ABSTRACT
BACKGROUND: Central nervous system (CNS) metastases are a catastrophic complication of non-small cell lung cancer (NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains challenging. CASE SUMMARY: We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor (EGFR). A standard dosage of icotinib (125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib (1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side effects. CONCLUSION: This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.
ABSTRACT
AIMS: Preventing stroke through endovascular treatment with vertebral artery stent remains a great challenge due to the occurrence of an in-stent restenosis. MATERIALS & METHODS: In this study, a retrospective analysis was conducted in 90 patients who had been treated with VAS between 2004 and 2011 in Nanjing Drum Tower Hospital. Patients were followed up at 3 months, 6 months,and 1 year after VAS treatment and annually thereafter. For each time point, neurological function tests, vessel ultrasound and computer tomography angiography were performed to preliminarily screen the vessel stenosis. Digital subtraction angiography was used to verify the narrow sign on CTA or ultrasound. Clinical features of each patient including clopidogrel metabolization genes (CYP2C19, CYP3A4, and P2Y12) were recorded with purpose to investigate the possible risk factors for the development of ISR. RESULTS: Single factor analysis dem-onstrated that hyperlipidemia (P < 0.05) and CYP2C19 (P < 0.01) loss-of-function geno-type increased the likelihood of ISR. A multiple logistic cox regression analysis also showed that stroke patients with hyperlipidemia (HR 3.719, 95% CI: 1.094-12.637, P = 0.035), and CYP2C19 loss-of-function genotype (HR 2.959, 95% CI: 1.325-6.610, P = 0.008) were more likely to suffer from ISR. Furthermore, CYP2C19 alleles were mainly divided into three groups: wt/wt (CYP2C19 *1/*1), wt/m (CYP2C19 *1/*2 and *1/*3), and m/m (CYP2C19 *2/*2,*2/*3 and*3/*3). Recurrent rate of ischemic stroke in m/m and wt/m groups was higher than the wt/wt group (OR: 0.141, 95% CI: 0.016-1.221, P = 0.042). CONCLUSION: The study leads to the conclusion that hyperlipidemia and CYP2C19 impotency are possible risk factors for the development of ISR in VAS-treated patients with ischemic. Moreover, VAS-treated patients with CYP2C19 impotency were susceptible to recurrent stroke during our 54-month follow-up.
