title: Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation.
abstract: Alectinib is a second generation ALK inhibitor that has significant clinical activity in central nervous system (CNS) metastases in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Pseudoprogression (PsP) due to radiation necrosis during alecitnib treatment of central nervous system (CNS) metastases from ALK-rearranged NSCLC as been reported. Hence, distinguishing radiation-related PsP from alectinib-induced radiographic changes is important to avoid erroneous early trial discontinuation and abandonment of an effective treatment. However, it remains difficult to assess casuality of radiation necrosis is related to recent direct radiation or induced by alectinib treatment or both. It is also unknown how long from previous radiation can alectinib still induce radiation necrosis. Here we reported a crizotinib-refractory ALK-positive NSCLC patient who develop radiation necrosis in one of his metastatic CNS lesions after approximately 12 months of alectinib treatment who otherwise had on-going CNS response on alectinib. His most recent radiation to his CNS metastases was 7 years prior to the start of alectinib. This case illustrates that in the setting of pror CNS radiation, given the significant clinical activity of alectinib in CNS metastases in ALK-positive NSCLC patients the risk of CNS radiation necrosis remains long after previous radiation to the CNS metastases has been completed and can occur after durable response of treatment.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, United States; Chao Family Comprehensive Cancer Center, Orange, CA 92868, United States. Electronic address: Ignatius.ou@uci.edu.
authors.forename: Sai-Hong Ignatius
authors.initials: SH
authors.lastname: Ou
authors.affiliation: Department of Emergency Medicine, Providence Saint John's Health Center, 2121 Santa Monica Blvd., Santa Monica, CA 90404, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Weitz
authors.affiliation: Department of Pathology, Providence Saint John's Health Center, 2121 Santa Monica Blvd., Santa Monica, CA 90404, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Jalas
authors.affiliation: St. John's Brain Tumor Center & Pituitary Disorders Program, 2200 Santa Monica Blvd., Santa Monica, CA 90404, United States.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Kelly
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, United States.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Wong
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, United States.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Azada
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, United States.
authors.forename: Oliver
authors.initials: O
authors.lastname: Quines
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, United States; Chao Family Comprehensive Cancer Center, Orange, CA 92868, United States.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Klempner
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary*; D002227:Carbazoles / Q000009:adverse effects* / Q000494:pharmacology; D000077547:Crizotinib; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D010880:Piperidines / Q000009:adverse effects* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011832:Radiation Injuries / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
keywords: ALK-positive non-small cell lung cancer; Alectinib; Pseudo-progression; Radiation necrosis