Background: Leptomeningeal metastasis is a neurological complication from HER2-positive breast cancer with a poor prognosis and limited treatment options. This study has evaluated the activity of neratinib in association with capecitabine in 10 patients with LM from HER2-positive BC after the failure of multiple lines of treatment, including trastuzumab-based therapy, within a compassionate program, and a comparison was made with a historical control group of 10 patients. Methods: Patients aged ≥ 18 years with histological diagnosis of primary HER2-positive BC, either amplified or mutated, and newly-diagnosed LM were enrolled. Coexistence of BM that has or has not received radiotherapy, as well as prior chemotherapy, hormone therapy, or monoclonal HER2-targeting antibodies or antibody–drug conjugates, were allowed, with the exclusion of lapatinib. Results: Six-months OS was 60% with a median OS of 10 months (95% CI: 2.00–17.0). Three-month intracranial PFS was 60% with a median intracranial PFS of 4.0 months (95% CI: 2.00–6.0). The neurological benefit was observed in 70% of patients with a median duration of neurological response of 6.5 months. The best radiological response was stable disease in 60% of patients. Conclusions: This small series shows that the combination of neratinib and capecitabine is a safe treatment in LM from heavily pretreated HER2-positive BC with clinical efficacy in some patients and is worth investigating in a larger study.
Background: The neuropsychological profile of progressive supranuclear palsy (PSP) patients is mainly characterized by executive dysfunction, but the relationship between the latter and midbrain atrophy is still unclear. Objective: The aims of the study were to investigate which test evaluating executive functioning is more frequently impaired in PSP patients and to evaluate the relationship between midbrain-based MRI morphometric measures and executive dysfunction. Methods: PSP patients who had undergone a neuropsychological battery assessing executive functioning with the Frontal Assessment Battery (FAB), the phonemic verbal fluency F-A-S, the Raven’s Progressive Colored Matrix, and the Stroop word colors test (time and errors) were enrolled in the study. A group of Parkinson’s disease (PD) patients matched by age, sex, education, and global cognitive status was selected. All the enrolled patients also underwent a volumetric T1-3D brain MRI. Results: Thirty-five PSP patients and 35 PD patients were enrolled. Patients with PSP as compared to patients with PD showed a significant greater impairment in verbal fluency (16.0±7.9 and 23.4±8.7 words/180 s; p < 0.001) and a significant lower score at the FAB total score (11.5±3.8 and 13.7±3.4; p = 0.013). Midbrain area was significantly smaller in PSP patients than in PD patients (83.9±20.1 and 134.5±19.9 mm2; p < 0.001). In PSP patients, a significant positive correlation between verbal fluency and the midbrain area (r = 0.421; p = 0.028) was observed. Conclusion: Our findings suggest that the phonemic verbal fluency is among the most frequently impaired executive functions in PSP patients and is strongly correlated to midbrain atrophy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.