Toshihide Yokoyama

Desire for Information and Involvement in Treatment Decisions: Lung Cancer Patients' Preferences and Their Physicians' Perceptions: Results from Okayama Lung Cancer Study Group Trial 0705

Introduction: This study explores patient preferences for involvement in lung cancer treatment decisions and the extent of concordance between the views of patients and physicians on decisional roles. The impact of demographic and psychosocial characteristics on the decisional role of patients is also examined. Methods: Patients with relapsed non-small cell lung cancer who were candidates for a phase II trial of erlotinib monotherapy were recruited. Patients were interviewed after they had learned of their relapse and the treatment decision had been made but before pharmacologic intervention. Results: Most of the 28 participants were married, had a smoking history, and were well educated. They reported moderate levels of depression and anxiety. Initially, 14% of the patients reported a preference for active decision making; later, 29% believed that the primary responsibility for the treatment decision had been theirs. Only 54% of the patients agreed with the physicians assessment of how the treatment decision was made (&kgr; = 0.31; test of symmetry, p = 0.23). The depression score was significantly associated with a patients preferred level of control (p < 0.01). Conclusions: The limited concordance between patient preference and perception and between patient and physician perceptions regarding how the treatment decision was made suggests that physicians should more accurately identify patient preferences by directly asking patients at the beginning of each clinical encounter.

Identifying the Cause of the "Saturation Gap": Two Cases of Dapsone-induced Methemoglobinemia

Diaphenylsulfone (DDS: Dapsone) is used for Pneumocystis pneumonia (PCP) prophylaxis, and methemoglobinemia has rarely been reported as a side effect of DDS. We herein report two cases of DDS-related methemoglobinemia in an 81-year-old man with organizing pneumonia and an 84-year-old woman with eosinophilic pneumonia under treatment with prednisolone. Both patients initially received trimethoprim/sulfamethoxazole for PCP prophylaxis and were switched to DDS due to side effects and subsequently exhibited a clinically unexplainable decrease in SpO2. Methemoglobinemia was diagnosed based on the findings of arterial blood gas analyses. In both cases, the methemoglobinemia improved after discontinuing DDS.

Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first‐line therapy for patients with EGFR‐mutated non–small‐cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression‐free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR‐TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR‐TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression‐free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial.

Does afatinib plus bevacizumab combination therapy induce positive conversion of T790M in previously-negative patients?

Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are markedly effective for T790M-positive patients. To confer their clinical benefit to more patients, a novel therapy to induce positive conversion in T790M-negative patients may be possible. We retrospectively reviewed medical records of patients who had received rebiopsy after completion of ABC-study: a prospective phase II study of Afatinib plus Bevacizumab Combination (ABC)-therapy after acquired resistance to EGFR-TKI. Between October 2014 and September 2016, 32 eligible patients were enrolled in ABC-study at our institutes. Eighteen patients were T790M-negative and 14 were T790M-positive before ABC-therapy. Rebiopsy was performed on 13 T790M-negative and 5 T790M-positive patients after progression of ABC-therapy. In 8 (62%) of 13 T790M-negative patients, T790M status changed from negative to positive after ABC-therapy. Seven of these 8 patients underwent osimertinib therapy. The response rate and median time to treatment failure were 86% and 12.2 months, respectively. There were no adverse events ≥grade 3, nor any treatment-related deaths. On the other hand, T790M remained positive after ABC-therapy in all 5 previous T790M-positive patients. ABC-therapy could induce positive conversion of T790M even in previously-negative patients. We hypothesize that ABC-therapy could provoke “clonal selection”, which purifies T790M-positive cancer cells in heterogeneous tumors. Further studies are warranted to confirm this phenomena.

Afatinib Plus Bevacizumab Combination After Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Multicenter, Single-Arm, Phase 2 Trial (ABC Study)

Preclinical studies suggested that the addition of bevacizumab could overcome acquired resistance (AR) to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The aim of this study was to evaluate the clinical efficacy and safety of a combination of afatinib and bevacizumab after AR.

Reenlargement of radiation necrosis after stereotactic radiotherapy for brain metastasis from lung cancer during bevacizumab treatment

We describe a 55-year-old man who received stereotactic radiotherapy (SRT) for the treatment of brain metastasis from lung adenocarcinoma. Fourteen months after SRT, right-sided hemiparesis developed, and magnetic resonance imaging revealed progression of perifocal edema and an enhanced lesion. Cerebral radiation necrosis was diagnosed, and treatment with bevacizumab was initiated. The lesion clearly responded to bevacizumab therapy, but reenlarged 8 months later and was surgically resected. Histopathological analysis of the resected specimen revealed large areas of necrosis; however, viable tumor cells were detected in the necrotic areas. Reenlargement of the necrotic lesion was attributed to the recurrence of lung cancer.

A statistical issue regarding the original paper by M. Tamiya and others (Med Oncol (2016) 33:2 DOI 10.1007/s12032-015-0715-7)

We read with great interest the original paper by Tamiya [1]. We think the conclusion of this trial should be that the primary outcome measure was ‘‘met’’ for the following reasons, even though M. Tamiya et al. concluded that the primary outcome measure was ‘‘not met.’’ The primary objective of this trial to demonstrate is the ‘‘(real) 1-year survival rate is higher than 35% (which means [35%).’’ The result of this test was that the estimated 1-year survival rate was 58%, and the lower limit of its two-sided 95% confidence interval was 42.9%, which is 35% higher than the set threshold value. Therefore, the test result is p\ 0.05 (two-sided), which is statistically significant. This obviously demonstrated that the ‘‘1-year survival rate exceeded 35% in a statistically significant way.’’ Thus, we believe that the null hypothesis (the 1-year survival rate is 35% or lower) was successfully denied and the data must be interpreted as a positive result in terms of statistics. Compliance with ethical standards

Retroperitoneal Metastasis from Lung Adenocarcinoma Mimics Retroperitoneal Fibrosis

Retroperitoneal Metastasis from Lung Adenocarcinoma Mimics Retroperitoneal Fibrosis Akihiro Nishiyama, MD,* Hiroshige Yoshioka, MD, PhD, Satoshi Ikeo, MD, Mitsunori Morita, MD, Naoyuki Sone, MD, Satoshi Ikeda, MD, Toshihide Yokoyama, MD, Tadashi Ishida, MD, PhD Division of Medical Oncology Cancer Research Institute, Kanazawa University, Kanazawa, Japan Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan