Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study

Lin Li; Wencai Li; Chunyan Wu; Yanfeng Xi; Lei Guo; Yuan Ji; Lili Jiang; Ji Li; Jingping Yun; Gang Chen; Yuan Li; Yueping Liu; Dianbin Mu; Yuchen Han; Leina Sun; Qingxin Xia; Xiaodong Teng; Nanying Che; Wei Wu; Xueshan Qiu; Chao Liu; Xiaochu Yan; Daiqiang Li; Zhihong Zhang; Zhe Wang; Yujun Li; Zheng Wang; Lingchuan Guo; Xiu Nie; Jingshu Geng; Jianhua Zhou; Jianming Ying

doi:10.1002/cac2.12593

Cancer Communications ›› 2024, Vol. 44 ›› Issue (09) : 992 -1004. DOI: 10.1002/cac2.12593

ORIGINAL ARTICLE

Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study

Author information +

¹. Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China

². Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P. R. China

³. Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, P. R. China

⁴. Department of Pathology, Cancer Hospital Affiliated to Shanxi Medical University, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, Shanxi, P. R. China

⁵. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, P. R. China

⁶. Department of Pathology, West China Hospital of Sichuan University, Chengdu, Sichuan, P. R. China

⁷. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China

⁸. Department of Pathology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China

⁹. Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, P. R. China

¹⁰. Department of Pathology, Department of Oncology, Fudan University Cancer Center, Shanghai Medical College of Fudan University, Shanghai, P. R. China

¹¹. Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P. R. China

¹². Department of Pathology, Shandong Cancer Hospital, Jinan, Shandong, P. R. China

¹³. Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, P. R. China

¹⁴. Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P. R. China

¹⁵. Department of Pathology, the Affiliated Cancer Hospital of Zhengzhou University, Henan Provincial Cancer Hospital, Zhengzhou, Henan, P. R. China

¹⁶. Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China

¹⁷. Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, P. R. China

¹⁸. Department of Pathology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, P. R. China

¹⁹. Department of Pathology, the First Hospital of China Medical University, Shenyang, Liaoning, P. R. China

²⁰. Department of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, P. R. China

²¹. Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P. R. China

²². Department of Pathology, the Second Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China

²³. Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China

²⁴. Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China

²⁵. Department of Pathology, theAffiliated Hospital ofQingdao University, Qingdao, Shandong, P. R. China

²⁶. Department of Pathology, Beijing Hospital, National Center of Gerontology, Beijing, P. R. China

²⁷. Department of Pathology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China

²⁸. Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China

²⁹. Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, P. R. China

³⁰. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, P. R. China

jmying@cicams.ac.cn

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Abstract

Background: Anaplastic lymphoma kinase (ALK) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring ALK gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of ALK gene rearrangements in advanced NSCLC.

Methods: In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an ALK rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive ALK gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of ALK gene rearrangement were investigated as well.

Results: The overall ALK gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall ALK gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all P < 0.05).

Conclusions: This study highlights the real-world variability and challenges of ALK test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in ALK-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined ALK test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.

Keywords

anaplastic lymphoma kinase / diagnosis / gene fusion / non-small cell lung cancer

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Lin Li, Wencai Li, Chunyan Wu, Yanfeng Xi, Lei Guo, Yuan Ji, Lili Jiang, Ji Li, Jingping Yun, Gang Chen, Yuan Li, Yueping Liu, Dianbin Mu, Yuchen Han, Leina Sun, Qingxin Xia, Xiaodong Teng, Nanying Che, Wei Wu, Xueshan Qiu, Chao Liu, Xiaochu Yan, Daiqiang Li, Zhihong Zhang, Zhe Wang, Yujun Li, Zheng Wang, Lingchuan Guo, Xiu Nie, Jingshu Geng, Jianhua Zhou, Jianming Ying. Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study. Cancer Communications, 2024, 44(09): 992-1004 DOI:10.1002/cac2.12593

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