Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.

BACKGROUND: Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs). METHODS: Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. RESULTS: Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. CONCLUSIONS: The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

Intrathecal trastuzumab in the management of HER2+ breast leptomeningeal disease: a single institution experience.

PURPOSE: Leptomeningeal disease is a rare and devastating presentation of advanced stage metastatic breast cancer with historically poor overall survival. We assessed the safety and feasibility of intrathecal (IT) trastuzumab in HER2+ leptomeningeal disease. METHODS: A total of 13 patients were treated at our institution with IT trastuzumab beginning November 2012 and followed until November 2017. Outcomes including craniospinal progression as well as overall survival (OS) following initiation of IT trastuzumab were assessed from review of the clinical chart and radiologic examinations. RESULTS: The median age of patients was 48 (range 29-75). Median time from breast cancer diagnosis to development of brain metastases was 87.7 months with a median of 4.6 months from brain metastases diagnosis to the development of leptomeningeal disease. Previous whole brain radiotherapy was received by the majority of patients (92%) and prior surgery for brain metastases was performed in 23%. Median duration of IT trastuzumab treatment was 6.4 months. Median time from IT trastuzumab start to craniospinal progression was 5.7 months with 6- and 12-month Kaplan-Meier rates of 41 and 21%, respectively. Sustained responses > 6 months were achieved in 4 patients. Median survival from the start of IT trastuzumab was 10.6 months with 6- and 12-month OS rates of 68 and 47%, respectively. IT trastuzumab was well tolerated with one patient developing ventriculitis, which resolved with IV antibiotics. CONCLUSIONS: IT trastuzumab was well tolerated with prolongation of OS over historical controls. IT trastuzumab should be considered for management of HER2+ leptomeningeal disease patients.

Plate-like osteoma cutis.

Osteoma cutis is the aberrant development of bone within the skin. The bone formation may be de novo (primary) or result from an injury to the skin (secondary). Here we present a healthy 53-year-old man with no known abnormalities in calcium or phosphate metabolism with plate-like osteoma cutis of the scalp. Plate- or plaque-like osteoma cutis was initially described as a congenital condition but has now been reported several times in the literature as an idiopathic process that occurs in adults. Treatment options are limited and are only required if the lesion is bothersome to the patient.

Imaging the cellular dynamics of Drosophila Argonaute proteins.

Drosophila melanogaster is used extensively as a model system to uncover genetic and molecular pathways that regulate various cellular activities. There are five members of the Argonaute protein family in Drosophila. Argonautes have been found to be localized to cytoplasmic ribonucleoprotein containing structures in both cultured Drosophila cells and developing embryos. However, in fixed cell preparations some Drosophila Argonaute family proteins co-localize with structures containing known as RNA processing (P) body components while others do not. The ability to image Argonaute family proteins in live Drosophila cells, (both cultured and within developing embryos) allows for accurate genetic dissection of the pathways involved in the assembly, mobility, disassembly, and other dynamic processes of Argonaute-containing bodies. Here we describe a method of rapidly creating vectors for, and assay the activity of, fluorescently tagged Argonaute proteins in cultured Drosophila cells and embryos.

Oral lichen planus.

A 42-year-old woman presented with a 2-year history of persistent, gray-white lip discoloration and discomfort that had not improved after empiric treatment with topical 5-fluorouracil cream. Histopathologic examination demonstrated interface dermatitis with epidermal atrophy. A diagnosis of oral lichen planus was made based on clinicopathologic correlation, and treatment with topical tacrolimus ointment was initiated.

Improvements in access to care for HIV and AIDS in a statewide Medicaid managed care system.

BACKGROUND: Some experimental Medicaid managed care systems have expanded eligibility criteria for chronically ill persons, but these systems' impact on access to care remains unknown. OBJECTIVE: To determine whether initiating a statewide Medicaid managed care system (TennCare) guaranteeing universal access for persons living with HIV or AIDS (PLWHs) increased their enrollment in public sector insurance. DESIGN, SETTING, AND PARTICIPANTS: A retrospective longitudinal descriptive analysis of trends in population characteristics during the study period was performed. The study population included all PLWHs in Tennessee (1992-1997) identified by the State Health Department. These data linked with Medicaid/TennCare enrollment files identified percentages of Tennessee's HIV/AIDS population enrolled in Medicaid (1993) or TennCare (1994-1997) and eligi-bility/demographics changes during program initiation. MAIN OUTCOME MEASURE: Annual percentage of PLWHs enrolled in Medicaid/TennCare. RESULTS: Absolute numbers of PLWHs served by Medicaid/TennCare increased 475% from 1992 (n = 593) to 1997 (n = 2818). Similar increases in Tennessee's overall HIV-positive population occurred. Percentages of PLWHs enrolled in Medicaid/TennCare increased (1993 to 1997): HIV (28% to 34%) and AIDS (32% to 44%). The largest percentage of PLWHs added to the program were uninsured/uninsurable. CONCLUSIONS: Absolute numbers of PLWHs covered by Medicaid/TennCare substantially increased. Percentages of PLWHs covered increased more modestly, partly owing to large increases in overall numbers of HIV-positive Tennesseans during the study period. Increases in coverage were greatest for the AIDS population. Tennessee's broad expansion of eligibility for PLWHs resulted in improved access, but did not result in enrollment of most PLWHs. States contemplating similar Medicaid expansions should not expect all PLWHs to crowd into public sector insurance programs.