Lorlatinib Should Be Considered as the Preferred First-Line Option in Patients With Advanced ALK-Rearranged NSCLC

Since the discovery of ALK-positive (ALK+) fusion in NSCLC in 2007, 1 ,2 we now know patients with ALK+ NSCLC can live up to 9 years after stage 4 diagnosis 3 , 4 , 5 but are constantly overshadowed by an unrelenting cumulative incidence of brain metastasis with time (>60% by year 6). 6 At the molecular level, the two most common EML4-ALK fusion variants, variant 1 (v1) and variant 3 (v3), have differential responses to ALK tyrosine kinase inhibitors (TKIs) 7 ,8 with the recalcitrant solvent-front ALK G1202R mutation arising more often from the background of EML4-ALK variant 3. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.12.021

Authors: Misako Nagasaka, Sai-Hong Ignatius Ou

EditorialKirk SmithMarch 27, 2021lorlatinib, First-Line, ALK-Rearranged, NSCLC

Two Cases of Krukenberg Tumors from ALK-Rearranged Lung Adenocarcinoma: An Uncommon Site of Metastasis

Approximately 5% of all NSCLCs harbor ALK receptor tyrosine kinase gene (ALK) rearrangements.1 ALK-rearranged NSCLC is more commonly associated with younger individuals and those without a smoking history. The most common ALK rearrangement is a fusion between the ALK gene and gene echinoderm microtubule associated protein like 4 gene (EML4).1 Several drugs targeting ALK-rearranged NSCLC are currently available. Unfortunately, almost all ALK-positive NSCLCs will eventually progress during treatment with ALK inhibitors. This is mainly due to ALK point mutations, most commonly a L1196M mutation and the G1269A mutation, although several others have been identified.2 NSCLC tends to spread to the bones, brain, liver, lungs, and adrenal glands. ALK-positive NSCLCs have an increased tendency to metastasize to the pericardium, pleura, and liver compared with other NSCLCs.3 Rarely, tumors can metastasize to the ovaries; such tumors are known as Krukenberg tumors. Typically, Krukenberg tumors ori..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2019.05.028

Authors: John (Jack) Ogden, Hao Xie, Randolph S. Marks, Konstantinos Leventakos

EditorialKirk SmithOctober 1, 2019Krukenberg Tumors, ALK-Rearranged, Lung Adenocarcinoma, Metastasis