Acrometastasis from an epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma

AbstractWe report the first case of epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma with acrometastasis in a 51-year-old woman who presented with a swelling on her right hand. Magnetic resonance imaging revealed an expansile lesion at the base of the 5th metacarpal bone of her right hand with cortical erosion and patchy enhancement suggestive of a malignant transformation of a giant-cell tumor. A core needle biopsy of this lesion showed a metastatic adenocarcinoma on histopathological examination which was immunoreactive to cytokeratin (CK) 7 and thyroid transcription factor (TTF)-1 but not to CK20 suggesting a lung primary. A chest radiograph and computed tomography (CT) scan revealed a right upper lobe lung mass. Fluoro-deoxyglucose hypermetabolism was noted in the lung mass and the right 5th metacarpal bone lesion but not elsewhere on positron-emission-tomography/CT scan. Needle biopsy of the lung mass showed adenocarcinoma with histopathological and immunohistochemical features similar to that of the right 5th metacarpal bone lesion. Both the primary lung adenocarcinoma and the acrometastatic lesion were tested positive for EGFR mutation in exon 21 (L858R substitution). She underwent R0 resection of her right upper and middle lobes with systematic mediastinal lymph nodes resection and wide excision of the metacarpal metastasis followed by cytotoxic chemotherapy. A curative approach with complete resection of the primary tumor and oligometastastic site in Stage IV non-small cell lung carcinoma (NSCLC) followed by additive cytotoxic chemotherapy has not been reported to date and as such there is still no data on disease-free survival with this approach

Quality Of Life Of Patients With Chronic Obstructive Pulmonary Disease Based On Clinical Phenotypes

Background and Aims: Spanish chronic obstructive pulmonary disease (COPD) guideline classifies COPD into 4 clinical phenotypes: nonexacerbator (A), asthma-COPD overlap (B), exacerbator with emphysema(C) and exacerbator with bronchitis (D). Methods: A cross-sectional study of quality of life (QOL) based on COPD phenotypes utilizing St George’s Respiratory Questionnaire (SGRQ-c) conducted in University Malaya Medical Center from 1 June 2017 – 31 May 2018. Results: Of 220 patients, 189 patients with post bronchodilator force expiratory volume in 1 second (FEV1)/force vital capacity (FVC) of <0.70 were recruited. Their demographic, clinical characteristics and SGRQ-c score are as shown in Table 1. Patients with phenotype C and D had poorer modified medical research center (MMRC) performance status and global initiative for COPD (GOLD) class based on FEV1. Nevertheless, only patients with phenotype D had significant higher total SGRQ-c score than others. They also scored significant higher in sub-components of COPD symptoms, activities and impacts. Patients with phenotypes B had numerically higher SGRQ-c total and symptoms score than those with phenotype A and C. The total and sub-components SGRQ-c score of patients with phenotype A and C were almost similar. Conclusion: Patients with phenotype D had poorest QOL, followed by phenotype B. These groups of patients need additional medical attention, in terms of pharmacology treatment, physiotherapy and rehabilitation

Acquired T790M Mutation in Patients Failing Treatment with First or Second-Generation EGFR-Tyrosine Kinase Inhibitors

Background: The majority of patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) develop resistance to first- or second-generation EGFR-tyrosine kinase inhibitor (TKI) after a median treatment period of 12 months. This study aimed to determine the prevalence and predictors of acquired T790M mutation as a resistance mechanism among these patients. Method: This was a retrospective study of patients with sensitising EGFR-mutant advanced NSCLC who experienced disease progression (PD) while on first- or second-generation EGFR-TKI treatment and underwent investigations to determine the resistance mechanisms in University of Malaya Medical Centre from 1st January 2015 to 31st December 2017. Result: Of 87 patients, acquired T790M mutation was detected in 55 (63.2%) patients at PD. T790M mutation was significantly more frequent in patients who achieved partial response (PR) as the best response (p ¼ 0.008) or had new lung metastasis (p ¼ 0.048); and significantly less frequent in patients who developed new symptomatic brain metastases (p ¼ 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p ¼ 0.077). In multivariate analysis, PR with EGFR-TKI treatment was a significant independent predictor of acquired T790M mutation (p ¼ 0.021) while having new symptomatic brain metastases (p ¼ 0.034) or new lymph node metastases (p ¼ 0.038) were significant independent predictors against acquired T790M mutation. Conclusion: Acquired T790M mutation was a common resistance mechanism leading to first- or second-generation EGFR-TKI treatment failure. Patients with tumours harbouring exon 19 deletion mutation were more likely to acquire T790M mutation. A best tumour response of PR to EGFR-TKI treatment was an independent predictor of acquiring this resistance. This information is helpful to clinicians in the early prognostication and management planning for patients with EGFR-mutant NSCLC

Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib

Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma

We report the first case of epithelial-to-mesenchymal transition (EMT) as the cause of acquired resistance to the second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib in a patient with advanced non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation. Patients with EGFRmutant NSCLC inevitably develop acquired resistance while on EGFR-TKI treatment. EMT which renders cancer cells more invasive and migratory is one of the mechanisms of acquired resistance to EGFR-TKIs and correlates with a poor prognosis. Possible therapeutic strategies in patients with EMT include blocking M2 muscarinic receptor signalling, targeting EMT with histone deacetylase inhibitors such as entinostat and MEK-inhibitors such as selumetinib, inhibition of microRNAs, immunotherapy and inhibiting fibroblast growth factor receptor-1

Bilateral pulmonary sequestrations mimicking advanced lung malignancy

Bilateral pulmonary sequestrations are extremely rare and uncommonly diagnosed during adulthood. It can present with severe symptoms such as hemoptysis. It can also be misdiagnosed as a primary lung malignancy

Epithelial‐to‐mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis. © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Lt