In advanced stages, patients with ALK-rearranged NSCLC, compared with EGFR-mutant NSCLC, were more likely to have lymphadenopathy (OR, 3.47; P < .001), pericardial metastasis (OR, 2.18; P = .04), pleural metastasis (OR, 2.07; P = .004), and lymphangitic carcinomatosis (OR, 3.41; P = .02), but less likely to have lung metastasis (OR, 0.52; P = .003).
We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05).
In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations who had received no previous treatment for metastatic disease to receive pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance therapy.
At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis.
In univariate analysis, patients with an ALK rearrangement were younger (P < .001) and were more likely to be men (P = .001), to have never smoked (P = .002), and to have pleural or pericardial metastases (P < .05) compared with those with EGFR mutations.
Here we report a case of pulmonary inflammatory myofibroblastic tumor with mediastinal nodal metastasis in a 74-year-old man, definitively diagnosed by EUS-FNA utilizing morphologic, immunohistochemical, and molecular findings, including fluorescent in situ hybridization studies for ALK gene rearrangement.
In another case, EML4-ALK fusion detected in the primary tumor was associated with ALKG1202R secondary resistance mutation in the post-treatment metastasis.
Considering this remarkable response, we conclude that the presence of adnexal metastasis in NSCLC patients with ALK rearrangement should be attentive.
Moreover, the concordance of ALK status was observed in these pairs.<b>Conclusions</b>: Our data suggested that hotspot mutations and ALK status in the primary-metastasis pairs had a high concordance in lung adenocarcinoma.
Treatment of two different ALK inhibitors, WHI-P154 and NVP-TAE684, resulted in the down-regulation of aberrant ALK signaling, shrinkage of tumor, and suppression of metastasis and significantly improved survival of ALK mutant-bearing mice.
We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs.
The findings suggested that patients with ALK rearrangements are more likely to be young, have EGFR wild-type, and more likely to exhibit mucus secretion, solid tumor growth, lymph node metastasis and pleural metastasis.
The mean number of metastatic disease sites in patients within the ALK rearranged cohort was significantly greater than that of the triple negative cohort (mean = 3.6 sites vs 2.5 sites, P < .0001).
We present the clinicopathologic features of three patients with metastatic NSCLC harboring the EML4-ALK translocation that developed isolated central nervous system (CNS) metastases in the presence of good disease control elsewhere in the body.
Using driver gene alternation and tumor burden, advanced NSCLC cases were divided into 3 groups: M1-I group, epidermal growth factor (EGFR)-positive and/or anaplastic lymphoma kinase (ALK)-positive; MI-II, wild-type EGFR and ALK with intrathoracic metastasis or 1 distant metastatic organ with ≤ 3 metastasis lesions; and MI-III, wild-type EGFR and ALK with 1 distant metastatic organ with > 3 metastasis lesions or multiple metastatic organs.
Since IRS1/2 interact with and transmits signals from the receptors of insulin, Insulin Like Growth Factor 1 (IGF1), prolactin, growth hormone (GH), leptin, Vascular Endothelial Growth Factor (VEGF), TrkB, ALK and integrins this promoted scientist to think that IRS1 may have functions in cell proliferation, tumorigenesis and metastasis.