Management of CNS disease in ALK-positive non-small cell lung cancer: Is whole brain radiotherapy still needed?

Management of CNS disease in ALK-positive non-small cell lung cancer: Is whole brain radiotherapy still needed? Cancer Radiother. 2019 Jul 19;: Authors: Wrona A Abstract Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier. Central nervous system-directed radiotherapy represents the most important strategy to control intracranial disease burden and extend the survival benefit with crizotinib. The role of whole brain irradiation in the treatment of brain metastases diminishes, as this technique is associated with the risk of neurocognitive decline. Stereotactic radiotherapy represents an alternative technique that delivers ablative doses of ionizing ra...
Source: Cancer Radiotherapie - Category: Cancer & Oncology Authors: Tags: Cancer Radiother Source Type: research

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Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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 st...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: CASE REPORTS Source Type: research
Authors: Melosky B, Cheema P, Agulnik J, Albadine R, Bebb DG, Blais N, Burkes R, Butts C, Card PB, Chan AMY, Hirsh V, Ionescu DN, Juergens R, Morzycki W, Poonja Z, Sangha R, Tehfe M, Tsao MS, Vincent M, Xu Z, Liu G Abstract Background: Inhibition of the anaplastic lymphoma kinase (alk) oncogenic driver in advanced non-small-cell lung carcinoma (nsclc) improves survival. In 2015, Canadian thoracic oncology specialists published a consensus guideline about the identification and treatment of ALK-positive patients, recommending use of the alk inhibitor crizotinib in the first line. New scientific literature warrants a...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Griesinger F, Roeper J, Pöttgen C, Willborn KC, Eberhardt WEE Abstract 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, ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionsYoung patients are associated with an increased likelihood of gene mutations and can receive a better prognosis when patients harboring gene mutations are treated with EGFR-TKIs or ALK inhibitors.
Source: Clinical and Translational Oncology - Category: Cancer & Oncology Source Type: research
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Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Conclusion: In this initial study, 18F-FLT radiotracer uptake correlated well with clinical outcome of the patients, successfully differentiating proliferative malignant lesions from other benign concomitant etiologies. Scan results demonstrated low grade to absent FLT tracer uptake in benign inflammatory/infective cells as compared to higher grade concentration in tumor cells.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Preclinical Probes for Oncology Posters Source Type: research
ConclusionsThis study demonstrates the clinical activity and manageable tolerability of ceritinib in a Japanese subset of chemotherapy- and crizotinib-pretreated patients withALK-rearranged non-small cell lung cancer who progressed on crizotinib, as was shown in the whole ASCEND-2 study population.ClinicalTrials.gov identifier: NCT01685060
Source: Japanese Journal of Clinical Oncology - Category: Cancer & Oncology Source Type: research
Abstract Crizotinib has achieved astonishing success in advanced non‐small‐cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real‐world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat‐sen University Cancer Center. Chi‐square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan–Meier methods and multivariable analyses were used to estimate progression‐free survival (PFS). A total of 291 advanced NSCLC patie...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
Publication date: Available online 24 January 2017 Source:The Lancet Author(s): Jean-Charles Soria, Daniel S W Tan, Rita Chiari, Yi-Long Wu, Luis Paz-Ares, Juergen Wolf, Sarayut L Geater, Sergey Orlov, Diego Cortinovis, Chong-Jen Yu, Maximillian Hochmair, Alexis B Cortot, Chun-Ming Tsai, Denis Moro-Sibilot, Rosario G Campelo, Tracey McCulloch, Paramita Sen, Margaret Dugan, Serafino Pantano, Fabrice Branle, Cristian Massacesi, Gilberto de Castro Background The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficac...
Source: The Lancet - Category: Journals (General) Source Type: research
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