$Case Report: Treatment of Alectinib in NSCLC With Brain Metastasis Patient Refractory to Radiotherapy After Resistance to Crizotinib$

Case Report: Treatment of Alectinib in NSCLC With Brain Metastasis Patient Refractory to Radiotherapy After Resistance to Crizotinib

This case revealed some new insights. First, liquid biopsy is complementary to tissue biopsy in patients with NSCLC, mainly in those with EGFR mutation. However, ALK rearrangement should be assessed using tissue biopsy as much as possible. Second, brain metastasis of NSCLC might respond to second-generation tyrosine kinase inhibitors (TKIs), such as alectinib and ceritinib, after resistance to crizotinib regardless of the presence or absence of ALK rearrangement in liquid biopsy. Finally, combined radiotherapy and TKI therapy appears optimal in patients with brain metastasis of NSCLC after resistance to crizotinib in the absence of a definitive driver gene. READ ARTICLE

Frontiers in Oncology DOI: 10.3389/fonc.2021.709188

Authors: Zhang Chunzhi

Case Study, group4Kirk SmithJune 28, 2021NSCLC, ALK+, radiotherapy

Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview

Over the past years, the identification of genetic alterations in oncogenic drivers in non-small cell lung cancer (NSCLC) has significantly and favorably transformed the outcome of patients who can benefit from targeted therapies such as tyrosine kinase inhibitors. Among these genetic alterations, anaplastic lymphoma kinase (ALK) rearrangements were discovered in 2007 and are present in 3–5% of patients with NSCLC. In addition, radiotherapy remains one of the cornerstones of NSCLC treatment. Moreover, improvements in the field of radiotherapy with the use of hypofractionated or ablative stereotactic radiotherapy have led to a better outcome for localized or oligometastatic NSCLC. To date, the effects of the combination of ALK inhibitors and radiotherapy are unclear in terms of safety and efficacy but could potently improve treatment. In this manuscript, we provide a clinical and preclinical overview of combining radiation therapy with ALK inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer. READ ARTICLE

Cancers DOI: 10.3390/cancers13102394

Authors: Delphine Antoni, Hélène Burckel, and Georges Noe

Review PaperKirk SmithMay 5, 2021NSCLC, ALK, TKI, radiotherapy

Effects of ALK inhibitors (PF-02341066 and PF-06463922) with radiotherapy in EML4 – ALK fusion positive (H2228 and 185IG) and negative (A549) experimental lung cancer cell lines

Purpose/Objective(s): The management of non-small cell lung cancer (NSCLC) patients with chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) is challenging. Indeed, the efficacy of the tyrosine kinase inhibitor (TKI) of novel generation may discuss the place of combined treatment with radiotherapy. We aimed to investigate the effects of combined radiotherapy and PF-02341066 or PF-06463922 in A549 and 185IG or H2228 cell lines, the former is a wild type ALK NSCLC model and the two latter are ALK-positive NSCLC models... Conclusion: In the current study, PF-02341066 induced notably cell cycle arrest at G2/M phase and PF-06463922 induced G1 arrest, in H2228 cells. Also, results suggest that the administration of PF-02341066 and PF-06463922 after irradiation could increase the induction of DNA damages due to IR in a panel of 3 NSCLC cell lines, compared to IR first followed by TKI treatment. These results could influence the clinical combination strategy for EML4 – ALK..... READ ARTICLE

International Journal of Radiation Oncology*Biology*Physics DOI:10.1016/j.ijrobp.2020.07.1599

Authors: D.N. Antoni, H. Burckel, G. Noel

When Should we Irradiate the Primary in Metastatic Lung Cancer?

Metastatic lung cancer encompasses a heterogenous group of patients in terms of burdens of disease, ranging from patients with extensive metastases to those with a limited number of metastatic lesions (oligometastatic disease). Histopathological heterogeneity also exists within two broad categories, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), portraying different patterns and evolution of disease. Local consolidative therapy to the primary tumour and metastatic sites, including surgery and/or radical dose radiotherapy, is increasingly being used to improve survival outcomes, particularly in the context of oligometastatic disease, with or without the use of molecular targeted therapy and immunotherapy. Recently, randomised studies in oligometastatic NSCLC have shown that local consolidative therapy may confer a survival advantage. This review explores whether treating just the primary tumour with radiotherapy may similarly produce improved clinical outcomes. Su..... READ ARTICLE

Clinical Oncology DOI:10.1016/j.clon.2019.07.012

Authors: A. M. Shiarli, F. McDonald, D. R. Gomez