Jong-Mu Sun1, Maruja Lira2, Kinnari Pandya2, Yoon-La Choi3, Jin Seok Ahn1, Mao Mao2, Joungho Han3, Keunchil Park1, Myung-Ju Ahn4, Jhingook Kim5. 1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 2. Pfizer Oncology, San Diego, CA, USA. 3. Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: silkahn@skku.edu. 5. Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: jhingookkim@gmail.com.
Abstract
OBJECTIVES: Anaplastic lymphoma kinase (ALK) rearrangement is a validated predictive marker to define patients with non-small cell lung cancer (NSCLC) who can benefit from selective ALK inhibitors. Therefore, accurate assessment of its prevalence and clinical characteristics is increasingly important in the treatment of NSCLC. Also, this ALK rearrangement was previously reported to be more common in patients with no smoking history or those with adenocarcinoma. PATIENTS AND METHODS: Never-smokers with completely resected pulmonary adenocarcinoma were screened for ALK rearrangements using Nanostring's gene expression platform. Clinicopathologic data, such as information about epidermal growth factor receptor (EGFR) and KRAS mutation status were retrospectively reviewed. RESULTS: Of 231 tumors screened, 20 (9%) had an ALK rearrangement and all were confirmed to be positive with immunohistochemical and fluorescent in situ hybridization analysis. Of the tumors with available data on the EGFR/KRAS mutation status, EGFR and KRAS mutation rates were 64% (69/108) and 5% (5/102), respectively. Amongst the tumors that were free of EGFR and KRAS mutations, the proportion of ALK rearrangements reached up to 33%. At the time of data cut-off, total of 68 tumors were recurred. Although the recurrence rate was similar between the ALK-positive and negative groups (30% vs. 29%), there was a tendency for ALK-positive tumors to recur more frequently in the pleural space (15% vs. 5%). The five-year disease-free survival (61%) and overall survival rates (79%) in the ALK-positive group were similar to those in the ALK-negative group (51% and 83%, respectively). Even after excluding two patients treated with crizotinib after disease recurrence, overall survival was similar between the two groups. CONCLUSION: In an NSCLC subpopulation based on smoking history, histology, and EGFR and KRAS mutation status, the prevalence of ALK rearrangements is considerably high. However, ALK rearrangement status itself has no prognostic relevance in patients with completely resected NSCLC.
OBJECTIVES:Anaplastic lymphoma kinase (ALK) rearrangement is a validated predictive marker to define patients with non-small cell lung cancer (NSCLC) who can benefit from selective ALK inhibitors. Therefore, accurate assessment of its prevalence and clinical characteristics is increasingly important in the treatment of NSCLC. Also, this ALK rearrangement was previously reported to be more common in patients with no smoking history or those with adenocarcinoma. PATIENTS AND METHODS: Never-smokers with completely resected pulmonary adenocarcinoma were screened for ALK rearrangements using Nanostring's gene expression platform. Clinicopathologic data, such as information about epidermal growth factor receptor (EGFR) and KRAS mutation status were retrospectively reviewed. RESULTS: Of 231 tumors screened, 20 (9%) had an ALK rearrangement and all were confirmed to be positive with immunohistochemical and fluorescent in situ hybridization analysis. Of the tumors with available data on the EGFR/KRAS mutation status, EGFR and KRAS mutation rates were 64% (69/108) and 5% (5/102), respectively. Amongst the tumors that were free of EGFR and KRAS mutations, the proportion of ALK rearrangements reached up to 33%. At the time of data cut-off, total of 68 tumors were recurred. Although the recurrence rate was similar between the ALK-positive and negative groups (30% vs. 29%), there was a tendency for ALK-positive tumors to recur more frequently in the pleural space (15% vs. 5%). The five-year disease-free survival (61%) and overall survival rates (79%) in the ALK-positive group were similar to those in the ALK-negative group (51% and 83%, respectively). Even after excluding two patients treated with crizotinib after disease recurrence, overall survival was similar between the two groups. CONCLUSION: In an NSCLC subpopulation based on smoking history, histology, and EGFR and KRAS mutation status, the prevalence of ALK rearrangements is considerably high. However, ALK rearrangement status itself has no prognostic relevance in patients with completely resected NSCLC.
Authors: Bojan Zaric; Vladimir Stojsic; Milana Panjkovic; Dragana Tegeltija; Vanesa Stepanov; Tomi Kovacevic; Tatjana Sarcev; Davorin Radosavljevic; Aleksandar Milovancev; Vasilis Adamidis; Paul Zarogoulidis; Wolfgang Hohenforst-Schmidt; Georgia Trakada; Aggeliki Rapti; Branislav Perin Journal: J Cancer Date: 2016-10-25 Impact factor: 4.207
Authors: Sang Yun Ha; So-Jung Choi; Jong Ho Cho; Hye Joo Choi; Jinseon Lee; Kyungsoo Jung; Darry Irwin; Xiao Liu; Maruja E Lira; Mao Mao; Hong Kwan Kim; Yong Soo Choi; Young Mog Shim; Woong Yang Park; Yoon-La Choi; Jhingook Kim Journal: Oncotarget Date: 2015-03-10