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).
In another case, EML4-ALK fusion detected in the primary tumor was associated with ALKG1202R secondary resistance mutation in the post-treatment metastasis.
In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal invasion, and lymphangitis.
In conclusion, we suggest that ALK positive/<i>NRAS</i> mutated metastases represent a specific subset of metastatic melanomas, associated with a better prognosis.
In ERMS, specific ALK gain in the primary tumor correlated with metastatic disease (100% in metastatic disease v 29% in nonmetastatic disease; P = .004) and poor disease-specific survival (5-year disease-specific survival: 62% v 82% for nonspecific or no gain; P = .046).
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.
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.
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.
Particularly, metastasis of myxoid liposarcoma was associated with ALK phosphorylation (P=0.0019), but not with ALK protein expression or gene signal gain.
Recently, there are several case reports of choroidal metastases in patients with anaplastic lymphoma kinase (ALK)-driven NSCLC one of which the patient's choroidal metastases had responded to crizotinib, multi-targeted tyrosine kinase inhibitor against ALK/ROS1/MET.
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.
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 histologic feature of ALK translocated non-small-cell lung cancer (NSCLC) has been studied, presence of signet-ring cells was a powerful histologic indicator of ALK rearrangement, and this characteristic histology was present both in primary sites and metastases.
The lack of exposure to second-generation ALK inhibitors and intracranial metastasis on initial diagnosis were independent negative prognostic factors of OS.
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).
Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis.