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Abstract Background To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

Abstract 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 Background The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. Methods This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. Results Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. Conclusion In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Abstract 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.

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.

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 Background The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies. Methods We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated. Results Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases. Conclusion Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy.

Background: Flexible bronchoscopy (FB) is a common method used for diagnostic sampling of the thorax. Although the safety and efficacy of FB in the general population are well-established, data on the elderly population are limited. This study aimed to determine the safety and efficacy of FB in elderly people aged ≥80 years. Materials and Methods: We retrospectively studied elderly patients aged ≥80 years who underwent FB at our hospital between April 2021 and March 2022. Outcomes, such as indications, sampling methods, diagnostic results, and complications, were compared with those of a control group of patients aged 18–79 years. Results: In total, 247 patients (154 men) were included in the study, with 65 and 182 patients in the elderly and non-elderly groups, respectively. The most frequent indication for FB was the presence of a mass or nodule, with transbronchial lung biopsy, transbronchial biopsy, and endobronchial ultrasound-guided transbronchial needle aspiration performed in 162 (65.6%), 29 (11.7%), and 36 (15.6%) patients, respectively. FB led to a diagnosis in 36 (57.1%) and 103 (56%) patients in the elderly and non-elderly groups, respectively, with no significant difference observed. There were no patient deaths or significant differences in the incidence of hemorrhage, hypoxia, pneumothorax, fever, or pneumonia between the two groups. Conclusions: The findings of this study indicate that FB can be performed effectively and safely in elderly patients aged ≥80 years, similar to non-elderly patients. Resumen: Antecedentes: La broncoscopia flexible (FB) es un método común utilizado para el muestreo diagnóstico del tórax. Aunque la seguridad y eficacia de la FB en la población general están bien establecidas, los datos sobre la población anciana son limitados. El objetivo de este estudio es determinar la seguridad y eficacia de la FB en ancianos ≥80 años. Materiales y métodos: Se estudiaron retrospectivamente los pacientes ancianos de ≥80 años sometidos a FB en nuestro hospital entre abril de 2021 y marzo de 2022. Los resultados, como las indicaciones, los métodos de muestreo, los resultados diagnósticos y las complicaciones, se compararon con los de un grupo control de pacientes de 18-79 años. Resultados: En total, 247 pacientes (154 hombres) fueron incluidos en el estudio, con 65 y 182 pacientes en los grupos de ancianos y no ancianos, respectivamente. La indicación más frecuente fue la presencia de una masa o nódulo, realizándose biopsia pulmonar transbronquial, biopsia transbronquial y aspiración transbronquial con aguja guiada por ecografía endobronquial en 162 (65,6%), 29 (11,7%) y 36 (15,6%) pacientes, respectivamente. Conclusiones: Los resultados de este estudio indican que la FB se puede Los resultados de este estudio indican que la FB puede realizarse de forma eficaz y segura en pacientes de edad ≥80 años, de forma similar a los pacientes no ancianos.

Abstract Background The incidence of nontuberculous mycobacterial lung disease (NTM-LD) peaks in middle- and old age groups, coinciding with senescence; thus, chronic infectious diseases can accelerate frailty and worsen mental health in the elderly. In this study, we aimed to compare the prevalence of physical and psychiatric frailty between patients with NTM-LD and bronchiectasis (BE). Methods The Kihon Checklist Questionnaire (KCQ) was used to assess physical and psychiatric frailties and identify those at risk of requiring care among patients with newly diagnosed NTM-LD and BE. Additionally, the Hospital Anxiety and Depression Scale (HADS) scores and chronic inflammatory biomarkers of the alveolar region (surfactant protein [SP]-A, SP-D, and human cationic antibacterial protein [hCAP]/LL-37) were assessed and compared between NTM-LD and BE patients. Results There were no significant differences in the background characteristics between the 33 NTM and 36 BE patients recruited. The KCQ revealed that the proportion of frail NTM patients at diagnosis was higher than that of frail BE patients (48.5% vs. 22.2%, p = 0.026). HADS scores were significantly higher in the NTM group than in the BE group (p

Abstract 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.

While immunotherapy with immune checkpoint inhibitors has achieved promising effects in advanced lung cancer treatment, it can induce some unique adverse events, known as immunotherapy-related adverse events (irAEs). Immunotherapy-related interstitial pneumonitis is one of the irAEs, and its incidence is reported as 3.5–8.3% in phase III trials of nivolumab with or without ipilimumab for advanced non-small cell lung cancer patients. However, in the real-world setting, pathology is not routinely used in the diagnostic process of interstitial pneumonitis because diagnosis is usually made using chest computed tomography (CT). Here, we report an educational case of pathologically diagnosed pulmonary lymphangitis carcinomatosa mimicking immunotherapy-related interstitial pneumonitis. The patient was diagnosed with advanced adenocarcinoma of the right lung (stage IVA) and received immunochemotherapy for 6 months. He manifested acute respiratory failure, and a chest CT scan revealed the emergence of diffuse grand-grass opacity predominantly in the left lung. Immunotherapy-induced interstitial pneumonitis was clinically suspected because the primary lesion was stable, and the level of the serum carcinoembryonic antigen decreased. However, the detection of adenocarcinoma cells in the bronchoalveolar lavage sample from the left lung confirmed the diagnosis of pulmonary lymphangitis carcinomatosa. Clinicians’ assumptions can sometimes mislead treatment methods; hence, this case draws attention to the perils of misdiagnoses.

Abstract We present a case report of a 92‐year‐old patient with thoracic empyema, who was successfully treated via CT‐guided insertion of a pigtail catheter. The advanced age of the patient often poses challenges in managing pyothorax due to limited physical activity and cognitive decline stemming from decreased activities of daily living. In instances where thoracic drainage is not feasible, the course of treatment is protracted and the prognosis is poor. Our case report exemplifies the successful treatment of pyothorax in a geriatric patient via CT‐guided insertion of a pigtail catheter. We believe that this educational case serves as a testament to the fact that even the most aged patients can be successfully treated with resourcefulness.

Since the FLAURA trial, epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) has generally been treated with osimertinib as a first-line therapy. However, there is still insufficient data on the therapeutic efficacy of EGFR-tyrosine kinase inhibitors in NSCLC patients with uncommon mutations. Many of these minor mutations are resistant to osimertinib; one such mutation is EGFR L718V or L718Q (L718V/Q), which may occur in combination with L858R. L718V/Q has been identified as a resistance gene to osimertinib when progressive disease occurs during treatment with osimertinib. Some reports have shown that EGFR L718V/Q with L858R is resistant to osimertinib but sensitive to afatinib. All cases of L718V/Q mutation-positive NSCLC reported in previous studies have presented with L718V/Q as the acquisition of resistance after treatment with osimertinib. In the present case report, we describe a rare case of NSCLC with de novo EGFR L718V and L858R mutations. Consistent with previous reports, the patient was resistant to osimertinib but responded well to afatinib.

Background: Molnupiravir is being widely used as a treatment for coronavirus disease 2019 (COVID-19); however, its acceptability and safety in older patients aged ≥ 80 years in real-world clinical practice is not well understood. Methods: We conducted a single-centre retrospective study and assessed the outcome of patients with COVID-19 treated with molnupiravir according to the following criteria: (A) discontinuation rate of molnupiravir; (B) type, frequency, and severity of adverse events; (C) all-cause mortality within 30 days of the diagnosis of COVID-19. Results: Forty-seven patients (46.1%) were aged ≥ 80 years (older patients) and 55 (53.9%) were aged < 80 years (younger patients). There were no significant differences in coexisting diseases and history of vaccination for COVID-19 between older and younger patients. Older patients were significantly more likely to have moderate disease (moderate 1 and 2) according to the Japanese Ministry of Health, Labour and Welfare classification than younger patients. During treatment, 8.5% of older patients and 1.8% of younger patients stopped taking molnupiravir, but the difference was not significant. Adverse events were observed in 39/102 (38.2%) patients. The most common adverse events were diarrhoea (9.8%), exacerbation of coexisting diseases (6.9%), bone marrow suppression (6.9%), liver dysfunction (5.9%), and loss of appetite (4.9%). Most adverse events were minor, ranging from grades 1 to 3. The all-cause mortality rate was 10.8%, and no molnupiravir-related deaths were observed. Conclusions: Molnupiravir treatment is acceptable and safe in older patients with COVID-19 aged ≥ 80 years.

The transformation to SCLC is a known mechanism of resistance against molecularly targeted therapies. This study reports a patient with untreated lung adenocarcinoma, characterized by a KRAS G12C mutation, which transformed into SCLC before treatment. Both the adenocarcinoma and SCLC components were responsive to sotorasib.

Malignant melanoma is a rare and high-grade cancer. It most commonly affects the skin, but it has the potential to involve all areas of the body. Primary pulmonary malignant melanoma is rare, accounting for only 0.01% of all pulmonary tumors. We present a case of primary pulmonary malignant melanoma in a 90-year-old patient. The pretreatment computed tomography (CT) showed a pulmonary mass in the right upper lobe, multiple pleural nodules, enlarged mediastinal lymph nodes, and bone metastases. Positron emission tomography-CT showed a region of fluorodeoxyglucose hyperaccumulation that was consistent with the abnormal shadows. Advanced stage lung cancer was initially suspected, but bronchoscopy revealed a malignant melanoma. The patient was diagnosed with a primary pulmonary malignant melanoma. Although the patient was older, he wanted to receive immediate treatment. Thus, he was treated with immune checkpoint inhibitors. He responded well to the medication, and neither major adverse events nor tumor size reduction was observed. We report a rare case of primary pulmonary malignant melanoma in an older adult. Immune checkpoint inhibitor therapy, as in this case, was a viable treatment option for older adults.

Abstract 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 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.

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 There are limited real‐world data on the treatment practices, outcomes, and safety of chemoradiotherapy (CRT) alone in potential candidates for immune checkpoint inhibitors (ICI) for unresectable non‐small cell lung cancer (NSCLC). In this study, we analyzed the safety and efficacy of CRT in patients who underwent CRT and would satisfy the key eligibility criteria for maintenance therapy with durvalumab (eg, no progression after CRT) in real‐world settings (m‐sub) for unresectable Stage III NSCLC between 1 January 2013 and 31 December 2015 at 12 sites in Japan. The m‐sub comprised 214 patients with a median follow‐up of 31.6 months (range 1.9‐65.8 months). Median overall survival (OS) and progression‐free survival (PFS) from completing CRT were 36.4 months (95% confidence interval [CI] 28.1 months to not reached) and 9.5 months (95% CI 7.7‐11.7 months), respectively. Consolidation chemotherapy did not influence OS or PFS. Median PFS was 16.9 vs 9.1 months in patients with vs without epidermal growth factor receptor (EGFR) mutations, with PFS rates of ~20% at 3‐4 years. Pneumonitis was the most common adverse event (according to MedDRA version 21.0J), and about half of events were grade 1. Pneumonitis mostly occurred 10‐24 weeks after starting CRT, peaking at 18‐20 weeks. Esophagitis and dermatitis generally occurred from 0 to 4 weeks, peaking at 2‐4 weeks after starting CRT. Pericarditis was rare and occurred sporadically. In conclusion, the results of the m‐sub provide real‐world insight into the outcomes of CRT, and will be useful for future evaluations of ICI maintenance therapy after CRT.

Abstract Background Spirometry is useful for evaluating respiratory health status and predicting health-related outcomes. As spirometry requires skilled technician and takes time, it is useful to find simple way for predicting lung function impairment. The aim of this study was to investigate which tests could predict lung function impairment among workers. Methods This prospective study included workers of manufacturing industry who underwent health check-ups in 2017. Subjects underwent the chronic obstructive pulmonary disease (COPD) assessment test (CAT), spirometry, and physical fitness assessments, including handgrip strength (HGS). Lung function impairment was defined as a decline in any of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), or a FEV1/FVC ratio less than the lower limit of normal (LLN). Results Complete data on 475 workers (366 men, 50.4% ever smokers) were available. Lung function impairment was observed in 99 subjects (64 men). Men with lung function impairment had significantly higher rate of ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS, compared with those without. On multivariate analyses, ever-smoking (odds ratio [OR], 2.50; 95% confidence intervals [CI], 1.25–4.97), passive smoking at home in childhood (OR, 2.71; 95% CI, 1.16–6.32), CAT scores (OR, 1.06; 95% CI, 1.01–1.12), and HGS (OR, 0.73; 95% CI, 0.57–0.92) were independently associated with lung function impairment in men. Conclusions Ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS are significantly associated with lung function impairment in men. Trial registration Registration number: UMIN000028011. Date of registration: July 1, 2017.

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.

Background: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response. Case presentation: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG. Conclusions: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.

Abstract Background In Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies. Aim We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non‐small cell lung cancer (NSCLC) aged ≥80 years. Methods We retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune‐related adverse events (irAEs) during ICI monotherapy. Results A total of 45 patients were reviewed. The patients' median age was 85 years. Twenty‐one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression‐free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia. Conclusion This study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs.

Key message It is well known that a phenomenon called hyperprogressive disease (HPD) often occurs during immunotherapy with immune checkpoint inhibitors. In the present case, we experienced a case of HPD in a potential metastatic thyroid tumour during immunotherapy. HPD can be life‐threatening depending on where it appears, so clinicians need to be careful.

Background: The coronavirus disease 2019 (COVID-19) pandemic is associated with a heavy burden on patient's mental and physical health, regional healthcare resources, and global economic activity. An aging society such as Japan has many retirement homes and long-term stay hospitals for the elderly and their inhabitants. During the COVID-19 pandemic, disease clusters are often identified in retirement homes and long-term stay hospitals. Although we hypothesize that additional burdens of nursing care for elderly patients will reinforce the anxiety and exhaustion of medical staff and healthcare resources in the aging society, the actual situation is not well understood. In this study, we aimed to evaluate the current situation and countermeasures of the COVID-19 pandemic in the aging society.Methods: We reviewed COVID-19 patients who required hospitalization at the National Hospital Organization Kyoto Medical Center, a 600-bed capacity hospital located in Kyoto, Japan, between 1 April 2020 and 31 March 2021. We assessed the characteristics of the COVID-19 patients, disease severity, duration of hospitalization, outcome at discharge, degree of activities of daily living (ADLs), and complications unique to elderly patients.Results: We enrolled 118 patients who required hospitalization during the study period. Approximately 40% of the patients were aged ≥ 80 years. Dementia (27.1%) was the most prevalent underlying disease, followed by diabetes mellitus (23.7%) and chronic kidney disease (23.7%). Approximately 60% of hospitalized COVID-19 patients had impaired ADL at admission. The COVID-19 patients aged 80 years or older required significantly more longer-term hospitalization than the COVID-19 patients aged under 80 years (15.5 ± 8.2 vs. 13.1 ± 7.7, P = 0.032). In elderly patients aged 80 years or older, approximately 50% of patients had geriatric mental disorders, and approximately 70% had bedridden status and feeding difficulty. Poor ADL at admission was significantly associated with COVID-19 mortality (Odds ratio, 5.6; 95% confidence interval, 1.04–45.2; p-value = 0.044).Conclusions: The proportion of elderly patients aged 80 years or older was relatively high during the hospitalization for COVID-19. Poor ADL at admission in these elderly patients was significantly associated with poor prognosis of COVID-19. We should keep in mind that healthcare workers are forced to have an additional burden of nursing care in the aging society during the COVID-19 pandemic. Therefore, interventions to reduce the burden are urgently required.

Abstract 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.

Pyopneumothorax is characterized by a pleural collection of pus and air requiring emergent thoracic drainage. A 65-year-old diabetic woman presented with a two-week history of fatigue and dyspnea but without fever. Chest computed tomography showed extensive pleural effusion and air in the left pleural cavity, which caused a mediastinal shift with peripheral circulatory failure. There was no evidence of a pulmonary fistula. Anaerobic bacteria were found in the pus smear after microscopy. After 17 days of chest drainage and 18 days of antibiotic treatment, the patient recovered without any complications. The etiology of pyopneumothorax in this case was slowly progressive pyothorax due to gas-producing anaerobic bacteria. In conclusion, we should pay careful attention to serious infectious diseases, including pyothorax, in diabetic patients due to the high prevalence and subclinical symptoms.

Lung cancer patients harbouring driver oncogene alterations are markedly responsive to molecular target agents, such as epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor (TKI), and echinoderm microtubule-associated protein like 4 – anaplastic lymphoma kinase (EML4-ALK)-TKI. We encountered an exceptionally rare case, harbouring both EGFR mutation and EML4-ALK fusion gene, and suffering from severe disseminated intravascular coagulation. In this case report, we present two notable points. First, our patient was successfully treated with a third-generation EGFR-TKI, osimertinib. Second, osimertinib could manage severe conditions, such as disseminated intravascular coagulation. Third-generation EGFR-TKIs may be a viable option for patients harbouring both EGFR mutations and EML4-ALK fusion genes, even in severe conditions.

Background and Objectives: Immune-checitors have been established as a novel standard treatment for non-small cell lung cancer (NSCLC). The aim of this study was to identify factors associated with efficacy and nivolumab-related interstitial pneumonia in NSCLC by evaluating clinical data at the initiation of and during treatment. Methods: We retrospectively reviewed the medical records of patients who underwent treatment with nivolumab between October 2015 and December 2017. Using pretreatment patient data, we investigated factors associated with overall survival (OS) and the onset of nivolumab-related pneumonitis. We investigated serum biochemistry during treatment to identify the determinants associated with progressive disease (PD) and the onset of nivolumab-related pneumonitis. Results: A total of 94 patients were included. Eleven patients continued treatment, and 54 patients were diagnosed with progressive disease. Nivolumab-related pneumonitis occurred in 15 patients. A pretreatment Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0 was linked to significantly longer OS than ECOG PS = 1 (median: 20.1 vs. 6.5 months, respectively; p < 0.001). There was a higher incidence of nivolumab-related pneumonitis in patients with a history of interstitial pneumonia than in those without it ( p = 0.008). During treatment, the level of albumin gradually decreased prior to PD and onset of nivolumab-related pneumonitis. Conclusion: These results suggest that the pretreatment ECOG PS is the determining factor that is associated with OS, whereas history of interstitial pneumonia is the factor associated with nivolumab-related pneumonitis. A decrease in albumin during treatment may be associated with both PD and nivolumab-related pneumonitis.

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.

Thymic carcinomas is rare and highly aggressive carcinoma. Most patients with them are diagnosed as being at surgically unresectable stages due to it. There are several reports which showed the effect of chemotherapy, however, it is controversial. Recently, immune checkpoint inhibitors have changed conventional chemotherapy due to their effect against various types of cancers. We administered nivolumab, anti-Programmed Cell Death (PD)-1 antibody, to four patients with unresectable thymic carcinomas who had previously undergone conventional chemotherapy. A histopathology on tumors from these patients revealed the presence of squamous cell carcinoma and PD-L1 high expression. After treatment with nivolumab, it seemed to be beneficial to all patients; The best clinical responses of 3 patients were partial response and that of the other one was stable disease. None of them experienced severe immune-related adverse events. Our results suggest the potential benefits of using these inhibitors to treat thymic carcinomas in real world clinical setting as is the cases in recent clinical trials for the evaluation of immune checkpoint inhibitors for the treatment of thymic carcinoma.

We report a rare case of transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), without epidermal growth factor receptor (EGFR) gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT) scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene. A clinical diagnosis of NSCLC (cT3N3M1a, stage IV) was made following a positron emission tomography (PET)–CT scan and enhanced brain magnetic resonance imaging. Docetaxel and bevacizumab were selected as the first-line chemotherapy regimen; however, after two cycles, the patient developed a gastrointestinal perforation, and discontinuation of cytotoxic chemotherapy was recommended. Owing to gradual disease progression, immunotherapy with nivolumab was selected as the second-line regimen. During the immunotherapy, the tumor continued to progress and some subcutaneous tumors emerged. Biopsy of a subcutaneous tumor revealed SCLC, with positive immunostaining for cluster of differentiation 56, synaptophysin, and thyroid transcription factor-1. Serum tumor markers of SCLC were also elevated. Based on these results, we concluded that in this case NSCLC had transformed to SCLC during immunotherapy with nivolumab.

The existence of a lung cavity on chest radiographs suggests the presence of lung disease, including benign or malignant disease. Lung cancer, tuberculosis, and fungal infection are all known for developing lung cavity. In addition, there are some characteristic findings in the differential diagnosis of cavitary disease, although these cavitary diseases often coexist. Here, we report two cases that presented cavitary lung cancer with concomitant chronic infectious disease. One patient showed pulmonary aspergillosis and lung adenocarcinoma, the other patient showed Mycobacterium avium complex lung disease and lung adenocarcinoma. These chronic infectious diseases develop slowly, and clinicians often follow up over several months. To reduce the delay in diagnosis of malignancy, clinicians should aggressively collect the specimens from cavitary lesions and make a correct diagnosis when encountering lung cavity in diagnostic clinical imaging. Keywords: Lung cavity, Lung cancer, Aspergillus, Nontuberculous mycobacteria

A 72‐year‐old woman presented with acute onset of shortness of breath and fatigue over several days, and was found to be in acute respiratory failure. Computed tomography of the chest revealed diffuse ground‐glass opacities, crazy‐paving, multiple nodules, and a large mass in the right lower lobe. She was diagnosed with B‐cell lymphoma and a pulmonary lymphoproliferative disorder (PLD). PLD is known to present with a variety of radiographic patterns. The course of PLD is usually one of slow progression, and acute respiratory failure is a rare presentation. Physicians should be aware that acute respiratory failure can be caused by PLD.

Objective/background: The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease, including Mycobacterium avium complex (MAC), varies widely according to geographic region. However, the factors that influence regional variations in pNTM disease prevalence remain unknown. This study was undertaken to examine whether environmental or occupational factors or host traits could influence regional variations in pNTM disease prevalence. Methods: We collected laboratory data on pulmonary tuberculosis (pTB) and pNTM from two hospitals in the West Harima area of Japan and five hospitals in Kyoto City, Japan from 2012 to 2013. We estimated microbiological pNTM disease prevalence by multiplying all pTB cases in each area with the ratio of pNTM cases and pTB cases at the survey hospitals in each area. We administered a standardized questionnaire to 52 patients and 120 patients with pulmonary MAC (pMAC) disease at Ako City Hospital and Kyoto University Hospital, respectively. Results: The estimated prevalence of microbiological pNTM disease in the West Harima area (85.4/100,000 population-years) was significantly higher than that observed in Kyoto City (23.6/100,000 population-years; p < .001). According to multiple logistic regression analysis, in Ako City Hospital, primary (activities directly related to natural resources) and secondary industries (construction, mining, and manufacturing primary industry produce; odds ratio [OR] = 4.79; 95% confidence interval [CI] = 1.49−14.0; p = .007) and soil exposure (OR = 13.6; 95% CI = 4.94−45.26; p < .001) were associated with pMAC disease. Conclusion: Environmental factors, both industrial structures associated with occupational dust and environmental soil exposure, could influence the regional variations in pNTM disease prevalence.

Recently, 2 small molecule kinase inhibitors (TKIs), targeting epidermal growth factor receptor (EGFR), have proven effective in the treatment of non-small cell lung cancer. However, it is unknown whether the EGFR double activating mutation of L858R in exon 21 and the in-frame deletion in exon 19 is a predictor of the effectiveness of EGFR-TKIs. We report for the first time a case of non-small cell lung cancer with central nervous system metastases harboring a rare EGFR double activating mutation who showed a good clinical response to erlotinib, regardless of his poor performance status, as swallowing is not possible. Therefore, we suggest that erlotinib may become a therapeutic choice in cases of central nervous system metastases even with poor performance status.

Background: Spinal metastases of patients with advanced stage lung cancer are an important target for palliative therapy, because their incidence is high, and they often cause severe symptoms and worsen the quality of life. Surgery is one of the most effective treatment options, but the indication of surgery is unclear as the procedure is invasive and patients with spinal metastasis have a rather short life expectancy. Furthermore, there have been few studies that have focused on lung cancer with poor prognosis. Methods: We reviewed all of the cases of lung cancer from January 1999 to July 2007 in the Department of Respiratory Medicine, Kyoto University Hospital, Japan. Thirteen patients with metastatic spinal tumor of lung cancer underwent surgery, and all of them had a poor performance status score (3 or 4). Results: Neurological improvement by at least 1 Frankel grade was seen in 10 of 14 cases (71%). Improvement of the movement capacity was noted in 9 of 14 cases (64%), and pain improvement was noted in 12 of 14 (86%). Median postoperative survival was 5 months (1–25 months). In particular, the group with a good postoperative performance status score (0–2) was shown to have a better median postoperative survival of 13 months. Conclusions: Surgical treatment for symptomatic metastatic spinal tumor of lung cancer can improve quality of life in a substantially high percentage of patients. Surgery should be considered even if preoperative performance status is poor.

Patients on dialysis have limited treatment options for advanced lung cancer because some chemotherapeutic agents are unavailable due to renal dysfunction. A man in his 70s on peritoneal dialysis presented with persistent fever refractory to antibiotics for 2 weeks. Subsequent whole-body CT showed a 5 cm diameter mass in the right lower lobe of the lung with right-sided pleural effusion and osteolytic metastasis of the right iliac bone. The patient was diagnosed with squamous cell carcinoma (cT3N2M1b, stage IVB) harbouring the p.Gly719Ala point mutation on exon 18 of the epidermal growth factor receptor. The patient developed severe respiratory failure due to malignant lymphangitis after a bronchoscopy. He received 30 mg/ day of afatinib, resulting in tumour shrinkage and recovery from respiratory failure. We advocate for aggressive screening of driver oncogenes in patients with lung cancer on dialysis, including those with squamous cell lung cancer. [ABSTRACT FROM AUTHOR]