Intracranial disease control forEGFR-mutant andALK-rearranged lung cancer with large volume or symptomatic brain metastases
- 1 September 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Neuro-Oncology
- Vol. 149 (2), 357-366
- https://doi.org/10.1007/s11060-020-03615-4
Abstract
Purpose/objective(s) Tyrosine kinase inhibitors (TKIs) are commonly employed for patients with brain metastases from lung cancer and specific driver mutations. We sought to identify the correlation between intracranial tumor burden and outcomes in patients with brain metastases treated with TKIs. Materials/methods We identified and retrospectively reviewed cases ofEGFR-mutant orALK-rearranged lung cancer with brain metastases at any time during their cancer course. Clinical characteristics and treatment information were abstracted from the medical records. Brain metastases were contoured to calculate total volume of disease at diagnosis and after initial therapy. High intracranial burden was defined as either > 10 brain metastases, volume of brain metastases > 15 cc, or largest lesion > 3 cm. Intracranial response was determined according to Response Assessment in Neuro-Oncology (RANO) criteria on the patient level. We determined the correlation between clinical and imaging characteristics and intracranial progression free survival (IC-PFS) and overall survival (OS). Results Fifty-seven patients withEGFR(n = 49) andALK(n = 8) alterations were identified. Median follow-up from initial brain metastasis diagnosis was 17 months. Neurological symptoms were present in 54% at brain metastasis diagnosis. For those receiving TKIs alone or TKIs with radiation, at least a partial intracranial response (>= 65% volume reduction) at 3 months from starting therapy was achieved in 94% and 58%. Progressive intracranial disease at 3 months occurred in 6.3% and 8.3%. Patients with high intracranial burden (n = 21) had a median 17 brain metastases, 6.5 cc volume, and 1.9 cm maximal tumor diameter. Median IC-PFS and OS for patients with high intracranial burden was 13.9 and 35.4 months. Patients with high intracranial burden and neurological symptoms at diagnosis had similar IC-PFS and OS compared to those with low burden and absence of neurological symptoms (p > 0.05 for each). Conclusion Most patients receiving TKIs as part of their initial therapy achieve an early and durable volumetric intracranial response, irrespective of presenting disease burden or neurologic symptoms.This publication has 25 references indexed in Scilit:
- The emerging treatment landscape of targeted therapy in non-small-cell lung cancerSignal Transduction and Targeted Therapy, 2019
- EGFR mutant locally advanced non-small cell lung cancer is at increased risk of brain metastasisClinical and Translational Radiation Oncology, 2019
- CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung CancerJournal of Clinical Oncology, 2018
- Osimertinib versus Standard of Care EGFR TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC: FLAURA Asian SubsetJournal of Thoracic Oncology, 2018
- Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: a single-centre, randomised, controlled, phase 3 trialThe Lancet Oncology, 2017
- Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional AnalysisJournal of Clinical Oncology, 2017
- Brain metastases in patients with EGFR -mutated or ALK -rearranged non-small-cell lung cancersLung Cancer, 2015
- Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 studyThe Lancet Oncology, 2014
- Isolated central nervous system progression on Crizotinib An Achilles heel of non-small cell lung cancer with EML4-ALK translocation?Cancer Biology & Therapy, 2012
- A New Prognostic Index and Comparison to Three Other Indices for Patients With Brain Metastases: An Analysis of 1,960 Patients in the RTOG DatabaseInternational Journal of Radiation Oncology*Biology*Physics, 2008