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Case Report

A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement

Min Hwan Kim1,2, Yehyun Park2, Hye Jung Park2, Ah-young Ji2, Changho Song2, Moo-Nyun Jin2, Young Ju Kim2, Sun Wook Kim2, Jung-Hee Lee2, In-Soo Kim2, Hye Ryun Kim1,2, Joohang Kim1,2, Byoung Chul Cho1,2
The Ewha Medical Journal 2014;37(1):46-51. Published online: March 25, 2014

1Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea.

2Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Corresponding author: Byoung Chul Cho. Division of Medical Oncology, Yonsei Cancer Center & Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-8126, Fax: 82-2-393-3562, cbc1971@yuhs.ac
• Received: September 27, 2013   • Accepted: January 14, 2014

Copyright © 2014. Ewha Womans University School of Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • The rearrangement of c-ros oncogene 1 (ROS1) has been recently identified as an important molecular target in non small cell lung cancer (NSCLC). ROS1 rearrangement and epidermal growth factor receptor (EGFR) mutation were mutually exclusive each other in previous studies, and the clinical implication of co-existence of the two genetic alterations has not been determined. We report a case of 46-year-old female never-smoker NSCLC patient whose tumor harbored ROS1 rearrangement and EGFR mutation concomitantly. She had undergone curative surgery for stage IIIA NSCLC, and the recurrence in left pleura and brain occurred at 2 years after the surgery. She received several lines of chemotherapy including docetaxel plus carboplatin, erlotinib, pemetrexed, and gemcitabine. Erlotinib therapy showed a favorable treatment response with progression-free survival of 9.5 months and partial response of tumor on radiologic evaluations. This case represents a successful erlotinib treatment in a NSCLC patient with concurrent ROS1 rearrangement and EGFR mutation.
  • Keywords: c-ros oncogene 1; Epidermal growth factor receptor; Non-small-cell lung carcinoma; Erlotinib
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Fig. 1
The treatment response of first-line docetaxel/carboplatin chemothearpy. (A) Chest computed tomography (CT) and brain magnetic resonance imaging of the patient at the initial diagnosis of non-small-cell lung cancer recurrence show newly developed left pleural metastasis and brain metastasis. Arrows indicate representative non-small cell lung cancer lesions, and names of the lesions are described in the right side of the figure (B) On the imagings after 4 cycles of docetaxel/carboplatin chemotherapy, partial response of lung lesions are noted on chest CT.
emj-37-46-g001.jpg
Fig. 2
The molecular characterization results of the patient's tumor. (A) Exon 19 deletion is noted in nucleotide sequencing of epidermal growth factor receptor (EGFR gene; exons 18 through 21). (B) The c-ros oncogene 1 (ROS1) rearrangement is noted in fluorescent in situ hybridization (FISH) assay on the patient's tumor. ROS1 Break Apart Rearrangement FISH Probe (Abbott Molecular) was used, and FISH positivity for ROS1 rearrangement was defined as >15% of tumor cells with a split signal (orange and green probes, ×1,000).
emj-37-46-g002.jpg
Fig. 3
The erlotinib treatment response. Comparision of chest computed tomography and brain magnetic resonance imaging of the patient (A) before and (B) after erlotinib treatment. Arrows indicate representative non-small cell lung cancer lesions, and names of the lesions are described in the right side of the (A) figure. After 2 cycles of erlotinib and whole brain radiotherapy (WBRT), the size of lung and brain metastasis are decreased
emj-37-46-g003.jpg
Fig. 4
Treatment courses of the patient from the initial diagnosis of recurrent non-small-cell lung cancer. PD, progression of disease; SD, stable disease; PR, partial response; PFS, progression-free survival.
emj-37-46-g004.jpg

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      A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement
      Ewha Med J. 2014;37(1):46-51.   Published online March 25, 2014
      DOI: https://doi.org/10.12771/emj.2014.37.1.46
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      A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement
      Ewha Med J. 2014;37(1):46-51.   Published online March 25, 2014
      DOI: https://doi.org/10.12771/emj.2014.37.1.46
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      A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement
      Image Image Image Image
      Fig. 1 The treatment response of first-line docetaxel/carboplatin chemothearpy. (A) Chest computed tomography (CT) and brain magnetic resonance imaging of the patient at the initial diagnosis of non-small-cell lung cancer recurrence show newly developed left pleural metastasis and brain metastasis. Arrows indicate representative non-small cell lung cancer lesions, and names of the lesions are described in the right side of the figure (B) On the imagings after 4 cycles of docetaxel/carboplatin chemotherapy, partial response of lung lesions are noted on chest CT.
      Fig. 2 The molecular characterization results of the patient's tumor. (A) Exon 19 deletion is noted in nucleotide sequencing of epidermal growth factor receptor (EGFR gene; exons 18 through 21). (B) The c-ros oncogene 1 (ROS1) rearrangement is noted in fluorescent in situ hybridization (FISH) assay on the patient's tumor. ROS1 Break Apart Rearrangement FISH Probe (Abbott Molecular) was used, and FISH positivity for ROS1 rearrangement was defined as >15% of tumor cells with a split signal (orange and green probes, ×1,000).
      Fig. 3 The erlotinib treatment response. Comparision of chest computed tomography and brain magnetic resonance imaging of the patient (A) before and (B) after erlotinib treatment. Arrows indicate representative non-small cell lung cancer lesions, and names of the lesions are described in the right side of the (A) figure. After 2 cycles of erlotinib and whole brain radiotherapy (WBRT), the size of lung and brain metastasis are decreased
      Fig. 4 Treatment courses of the patient from the initial diagnosis of recurrent non-small-cell lung cancer. PD, progression of disease; SD, stable disease; PR, partial response; PFS, progression-free survival.

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      A Favorable Treatment Response of Erlotinib in Lung Adenocarcinoma with Concomitant Activating EGFR Mutation and ROS1 Rearrangement
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