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.Item Precision medicine for metastatic colorectal cancer: an evolving era(2019) Guler, Irem; Askan, Gokce; Klostergaard, Jim; Sahin, Ibrahim Halil; 31475851Introduction: Metastatic colorectal cancer (CRC) remains a dilemma for cancer researchers with an increasing incidence in the younger patient population. Until the last decade, limited therapeutic options were available for metastatic CRC patients leading to relatively poor clinical outcomes. Areas covered: With advances in genome sequencing technology and reductions in the cost of next-generation sequencing, molecular profiling has become more accessible for cancer researchers and clinical investigators, which has furthered our understanding of the molecular behavior of CRC. This progress has recently translated into significant advances in molecular-based therapeutics and led to the development of new target-specific agents in metastatic CRC patients. In this review article, we extensively elaborate on genomic alterations seen in CRC patients including, but not limited to, EGFR, MMR, BRAF, HER2, NTRKs, FGFR, BRCA1/2, PALB2, POLE, and POLD1 genes, all of which are potentially actionable by either an FDA-approved agent or in a clinical trial setting. Expert opinion: We strongly recommend molecular profiling in metastatic CRC patients during the early course of their disease, as this may provide therapeutic and prognostic information that can guide clinicians to practice precision medicine. Patients with potentially actionable genes should be considered for targeting agents based on molecular alterations.