P3.01-003 Study of the Relationship between EGFR Mutation Status and Bone Metastasis in Advanced Lung Adenocarcinoma

P3.01-003 Study of the Relationship between EGFR Mutation Status and Bone Metastasis in Advanced Lung Adenocarcinoma

ABSTRACTS POSTER SESSIONS— WEDNESDAY, OCTOBER 18, 2017 P3.01-001 Comparisons of Two Plasma EGFR Platforms (ddPCR and Cobas) in Patients with Radiologi...

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ABSTRACTS POSTER SESSIONS— WEDNESDAY, OCTOBER 18, 2017 P3.01-001 Comparisons of Two Plasma EGFR Platforms (ddPCR and Cobas) in Patients with Radiological Metastatic Lung Cancer J. Li,1 K. Wan,1 W. Lau,2 W. Cheuk2 1Clinical Oncology, Queen Elizabeth Hospital, Hong Kong/HK, 2Pathology, Queen Elizabeth Hospital, Hong Kong/HK Background: The treatment for stage IV non-small cell lung cancer relies on molecular diagnosis on tumor DNA for guiding systemic therapy. Liquid biopsy provides a timely and non-invasive way of detecting potential therapeutic targets and spares the need of performing a confirmatory biopsy procedure in patients with a positive result. Method: We report local experience on epidermal growth factor receptor (EGFR) mutations detected by two platforms (droplet digital polymerase chain reaction (ddPCR) technique and Cobas EGFR v2) on cell free tumor DNA from radiological stage IV lung cancer patients, guiding first- and second-generation EGFR tyrosine kinase inhibitor (TKI) therapy. All these patients who had either plasma EGFR platforms done from Nov 2015 to May 2017 are retrospectively identified and analyzed. Result: 97 patients identified. 11 out of 39 (28.2%) and 16 out of 58 (27.6%) has detectable EGFR mutation in plasma by using ddPCR and Cobas techniques respectively. Much higher detection rate is noted in never smokers (23/46, 50.0%) compared with chronic/ever smokers (4/41, 9.8%) and is highly statistically significant for difference (p-value: <0.001). The types of EGFR mutations detected are as follows: ddPCR method: 4 (36.4%) del 19, 7 (63.6%) L858R. Cobas method: 5 (31.3%) del 19, 9 (56.3%) L858R, 2 (12.5%) G719X. 20 (74.1%) patients were eventually put on 1st or 2nd EGFR-TKI as first line treatment and, among those, 17 (85%) attained partial response as the best treatment response and the median PFS and OS of is not reached. Among the 56 patients who obtained tissue biopsy/cytology along the course of disease, 6 (10.7%) of which carries histology (3 squamous cell carcinoma, 1 peripheral nerve sheath tumor, and 1 small cell carcinoma and 1 large cell tumor neuroendocrine tumor) that’s not normally sent for EGFR molecular testing, as well as 11 (19.6%) patients having NSCLC-NOS histology only. Conclusion: ddPCR and Cobas EGFR v2 platforms have similar detection rate and chance of avoiding the need of a confirmatory tissue biopsy. A simple clinical history of smoking status determines the yield of a positive result. Plasma liquid biopsy provides a non-invasive and promising way for treatment initiation in radiological lung cancer. Keywords: Cobas EGFR v2, ddPCR, liquid biopsy

P3.01-002 Concurrent EGFR T790M Secondary Mutation and EMT in a Lung Adenocarcinoma Patient with EGFR TKI Drug Resistance S. Xu,1 X. Liu,2 R. Liu,1 T. Shi,3 X. Li,1 D. Zhong,2 Y. Wang,2 G. Chen,1 J. Chen1 1Dept.Of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin/CN, 2Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin/CN, 3Department of Pathology, Tianjin Medical University General Hospital, Tianjin/CN Background: Almost all EGFR-mutant lung cancers develop resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Several mechanisms

for this acquired resistance have been identified, including development of an EGFR T790M mutation, MET amplification, hepatocyte growth factor (HGF) overexpression, loss of PTEN expression, epithelial to mesenchymal transition (EMT) and transformation to small cell lung cancer. Method: We presented a lung cancer patient with EGFR exon 19 deletion who was resistant to EGFR TKI treatment during disease progression. The original lung tumor started to enlarge and bred a secondary growing nodule adjacently. A left upper lobectomy plus systematic mediastinal lymphadenectomy by VATS was performed after a whole body evaluation which had no sign of extrapulmonary abnormalities. The pathological examination, genetic sequencing, and histological staining of E-cadherin and Vimentin were performed on the TKI resistant postoperative specimens. Result: The original lung tumor was confirmed to be adenocarcinoma according to the typical morphology and positivity of TTF1 and CK7. The secondary lung tumor has sarcomatoid histology showing a more spindle-like mesenchymal morphology with CK and Vimentin positivity. Next generation sequencing (NGS) test confirmed that the original lung adenocarcinomata retained EGFR exon 19 deletion but was also found T790M mutation in EGFR exon 20. The secondary sarcomatoid carcinoma retained EGFR exon 19 deletion as well. Besides, sarcomatoid carcinoma had genetic mutation on FANCL and BCL2L2, and amplification on CDK4, MDM2, APFRP1, GNAS, CIC, FANCE, Notch4 and AKT2. In addition, in comparison with adenocarcinoma from biopsy and postoperative specimens, the second growing sarcomatoid tumor is strongly positive for Vimentin and nearly negative for E-cadherin, indicating that sarcomatoid histology probably underwent EMT. Conclusion: The clinical implication of this case provides significant insights into our understanding that two or more mechanisms might be involved simultaneously in the EGFR TKI resistance. Therefore, if possible, it is necessary to perform tumor biopsies after the development of resistance to identify the best treatment options for patients. Keywords: drug resistance, EGFR-TKI

P3.01-003 Study of the Relationship between EGFR Mutation Status and Bone Metastasis in Advanced Lung Adenocarcinoma Z. Bing, A. Xiaoye, A. Yasheng Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi/CN Background: To investigate the relationship between EGFR mutation status and bone metastasis in lung adenocarcinoma. Method: We collected the data of 331 patients with advanced lung adenocarcinoma, and the status of EGFR mutation was detected by RT-PCR. Follow-up with these patients was performed. Result: 331 cases of advanced lung adenocarcinoma, EGFR mutation rate was 52.2%. The incidence of bone metastases (54.9%) and brain metastases (29.4%) with EGFR mutant patients was higher than that wild type. Compared with the number of metastases, EGFR mutant bone metastases were more than 2 and more, and the proportion of wild type single-site metastasis was more. The median survival of bone metastases in advanced lung adenocarcinoma was 14.7 months. EGFR gene mutant group, bone metastasis group median survival in 18.2 months, no bone metastasis group median survival in 21.8 months. In the wild-type group, the median survival of the bone metastases group was 11.5 months, and the median survival in the non-bone metastases group was 15.5 months. Conclusion: EGFR mutations in patients with advanced lung adenocarcinoma are more likely to develop bone metastasis and brain metastasis. Keywords: lung adenocarcinoma, EGFR, bone metastasis

Journal of Thoracic Oncology

Vol. 12 No. 11S2: S2201-S2364