Archivos de Bronconeumología (English Edition) Archivos de Bronconeumología (English Edition)
Arch Bronconeumol 2017;53:37-8 - Vol. 53 Num.1 DOI: 10.1016/j.arbr.2016.11.017
Scientific Letter
Management Difficulties in a Patient With EGFR-Mutation Positive Lung Adenocarcinoma and Cerebral Metastases
Difícil manejo en paciente con adenocarcinoma de pulmón con mutación de EGFR y enfermedad cerebral
Patricia Cruz, , Leticia de Lujan, Javier de Castro
Departamento de Oncología Médica, Hospital Universitario La Paz, Madrid, Spain
To the Editor:

We report the case of a 49-year-old man, who was an occasional smoker. In 2007, a chest radiograph was obtained during an episode of acute bronchitis, which showed a solitary pulmonary nodule, subsequently confirmed on computed tomography (CT). Fiberoptic bronchoscopy did not yield any histological material, so a fine needle aspiration biopsy was performed, which revealed the presence of lung adenocarcinoma. After the case was discussed by the tumor committee, surgical intervention was performed. The pathology study reported adenocarcinoma requiring adjuvant chemotherapy. One year later, contralateral pulmonary and hepatic relapse was revealed on CT. Given the early tumor relapse, the likelihood of the tumor being resistant to chemotherapy, and the clinical characteristics of the patient, the tumor was biopsied again and the sample was sent for molecular analysis, including determination of epidermal growth factor receptor (EGFR) status. This test was positive, reporting an exon 19 deletion, so treatment began with erlotinib. Six months later, the CT showed complete response, subsequently confirmed on PET/CT. The patient continued on the same treatment, with regular assessments, for another 5 years. At that time, as the various radiological tests performed during the previous 5 years showed no evidence of disease, we decided to discontinue treatment under close monitoring. Two months later, the patient presented with headache, vomiting and instability. A head CT was performed, revealing a cerebellar lesion measuring 3×4cm, with intense perilesional edema. After the possibility of systemic relapse was ruled out by CT and PET/CT, oligometastasis was confirmed and it was decided that the best treatment was local resection of the lesion, in accordance with the various clinical guidelines that advocate local treatment as the best approach in oligometastatic disease, if feasible. Histological analysis confirmed that the lesion was metastasis from the previous lung adenocarcinoma. Development of a T790M resistance mutation was suspected, so the EGFR analysis was repeated. This ruled out secondary resistance and confirmed the presence of the exon 19 deletion. Despite the absence of systemic disease, the high risk of relapse led us to reinitiate anti-EGFR treatment, and the patient currently remains free of both systemic and cerebral disease.

Our case illustrates the difficulties encountered in managing patients with EGFR mutations and predicting their clinical progress. EGFR belongs to the ErbB family of membrane receptors with tyrosine kinase activity. Between 5% and 10% of non-small cell lung cancers have EGFR mutations; they occur more commonly in women and are associated with little or no consumption of tobacco.1 The finding of a mutation of this type predicts a better response to targeted drug treatment than to cytotoxic chemotherapy. However, not all mutations are the same: exon 19 deletion is the most common and predicts a better treatment response, followed by exon 21 insertion (L858R); finally, exon 20 alterations are associated with drug resistance.2,3 It should be emphasized here that the typical evolution of this tumor is marked by an initially good response to the inhibitor, followed by the development of secondary resistance, the most common mechanism being the appearance of the T790M mutation.4

In our patient, the excellent response and disappearance of systemic disease led us to question the need to continue with treatment, since no clear directives are currently available. During his off-treatment period, the patient presented cerebral progression. This led us to consider 2 hypotheses: either a T790M resistance mutation had occurred, or the tumor was extremely dependent on the EGFR pathway, and when the drug was withdrawn, breakthrough disease developed with progression in a sanctuary site. After molecular analysis, the second option appears more plausible, and raises once again the issue of the best management of long-term survivors receiving anti-EGFR treatment.

N.I. Lindeman,P.T. Cagle,M.B. Beasley,D.A. Chitale,S. Dacic,G. Giaccone
Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology
Arch Pathol Lab Med, 137 (2013), pp. 828-860
R. Rosell,E. Carcereny,R. Gervais,A. Vergnenegre,B. Massuti,E. Felip
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial
Lancet Oncol, 13 (2012), pp. 239-246
C.K. Lee,C. Brown,R.J. Gralla,V. Hirsh,S. Thongprasert,C.M. Tsai
Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis
J Natl Cancer Inst, 105 (2013), pp. 595-605
P.A. Jänne,J.C. Yang,D.W. Kim,D. Planchard,Y. Ohe,S.S. Ramalingam
AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer
N Engl J Med, 372 (2015), pp. 1689-1699

Please cite this article as: Cruz P, de Lujan L, de Castro J. Difícil manejo en paciente con adenocarcinoma de pulmón con mutación de EGFR y enfermedad cerebral. Arch Bronconeumol. 2017;53:37–38.

Corresponding author.
Copyright © 2016. SEPAR
Arch Bronconeumol 2017;53:37-8 - Vol. 53 Num.1 DOI: 10.1016/j.arbr.2016.11.017