Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA.

The impact of clinical stage on the effectiveness of osimertinib for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) remains unexamined. We investigated osimertinib therapeutic efficacy variation between stage IVA or lower and stage IVB EGFR mutation-positive lung cancers, focusing on differences in pretreatment co-occurring genetic alterations in circulating tumor DNA. This was a secondary analysis of the ELUCIDATOR study, a multicenter prospective observational study in Japan that assessed the mechanisms underlying resistance to osimertinib as a first-line treatment for advanced NSCLC with EGFR mutations.

YAP regulates HER3 signaling-driven adaptive resistance to RET inhibitors in RET-aberrant cancer.

Purpose: Rearranged during transfection (RET) aberrations represent a targetable oncogene in several tumor types, with RET inhibitors displaying marked efficacy. However, some patients with RET-aberrant cancer are insensitive to RET tyrosine kinase inhibitors (TKIs). Recently, drug-tolerant mechanisms have attracted attention as targets for initial therapies to overcome drug resistance.

Randomized Phase II Trial of Amrubicin Plus Irinotecan Versus Cisplatin Plus Irinotecan in Chemo-naïve Patients With Extensive-Disease Small-Cell Lung Cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08-01.

Background: We conducted a randomize phase II study to evaluate the efficacy and safety of topoisomerase II inhibitor amrubicin plus topoisomerase I inhibitor irinotecan (AI) compared with cisplatin plus irinotecan (PI) as first-line therapy in patients with extensive-disease (ED) small-cell lung cancer (SCLC).

Patients And Methods: Chemo-naïve patients with pathologically proven ED-SCLC (including limited disease (LD) SCLC with malignant effusion) were enrolled. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m on day 1 and irinotecan 50mg/m on days 1 and 8 of a 21-day cycle) or PI (cisplatin 60mg/m on day 1 and irinotecan 60mg/m on days 1, 8 and 15 of a 28-day cycle).

Safety and Efficacy of Durvalumab After Chemoradiotherapy in Antinuclear Antibody-positive Patients With Non-small Cell Lung Cancer.

Background/aim: Pneumonitis during durvalumab consolidation therapy after chemoradiotherapy (CRT) is a major cause of treatment discontinuation. Although previous studies have revealed an association between antinuclear antibody (ANA) positivity and the safety and efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC), there are no reports on durvalumab consolidation therapy. This study investigated the safety and efficacy of durvalumab after CRT in ANA-positive patients.

Baseline genetic abnormalities and effectiveness of osimertinib treatment in patients with chemotherapy-naïve EGFR-mutated NSCLC based on performance status.

Background/aim: For patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment.

Mechanisms of resistance and correlation between pre-treatment co-alterations and p-prognosis to osimertinib in chemo-naïve advanced non-small cell lung cancer.

Background: Several patients treated with osimertinib experience progressive disease. The aim was to clarify the mechanisms underlying resistance to osimertinib.

Methods: ELUCIDATOR: A multi-centre, prospective, observational study involved chemotherapy-naive patients with advanced non-small cell lung cancer receiving osimertinib.

Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

Background: Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce.

Objective: We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy.

Real-world outcomes of nivolumab plus ipilimumab and pembrolizumab with platinum-based chemotherapy in advanced non-small cell lung cancer: a multicenter retrospective comparative study.

Introduction: Nivolumab plus ipilimumab with chemotherapy (NICT) and pembrolizumab with chemotherapy (PCT) are commonly used in patients with advanced non-small cell lung cancer (NSCLC). Compared with immune checkpoint inhibitor (ICI) monotherapy, ICI combination therapy can increase immune-related toxicity instead of prolonging survival. This study aimed to compare the efficacy and safety of NICT and PCT to decide on the favorable treatment.

Pneumonitis During Durvalumab Consolidation Therapy Affects Survival in Stage III NSCLC.

Introduction: Durvalumab consolidation therapy is the standard of care after concurrent chemoradiotherapy (CRT) for stage III NSCLC. Immune-related pneumonitis during durvalumab treatment is potentially fatal; however, information is lacking regarding the impact of pneumonitis on patient survival. This study investigates the effect of pulmonary and nonpulmonary immune-related adverse events (irAEs) on the efficacy of durvalumab treatment in patients with stage III NSCLC.

Enhancing tumour content and tumour cell count using microdissection contributes to higher detection rate of genetic mutations by next-generation sequencers.

Background: Next-generation sequencing (NGS) analysis is becoming indispensable for the treatment of advanced lung cancer. NGS analysis requires a large number of cancer cell-containing tissues; however, it is often difficult for small biopsies to obtain the required quantities. In microdissection, only the tumour parts of a tissue specimen are obtained, which thereby increases the tumour content and tumour cell count of the tissue specimen.

Long-term survival of patients with advanced non-small cell lung cancer treated using immune checkpoint inhibitors.

Lung cancer is the leading cause of cancer-related deaths worldwide and has a high incidence of metastasis. For patients with advanced non-small cell lung cancer (NSCLC) without targetable genomic driver mutation, the development of specific antibodies called immune checkpoint inhibitors (ICIs) against the programmed death-1 receptor, its partner programmed death ligand-1, and the cytotoxic T-lymphocyte-associated protein 4 receptor have proved more effective than standard therapies in phase III trials and have led to unprecedented prolonged survival in the first-line setting. Long-lasting effects of ICI treatment have also been recorded and reported to persist even after the treatment is discontinued.

A case of reflux laryngitis after iodine staining for esophageal squamous cell carcinoma.

Iodine staining allows for clear visualization of the lesion boundaries of esophageal squamous cell carcinoma and is used as the gold standard for detecting and diagnosing the extent of the cancer. Heartburn and retrosternal pain are known side effects; however, no reports of pharyngitis or laryngitis exist. Therefore, we present a case of laryngitis caused by iodine reflux.

Impact of Lymphopenia Recovery After Chemoradiotherapy on Durvalumab Consolidation Therapy in Stage III NSCLC.

Introduction: Durvalumab maintenance therapy after definitive concurrent chemoradiotherapy (CRT) is the standard treatment modality for stage III NSCLC. Although severe treatment-related lymphopenia (TRL) during CRT may impair the efficacy of subsequent durvalumab therapy, data on the effect of TRL recovery on consolidation durvalumab therapy are lacking.

Methods: This retrospective study evaluated patients with unresectable stage III NSCLC treated with durvalumab after concurrent CRT.

A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With -Positive NSCLC in Japan.

Introduction: Lorlatinib is an ALK tyrosine kinase inhibitor approved in Japan for the treatment of advanced + NSCLC. There has been little evidence about lorlatinib efficacy after first-line (1L) alectinib in clinical practice in Japan.

Methods: We retrospectively analyzed patients with advanced + NSCLC previously treated with 1L alectinib at multiple sites in Japan.

Possible False Results With cobas EGFR Mutation Test v2 and Oncomine Dx Target Test for Mutation.

Background/aim: Disparities in the results of next-generation sequencing-based multiplex gene panel tests and those of single-gene tests when detecting epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) have been reported. However, the possible underlying causes have not been investigated. The aim of this study was to explore the possibilities and causes of false results obtained using cobas EGFR Mutation Test v2 (cobas EGFR) and Oncomine Dx Target Test (ODxTT).

Right-sided vocal cord paralysis following stereotactic body radiation therapy for non-small-cell lung cancer: A case report.

Vocal code paralysis (VCP) is a rare complication of stereotactic body radiation therapy (SBRT). In most previously reported cases of VCP after SBRT, VCP was left-sided because of anatomic vulnerability. Here, we report a case of right-sided VCP following SBRT for non-small-cell lung cancer.

Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF-V600E-positive non-small cell lung cancer: A case report.

Dabrafenib plus trametinib is the standard treatment for BRAF V600E-mutated non-small cell lung cancer. No treatment-related cerebral infarction (CI) has been reported in previous clinical trials. Here, we described a 61-year-old Japanese man with BRAF V600E-mutated lung adenocarcinoma treated with dabrafenib plus trametinib as a third-line treatment.

Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting.

Background/aim: Regimens with bevacizumab (Bev) have high response rates. We previously showed the efficacy of Bev plus carboplatin (CBDCA)/nab-paclitaxel (nab-PTX) in the treatment of non-squamous (non-SQ) non-small lung cell cancer (NSCLC) with malignant pleural effusion in a phase II trial. However, few studies have reported the efficacy and safety of this regimen.

Sequencing strategies with ramucirumab and docetaxel following prior treatments for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

Objectives: Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy for advanced non-small cell lung cancer (NSCLC). Therefore, we aimed to elucidate sequencing strategies of RAM and DOC following prior treatments, including immune checkpoint inhibitor (ICI), cytotoxic agent (CTx) alone, bevacizumab (BEV), and tyrosine kinase inhibitor (TKI).

Methods: We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx alone, BEV, and TKI, respectively.

The Impact of Estrogen Receptor Expression on Mutational Status in the Evolution of Non-Small Cell Lung Cancer.

Background: The role of estrogen receptor (ER) status in the carcinogenesis of lung cancer and its impact on prognosis remain unclear.

Materials And Methods: We previously reported a prospective, multicenter, molecular epidemiology study (Japan Molecular Epidemiology for Lung Cancer Study [JME]). We examined the relationship of ER status with reproductive and hormonal factors, mutational profile, and survival using JME study data.

Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes.

Background: KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23-35% and 13-20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome.