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Background: There have been several reports demonstrating the safety of flexible bronchoscopy (FB) in the elderly, but none have focused specifically on lung cancer, which is a frequent biopsy procedure. Methods: In this study, we retrospectively evaluated the safety of FB and subsequent treatment in elderly patients with suspected primary lung cancer. Elderly patients were defined as 75 years of age or older. Results: A total of 141 patients, 77 in the elderly group and 64 in the nonelderly group, were reviewed. The median age of the elderly group was 80 years. Transbronchial lung biopsy was performed in more than 80% of all patients. Primary lung cancer was diagnosed in 42 (54.4%) of the elderly group and 35 (54.7%) of the nonelderly group (p = 0.38). Approximately 70% of the elderly patients with a confirmed diagnosis were treated, while more than half of the undiagnosed elderly patients had best supportive care. Complications such as bleeding, pneumothorax, fever, and pneumonia were similar in the elderly and nonelderly groups. Conclusions: This study suggests that flexible bronchoscopy can be performed as safely in the elderly as in the nonelderly. Furthermore, even elderly patients may have a greater chance of receiving treatment when a definitive diagnosis is achieved. [ABSTRACT FROM AUTHOR]

Searching for driver gene alteration is a prerequisite for chemotherapy of non‐small cell lung cancer. Due to its high sensitivity and concordance rate, the Amoy Dx Pan Lung Cancer PCR panel has been approved and is widely used in Japan. In this report, we describe a case in which a positive result for Kristen rat sarcoma virus (KRAS) exon2 p.G12F, a rare KRAS mutation, may have led to a false‐positive result for KRAS exon2 p.G12C on AMOY. Genetic analysis in this case was performed by LC‐SCRUM‐Asia. [ABSTRACT FROM AUTHOR]

This report describes the case of a 79‐year‐old Japanese man diagnosed with orbital extranodal marginal zone lymphoma (EMZL) and stage IIIA lung cancer. The patient received concurrent chemoradiation for lung cancer with carboplatin/paclitaxel treatment, resulting in regression of both the lymphoma and lung cancer. To our knowledge, this is the first reported case of concurrent orbital EMZL and lung cancer. In this case, a treatment strategy that prioritized lung cancer treatment was deemed appropriate. This case suggests that chemotherapy with carboplatin and paclitaxel may serve as an effective treatment for both lung cancer and lymphoma. [ABSTRACT FROM AUTHOR]

Introduction: Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in combination with cytotoxic chemotherapy. The most frequent side effects of G-CSF are pain and fever; aortitis, in contrast, is a rare and serious side effect. Case Presentation: A 73-year-old man with small-cell lung cancer was treated with a full dose of a combination of carboplatin/etoposide/durvalumab and pegfilgrastim. The patient developed fever and right ear pain 12 days after pegfilgrastim administration and was diagnosed with aortitis by contrast-enhanced computed tomography 5 days later. Because the patient had already been administered the immune checkpoint inhibitor and had a history of hepatitis B, the patient was followed up without corticosteroid administration, and the patient's symptoms resolved spontaneously. Conclusion: In situations where immunosuppression should be avoided, we believe that follow-up without corticosteroids for G-CSF-induced aortitis is a promising option. [ABSTRACT FROM AUTHOR]

Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis. [ABSTRACT FROM AUTHOR]

Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction. We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12 months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab. In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy. We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis. [ABSTRACT FROM AUTHOR]

In advanced lung cancer treatment, immunotherapy provides durable responses in some patients. However, other patients experience progressive disease and the resistance mechanisms to immunotherapy have yet been fully elucidated. Small cell transformation of non‐small cell lung cancer (NSCLC) is commonly recognized as one of the resistance mechanisms to epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors in EGFR‐mutant NSCLC treatment. As a resistant mechanism for immunotherapy, we report the first case of small cell transformation in 2017. Since then, eight similar cases have been reported and the concept of small cell transformation is now becoming more prevalent as a mechanism of immunotherapy resistance. In our facility, we have experienced four cases of small cell transformation after immunotherapy (including the reported case in 2017). The histology of each primary tumor was squamous cell carcinoma, large cell type neuroendocrine carcinoma, or poorly differentiated NSCLC. None had driver gene mutations. Nivolumab was administered in all four cases and atezolizumab was administered as a next line to nivolumab treatment in one case. The best response to immunotherapy was partial response or stable disease. There was a wide range of periods from the start of immunotherapy to confirmation of small cell transformation (from 2 weeks to almost 3 years). In conclusion, small cell transformation is an important resistance mechanism in cancer immunotherapy. When NSCLC progresses after immunotherapy, the possibility of small cell transformation and rebiopsy should always be encouraged, as it leads to clarification of the resistance mechanisms and frequency. [ABSTRACT FROM AUTHOR]

Background: A synergistic effect of cyclooxygenase inhibitors (COX‐I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX‐I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX‐I use and the efficacy of ICI in patients with non‐small cell lung cancer (NSCLC). Methods: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX‐I use as regular use of COX‐I other than low‐dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX‐I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis. Results: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX‐I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77–5.19 vs. 2.20–4.60 months; p = 0.630), COX‐I users had significantly shorter OS than non‐COX‐I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78–11.66 vs. 9.49–19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03–14.92 vs. 9.49–19.32 months; p = 0.081). Conclusions: There was no additional or negative impact of COX‐I use on the efficacy of ICIs in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Over the past two decades, antiresorptive agent‐related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real‐world clinical setting. To our knowledge, we are the first to do so. Patients and methods: We retrospectively analyzed lung cancer patients with bone metastases who had received anti‐resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria. Results: A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%) and three (23.1%) had adenocarcinoma, squamous carcinoma and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of antiresorptive agents (odds ratio [OR] = 11.54; 95% confidence interval [CI], 2.47–53.99; P < 0.01), use of immune checkpoint inhibitors (ICIs; OR = 5.05; 95% CI, 1.56–16.37; P < 0.01) and longer survival duration (≥2 years; OR = 12.16; 95% CI, 3.17–46.65; P < 0.01) were independently associated with ARONJ in a multivariate analysis. Conclusions: The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using antiresorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists, especially in patients receiving ICIs. [ABSTRACT FROM AUTHOR]

The current coronavirus disease 2019 (COVID‐19) pandemic is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. Many patients with lung cancer are thought to be affected by this situation. Therefore, in this study, we aimed to evaluate the impact of COVID‐19 pandemic on lung cancer treatment scheduling. We retrospectively reviewed the medical records of lung cancer patients who were undergoing anticancer treatment at the National Hospital Organization Kyoto Medical Center (600 beds) in Kyoto, Japan, between 1 March 2020 and 31 May 2020. After the medical records were reviewed, the patients were assigned to one of two groups, depending on whether their lung cancer treatment schedule was delayed. We assessed the characteristics, types of histopathology and treatment, and the reason for the delay. A total 15 (9.1%) patients experienced a delay in lung cancer treatment during the COVID‐19 pandemic. Patients with a treatment delay received significantly more immune checkpoint inhibitor (ICI) monotherapy than patients without a treatment delay (P = 0.0057). On the contrary, no patients receiving molecular targeted agents experienced a treatment delay during the COVID‐19 pandemic period (P = 0.0027). The treatments of most of the patients were delayed at their request. We determined that 9.1% lung cancer patients suffered anxiety and requested a treatment delay during the COVID‐19 pandemic. Oncologists should bear in mind that patients with cancer have more anxiety than expected under unprecedented circumstances such as the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficacy and safety of retreatment with anti‐programmed death 1 (anti‐PD‐1) antibodies in patients with advanced non‐small cell lung cancer (NSCLC) after prior treatment with anti‐programmed death‐ligand 1 (anti‐PD‐L1) antibodies. Methods: Data (N = 15) on patients' characteristics, number of cycles, regimens, their best response and immune‐related adverse events (irAEs) were recorded retrospectively. Results: NSCLC was initially treated with anti‐PD‐L1 antibody atezolizumab (N = 14) or durvalumab (N = 1). No patients had a high (≥50%) tumor expression of PD‐L1. The median cycles for atezolizumab were five (range 1–15), and median progression‐free survival was 2.8 and 6.0 months for atezolizumab and durvalumab, respectively. Five (33.3%) and nine (60.0%) patients showed stable and progressive disease as their best response, respectively. No differences in irAEs between anti‐PD‐L1 and anti‐PD‐1 antibodies occurred. Conclusion: Patients treated with anti‐PD‐L1 antibodies for NSCLC received limited benefits from retreatment with anti‐PD‐1 antibodies. [ABSTRACT FROM AUTHOR]

Unlike cytotoxicity, haematological toxicity is a rare immune‐related adverse event that is occasionally irreversible and refractory. A 67‐year‐old man was diagnosed with advanced lung squamous cell carcinoma. After 41 cycles of nivolumab as third‐line chemotherapy, the patient developed severe neutropenia and thrombocytopenia. The bone marrow biopsy and serum immunological tests indicated no evidence of bone marrow failure and suggested autoimmune mature blood cell destruction. After initiating treatment with prednisolone 50 mg orally and filgrastim 75 μg subcutaneously once daily, neutropenia and thrombocytopenia recovered within four and nine days, respectively. The filgrastim was discontinued four days later, and the corticosteroid was discontinued three months later; there has been no haemocytopenia recurrence since then. The patient has remained untreated for more than two years without progression of lung cancer. In conclusion, corticosteroids should be considered for the treatment of autoimmune haemocytopenia if refractory bone marrow dysplasia can be ruled out. [ABSTRACT FROM AUTHOR]

Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors (ICIs) presents complications of infectious diseases, including tuberculosis. Incidence of tuberculosis during immunotherapy remains unclear. We found that 1.7% of patients developed active tuberculosis during immunotherapy at our institution. In patients with a positive interferon-gamma release assay status before ICI therapy, physicians should pay close attention to developing tuberculosis. [ABSTRACT FROM AUTHOR]

Background: The risk of developing lung cancer is high in patients with interstitial lung disease (ILD), as few treatment options are available. Immune checkpoint inhibitors (ICI) are used for the treatment of non‐small cell lung cancer (NSCLC) in clinical practice; however, in patients with preexisting ILD, the risk of ICI‐related pneumonitis is unknown. We evaluated the efficacy and lung toxicity of nivolumab in patients with NSCLC and ILD. Methods: We retrospectively reviewed the medical records of 216 NSCLC patients who had received nivolumab therapy. The existence of ILD in these patients was determined by lung computed tomography findings; 26 patients had ILD. We evaluated the efficacy of nivolumab by measuring the response rate (RR), progression‐free survival (PFS) duration, and lung toxicity by incidence, severity, and outcome of nivolumab‐related ILD. Results: The RR and median PFS of the ILD and non‐ILD groups were 27% versus 13% (P = 0.078) and 2.7 (95% confidence interval [CI], 1.7–5.3) versus 2.9 months (95% CI 2.1–3.4; P = 0.919), respectively. The incidences of total and severe nivolumab‐related pneumonitis were significantly higher in the ILD group than in the non‐ILD group (31% vs. 12%, P = 0.014 and 19% vs. 5%, P = 0.022, respectively). No death from nivolumab‐related pneumonitis occurred. Over 50% of the patients in both groups with nivolumab‐related pneumonitis showed improvement over time. Conclusion: Relative to the non‐ILD group, nivolumab‐related pneumonitis was observed more frequently in the ILD group; however, most cases were manageable. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is a common cancer in haematology. We report a case of DLBCL mimicking malignant pleural mesothelioma (MPM). A 75-year-old man with a 1-week exacerbation of dyspnoea on exertion and right pleural effusion on chest radiography was admitted to our hospital. Positron emission tomography/computed tomography revealed diffuse pleural thick lesions and massive pleural effusion, and these lesions had accumulation of fluorodeoxyglucose. Because we suspected MPM or lung cancer, we performed a biopsy with thoracoscopy to confirm the diagnosis. A biopsy of the pleural effusion with thoracoscopy revealed DLBCL. Chemotherapy was immediately selected, and the diffuse thickened pleural wall and massive pleural effusion of the right chest were significantly improved after two cycles of chemotherapy. [ABSTRACT FROM AUTHOR]

Immunotherapy with immune checkpoint inhibitors (ICIs), while ameliorating lung cancer, can cause infectious diseases, including tuberculosis, in addition to immune-related noninfectious complications. In the clinical setting, the efficacy of ICIs to treat mycobacterial infection remains controversial. We report 3 cases of acute Mycobacterium avium complex lung disease during immunotherapy with ICIs. [ABSTRACT FROM AUTHOR]