PubMed Kapalı Erişimli Yayınlar
Permanent URI for this collectionhttps://hdl.handle.net/11727/10764
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Item Effect of Asbestos Exposure on the Frequency of EGFR Mutations and ALK/ROS1 Rearrangements in Patients With Lung Adenocarcinoma A Multicentric Study(2021) Yilmaz, Senay; Demirci, Nilgun Yilmaz; Metintas, Selma; Zamani, Adil; Karadag, Mehmet; Guclu, Ozge A.; Kabalak, Pinar Akin; Yilmaz, Ulku; Ak, Guntulu; Kizilgoz, Derya; Ozturk, Akin; Yilmaz, Ufuk; Batum, Ozgur; Kavas, Murat; Serifoglu, Irem; Unsal, Meftun; Komurcuoglu, Berna E.; Cengiz, Tuba Inal; Ulubay, Gaye; Ozdemirel, Tugce S; Ozyurek, Berna A.; Kavurgaci, Suna; Alizoroglu, Dursun; Celik, Pinar; Erdogan, Yurdanur; In, Erdal; Aksoy, Asude; Altin, Sedat; Gunluoglu, Gulsah; Metintas, Muzaffer; 33399308Objective: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. Methods: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. Results: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. Conclusions: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.Item GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients(2020) Sezer, Ahmet; Ozyilkan, Ozgur; 0000-0002-6445-1439; 0000-0001-8825-4918; 32799090; AAD-2667-2020; AAD-2817-2021Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1( + ) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK( + ) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 +/- 1.6 months and median overall survival (mOS) was 89.1 +/- 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 +/- 2.5 months and mOS of 90.3 +/- 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 +/- 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 +/- 24 months is unprecedented for ROS1( + ) NSCLC.