Kazutoshi Isobe

Comprehensive genomic profiling (CGP) is increasingly important for identifying actionable driver mutations and selecting targeted therapies in advanced lung adenocarcinoma, particularly when tissue re-biopsy is precluded by severe complications. A 74-year-old woman with no history of smoking presented with hemoptysis and abnormal findings on chest imaging. She was diagnosed with lung adenocarcinoma, cT2bN2M1c, Stage IVB, with bone and brain metastases. Initial molecular testing using AmoyDx® (AmoyDx Essential NGS Panel, Amoy Diagnostics, Xiamen, China) did not reveal any actionable driver mutations. Despite multiple lines of systemic therapy and whole-brain irradiation, the disease progressed with multiple liver metastases and cancer-associated disseminated intravascular coagulation (DIC). Given the patient's never-smoking status and the lack of residual tissue for repeat testing, comprehensive liquid biopsy-based genomic profiling was performed using FoundationOne® Liquid CDx (Foundation Medicine, Boston, MA, US). This analysis identified a human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutation (p.G776delinsAVGC). Treatment with trastuzumab deruxtecan (T-DXd) resulted in marked tumor shrinkage and prompt resolution of DIC. During the sixth cycle of T-DXd, the patient developed Grade 3 drug-induced interstitial lung disease (ILD)/pneumonitis, necessitating permanent discontinuation of T-DXd and high-dose corticosteroid therapy. Subsequently, the patient developed carcinomatous meningitis and was transitioned to palliative care. This case demonstrates that liquid biopsy-based CGP can identify actionable alterations and enable life-saving targeted therapy in patients with advanced lung adenocarcinoma complicated by severe DIC; however, severe drug-induced toxicities, such as ILD, remain a critical bottleneck that requires careful monitoring to balance treatment efficacy and safety.

Acute exacerbation of interstitial pneumonia (IP‐AE) is a type of severe respiratory failure that occurs in patients with chronic interstitial pneumonia. Herein, we report a case of multiple pulmonary thrombi caused by antiphospholipid antibody syndrome ( APS ), which required differentiation from IP ‐ AE in a patient with chronic interstitial pneumonia. A 77‐year‐old male patient presented with acute respiratory failure and bilateral ground‐glass opacities on chest computed tomography ( CT ), which initially indicated IP ‐ AE . However, the contrast‐enhanced CT scan revealed multiple pulmonary thrombi, and the laboratory examination showed positivity for antiphospholipid antibodies. The patient was diagnosed with APS and was successfully treated with anticoagulant therapy and systemic corticosteroids. The pulmonary manifestations of APS may mimic those of IP ‐ AE and may be under‐recognised. Thus, APS should be considered in the differential diagnosis of acute respiratory deterioration in patients with interstitial pneumonia.

A 71-year-old female with postoperative recurrence of lung adenocarcinoma was treated with chemotherapy plus immunotherapy (carboplatin, pemetrexed, and pembrolizumab). On day eight after the first cycle, she presented with fever and loss of appetite. Laboratory tests showed severe pancytopenia. Bone marrow biopsy revealed hypocellular marrow consistent with aplastic anemia (AA), which is considered an immune-related adverse event (irAE). Treatment with pulse glucocorticoid (GC) therapy, granulocyte colony-stimulating factor, and cyclosporine had a limited effect. On day 24, eltrombopag, a thrombopoietin receptor agonist, was started, subsequently leading to gradual hematologic recovery and discharge on day 34. IrAE-induced AA has a poor prognosis, with no established standard treatment. This case demonstrates the potential of thrombopoietin receptor agonists as a therapeutic option in GC-resistant irAE-induced AA.

Rationale: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in older adults. In systemic sclerosis, interstitial lung disease is a frequent, serious complication requiring immunosuppressive therapy. Differentiating RSV pneumonia from systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential for appropriate management and to avoid initiating immunosuppressive agents that may be harmful in cases of RSV pneumonia. Patient concerns: An 85-year-old woman with limited cutaneous systemic sclerosis and dementia presented with a 1-week history of nonproductive cough and fever. Diagnoses: Chest computed tomography (CT) showed bilateral consolidations, bronchial wall thickening, and mucus plugs, suggesting airway infection. However, both respiratory symptoms and CT findings worsened, and sputum and blood cultures remained negative. To differentiate SSc-ILD from viral infection, multiplex PCR testing (FilmArray) of a pharyngeal swab was performed, detecting RSV and confirming RSV pneumonia. Interventions: The patient was initially treated with intravenous ceftriaxone, then given prednisolone at 0.6 mg/kg/d after RSV was diagnosed. Outcomes: Her respiratory symptoms and CT findings improved, and she was discharged on day 16 with tapering corticosteroids. Lessons: Multiplex PCR is useful for detecting RSV pneumonia in patients with autoimmune diseases. Clinicians should be aware that RSV infection can occur in these patients and should consider RSV pneumonia as an important differential diagnosis of SSc-ILD.

Bronchobiliary fistula (BBF) is a rare condition characterised by a pathological communication between the biliary tract and bronchial tree secondary to various diseases. Treatment includes bronchial occlusion using reusable bronchoscopes, although the use of single‐use bronchoscopes (SUBs) for this purpose has not been reported. This case report describes a 62‐year‐old male who developed a BBF after anterior hepatic segmentectomy for hepatocellular carcinoma. The patient was admitted to the intensive care unit for severe pneumonia and respiratory failure. Bedside bronchoscopy using SUBs revealed bile leakage from the right B7 bronchus, leading to the diagnosis of BBF. Due to his critical condition and transport difficulties, bronchial occlusion was successfully performed at bedside using an SUB. The patient was extubated on day 12 and discharged on day 25 without recurrence. This case highlights the utility of SUBs for diagnostic and therapeutic intervention in critically ill patients.

Pembrolizumab can cause extremely serious skin disorders with high mortality rates, such as Stevens–Johnson syndrome (SJS), with most cases occurring early after immune checkpoint inhibitor treatment. This report describes a patient that developed SJS triggered by methicillin‐susceptible Staphylococcus aureus (MSSA) infection 8 months into pembrolizumab treatment for lung squamous cell carcinoma. A 74‐year‐old male developed fever, oral mucosal damage, oedematous erythema with erosions predominantly in the trunk and renal dysfunction 8 months after starting pembrolizumab monotherapy for the postoperative recurrence of lung squamous cell carcinoma. SJS was diagnosed and the patient was hospitalised. Cultures of purulent exudates from the facial skin and sputum revealed MSSA. The skin and mucosa findings did not improve despite steroid pulse therapy, but gradual improvements were seen after treatment with ampicillin–sulbactam, vancomycin and four sessions of plasma exchange therapy.

Background: Autoimmune diseases (AIDs) are often associated with lung cancer, but their clinical characteristics remain unclear. Purpose: The study aimed to elucidate the clinical features of non-small cell lung cancer (NSCLC) in patients with AIDs. Methods: This single-center, retrospective observational study was conducted between June 2016 and October 2024. It included patients diagnosed with primary NSCLC and comorbid AIDs who received lung cancer treatment. Results: A total of 32 patients (median age: 68 years; male/female: 14/18) were enrolled. Rheumatoid arthritis was the most common AID (10 cases, 31.3%), followed by Graves’ disease, Hashimoto’s thyroiditis, and ulcerative colitis (four cases each, 12.5%). Other AIDs included systemic lupus erythematosus (two cases, 6.3%) and one case (3.1%) each of Behçet’s disease, dermatomyositis, myasthenia gravis, scleroderma, Schmidt’s syndrome, psoriasis, and sarcoidosis. Immune checkpoint inhibitors (ICIs) were administered to 11 patients (34.3%), with a response rate and disease control rate of 63.6%. Immune-related adverse events (irAEs) occurred in 72.7% (8/11) of patients, including one grade 3 event. Of which, AID exacerbation related to ICI occurred in 45.5% (5/11) of patients. The median progression-free survival was 126 days, and the median overall survival (OS) was 1,594 days. Among patients without driver mutations who received ICI therapy, the median OS was significantly longer compared to those with driver mutations (2,274 vs. 654 days; P < 0.001). Multivariate analysis revealed that good performance status, adenocarcinoma history, and ICI administration were associated with better OS. Conclusions: ICIs may be effective in selected NSCLC patients with AIDs; however, careful monitoring is essential due to the risk of irAE and AID exacerbation.

BRAF is a mediator that activates the mitogen‐activated protein kinase pathway. A mutation in BRAF can cause abnormal pathway activation, leading to cell proliferation. In a Phase II study, the combination therapy of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib was found to be effective in non‐small cell lung cancer (NSCLC) patients with the BRAF mutation. However, this study has limited efficacy and safety data for elderly patients. We present a case of a patient who started treatment at 87 years old and showed a good prognosis, remaining alive 73 months from the start of treatment with no significant adverse events. The patient also maintained a partial response (PR) according to RECIST 1.1 at the last follow‐up. This case suggests that the dabrafenib and trametinib combination therapy is safe and effective for elderly NSCLC patients with the BRAF mutation.

Comparison of the background between this study and the PACIFIC study