Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005).

PURPOSE: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD). METHODS: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD. RESULTS: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively. CONCLUSION: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD.

Superior vena cava syndrome induced by lung hyperinflation in chronic obstructive pulmonary disease: a case report.

BACKGROUND: Superior vena cava syndrome is rarely attributed to chronic obstructive pulmonary disease. CASE PRESENTATION: We present the case of an 82-year-old Japanese man who experienced gradually progressive dyspnea on exertion. His physical examination revealed small vascular dilatations on his chest and upper abdominal skin characterized by blood flow from head to leg, indicating superior vena cava syndrome. Radiographic findings included lung hyperinflation with a drop-like heart on chest X-ray, and emphysematous changes on computed tomography. The superior vena cava appeared extremely narrow and slit-like, with no adjacent mass or giant bulla. Pulmonary function testing indicated a forced expiratory volume in 1 second of 0.82L (44.4% of predicted value) and a forced expiratory volume in 1 second/forced vital capacity of 31.29%. A diagnosis of chronic obstructive pulmonary disease was made. We discuss how longitudinal forces can narrow the superior vena cava, particularly when it protrudes toward the lung field due to its anatomical location in the upper mediastinum. The absence of mediastinal adipose tissue may render the superior vena cava susceptible to compression, resulting in a loss of its typical columnar structure. The protrusion of the superior vena cava toward the lung field may be a contributing factor to superior vena cava narrowing in chronic obstructive pulmonary disease. CONCLUSION: This case represents the first reported instance of superior vena cava syndrome associated with chronic obstructive pulmonary disease, characterized by lung hyperinflation, in the absence of a giant bulla.

Autopsy Findings of Severe COVID-19 Pneumonia Combined with Pulmonary Aspergillosis, Pneumothorax, and Pulmonary Thromboembolisms.

BACKGROUND COVID-19-associated pulmonary aspergillosis (CAPA), acute respiratory distress syndrome (ARDS), pulmonary thromboembolism (PTE), and pneumothorax are complications in severe COVID-19 patients. CASE REPORT A 64-year-old Japanese man was diagnosed with COVID-19. His past medical history included uncontrolled diabetes mellitus. He had no vaccination for COVID-19. Despite oxygen inhalation, remdesivir, dexamethasone (6.6 mg per day), and baricitinib (4 mg per day for 12 days), the disease progressed. The patient was supported with mechanical ventilation. Dexamethasone was switched to methylprednisolone (1000 mg per day for 3 days, and then reduced by half every 3 days), and intravenous heparin was initiated. Voriconazole (800 mg on the first day and then 400 mg per day for 14 days) was also started because Aspergillus fumigatus was detected in intratracheal sputum. However, he died of respiratory failure. Pathological findings of autopsy showed: (1) diffuse alveolar damage in a wide area of the lungs, which is consistent with ARDS due to COVID-19 pneumonia, (2) PTEs in peripheral pulmonary arteries, (3) CAPA, and (4) pneumothorax induced by CAPA. These conditions were all active states, suggesting that the treatments were insufficient. CONCLUSIONS Autopsy revealed active findings of ARDS, PTEs, and CAPA in a severe COVID-19 patient despite heavy treatment for each condition. CAPA can be a cause of pneumothorax. It is not easy to improve these conditions simultaneously because their treatments can induce antagonizing biological actions. To prevent severe COVID-19, it is important to reduce risk factors, such as by vaccination and appropriate blood glucose control.

Clinical features of patients with lung cancer accompanied by thromboembolism or disseminated intravascular coagulation.

PURPOSE: Thromboembolism (TE) and disseminated intravascular coagulation (DIC) are often present concomitantly. This study aimed to investigate the clinical features of patients with lung cancer and TE and/or DIC. PATIENTS AND METHODS: Data on 716 patients with pathologically confirmed diagnoses of lung cancer were retrospectively analyzed for TE/DIC. RESULTS: TE was identified in 16 patients (2.2%) and DIC was identified in 5 (0.7%) during the diagnosis of cancer. TE was more often observed in adenocarcinoma (4.0%). Both TE and DIC were more often observed in stage IV (4.7% and 1.5%, respectively). In patients with stage IV adenocarcinoma who received some systemic treatment, overall survival (OS) was significantly shorter in patients with TE (median 280 days) and with DIC (72 days) than in non-TE/DIC patients (538 days). Multivariate analysis showed that older age, poor performance status, greater number of metastatic organs, no EGFR mutation/ALK fusion, presence of interstitial lung disease, and DIC were poor prognostic factors for OS. In 339 patients in stage IV, 25 (7.4%) and 21 (6.2%) patients had TE and DIC, respectively, during the course. Six patients exhibited both TE and DIC. TE was more often observed in adenocarcinoma (20 of 196 patients; 10.2%). Patients with DIC had extremely shorter survival (median 13 days) after onset. Cancer control by systemic therapy, such as chemotherapy and molecular-targeted therapy, contributed to long survival. CONCLUSION: Patients with TE/DIC had shorter OS than patients without TE/DIC. Control of lung cancer by systemic therapy was important for longer survival after the onset of events.

Subacute Sensorimotor Neuropathy Accompanied by Anti-ganglioside GM1 Antibody in a Patient with Lung Cancer.

A 66-year-old man presented with subacute sensorimotor neuropathy in association with small cell lung cancer. Tests for the anti-ganglioside antibody GM1-IgM were positive. Chemotherapy and intravenous immunoglobulin treatment led to a slight improvement in neurological symptoms. Four additional cases of neuropathy accompanied by anti-ganglioside antibody and lung cancer have been reported. The most commonly reported pattern was subacute sensorimotor neuropathy. Patients died from cancer progression after 5 to 18 months. There is evidence that anti-ganglioside antibody inhibits tumor progression, prolonging the patient survival. However, severe neurological disturbance may offset the survival benefit of anti-ganglioside antibody in patients with paraneoplastic neurological syndrome.