Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood–brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.National Institutes of Health (U.S.) (Grant R01 EB006365-06)Brain Science Foundation (Private Grant 106708

Distinguishing grade I meningioma from higher grade meningiomas without biopsy

BACKGROUND: Many meningiomas are identified by imaging and followed, with an assumption that they are WHO Grade I tumors. The purpose of our investigation is to find clinical or imaging predictors of WHO Grade II/III tumors to distinguish them from Grade I meningiomas. METHODS: Patients with a pathologic diagnosis of meningioma from 2002-2009 were included if they had pre-operative MRI studies and pathology for review. A Neuro-Pathologist reviewed and classified all tumors by WHO 2007. All Brain MRI imaging was reviewed by a Neuro-radiologist. Pathology and Radiology reviews were blinded from each other and clinical course. Recursive partitioning was used to create predictive models for identifying meningioma grades. RESULTS: Factors significantly correlating with a diagnosis of WHO Grade II-III tumors in univariate analysis: prior CVA (p = 0.005), CABG (p = 0.010), paresis (p = 0.008), vascularity index = 4/4: (p = 0.009), convexity vs other (p = 0.014), metabolic syndrome (p = 0.025), non-skull base (p = 0.041) and non-postmenopausal female (p = 0.045). Recursive partitioning analysis identified four categories: 1. prior CVA, 2. vascular index (vi) = 4 (no CVA), 3. premenopausal or male, vi \u3c 4, no CVA. 4. Postmenopausal, vi \u3c 4, no CVA with corresponding rates of 73, 54, 35 and 10% of being Grade II-III meningiomas. CONCLUSIONS: Meningioma patients with prior CVA and those grade 4/4 vascularity are the most likely to have WHO Grade II-III tumors while post-menopausal women without these features are the most likely to have Grade I meningiomas. Further study of the associations of clinical and imaging factors with grade and clinical behavior are needed to better predict behavior of these tumors without biopsy

Correction for Upadhyay et al., Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain

Correction for “Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain,” by Urvashi M. Upadhyay, Betty Tyler, Yoda Patta, Robert Wicks, Kevin Spencer, Alexander Scott, Byron Masi, Lee Hwang, Rachel Grossman, Michael Cima, Henry Brem, and Robert Langer, which appeared in issue 45, November 11, 2014, of Proc Natl Acad Sci USA (111:16071–16076; first published October 27, 2014, 10.1073/pnas.1313420110)