Frequency and clinical relevance of EGFR mutations and EML4–ALK translocations in octogenarians with non-small cell lung cancer
Authors Tufman A, Kahnert K, Duell T, Kauffmann-Guerrero D, Milger K, Schneider C, Stump J, Syunyaeva Z, Huber RM, Reu S
Received 26 April 2017
Accepted for publication 6 August 2017
Published 25 October 2017 Volume 2017:10 Pages 5179—5186
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Jianmin Xu
Amanda Tufman,1,2 Kathrin Kahnert,1,2 Thomas Duell,2,3 Diego Kauffmann-Guerrero,1,2 Katrin Milger,1,2 Christian Schneider,2,4 Julia Stump,1,2 Zulfiya Syunyaeva,1,2 Rudolf Maria Huber,1,2 Simone Reu2,5
1Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich, Ludwig-Maximilians University, 2German Center for Lung Research, Comprehensive Pneumology Center (DZL CPC-M), 3Asklepios Pulmonary Hospital in Munich-Gauting, 4Department of Thoracic Surgery, 5Pathology Institute, Ludwig-Maximilians University, Munich, Germany
Background: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described.
Patients and methods: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70–74, 75–79 and >80 years). We then assessed a second cohort, including all patients with lung cancer over the age of 80 years diagnosed in 2014. We also analyzed smoking history, treatment and response.
Results: In the 2015 cohort of 179 patients, 16 were 80 years or older at diagnosis. Six of eight (75%) octogenarians with non-squamous NSCLC were EGFR or ALK positive. The 2014 cohort confirmed the high rate of driver alterations in octogenarians. Of 334 patients, 32 were 80 years or older and, of these, 10 had non-squamous histology and were tested for driver alterations (four of 10 [40%] EGFR or ALK positive). Rates of genetic drivers were somewhat lower in patients with non-squamous NSCLC aged 70–74 years (27.0%) and 75–79 years (26.7%). When treated with a TKI, octogenarians had high response rates and progression-free survival. Most octogenarians with lung adenocarcinoma were never smokers, with an inverse correlation of pack-years smoked to age at diagnosis.
Conclusion: Very elderly patients with non-squamous NSCLC show high rates of driver alterations in EGFR and ALK. This, often frail and comorbid, population may not be fit for treatment with cytotoxic chemotherapy and may benefit from targeted treatments. Testing for EGFR and ALK alterations should not be restricted to younger patients. The biology of lung cancer in the very elderly may differ from that of moderately elderly patients, as longevity may select for individuals more resistant to, or with little exposure to, environmental carcinogens.
Keywords: molecular biology, pathology, elderly, very elderly, NSCLC, biomarker, targeted therapy
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