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Purpose: Diffusion tensor imaging for evaluation of white matter tracts is used with magnetic resonance spectroscopy (MRS) to improve management of diffuse intrinsic pontine glioma (DIPG). Changes in the apparent diffusion coefficient (ADC), fractional anisotropy (FA), and tumor metabolite ratios have been reported after initial radiation for DIPG, but these markers have not been studied sequentially in patients undergoing reirradiation for progressive DIPG. Here, we report a case series of 4 patients who received reirradiation for progressive DIPG on a prospective clinical trial in which we evaluated quantitative changes in FA, ADC, and tumor metabolites and qualitative changes in white matter tracts. Methods and Materials: The median reirradiation dose was 25.2 Gy (24-30.8 Gy). Fiber tracking was performed using standard tractography analysis. The FA and ADC values for the corticospinal and medial lemniscus tracts were calculated before and after reirradiation. Multivoxel MRS was performed. Findings were correlated with clinical features and conventional MRI of tumors. Results: All patients had an initial response to reirradiation as shown by a decrease in tumor size. In general, FA increased with disease response and decreased with progression, whereas ADC decreased with disease response and increased with progression. At second progression, the FA fold change relative to values during disease response decreased in both patients with available imaging at second progression. Visualization of tracts demonstrated robust reconstitution of previously disrupted paths during tumor response; conversely, there was increased fiber tract disruption and infiltration during tumor progression. The MRS analysis revealed a decrease in choline:creatinine and choline:N-acetylaspartate ratios during tumor response and increase during progression. Conclusions: Distinct changes in white matter tracts and tumor metabolism were observed in patients with DIPG undergoing reirradiation on a prospective clinical trial. Changes related to tumor response and progression were observed after 24 to 30.8 Gy reirradiation.

Different methodologies to deliver craniospinal irradiation (CSI) to patients have been implemented due to the toxicity and planning challenges associated with traditional three-dimensional conformal radiation therapy. Patient outcomes data are needed to assess the feasibility and safety of these methods. We describe the set up and planning methodology used in our clinic to treat adult patients undergoing CSI using volumetric-modulated arc therapy (VMAT). Eight patients treated with CSI using VMAT delivery were reviewed for treatment-associated toxicities and survival. Median follow-up time was 7.5 months (range 1–44 months), and median radiation dose was 36 Gy (range 23.4–36 Gy). The most common acute toxicities experienced were nausea (n = 5, 62.5%), fatigue (n = 4, 50%), and sore throat (n = 3, 37.5%). Grade III toxicities included leukopenia (n = 2, 25%), fatigue (n = 1, 12.5%), anemia (n = 1, 12.5%), and nausea (n = 1, 12.5%). There were no grade IV or V toxicities. Only patients receiving adjuvant chemotherapy (n = 2) had hematologic toxicities (grade II anemia, n = 1; grade III anemia n = 1; grade III leukopenia, n = 2). VMAT radiation delivery is feasible and well tolerated in adult patients receiving CSI. The addition of adjuvant chemotherapy carries an increased risk for hematologic toxicity.

Highlights • No difference in pseudoprogression rate six months after proton or photon therapy. • Oligodendrogliomas develop pseudoprogression sooner after protons vs. photons. • Astrocytomas develop pseudoprogression at similar time after protons vs. photons., Background and purpose Proton therapy is increasingly used to treat primary brain tumors. There is concern for higher rates of pseudoprogression (PsP) after protons compared to photons. The purposes of this study are to compare the rate of PsP after proton vs. photon therapy for grade II and III gliomas and to identify factors associated with the development of PsP. Materials and methods Ninety-nine patients age >18 years with grade II or III glioma treated with photons or protons were retrospectively reviewed. Demographic data, IDH and 1p19q status, and treatment factors were analyzed for association with PsP, progression free survival (PFS), and overall survival (OS). Results Sixty-five patients were treated with photons and 34 with protons. Among those with oligodendroglioma, PsP developed in 6/42 photon-treated patients (14.3%) and 4/25 proton-treated patients (16%, p = 1.00). Among those with astrocytoma, PsP developed in 3/23 photon-treated patients (13%) and 1/9 proton-treated patients (11.1%, p = 1.00). There was no difference in PsP rate based on radiation type, radiation dose, tumor grade, 1p19q codeletion, or IDH status. PsP occurred earlier in oligodendroglioma patients treated with protons compared to photons, 48 days vs. 131 days, p

We previously isolated an IL-11–mimic motif (CGRRAGGSC) that binds to IL-11 receptor (IL-11R) in vitro and accumulates in IL-11R–expressing tumors in vivo . This synthetic peptide ligand was used as a tumor-targeting moiety in the rational design of BMTP-11, which is a drug candidate in clinical trials. Here, we investigated the specificity and accessibility of IL-11R as a target and the efficacy of BMTP-11 as a ligand-targeted drug in lung cancer. We observed high IL-11R expression levels in a large cohort of patients ( n = 368). In matching surgical specimens (i.e., paired tumors and nonmalignant tissues), the cytoplasmic levels of IL-11R in tumor areas were significantly higher than in nonmalignant tissues ( n = 36; P = 0.003). Notably, marked overexpression of IL-11R was observed in both tumor epithelial and vascular endothelial cell membranes ( n = 301; P in vitro cell death in a representative panel of human lung cancer cell lines. BMTP-11 treatment attenuated the growth of subcutaneous xenografts and reduced the number of pulmonary tumors after tail vein injection of human lung cancer cells in mice. Our findings validate BMTP-11 as a pharmacologic candidate drug in preclinical models of lung cancer and patient-derived tumors. Moreover, the high expression level in patients with non-small cell lung cancer is a promising feature for potential translational applications.

The major barriers to the clinical success of orthopedic and dental implants are poor integration of fixtures with bone tissue and biomaterial-associated infections. Although multifunctional device coatings have long been considered a promising strategy, their development is hindered by difficulties in integrating biocompatibility, anti-infective activity and antithrombotic properties within a single grafting agent. In this study, we used cell adhesion assays and confocal microscopy of primary murine osteoblasts and human osteoblast cell lines MG-63 and Saos-2 to demonstrate that a streptococcal collagen-like protein engineered to display the α1 and α2 integrin recognition sequences enhances osteoblast adhesion and spreading on titanium fixtures. By measuring calcium deposition and alkaline phosphatase activity, we also showed that selective activation of α2β1 integrin induces osteoblast differentiation, osteoid formation and mineralization. Moreover, cell adhesion assays and scanning electron microscopy of clinical isolates Staphylococcus aureus Philips and Staphylococcus epidermidis 9491 indicated that streptococcal collagen-mimetic proteins inhibit bacterial colonization and biofilm formation irrespective of their interaction with integrins. Given that streptococcal collagenous substrates neither interact with platelets nor trigger a strong immune response, this novel bioactive coating appears to have desirable multifaceted properties with promising translational applications.