Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non–Small Cell Lung Cancer
| العنوان: | Dichotomous ALK-IHC Is a Better Predictor for ALK Inhibition Outcome than Traditional ALK-FISH in Advanced Non–Small Cell Lung Cancer |
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| المؤلفون: | Ernst-Jan M. Speel, Nils A. 't Hart, B. E. van den Borne, E. Van Der Heijden, Monika G. Looijen-Salamon, S. Riemersma, Lizza E.L. Hendriks, A. J. van der Wekken, Harry J.M. Groen, Ed Schuuring, Wim Timens, R. Pelgrim, A. Van Den Berg, Thijo J N Hiltermann, A.J. de Langen, N Werner, J. Staal-van den Brekel, Anne-Marie C. Dingemans, M. F. Mastik |
| المساهمون: | Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), CCA - Cancer Treatment and quality of life, Pulmonary medicine, Pulmonologie, Promovendi ODB, MUMC+: MA Med Staf Spec Longziekten (9), RS: GROW - R2 - Basic and Translational Cancer Biology, Pathologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Epidemiologie |
| المصدر: | Clinical Cancer Research, 23(15), 4251-4258. AMER ASSOC CANCER RESEARCH Europe PubMed Central Clinical Cancer Research, 23(15), 4251-4258. American Association for Cancer Research Inc. Clinical Cancer Research, 23, 4251-4258 Clinical Cancer Research, 23, 15, pp. 4251-4258 Van Der Wekken, A J, Pelgrim, R, T Hart, N, Werner, N, Mastik, M F, Hendriks, L, Van Der Heijden, E H F M, Looijen-Salamon, M, De Langen, A J, Staal-Van Den Brekel, J, Riemersma, S, Van Den Borne, B E, Speel, E J M, Dingemans, A M C, Hiltermann, T J N, Van Den Berg, A, Timens, W, Schuuring, E & Groen, H J M 2017, ' Dichotomous ALK-IHC is a better predictor for ALK inhibition outcome than traditional ALK-FISH in advanced non–small cell lung cancer ', Clinical Cancer Research, vol. 23, no. 15, pp. 4251-4258 . https://doi.org/10.1158/1078-0432.CCR-16-1631Test |
| بيانات النشر: | American Association for Cancer Research (AACR), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, Pathology, Pyridines, FUSION, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, GENE REARRANGEMENT, In Situ Hybridization, Fluorescence, CRIZOTINIB THERAPY, medicine.diagnostic_test, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, CARCINOMAS, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], medicine.drug, Adult, medicine.medical_specialty, Biopsy, Fine-Needle, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Disease-Free Survival, 03 medical and health sciences, Crizotinib, Internal medicine, Biopsy, Biomarkers, Tumor, medicine, Carcinoma, Humans, IMMUNOHISTOCHEMISTRY, Lung cancer, Aged, IDENTIFICATION, business.industry, Receptor Protein-Tyrosine Kinases, Cancer, ADENOCARCINOMA, Gene rearrangement, IN-SITU HYBRIDIZATION, medicine.disease, COPY NUMBER, 030104 developmental biology, Pyrazoles, business |
| الوصف: | Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non–small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH. Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH–positive advanced NSCLC from four other hospitals were used for validation. Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC–positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH–positive but ALK-IHC–negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P = 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P = 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P = 0.01, respectively]. Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy. Clin Cancer Res; 23(15); 4251–8. ©2017 AACR. |
| وصف الملف: | application/pdf |
| تدمد: | 1557-3265 1078-0432 4251-4258 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::294301d2488887f96efb73185cf8e257Test https://doi.org/10.1158/1078-0432.ccr-16-1631Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....294301d2488887f96efb73185cf8e257 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 42514258 |
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