with epidermal growth factor receptor (EGFR) mutations by histological subtypes.

Methods: The study cohort included 214 lung adenocarcinomas harboring EGFR mutations.

RECIST progression patterns during EGFR tyrosine kinase inhibitor treatment of advanced non-small cell lung cancer patients harboring an EGFR mutation.

Background: Progression patterns at the response evaluation criteria in solid tumors-progressive disease (RECIST-PD) during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for advanced non-small cell lung cancer (NSCLC) in patients harboring an EGFR mutation are clinically heterogeneous. We evaluated the association between progression patterns during EGFR-TKI treatment and prognosis after treatment in such patients.

Methods: From 2008 to 2012, 160 consecutive patients with advanced NSCLC harboring an EGFR mutation were treated with EGFR-TKIs (erlotinib or gefitinib).

Unique intravascular tumor microenvironment predicting recurrence of lung squamous cell carcinoma.

Purpose: Histological vascular invasion (VI) by tumors is a risk factor for recurrence after surgical resection. However, VI features vary histologically. The aim of this study was to identify characteristic VI features that are associated with recurrence in squamous cell carcinoma (SCC) of the lung.

Impact of single nucleotide polymorphisms on severe hepatotoxicity induced by EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring EGFR mutations.

Background: Many patients are forced to discontinue treatment with EGFR tyrosine kinase inhibitors (TKIs), particularly gefitinib, due to severe hepatotoxicity. Here, we investigated the association between the rate of severe hepatotoxicity and single nucleotide polymorphisms (SNPs) in metabolic enzymes.

Materials And Methods: Multi-SNP analyses were performed in 60 patients with EGFR-mutated non-small cell lung cancer using blood samples obtained prior to starting treatment with gefitinib.

Phase II study of amrubicin at a dose of 45 mg/m2 in patients with previously treated small-cell lung cancer.

Objective: Most of the previous studies of amrubicin in patients with previously treated small-cell lung cancer were conducted at a dose of 40 mg/m(2). The aim of this study was to assess the efficacy and safety of amrubicin at a dose of 45 mg/m(2) in patients with relapsed or refractory small-cell lung cancer.

Methods: Previously treated small-cell lung cancer patients were eligible.

Second-line docetaxel for patients with platinum-refractory advanced non-small cell lung cancer and interstitial pneumonia.

Purpose: The role of second-line chemotherapy in patients with non-small cell lung cancer (NSCLC) and preexisting interstitial pneumonia (IP) previously treated with platinum-based chemotherapy remains uncertain. This study was conducted to elucidate the efficacy and tolerability of second-line docetaxel monotherapy for patients with platinum-refractory advanced (stage IIIB, IV, or relapse) NSCLC and preexisting IP.

Methods: A total of 35 patients (median age, 67 years) treated with docetaxel monotherapy in a second-line setting following first-line platinum-based chemotherapy between January 2002 and December 2013 were retrospectively reviewed.

Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth.

Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC). Here we explore whether CAFs expressing PDPN influence proliferation of SCLC cells. Compared with control group (SCLC cells co-cultured with CAFs-Ctrl), numbers of SCLC cells co-cultured with CAFs overexpressing PDPN were decreased.

Docetaxel for platinum-refractory advanced thymic carcinoma.

Objective: Thymic carcinoma is a rare mediastinal neoplasm. While platinum-based chemotherapy has been reported to be effective for advanced thymic carcinoma in a first-line setting, little information is available regarding the benefits of salvage chemotherapy for platinum-refractory thymic carcinoma. This study assessed the efficacy and safety profiles of docetaxel monotherapy for platinum-refractory thymic carcinoma.

Vinorelbine and cisplatin in patients with advanced non-small cell lung cancer with interstitial pneumonia.

Aim: The aim of the present study was to investigate the efficacy and tolerability of vinorelbine and cisplatin for the treatment of patients with advanced (stage IIIB, IV or relapse) non-small cell lung cancer (NSCLC) with interstitial pneumonia (IP).

Patients And Methods: A total of 67 patients treated with vinorelbine and cisplatin as a first-line chemo therapy between January 2002 and December 2013 were retrospectively reviewed.

Results: The overall response rate was 34.

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung.

Purpose: Immunohistochemical analysis for the identification of clinically relevant biomarkers is important. However, there have been no detailed reports about the heterogeneous expressions of the various markers in squamous cell carcinoma of the lung.

Methods: A total of 113 patients with squamous cell carcinoma of the lung with lymph node metastasis were included.

Presence of podoplanin-positive cancer-associated fibroblasts in surgically resected primary lung adenocarcinoma predicts a shorter progression-free survival period in patients with recurrences who received platinum-based chemotherapy.

Purpose: The influence of microenvironmental factors on the effectiveness of chemotherapy is being increasingly recognized. The purpose of this study was to investigate the relationships between cancer cell and stromal cell phenotypes in primary tumors and the progression-free survival (PFS) of recurrent lung cancer patients who received platinum-based chemotherapy.

Methods: We retrospectively analyzed 87 postoperative recurrent lung adenocarcinoma patients treated with platinum-based chemotherapy.

Podoplanin-positive cancer-associated fibroblasts in the tumor microenvironment induce primary resistance to EGFR-TKIs in lung adenocarcinoma with EGFR mutation.

Purpose: The biologic characteristics of microenvironmental constituents, especially cancer-associated fibroblasts (CAF), can be key regulators of the cellular sensitivity to molecular-targeted therapy. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) have marked therapeutic effects against non-small cell lung cancer (NSCLC) with EGFR mutations, but some patients have exhibited primary resistance to EGFR-TKIs. We recently reported that podoplanin-positive fibroblasts are associated with a tumor-promoting phenotype of CAFs in lung adenocarcinoma.