RESUMEN
BACKGROUND: Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD. METHODS: Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. RESULTS: 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD. CONCLUSIONS: Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.
Asunto(s)
Neoplasias Encefálicas , Enfermedades de la Mama , Neoplasias de la Mama , Neoplasias del Sistema Nervioso Central , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Neoplasias Encefálicas/secundario , Lapatinib , Estudios Retrospectivos , Estudios Prospectivos , Irradiación Craneana , Enfermedades de la Mama/complicaciones , Receptor ErbB-2RESUMEN
This review explores imaging's crucial role in acute Coronavirus Disease 2019 (COVID-19) assessment. High Resolution Computer Tomography is especially effective in detection of lung abnormalities. Chest radiography has limited utility in the initial stages of COVID-19 infection. Lung Ultrasound has emerged as a valuable, radiation-free tool in critical care, and Magnetic Resonance Imaging shows promise as a Computed Tomography alternative. Typical and atypical findings of COVID-19 by each of these modalities are discussed with emphasis on their prognostic value. Considerations for pediatric and immunocompromised cases are outlined. A comprehensive diagnostic approach is recommended, as radiological diagnosis remains challenging in the acute phase.
Asunto(s)
COVID-19 , Pulmón , Imagen por Resonancia Magnética , SARS-CoV-2 , Tomografía Computarizada por Rayos X , Ultrasonografía , Humanos , COVID-19/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Ultrasonografía/métodosRESUMEN
Leptomeningeal disease (LMD) occurs when tumors seed into the leptomeningeal space and cerebrospinal fluid (CSF), leading to severe neurological deterioration and poor survival outcomes. We utilized comprehensive multi-omics analyses of CSF from patients with lymphoma LMD to demonstrate an immunosuppressive cellular microenvironment and identified dysregulations in proteins and lipids indicating neurodegenerative processes. Strikingly, we found a significant accumulation of toxic branched-chain keto acids (BCKA) in the CSF of patients with LMD. The BCKA accumulation was found to be a pan-cancer occurrence, evident in lymphoma, breast cancer, and melanoma LMD patients. Functionally, BCKA disrupted the viability and function of endogenous T lymphocytes, chimeric antigen receptor (CAR) T cells, neurons, and meningeal cells. Treatment of LMD mice with BCKA-reducing sodium phenylbutyrate significantly improved neurological function, survival outcomes, and efficacy of anti-CD19 CAR T cell therapy. This is the first report of BCKA accumulation in LMD and provides preclinical evidence that targeting these toxic metabolites improves outcomes.