Brain metastases in ALK-positive NSCLC – time to adjust current treatment algorithms
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Frank Griesinger1, Julia Roeper1, Christoph Pöttgen2, Kay C. Willborn3 and Wilfried E.E. Eberhardt4
1Department of Hematology and Oncology, University Department Internal Medicine-Oncology, Pius-Hospital, Medical Campus University of Oldenburg, Oldenburg, Germany
2Department of Radiotherapy, University Hospital Essen, Essen, Germany
3Department of Radiotherapy and Radiooncology, University Department of Medical Physics, Pius-Hospital Oldenburg, University of Oldenburg, Oldenburg, Germany
4Department of Medical Oncology, West German Cancer Center, Ruhrlandklinik, University of Duisburg-Essen, Essen, Germany
Frank Griesinger, email: [email protected]
Keywords: non-small cell lung cancer; ALK-positive; brain metastases; ALK-inhibitors
Received: January 18, 2018 Accepted: August 05, 2018 Published: October 12, 2018
The progress in molecular biology has revolutionized systemic treatment of advanced non-small-cell lung cancer (NSCLC) from conventional chemotherapy to a treatment stratified by histology and genetic aberrations. Tumors harboring a translocation of the anaplastic-lymphoma-kinase (ALK) gene constitute a distinct genetic and clinico-pathologic NSCLC subtype with patients with ALK-positive disease being at a higher risk for developing brain metastases. Due to the introduction of effective targeted therapy with ALK-inhibitors, today, patients with advanced ALK-positive NSCLC achieve high overall response rates and remain progression-free for long time intervals. Moreover, ALK-inhibitors seem to exhibit efficacy in the treatment of brain metastases. In the light of this, it needs to be discussed how treatment algorithms for managing patients with brain metastases should be modified. By integrating systemic ALK-inhibitor therapy, radiotherapy, in particular whole brain radiotherapy might be postponed deferring potential long-term impairment by neurocognitive deficits to a later time point in the course of the disease. An early treatment of asymptomatic brain metastases might offer patients a longer time without impairment of cerebral symptoms or radiotherapeutic interventions. Based on an updated extensive review of the literature this article provides an overview on the epidemiology and the treatment of patients’ brain metastases. It describes the specifics of ALK-positive disease and proposes an algorithm for the treatment of patients with advanced ALK-positive NSCLC and brain metastases.
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