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P3.03-004 The Frequency and Clinical Implication of ALK, ROS1, RET and NTRK1 Gene Rearrangements in Adenosquamous Lung Carcinoma Patients
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P3.03-003 ABCB1 3435C[T Polymorphism Influences the Toxicity and Clinical Outcome of Patients with Taxane-Based Chemotherapy J. Zhong,1 J. Zhao,1 Z. Guo,2 L. Fan2 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing/CN, 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing/CN Background: Taxane-based chemotherapy including paclitaxel, docetaxel, paclitaxel-albumin was wildly used in solid tumors. ABCB1 (Pglycoprotein, multidrug resistance 1) is a trans-membrane protein that acts as an energy-dependent drug efflux pump for chemotherapeutic drugs, including taxanes. In addition, ABCB1 has been suggested to have a role in the prediction of treatment response and toxicity of chemotherapy in breast cancer, gastric cancer et.al. In this retrospective study, we explore the influence of ABCB1 polymorphism on toxicity and taxane-based chemotherapy. Method: 118 patients (lung cancer 103, others 15) with taxane-based chemotherapy (paclitaxel 56 cases, docetaxel 55 cases, paclitaxel-albumin 7 cases) treatment were included in this study. Fluorescence in situ hybridization (FISH) was used for ABCB1 polymorphism detection. Statistical analysis was performed using SPSS 20.0. Result: The frequency of the ABCB1 3435 site homozygous mutation (TT genotype), heterozygous mutation (TC genotype) and wild type (CC genotype) was 11.0% (13/118), 45.8%(54/ 118) and 43.2%(51/118) respectively. The occurrence of neurotoxicity was higher in patients had TT genotype (62.9%) compared with patients had TC (25.9%) and CC genotype (37.3%)(P¼0.310). Especially in the docetaxol subgroup, the difference of chemotherapy-induced neurotoxicity was statistically significant (TT 75.0%, TC 9.5%, CC 11.5%, P¼0.007). There was not significant difference between the three ABCB1 genotypes with regarding to other chemotherapy-induced toxicity, including diarrhea, constipation, leukocytes, neutrophils, anemia and thrombocytopenia. For non-small cell lung cancer (NSCLC) patients in this study, patient harboring ABCB1 3435 site CC genotype had longer median progression free survival (PFS) (5.1 months) than TC genotype (4.7 months) and TT genotype (2.6 months)(P¼0.42). Especially in the paclitaxel subgroup (n¼21), the median progression was significantly longer in patients with CC genotype when compared with TC and TT genotype (9.8 months vs. 4.5 months vs. 1.6 month, P¼0.06). We failed to find the difference in either response rate or disease control rate between the different genotype, even in subgroup analysis. Conclusion: ABCB1 3435 site polymorphism is associated with neurotoxicity of taxane-based chemotherapy. It can also predict clinical outcomes for NSCLC. Keywords: ABCB1, chemotherapy, toxicity
P3.03-004 The Frequency and Clinical Implication of ALK, ROS1, RET and NTRK1 Gene Rearrangements in Adenosquamous Lung Carcinoma Patients X. Shi, S. Wu, H. Duan, Y. Liu, X. Zeng, Z. Liang Pathology, Peking Union Medical College Hospital, Beijing/CN Background: Adenosquamous lung carcinoma (ASC) is a hybrid tumor made of adenocarcinoma and squamous cell carcinoma in one tumor. It is a rare disease with poorer prognosis comparing with the other common variants of non-small cell lung cancer (NSCLC). There is a persisting need for identifying more effective targeted therapy
Journal of Thoracic Oncology
Vol. 12 No. 11S2
methods. Our previous study had examined the EGFR mutation status in lung ASC, the results showed that its mutation rate is similar with that of lung adenocarcinoma. Because the rarity of lung ASC, little is known about its gene rearrangement status and its relationship with the clinical characteristics. Method: ALK, ROS1, RET and NTRK1 gene rearrangement in lung ASC were examined by next generation sequencing methods, and further confirmed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry methods. Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) lung ASC cases were used in this study. Result: This study included 53 cases of lung ASC totally. ALK/EML4 gene rearrangement was detected in 3 cases (5.7%), ROS1 fusion gene was detected in 1 cases (1.9%), RET gene rearrangement was detected in 1 case (1.9%). One of the ALK/EML4 rearrangement case had a concurrent EGFR exon 21 L858R mutation. All the rearrangement results can be further confirmed by FISH and/or immunohistochemistry methods. No association were identified between ALK/EML4 rearrangement and patient age, tumor size, clinical stage, positive pleural invasion, lymphovascular invasion, smoking status, lymph node metastasis, therapy methods, recurrence free survival (RFS) time or overall survival duration. Conclusion: The gene rearrangement rate of lung ASC is similar with that of lung adenocarcinoma, which further support our suggestion that lung ASC is a peculiar subtype of lung adenocarcinoma with a poorer prognosis than lung adenocarcinoma. Keywords: lung adenosquamous cell carcinoma, gene rearrangement, EGFR mutation
P3.03-005 Diagnosis and Treatment Analysis of Lung Enteric Adenocarcinoma: 6 Case Report and Review of the Literature C. Xu,1 W. Wang,2 L. Lin,3 W. Zhuang,4 Y. Shao,5 Y. Tai,5 G. Chen1 1 Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 2Zhejiang Cancer Hospital, Hangzhou/CN, 3Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing/ CN, 4Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5 Pathology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing/CN Background: Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. This study mainly discusses the clinicopathological characteristics, diagnosis and treatment of primary lung enteric adenocarcinoma. Method: Retrospectively analyzed clinical records of 6 cases admitted in hospital from Feb. 2013 to May 2016, and reviewed the literature of primary lung enteric adenocarcinoma. Result: Two patients were male and four patients were female with the age ranged from 25 to 78 years. Their symptoms consisted mainly of cough chest stuffy with 4 patients, neck mass with 1 case, dizziness nausea vomiting with 1 case; imagining scan showed mass of lung and or mediastinal, pathology form and the immunochemistry showed all positive for intestinal immune phenotypes and some positive for lung cancer immunophenotypic. But no tumor was found by gastrointestinal endoscopes; 1 case recurrence and metastasis after radical operation; 1 patient underdone palliative surgery, 1 patient with brain solitary metastasis onset received Cyber Knife and without system treatment, and 5 patients underwent chemotherapy. At the end of follow-up, 4 patients died, over survival time as long as 32 months. Conclusion: The primary lung enteric adenocarcinoma is easily confused with pulmonary metastases from colorectal cancer, confirmed diagnosis need to rule out intestinal lesion, the main early treatment is surgery, and systematic treatment programs need to be further studied. Keywords: diagnosis, Lung enteric adenocarcinoma, Immunohistochemistry
P3.03-003 ABCB1 3435C[T Polymorphism Influences the Toxicity and Clinical Outcome of Patients with Taxane-Based Chemotherapy J. Zhong,1 J. Zhao,1 Z. Guo,2 L. Fan2 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology-I, Peking University Cancer Hospital & Institute, Beijing/CN, 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pharmacy, Peking University Cancer Hospital & Institute, Beijing/CN Background: Taxane-based chemotherapy including paclitaxel, docetaxel, paclitaxel-albumin was wildly used in solid tumors. ABCB1 (Pglycoprotein, multidrug resistance 1) is a trans-membrane protein that acts as an energy-dependent drug efflux pump for chemotherapeutic drugs, including taxanes. In addition, ABCB1 has been suggested to have a role in the prediction of treatment response and toxicity of chemotherapy in breast cancer, gastric cancer et.al. In this retrospective study, we explore the influence of ABCB1 polymorphism on toxicity and taxane-based chemotherapy. Method: 118 patients (lung cancer 103, others 15) with taxane-based chemotherapy (paclitaxel 56 cases, docetaxel 55 cases, paclitaxel-albumin 7 cases) treatment were included in this study. Fluorescence in situ hybridization (FISH) was used for ABCB1 polymorphism detection. Statistical analysis was performed using SPSS 20.0. Result: The frequency of the ABCB1 3435 site homozygous mutation (TT genotype), heterozygous mutation (TC genotype) and wild type (CC genotype) was 11.0% (13/118), 45.8%(54/ 118) and 43.2%(51/118) respectively. The occurrence of neurotoxicity was higher in patients had TT genotype (62.9%) compared with patients had TC (25.9%) and CC genotype (37.3%)(P¼0.310). Especially in the docetaxol subgroup, the difference of chemotherapy-induced neurotoxicity was statistically significant (TT 75.0%, TC 9.5%, CC 11.5%, P¼0.007). There was not significant difference between the three ABCB1 genotypes with regarding to other chemotherapy-induced toxicity, including diarrhea, constipation, leukocytes, neutrophils, anemia and thrombocytopenia. For non-small cell lung cancer (NSCLC) patients in this study, patient harboring ABCB1 3435 site CC genotype had longer median progression free survival (PFS) (5.1 months) than TC genotype (4.7 months) and TT genotype (2.6 months)(P¼0.42). Especially in the paclitaxel subgroup (n¼21), the median progression was significantly longer in patients with CC genotype when compared with TC and TT genotype (9.8 months vs. 4.5 months vs. 1.6 month, P¼0.06). We failed to find the difference in either response rate or disease control rate between the different genotype, even in subgroup analysis. Conclusion: ABCB1 3435 site polymorphism is associated with neurotoxicity of taxane-based chemotherapy. It can also predict clinical outcomes for NSCLC. Keywords: ABCB1, chemotherapy, toxicity
P3.03-004 The Frequency and Clinical Implication of ALK, ROS1, RET and NTRK1 Gene Rearrangements in Adenosquamous Lung Carcinoma Patients X. Shi, S. Wu, H. Duan, Y. Liu, X. Zeng, Z. Liang Pathology, Peking Union Medical College Hospital, Beijing/CN Background: Adenosquamous lung carcinoma (ASC) is a hybrid tumor made of adenocarcinoma and squamous cell carcinoma in one tumor. It is a rare disease with poorer prognosis comparing with the other common variants of non-small cell lung cancer (NSCLC). There is a persisting need for identifying more effective targeted therapy
Journal of Thoracic Oncology
Vol. 12 No. 11S2
methods. Our previous study had examined the EGFR mutation status in lung ASC, the results showed that its mutation rate is similar with that of lung adenocarcinoma. Because the rarity of lung ASC, little is known about its gene rearrangement status and its relationship with the clinical characteristics. Method: ALK, ROS1, RET and NTRK1 gene rearrangement in lung ASC were examined by next generation sequencing methods, and further confirmed by fluorescent in situ hybridization (FISH) and/or immunohistochemistry methods. Tissue microarrays (TMAs) containing formalin fixed paraffin embedded (FFPE) lung ASC cases were used in this study. Result: This study included 53 cases of lung ASC totally. ALK/EML4 gene rearrangement was detected in 3 cases (5.7%), ROS1 fusion gene was detected in 1 cases (1.9%), RET gene rearrangement was detected in 1 case (1.9%). One of the ALK/EML4 rearrangement case had a concurrent EGFR exon 21 L858R mutation. All the rearrangement results can be further confirmed by FISH and/or immunohistochemistry methods. No association were identified between ALK/EML4 rearrangement and patient age, tumor size, clinical stage, positive pleural invasion, lymphovascular invasion, smoking status, lymph node metastasis, therapy methods, recurrence free survival (RFS) time or overall survival duration. Conclusion: The gene rearrangement rate of lung ASC is similar with that of lung adenocarcinoma, which further support our suggestion that lung ASC is a peculiar subtype of lung adenocarcinoma with a poorer prognosis than lung adenocarcinoma. Keywords: lung adenosquamous cell carcinoma, gene rearrangement, EGFR mutation
P3.03-005 Diagnosis and Treatment Analysis of Lung Enteric Adenocarcinoma: 6 Case Report and Review of the Literature C. Xu,1 W. Wang,2 L. Lin,3 W. Zhuang,4 Y. Shao,5 Y. Tai,5 G. Chen1 1 Pathology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 2Zhejiang Cancer Hospital, Hangzhou/CN, 3Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing/ CN, 4Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou/CN, 5 Pathology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing/CN Background: Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. This study mainly discusses the clinicopathological characteristics, diagnosis and treatment of primary lung enteric adenocarcinoma. Method: Retrospectively analyzed clinical records of 6 cases admitted in hospital from Feb. 2013 to May 2016, and reviewed the literature of primary lung enteric adenocarcinoma. Result: Two patients were male and four patients were female with the age ranged from 25 to 78 years. Their symptoms consisted mainly of cough chest stuffy with 4 patients, neck mass with 1 case, dizziness nausea vomiting with 1 case; imagining scan showed mass of lung and or mediastinal, pathology form and the immunochemistry showed all positive for intestinal immune phenotypes and some positive for lung cancer immunophenotypic. But no tumor was found by gastrointestinal endoscopes; 1 case recurrence and metastasis after radical operation; 1 patient underdone palliative surgery, 1 patient with brain solitary metastasis onset received Cyber Knife and without system treatment, and 5 patients underwent chemotherapy. At the end of follow-up, 4 patients died, over survival time as long as 32 months. Conclusion: The primary lung enteric adenocarcinoma is easily confused with pulmonary metastases from colorectal cancer, confirmed diagnosis need to rule out intestinal lesion, the main early treatment is surgery, and systematic treatment programs need to be further studied. Keywords: diagnosis, Lung enteric adenocarcinoma, Immunohistochemistry