Radiolucent Loading Device for Computed Tomography Imaging

There is a limited availability of portable compressional loading devices, none of which work within a computed tomography (CT) scanner. This is due to the lack of radiolucent materials these devices are made of, which make artifacts that disrupt the final CT image. Combining both testing and imaging can advance understanding of how materials behave at a microstructural level. This paper describes the design and fabrication of a novel device that can be used within a CT scanner to collect images of compressed bone samples. Validation testing showed that specimens could be compressed up to 2000 Newtons of force over 26 millimeters of displacement within 8 Newtons and 0.071 millimeters of accuracy

ELEMENTARY SCHOOL STEM EDUCATION

Educating young students in the engineering field helps to increase their ability to analyze problems and develop critical skills early in life. The goal of this project is to utilize Tufts Universitys Novel Engineering Program in the first grade classrooms at John F. Kennedy Elementary School in Jamaica Plain in order to engage students in STEM programs at an early age. We will aim to break down barriers within the classroom and have useful tools that the teachers can use in the future for the students

iPS Cells as a potential replacement for ES Cells

The purpose of this project was to investigate whether induced pluripotent stem cells (iPSCs) can potentially replace the more controversial embryonic stem cells (ESCs) in therapies. A literature review was performed followed by interviews with key stakeholders in the stem cell field. Our findings indicate that several potential problems exist with iPSCs before they can be used in human therapies, including their slow expansion, the potential for cancer, and the potential for immune-rejection of the injected cells. We identified several best-practice procedures for overcoming each of these problems, but conclude that more studies should be performed directly comparing the effectiveness of iPSCs versus ESCs for specific therapies

Objective response rate targets for recurrent glioblastoma clinical trials based on the historic association between objective response rate and median overall survival

Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P &lt; .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P &lt; .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P &lt; .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR&gt;25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P &lt; .01) and adequate power (&gt;80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR &gt;25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study.</p

ATIM-14. ALLIANCE A071101: A&nbsp;PHASE II RANDOMIZED TRIAL COMPARING THE EFFICACY OF HEAT SHOCK PROTEIN PEPTIDE COMPLEX-96 (HSPPC-96) VACCINE GIVEN WITH BEVACIZUMAB VERSUS BEVACIZUMAB ALONE IN THE TREATMENT OF SURGICALLY RESECTABLE RECURRENT GLIOBLASTOMA

Abstract BACKGROUND Heat shock protein vaccines can be used to stimulate anti-tumor immune responses. An autologous vaccine (HSPPC-96) generated from patient resected tumors has been previously studied in single arm phase I/II trials for newly diagnosed and recurrent GBM. Based on promising survival in these studies, a randomized, multi-centered phase II trial of HSPPC-96 for recurrent GBM compared to bevacizumab was undertaken (NCT01814813). METHODS Patients with 1st/2nd recurrence of resectable GBM were enrolled and underwent surgery with generation of HSPPC-96 from autologous tumors. Post-operative eligibility included a volumetric extent of resection ≥90% (by central review) and sufficient tumor to generate a minimum of 4 vaccine doses. Patients were randomized (1:1:1) to receive HSPPC-96 vaccine followed by bevacizumab at subsequent progression vs. concurrent HSPPC-96 vaccine and bevacizumab vs. bevacizumab alone. The primary endpoint was overall survival (OS) aiming to detect a 36% reduction in HR with 85% power and alpha=0.1 for pooled HSPPC-96 groups vs. bevacizumab alone. Planned enrollment was 165 patients (n=55/arm). An interim analysis was pre-planned at 50% of events (65 deaths). Secondary endpoints included progression-free survival and adverse events. RESULTS At final analysis, 90 patients were enrolled with a distribution of 29:30:31. The study was terminated for futility after the interim analysis. In the intention to treat population, OS for the HSPPC-96 treated groups was 7.5 vs. 10.7&nbsp;months for bevacizumab alone (HR=2.06 [95% CI 1.18–3.60], p=0.008). Among patients treated per protocol (n=73), OS for HSPPC-96 patients was 8.6 vs. 12.3&nbsp;months (HR=1.99 [95% CI 1.03–3.81], p=0.03). Trends were similar for progression-free survival between groups. HSPPC-96 toxicity was well tolerated with no attributable serious adverse events. CONCLUSIONS The study failed to demonstrate a survival benefit for patients treated with HSPPC-96 alone or in combination with bevacizumab compared to bevacizumab alone. Correlative analyses are ongoing. SUPPORT: U10CA180882, U10CA180821, U10CA180868, U24CA196171

Objective response rate targets for recurrent glioblastoma clinical trials based on the historic association between objective response rate and median overall survival

Durable objective response rate (ORR) remains a meaningful endpoint in recurrent cancer; however, the target ORR for single-arm recurrent glioblastoma trials has not been based on historic information or tied to patient outcomes. The current study reviewed 68 treatment arms comprising 4793 patients in past trials in recurrent glioblastoma in order to judiciously define target ORRs for use in recurrent glioblastoma trials. ORR was estimated at 6.1% [95% CI 4.23; 8.76%] for cytotoxic chemothera + pies (ORR = 7.59% for lomustine, 7.57% for temozolomide, 0.64% for irinotecan, and 5.32% for other agents), 3.37% for biologic agents, 7.97% for (select) immunotherapies, and 26.8% for anti-angiogenic agents. ORRs were significantly correlated with median overall survival (mOS) across chemotherapy (R2= 0.4078, P &lt; .0001), biologics (R2= 0.4003, P = .0003), and immunotherapy trials (R2= 0.8994, P &lt; .0001), but not anti-angiogenic agents (R2= 0, P = .8937). Pooling data from chemotherapy, biologics, and immunotherapy trials, a meta-analysis indicated a strong correlation between ORR and mOS (R2= 0.3900, P &lt; .0001; mOS [weeks] = 1.4xORR + 24.8). Assuming an ineffective cytotoxic (control) therapy has ORR = 7.6%, the average ORR for lomustine and temozolomide trials, a sample size of ≥40 patients with target ORR&gt;25% is needed to demonstrate statistical significance compared to control with a high level of confidence (P &lt; .01) and adequate power (&gt;80%). Given this historic data and potential biases in patient selection, we recommend that well-controlled, single-arm phase II studies in recurrent glioblastoma should have a target ORR &gt;25% (which translates to a median OS of approximately 15 months) and a sample size of ≥40 patients, in order to convincingly demonstrate antitumor activity. Crucially, this response needs to have sufficient durability, which was not addressed in the current study

Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group.

Currently, the most widely used criteria for assessing response to therapy in high-grade gliomas are based on two-dimensional tumor measurements on computed tomography (CT) or magnetic resonance imaging (MRI), in conjunction with clinical assessment and corticosteroid dose (the Macdonald Criteria). It is increasingly apparent that there are significant limitations to these criteria, which only address the contrast-enhancing component of the tumor. For example, chemoradiotherapy for newly diagnosed glioblastomas results in transient increase in tumor enhancement (pseudoprogression) in 20% to 30% of patients, which is difficult to differentiate from true tumor progression. Antiangiogenic agents produce high radiographic response rates, as defined by a rapid decrease in contrast enhancement on CT/MRI that occurs within days of initiation of treatment and that is partly a result of reduced vascular permeability to contrast agents rather than a true antitumor effect. In addition, a subset of patients treated with antiangiogenic agents develop tumor recurrence characterized by an increase in the nonenhancing component depicted on T2-weighted/fluid-attenuated inversion recovery sequences. The recognition that contrast enhancement is nonspecific and may not always be a true surrogate of tumor response and the need to account for the nonenhancing component of the tumor mandate that new criteria be developed and validated to permit accurate assessment of the efficacy of novel therapies. The Response Assessment in Neuro-Oncology Working Group is an international effort to develop new standardized response criteria for clinical trials in brain tumors. In this proposal, we present the recommendations for updated response criteria for high-grade gliomas

RANO 2.0:Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults

PURPOSE: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria. METHODS: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.0). RESULTS: We recommend a standard set of criteria for both high- and low-grade gliomas, to be used for all trials regardless of the treatment modalities being evaluated. In the newly diagnosed setting, the postradiotherapy magnetic resonance imaging (MRI), rather than the postsurgical MRI, will be used as the baseline for comparison with subsequent scans. Since the incidence of pseudoprogression is high in the 12 weeks after radiotherapy, continuation of treatment and confirmation of progression during this period with a repeat MRI, or histopathologic evidence of unequivocal recurrent tumor, are required to define tumor progression. However, confirmation scans are not mandatory after this period nor for the evaluation of treatment for recurrent tumors. For treatments with a high likelihood of pseudoprogression, mandatory confirmation of progression with a repeat MRI is highly recommended. The primary measurement remains the maximum cross-sectional area of tumor (two-dimensional) but volumetric measurements are an option. For IDH wild-type glioblastoma, the nonenhancing disease will no longer be evaluated except when assessing response to antiangiogenic agents. In IDH-mutated tumors with a significant nonenhancing component, clinical trials may require evaluating both the enhancing and nonenhancing tumor components for response assessment. CONCLUSION: The revised RANO 2.0 criteria refine response assessment in gliomas.</p

Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.

Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research