Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study
Abstract Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not current...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-020-00866-6 |
| _version_ | 1818331138818572288 |
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| author | Chang Lu Xiao-Rong Dong Jun Zhao Xu-Chao Zhang Hua-Jun Chen Qing Zhou Hai-Yan Tu Xing-Hao Ai Xiao-Feng Chen Gai-Li An Jun Bai Jin-Lu Shan Yi-Na Wang Shuan-Ying Yang Xiang Liu Wu Zhuang Hui-Ta Wu Bo Zhu Xue-Feng Xia Rong-Rong Chen De-Jian Gu Hua-Min Xu Yi-Long Wu Jin-Ji Yang |
| author_facet | Chang Lu Xiao-Rong Dong Jun Zhao Xu-Chao Zhang Hua-Jun Chen Qing Zhou Hai-Yan Tu Xing-Hao Ai Xiao-Feng Chen Gai-Li An Jun Bai Jin-Lu Shan Yi-Na Wang Shuan-Ying Yang Xiang Liu Wu Zhuang Hui-Ta Wu Bo Zhu Xue-Feng Xia Rong-Rong Chen De-Jian Gu Hua-Min Xu Yi-Long Wu Jin-Ji Yang |
| author_sort | Chang Lu |
| collection | DOAJ |
| description | Abstract Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal. |
| first_indexed | 2024-12-13T13:15:05Z |
| format | Article |
| id | doaj.art-65892830cd4a4799975b53c363390d15 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-13T13:15:05Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-65892830cd4a4799975b53c363390d152022-12-21T23:44:34ZengBMCJournal of Hematology & Oncology1756-87222020-04-0113111210.1186/s13045-020-00866-6Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter studyChang Lu0Xiao-Rong Dong1Jun Zhao2Xu-Chao Zhang3Hua-Jun Chen4Qing Zhou5Hai-Yan Tu6Xing-Hao Ai7Xiao-Feng Chen8Gai-Li An9Jun Bai10Jin-Lu Shan11Yi-Na Wang12Shuan-Ying Yang13Xiang Liu14Wu Zhuang15Hui-Ta Wu16Bo Zhu17Xue-Feng Xia18Rong-Rong Chen19De-Jian Gu20Hua-Min Xu21Yi-Long Wu22Jin-Ji Yang23The Second School of Clinical Medicine, Southern Medical UniversityCancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & InstituteGuangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesGuangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical SciencesShanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityOncology Department, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Clinical Oncology, Shaanxi Provincial People’s HospitalDepartment of Clinical Oncology, Shaanxi Provincial People’s HospitalDaping Hospital, Army medical center of PLADepartment of Oncology, The First Affiliated Hospital of Zhejiang UniversityThe Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Cardiothoracic Surgery, The Second Affiliated Hospital, University of South ChinaFujian Provincial Cancer HospitalDepartment of Oncology, Zhongshan Hospital, Xiamen UniversityInstitute of Cancer, Xinqiao Hospital, Third Military Medical UniversityGeneplus-Beijing InstituteGeneplus-Beijing InstituteGeneplus-Beijing InstituteGeneplus-Beijing InstituteThe Second School of Clinical Medicine, Southern Medical UniversityThe Second School of Clinical Medicine, Southern Medical UniversityAbstract Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.http://link.springer.com/article/10.1186/s13045-020-00866-6Advanced NSCLCRET rearrangementNext-generationsequencingTP53Immune checkpoint inhibitor |
| spellingShingle | Chang Lu Xiao-Rong Dong Jun Zhao Xu-Chao Zhang Hua-Jun Chen Qing Zhou Hai-Yan Tu Xing-Hao Ai Xiao-Feng Chen Gai-Li An Jun Bai Jin-Lu Shan Yi-Na Wang Shuan-Ying Yang Xiang Liu Wu Zhuang Hui-Ta Wu Bo Zhu Xue-Feng Xia Rong-Rong Chen De-Jian Gu Hua-Min Xu Yi-Long Wu Jin-Ji Yang Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study Journal of Hematology & Oncology Advanced NSCLC RET rearrangement Next-generationsequencing TP53 Immune checkpoint inhibitor |
| title | Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study |
| title_full | Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study |
| title_fullStr | Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study |
| title_full_unstemmed | Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study |
| title_short | Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study |
| title_sort | association of genetic and immuno characteristics with clinical outcomes in patients with ret rearranged non small cell lung cancer a retrospective multicenter study |
| topic | Advanced NSCLC RET rearrangement Next-generationsequencing TP53 Immune checkpoint inhibitor |
| url | http://link.springer.com/article/10.1186/s13045-020-00866-6 |
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