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Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases

Authors Zhu VW, Nagasaka M, Kubota T, Raval K, Robinette N, Armas O, Al-Holou W, Ou SI

Received 27 July 2019

Accepted for publication 20 December 2019

Published 14 January 2020 Volume 2020:11 Pages 13—18


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Joseph Locker

Viola W Zhu, 1,* Misako Nagasaka, 2, 3,* Takafumi Kubota, 4 Kunil Raval, 5 Natasha Robinette, 6 Octavio Armas, 7 Wajd Al-Holou, 8 Sai-Hong Ignatius Ou 1

1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California Irvine, Orange, CA, USA; 2Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA; 3Department of Advanced Medical Innovations, St. Marianna University Graduate School of Medicine, Kawasaki, Japan; 4Department of Neurology, Sapporo Nishimaruyama Hospital, Sapporo, Japan; 5Department of Pathology, Wayne State University, Detroit, MI, USA; 6Department of Oncology, Imaging Division, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA; 7Department of Pathology, Sharp Grossmont Hospital, La Mesa, CA, USA; 8Department of Neurosurgery, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA

*These authors contributed equally to this work

Correspondence: Sai-Hong Ignatius Ou
Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology/Oncology, University of California Irvine, 200 Manchester Dr, Suite 410, Orange, CA 92868, USA
Tel +1714-456-8104
Fax +1714-456-2242

Abstract: Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs.

Keywords: CNS, radiation necrosis, lorlatinib, ALK-rearranged NSCLC, alectinib

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