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Four lines of anaplastic lymphoma kinase inhibitors and brain radiotherapy in a long-surviving non-small-cell lung cancer anaplastic lymphoma kinase-positive patient with leptomeningeal carcinomatosis

Onesti, Concetta E.a,b; Iacono, Danielac; Angelini, Silviad,e; Mazzotta, Marcod,e; Giusti, Raffaeled; Lauro, Salvatored,e; Marchetti, Paolod,e

doi: 10.1097/CAD.0000000000000699

Lung cancer is the most common tumor and the leading cause of cancer-related death worldwide. Approximately 6.7% of non-small-cell lung cancers (NSCLCs) show anaplastic lymphoma kinase (ALK) rearrangement and could benefit from ALK-targeted treatment. Various anti-ALK drugs have been developed during the past years, but it is actually controversial which sequence and which ALK inhibitor is recommended for a single patient. Leptomeningeal carcinomatosis (LC) is associated with a poor prognosis, with an overall survival of 2–4 months for treated patients. The data about LC management derive mainly from retrospective studies, being an exclusion criterion for most trials. Intrathecal chemotherapy and whole-brain radiotherapy (WBRT), associated with a systemic treatment, are the most commonly used approach. Here we present a case of NSCLC harboring an ALK translocation treated with four lines of ALK inhibitors and receiving WBRT for LC, showing an overall survival of ∼5 years from the diagnosis of metastatic disease. This case report focuses mainly on several controversial clinical aspects, that is, the sequence of treatment in ALK-positive NSCLC, the ALK inhibitors’ efficacy on brain disease and beyond progression, the management of LC, and the role of WBRT despite the risk of cognitive impairment.

aDepartment of Medical Oncology, University Hospital (CHU)

bLaboratory of Human Genetics, Department of Medical Oncology, GIGA Research Institute, University of Liège, Liège, Belgium

cDepartment of Pulmonary Oncology, St Camillo Forlanini Hospital

dDepartment of Medical Oncology, Sant’Andrea Hospital of Rome

eDepartment of Clinical and Molecular Medicine, ‘Sapienza’ University of Rome, Rome, Italy

Correspondence to Raffaele Giusti, MD, Department of Medical Oncology, Sant’Andrea Hospital of Rome, Via di Grottarossa 1035-39, 00189 Rome, Italy Tel: +39 633 777 721; fax: +39 633 776 346; e-mail:

Received May 24, 2018

Accepted September 11, 2018

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