Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings. Our study substantiated the potent CNS activity of alectinib in real-world settings. Patients with symptomatic and asymptomatic BM could benefit from alectinib comparatively, which indicated that alectinib alone might defer the timing of local treatment. However, our results should be treated cautiously owing to limited sample size. READ ARTICLE

BMC Med DOI:10.1186/s12916-021-02207-x

Authors: Zou Z, Xing P, Hao X, Wang Y, Song X, Shan L, Zhang C, Liu Z, Ma K, Dong G, Li J.

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 ( n = 5), 1 ( n = 26) or none ( n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared..... READ ARTICLE

Translational Oncology DOI:10.1016/j.tranon.2021.101121

Authors: Sergey V. Orlov, Aglaya G. Iyevleva, Elena A. Filippova, Alexandra M. Lozhkina, Svetlana V. Odintsova, Tatiana N. Sokolova, Natalia V. Mitiushkina, Vladislav I. Tiurin, Elena V. Preobrazhenskaya, Alexandr A. Romanko, Alexandr S. Martianov, Alexandr O. Ivantsov, Svetlana N. Aleksakhina, Alexandr V. Togo, Evgeny N. Imyanitov.

Brain Mets & CNS Coverage of MET signaling in NSCLC

Colorado University Updates on Lung Cancer Research: The Future for Lung Cancer & Targeted Therapies. SEE VIDEO

Author: University of colorado Cancer Center

Video, group5Kirk SmithJune 11, 2021Brain metastases, CNS, MET, NSCLC

A case of one lung adenocarcinoma patient harboring a novel FAM179A-ALK (F1, A19) rearrangement responding to lorlatinib treatment

The FAM179A gene has recently been screened as a new fusion partner fusing to the anaplastic lymphoma kinase gene (ALK) in plasma cell-free DNA (cfDNA) of patients with non-small-cell lung cancer (NSCLC). However, the response of patients with NSCLC harboring the FAM179A–ALK fusion to ALK inhibitors remains unknown. In this study we report a novel FAM179A–ALK rearrangement variant (F1, A19) identified by next-generation sequencing in an NSCLC patient with multiple brain metastases (M1c). This patient responded sensitively to lorlatinib as evaluated by brain MRI and chest CT, followed up using plasma cfDNA. The conclusion is that we found a novel FAM179A–ALK rearrangement variant (F1, A19) and provided evidence of its sensitivity to ALK inhibitors. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2020.06.026

Authors: Jing Yan, Xijian Zhou, Dejian Pan

Case StudyKirk SmithSeptember 1, 2020ALK, NSCLC, Lorlatinib, Brain metastases

Intracranial disease control for EGFR-mutant and ALK-rearranged lung cancer with large volume or symptomatic brain metastases

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.... 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. READ ARTICLE

Journal of Neuro-Oncology volume DOI:10.1007/s11060-020-03615-4

Authors: Sunil W. Dutta, Marie L. Mack, Eric Aliotta, Kristin A. Ward, Donald A. Muller, James M. Larner, Camilo E. Fadul, Richard D. Hall, Ryan D. Gentzler, Jason P. Sheehan

Real-World OutcomesKirk SmithAugust 9, 2020TKI, Radiation, Brain metastases, NSCLC

Radiomic prediction of mutation status based on MR imaging of lung cancer brain metastases

Lung cancer metastases comprise most of all brain metastases in adults and most brain metastases are diagnosed by magnetic resonance (MR) scans. The purpose of this study was to conduct an MR imaging-based radiomic analysis of brain metastatic lesions from patients with primary lung cancer to classify mutational status of the metastatic disease. We retrospectively identified lung cancer patients with brain metastases treated at our institution between 2009 and 2017 who underwent genotype testing of their primary lung cancer. Brain MR Images were used for segmentation of enhancing tumors and peritumoral edema, and for radiomic feature extraction. The most relevant radiomic features were identified and used with clinical data to train random forest classifiers to classify the mutation status. Of 110 patients in the study cohort (mean age 57.51 ± 12.32 years; M: F = 37:73), 75 had an EGFR mutation, 21 had an ALK translocation, and 15 had a KRAS mutation. One patient had both ALK transloca..... READ ARTICLE

Magnetic Resonance Imaging DOI:10.1016/j.mri.2020.03.002

Authors: Bihong T. Chen, Taihao Jin, Ningrong Ye, Isa Mambetsariev, Ebenezer Daniel, Tao Wang, Chi Wah Wong, Russell C. Rockne, Rivka Colen, Andrei

Brain metastases from non-small cell lung cancer with EGFR or ALK mutations: A systematic review and meta-analysis of multidisciplinary approaches

Background and purpose: To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT. Conclusion: NSCLC patients with brain metastases harboring EGFR or ALK mutations have superior OS compared to wild-type patients. No PFS or OS benefit was found with the addition of TKIs to RT. READ ARTICLE

Radiotherapy and Oncology. DOI: 10.1016/j.radonc.2019.11.010

Authors: Raj Singh, Eric J. Lehrer, Stephen Ko, Jennifer Peterson, Yanyan Lou, Alyx B. Porter, Rupesh Kotecha, Paul D. Brown, Nicholas G. Zaorsky, Daniel M. Trifiletti

Review PaperKirk SmithDecember 6, 2019Radiosurgery, ALK, EGFR, Mutated, Brain metastases

Management of Central Nervous System Metastases in Patients With Advanced Anaplastic Lymphoma Kinase-Rearranged Non–Small-Cell Lung Cancer During Crizotinib Treatment

"Background: Central nervous system (CNS) progression is a common manifestation of acquired resistance to crizotinib in anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC). However, an optimal tailored treatment approach has not been established in patients with CNS failure during crizotinib treatment. Conclusion: Although CBPD is an option in patients with isolated CNS progression during crizotinib treatment, sequential treatment with a second ALK TKI, particularly brigatinib, might be preferable. The newly approved TKI, brigatinib, showed promise in the control of brain metastases, even without radiotherapy. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.06.013

Authors: Yiming Zhao, Bo Zhang, Shuyuan Wang, Rong Qiao, Jianlin Xu, Lele Zhang, Yanwei Zhang, Baohui Han"

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

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 ..... READ ARTICLE

Cancer/Radiothérapie DOI:10.1016/j.canrad.2019.03.009

Authors: A. Wrona

Management of brain metastases in non-small cell lung cancer in the era of tyrosine kinase inhibitors

Lung cancer represents the most common cause of brain dissemination. Oncogene-addicted (EGFR- and ALK-positive) non-small cell lung cancers (NSCLCs) are characterized by a unique metastatic neurotropism resulting in a particularly high incidence of brain metastases. The goal of optimal brain metastases management is to improve both overall survival and quality of life, with the focus on neurocognitive function preservation.
Neurosurgery is offered to patients presenting with limited intracranial tumor burden located in surgically accessible un-eloquent regions of the brain, whereas stereotactic radiosurgery represents the preferred radiotherapy option for patients not amenable to surgery. Whole brain radiotherapy, owing to its neurocognitive sequelae, should be reserved for patients with multiple lesions.
EGFR and ALK tyrosine kinase inhibitors (TKIs) provide significantly superior systemic response rates and progression-free survival compared to standard chemotherapy in the molecularl..... READ ARTICLE

Cancer Treatment Reviews DOI:10.1016/j.ctrv.2018.10.011

Authors: Anna Wrona, Rafał Dziadziuszko, Jacek Jassem

Excellent Outcomes with Radiosurgery for Multiple Brain Metastases in ALK and EGFR Driven Non–Small Cell Lung Cancer

Radiosurgery for multiple BMs is controversial, yet patients with EGFR-mutated and ALK-rearranged NSCLC may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2017.12.006

Authors: Tyler P. Robin, Ross Camidge, Kelly Stuhr, Sameer K. Nath, Robert E. Breeze, Jose M. Pacheco, Arthur K. Liu, Laurie E. Gaspar, Thomas Purcell, Robert C. Doebele, Brian D. Kavanagh and Chad G. Rusthoven