1. ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib
- Author
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Egbert F. Smit, Buge Oz, Lukas Bubendorf, Stephen P. Finn, Lukas C. Heukamp, M. van den Heuvel, I. Marondel, A.O Grady, John R. Gosney, Anders Mellemgaard, Fabrice Duplaquet, Idris Bahce, Sayed M.S. Hashemi, Birgit Weynand, Xavier Durando, S.M.S. Samii, Patrick Pauwels, Pieter E. Postmus, Kim Monkhorst, Frédérique Penault-Llorca, S. Duin, Monika G. Looijen-Salamon, M.A. van der Drift, Ernst-Jan M. Speel, Wim Timens, Reinhard Buettner, N. Akyurek, Birgit I. Lissenberg-Witte, Erik Thunnissen, Birgit Guldhammer Skov, Ed Schuuring, Jens Benn Sørensen, Juergen Wolf, A.J. de Langen, Anne-Marie C. Dingemans, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - (MGD) Service d'anatomie pathologique, UCL - (MGD) Service de pneumologie, Pathology, Epidemiology and Data Science, APH - Methodology, CCA - Cancer Treatment and quality of life, and Pulmonary medicine
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Lung Neoplasms ,INTERNATIONAL-ASSOCIATION ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,0302 clinical medicine ,alk ,Non-small cell lung cancer ,Carcinoma, Non-Small-Cell Lung ,hemic and lymphatic diseases ,Anaplastic lymphoma kinase ,Anaplastic Lymphoma Kinase ,Prospective Studies ,In Situ Hybridization, Fluorescence ,Gene Rearrangement ,fluorescence in situ hybridisation ,medicine.diagnostic_test ,treatment ,REARRANGEMENT ,Middle Aged ,OF-AMERICAN-PATHOLOGISTS ,Prognosis ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,Immunohistochemistry ,PREVALENCE ,Survival Rate ,LUNG-CANCER PATIENTS ,Treatment Outcome ,030220 oncology & carcinogenesis ,immunohistochemistry ,%22">Fish ,Female ,Non small cell ,medicine.drug ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9] ,03 medical and health sciences ,MOLECULAR TESTING GUIDELINE ,All institutes and research themes of the Radboud University Medical Center ,Crizotinib ,Internal medicine ,Biopsy ,medicine ,Humans ,Protein Kinase Inhibitors ,non-small cell lung cancer ,business.industry ,ADENOCARCINOMA ,Treatment ,030104 developmental biology ,COPY NUMBER ,ALK ,KINASE INHIBITORS GUIDELINE ,Fluorescence in situ hybridisation ,Human medicine ,prognosis ,business ,Stage iv ,Fluorescence in situ hybridization ,IHC - Abstract
Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH +). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC) +). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases.Materials and methods: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH.Results: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC + /FISH +) and 16 discordant (ALK IHC + /FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR = 4.5; 95% CI = 1.2-15.9; p = 0.010.Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.
- Published
- 2019
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