Anaplastic lymphoma kinase (ALK) translocation is a rare driver mutation in lung cancer. This study was aimed to report on the efficacy of lorlatinib in real-world practice and to evaluate the impact of prior ALK inhibitor treatments. We retrospectively evaluated patients with ALK-positive non-small cell lung cancer (NSCLC) treated with lorlatinib regarding its efficacy, the impact of prior ALK inhibitor treatments and the adverse events, in particular dyslipidemia. A total of 22 ALK-positive patients were analyzed. All patients had received at least one second-generation ALK inhibitor(s), while 12 patients had a history of crizotinib treatment. For lorlatinib, the objective response rate was 35.7%, and disease control rate was 64.3%. Their progression-free survival (PFS) was 6.2 months. With prior therapies, patients receiving only second-generation ALK inhibitor(s) treatment showed PFS longer than those with both crizotinib and second-generation ALK inhibitor(s) treatments (15.2 vs. 6.2 months). Moreover, patients who showed benefits from prior ALK inhibitor(s) also had a PFS longer than those who did not (6.5 vs. 3.5 months). Regarding adverse events, 94.7% of patients had dyslipidemia and 21.1% of them were in grade 3 or 4. None of these patients discontinued the treatment due to dyslipidemia.No acute complication occurred with dyslipidemia. The real-world efficacy of lorlatinib and adverse events were similar to those reported in clinical trials. Interestingly, the history and responses of prior ALK inhibitor treatments may influence the efficacy of subsequent lorlatinib treatment.

Early and prolonged prone positioning (PP) therapy improve survival in advanced ARDS; however, the predictors of mortality remain unclear. The study aims to identify predictive factors correlated with mortality and build-up the prognostic score in patients with severe ARDS who received early and prolonged PP therapy. A total of 116 patients were enrolled in this retrospective cohort study. Univariate and multivariate regression models were used to estimate the odds ratio (OR) of mortality. Factors associated with mortality were assessed by Cox regression analysis and presented as the hazard ratio (HR) and 95% CI. In the multivariate regression model, renal replacement therapy (RRT; OR: 4.05, 1.54–10.67), malignant comorbidity (OR: 8.86, 2.22–35.41), and non-influenza-related ARDS (OR: 5.17, 1.16–23.16) were significantly associated with ICU mortality. Age, RRT, non-influenza-related ARDS, malignant comorbidity, and APACHE II score were included in a composite prone score, which demonstrated an area under the curve of 0.816 for predicting mortality risk. In multivariable Cox proportional hazard model, prone score more than 3 points was significantly associated with ICU mortality (HR: 2.13, 1.12–4.07, p = 0.021). We suggest prone score ≥3 points could be a good predictor for mortality in severe ARDS received PP therapy.

We aimed to evaluate whether different driver mutations have varying impacts on the programmed cell death-ligand 1 (PD-L1) expression of non-small cell lung cancer (NSCLC), and whether the prognostic roles of PD-L1 amongst our patients were divergent. This was a single-institute study that included patients with NSCLC. Six driver mutations, PD-L1 status, and the outcomes of treatment were assessed. A total of 1,001 NSCLC patients were included for analysis. Overall, the PD-L1 positive (TPS ≥ 1%) and strong positive (TPS ≥ 50%) rates were 52.2% and 17.3%, respectively. As compared with wild type lung adenocarcinoma, EGFR-mutant and HER2-mutant patients had similarly low PD-L1 and strong PD-L1 positive rates. BRAF-mutant patients had numerically higher PD-L1 and strong PD-L1 positive rates. Patients with fusion mutation (ALK and ROS1) (aOR 2.32 [95% CI 1.10–4.88], P = 0.027 and 2.33 [95% CI 1.11–4.89], P = 0.026), KRAS mutation (aOR 2.58 [95% CI 1.16–5.75], P = 0.020 and 2.44 [95% CI 1.11–5.35], P = 0.026), and non-adenocarcinoma histology (aOR 2.73 [95% CI 1.72–4.34], P < 0.001 and 1.93 [95% CI 1.13–3.30], P = 0.016) all had significantly higher PD-L1 and strong PD-L1 positive rates. A trend towards longer survival was noted in ROS-1 rearranged and KRAS-mutant patients with strong PD-L1 expression who had received crizotinib and chemotherapy, respectively. In conclusion, individual driver mutations had various impacts on the PD-L1 expression of NSCLC patients. The prognostic role of PD-L1 may also be divergent amongst patients harboring different driver mutations.

Pleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.

No abstract

Pulmonary embolism is a life-threatening disease. Its development is generally thought to be due to causes collectively known as the Virchow’s triad. Chronic inflammations are associated with the activation of coagulation and increased risks of venous thromboembolic events. Asthma is one of the chronic inflammatory diseases associated with procoagulants and antifibrinolytic activities in the airways. Coagulation is activated in patients with asthma with the following steps of pathophysiology: Increased tissue factor expression in various cell types, decreased activity of the anticoagulant protein C system and inhibition of fibrinolysis through over-production of plasminogen activator inhibitor type 1 (PAI-1). Asthma is therefore likely a risk factor for pulmonary embolism, especially in those patients with severe disease conditions together with frequent exacerbation. Here we present a case of severe asthma associated with coagulopathy and complicated by massive pulmonary embolism, presented with typical S1Q3T3 on electrocardiography (ECG) and massive thrombosis on computed tomography angiography, successfully treated with directed catheter thrombolytic therapy.

Background and Objectives: Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is one of the standard-of-care therapies in patients with EGFR-mutant lung adenocarcinoma; however, acquired resistance inevitably developed. Despite the proposition of histological transformation being one of the resistance mechanisms, its incidence and influence on outcome remain unclear. Materials and Methods: This was a retrospective study conducted at Taichung Veterans General Hospital on patients with advanced EGFR-mutant lung adenocarcinoma receiving the third-generation EGFR-TKI. Only patients receiving rebiopsy were included in the analysis. Results: A total of 55 patients were studied. Eight patients (14.5%) showed histological transformation, including three small cell carcinoma, three squamous cell carcinoma, one large cell neuroendocrine carcinoma, and one with a mixture of adenocarcinoma and squamous cell carcinoma components. The median treatment duration of the third-generation EGFR-TKI before rebiopsy was numerically longer in patients with histological transformation than those without (16.0 vs. 10.9 months). Both the overall survival time from the start of third-generation EGFR-TKI initiation (30.8 vs. 41.2 months) and from rebiopsy (6.6 vs. 12.9 months) to mortality were numerically shorter amongst the transformed population. All patients in the transformed group did not respond to the next line of systemic treatment. One patient with histological transformation receiving local treatment for the metastatic site had a longer overall survival. Conclusions: Repeating biopsy to identify histological transformation should be considered in patients with progression to the third-generation EGFR-TKI. Histological transformations could contribute to the acquired resistance with the implication of a worse prognosis. Further studies are needed to determine the optimal therapy for these patients.

Angiosarcomas are rare soft‐tissue sarcomas of endothelial cell origin and have a poor prognosis. Diffuse alveolar haemorrhage (DAH) is a syndrome characterized by the accumulation of intra‐alveolar red blood cells. However, neoplastic diseases are not commonly considered in the differential diagnosis of DAH. We report a case of a 27‐year‐old female with the diagnosis of primary breast angiosarcoma developing DAH. This raised our concern that angiosarcoma with lung metastasis may present with DAH and should be considered as an important fatal differential diagnosis of DAH.