Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox’s regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox’s regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity.
(age range, 43-61 years) and all had brain metastases at baseline. All four patients achieved an objective partial response to ensartinib, including one patient with an acquired ALK F1174V crizotinib resistance mutation. Intracranial responses included one partial response, two stable disease, and resolution of a non-target lesion in another patient. The median progression free survival was 12.5 months (range, 8-15 months) and the median decrease in tumor size was 42% (range, 39-48%). Primary sites of disease progression included lung (n¼1), brain (n¼2), both lung and brain (n¼1). No somatic alterations were identified in the two patients who received post-ensartinib ctDNA sequencing. At progression, all patients received brigatinib as subsequent therapy with clinical benefit; one received lorlatinib after brigatinib failure and response is ongoing. Median post-ensartinib survival was 27 months (range, 20-38 months). Two patients remain alive 27 and 95 months after first anti-cancer therapy. The most common adverse events with ensartinib were mild rash, diarrhea, and fatigue that did not require dose reduction. Conclusion: Ensartinib is well tolerated and has clinical activity in advanced ALK-rearranged NSCLC patients with brain metastases, despite previously progressing on crizotinib, with durable post-ensartinib survival on subsequent next-generation ALK inhibitors such as brigatinib and lorlatinib.
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