Next-generation sequencing clarified why first-line treatment with osimertinib was ineffective in an autopsied case of EGFR-mutated lung squamous cell carcinoma.

Epidermal growth factor receptor (EGFR)-mutated squamous cell carcinoma (SCC) is less common than adenocarcinoma. The third-generation EGFR-tyrosine kinase inhibitor, osimertinib, is effective in EGFR-mutated lung adenocarcinoma, but its efficacy in EGFR-mutated lung SCC is unclear. The patient was an 83-year-old male. He was diagnosed with SCC of the lung, and molecular analysis revealed that the tumor was positive for EGFR exon19 deletion. He was treated with osimertinib 80 mg/day. No adverse events were observed, but after 18 days of therapy, he complained of dyspnea, and a computed tomography scan showed enlarged lung cancer. The case was categorized as a progressive disease. The patient died 3 weeks later. The autopsy findings confirmed the diagnosis of lung SCC, with morphology and immunohistochemical staining identical to the tumor obtained by bronchoscopy. Next-generation sequencing showed the presence of TP53 R158L, CDK6, and KRAS amplifications. The current case report shows that next-generation sequencing can explain why osimertinib is ineffective in EGFR-mutated SCC.

Is the Efficacy of Adding Ramucirumab to Docetaxel Related to a History of Immune Checkpoint Inhibitors in the Real-World Clinical Practice?

Reports on the efficacy of second-line treatment with cytotoxic agents after treatment with immune checkpoint inhibitors are limited. Here, we retrospectively evaluated patients in the real-world clinical practice treated with docetaxel or docetaxel plus ramucirumab. Ninety-three patients treated with docetaxel or docetaxel plus ramucirumab as a second- or later-line therapy were included. The patients were categorized into the following four treatment groups: docetaxel group (n = 50), docetaxel/ramucirumab group (n = 43) and pretreated (n = 45) and untreated (n = 48) with immune checkpoint inhibitor groups. The docetaxel/ramucirumab group showed an overall response rate of 57.1% in patients pretreated with immune checkpoint inhibitors and 20% in untreated patients. The docetaxel group showed an overall response rate of 15.4% in patients pretreated with immune checkpoint inhibitors and 5.0% in untreated patients. The median time-to-treatment failure and the median survival time were longer in the docetaxel/ramucirumab group than in the docetaxel group in both immune checkpoint inhibitor-pretreated and -untreated groups. There was no difference in time-to-treatment failure and overall survival between immune checkpoint inhibitor-pretreated and -untreated groups in each docetaxel and docetaxel/ramucirumab treatment group. In conclusion, our real-world data show that the addition of ramucirumab to docetaxel was superior to docetaxel monotherapy for improving time-to-treatment failure and overall survival, irrespective of previous treatment with immune checkpoint inhibitors.

Complete withdrawal of glucocorticoids after dupilumab therapy in allergic bronchopulmonary aspergillosis: A case report.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to Aspergillus species that aggravates bronchial asthma. Previous studies demonstrated the glucocorticoid-sparing effect of dupilumab in patients with ABPA. There is no report of complete withdrawal of glucocorticoids after dupilumab. CASE SUMMARY: The patient was a 54-year-old woman with bronchial asthma treated with inhaled corticosteroids and a long-acting beta-2 agonist. She consulted our institution for productive cough and fever in March 2017. Chest computed tomography scan revealed mucoid impaction, and the bronchial lavage fluid culture was positive for Aspergillus fumigatus. The diagnosis was ABPA. The patient was treated with oral glucocorticoids from April 2017 to November 2017. In January 2019, she had bronchial asthma exacerbation, and a chest computed tomography scan showed recurrent mucoid impaction. She was treated with oral glucocorticoids and itraconazole. In February 2020, during tapering of oral glucocorticoid, she had the third episode of bronchial asthma exacerbation and a mucoid impaction. The patient was treated with dupilumab in addition to oral glucocorticoid and itraconazole. The clinical response improved, and oral glucocorticoid was discontinued in June 2020. CONCLUSION: This is the first case of ABPA in which complete withdrawal of glucocorticoid was possible after treatment with dupilumab.

Second-line therapy with first- or second-generation tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer patients with T790M-negative or unidentified mutation.

BACKGROUND: T790M mutation causes resistance to tyrosine kinase inhibitors (TKIs) in approximately 49% of patients with epidermal growth receptor-mutant non-small cell lung cancer (NSCLC). The cause of resistance in the remaining half of the cases is a minor mutation or unknown. Here, we conducted a retrospective study of epidermal growth receptor-mutant NSCLC patients with T790M-negative or an unidentified mutation to appraise the therapeutic response to first- or second-generation tyrosine kinase inhibitors as a second-line treatment. METHODS: The study included 39 patients treated in our institution from April 2012 through March 2020 with second-line tyrosine kinase inhibitors or chemotherapy after completing a first-line therapy with tyrosine kinase inhibitors. RESULTS: The patients were allocated to two groups: chemotherapy (n = 28) and a tyrosine kinase inhibitor (n = 11) groups. The median progression-free survival (PFS) was 5.4 months in the chemotherapy group and 3.4 months in the tyrosine kinase inhibitor group (p-value = 0.36), while the median overall survival (OS) was 16.1 months in the chemotherapy group and 12.8 months in the tyrosine kinase inhibitor group (p- value = 0.20). This study showed no significant difference in PFS and OS between the chemotherapy and tyrosine kinase inhibitor groups. CONCLUSIONS: These observations suggest that first- and second-generation tyrosine kinase inhibitors are not recommended for second-line treatment in epidermal growth factor receptor-mutated NSCLC patients with T790M-negative mutation who have received tyrosine kinase inhibitors as first-line treatment.

Extensive calcification in adenocarcinoma of the lung: A case report.

Calcification in lung nodules usually indicates a benign lesion. Here, we report the case of a 59-year-old male patient with a well defined 30 mm calcified nodule in his right upper lung lobe and calcified mediastinal lymph nodes. The mass was diagnosed as adenocarcinoma by transbronchial biopsy. He received systemic chemotherapy, followed by lobectomy and mediastinal lymph node dissection. During surgery, the lymph nodes were tightly adherent to the superior vena cava with invasion of the vascular wall. Pathological diagnosis confirmed acinar adenocarcinoma and psammoma bodies (PBs). Immunohistochemical analysis revealed tumor cells positive for parathyroid hormone-related proteins 1 and 2. Calcification of primary lung adenocarcinoma is rare. We report a calcified lesion where the secretion of parathyroid hormone by the tumor may have caused the accumulation of PBs. Calcification of metastatic lymph nodes may increase the risk of adhesion, requiring care during surgery. KEY POINTS: Significant findings of the study Lung adenocarcinoma with extensive calcification in primary and metastatic lymph node lesions is rare and the mechanism involved is poorly understood. Of significance, calcification in our case was related to parathyroid hormone-related proteins 1 and 2 secreted by the tumor. What this study adds This study suggests the potential role of parathyroid hormone-related proteins in lung tumor calcification. The implications for clinicians are that calcified metastatic lymph nodes and tumors might be tightly fused to tissues. Therefore, surgery should be conducted with care.