Universität zu Köln

Thunnissen, E., Lissenberg-Witte, B., I, van den Heuvel, M. M., Monkhorst, K., Skov, B. G., Sorensen, J. B., Mellemgaard, A., Dingemans, A. M. C., Speel, E. J. M., de Langen, A. J., Hashemi, S. M. S., Bahce, I, van der Drift, M. A., Looijen-Salamon, M. G., Gosney, J., Postmus, P. E., Samii, S. M. S., Duplaquet, F., Weynand, B., Durando, X., Penault-Llorca, F., Finn, S., Grady, A. O., Oz, B., Akyurek, N., Buettner, R., Wolf, J., Bubendorf, L., Duin, S., Marondel, I, Heukamp, L. C., Timens, W., Schuuring, E. M. D., Pauwels, P. and Smit, E. F. (2019). ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib. Lung Cancer, 138. S. 13 - 19. CLARE: ELSEVIER IRELAND LTD. ISSN 1872-8332

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Thunnissen, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lissenberg-Witte, B., I UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Heuvel, M. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Monkhorst, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Skov, B. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sorensen, J. B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mellemgaard, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dingemans, A. M. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Speel, E. J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Langen, A. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hashemi, S. M. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahce, I UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Drift, M. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Looijen-Salamon, M. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gosney, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Postmus, P. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Samii, S. M. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Duplaquet, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weynand, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Durando, X. UNSPECIFIED UNSPECIFIED UNSPECIFIED Penault-Llorca, F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Finn, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grady, A. O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oz, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Akyurek, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bubendorf, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Duin, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marondel, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, L. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Timens, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuuring, E. M. D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pauwels, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Smit, E. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-125741
DOI:	10.1016/j.lungcan.2019.09.023
Journal or Publication Title:	Lung Cancer
Volume:	138
Page Range:	S. 13 - 19
Date:	2019
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1872-8332
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOLECULAR TESTING GUIDELINE; KINASE INHIBITORS GUIDELINE; OF-AMERICAN-PATHOLOGISTS; LUNG-CANCER PATIENTS; INTERNATIONAL-ASSOCIATION; COPY NUMBER; REARRANGEMENT; IHC; ADENOCARCINOMA; PREVALENCE Multiple languages Oncology; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12574