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At least 145 records · Page 8

Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study

Purpose: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). Patients and Methods: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m{sup 2} during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. Results: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6-inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non-codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m{sup 2}/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. Conclusions: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor-prognosis patient subgroups with HGG.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial

Purpose: To determine the maximum tolerated dose (MTD) of vorinostat, a histone deacetylase inhibitor, given concurrently with stereotactic radiosurgery (SRS) to treat non-small cell lung cancer (NSCLC) brain metastases. Secondary objectives were to determine toxicity, local failure, distant intracranial failure, and overall survival rates. Materials and Methods: In this multicenter study, patients with 1 to 4 NSCLC brain metastases, each ≤2 cm, were enrolled in a phase 1, 3 + 3 dose escalation trial. Vorinostat dose levels were 200, 300, and 400 mg orally once daily for 14 days. Single-fraction SRS was delivered on day 3. A dose-limiting toxicity (DLT) was defined as any Common Terminology Criteria for Adverse Events version 3.0 grade 3 to 5 acute nonhematologic adverse event related to vorinostat or SRS occurring within 30 days. Results: From 2009 to 2014, 17 patients were enrolled and 12 patients completed study treatment. Because no DLTs were observed, the MTD was established as 400 mg. Acute adverse events were reported by 10 patients (59%). Five patients discontinued vorinostat early and withdrew from the study. The most common reasons for withdrawal were dyspnea (n=2), nausea (n=1), and fatigue (n=2). With a median follow-up of 12 months (range, 1-64 months), Kaplan-Meier overall survival was 13 months. There were no local failures. One patient (8%) at the 400-mg dose level with a 2.0-cm metastasis developed histologically confirmed grade 4 radiation necrosis 2 months after SRS. Conclusions: The MTD of vorinostat with concurrent SRS was established as 400 mg. Although no DLTs were observed, 5 patients withdrew before completing the treatment course, a result that emphasizes the need for supportive care during vorinostat administration. There were no local failures. A larger, randomized trial may evaluate both the tolerability and potential local control benefit of vorinostat concurrent with SRS for brain metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Commissioning of Phase 1 of the LANL RFQ Test Stand - Beam Characterization

A series of numerical start-to-end simulations of Phase 1 of the 750 keV RFQ Test Stand which includes the ion source (H+ duoplasmatron), a 1-Solenoid LEBT, an emittance scan station and a Faraday cup were performed to find a mechanism for the characterization of the proton beam extracted from the duoplasmatron.

43 PARTICLE ACCELERATORS↗

NASA's UAS Integration into the NAS: A Report on the Human Systems Integration Phase 1 Activities

This presentation summarizes the technical activities undertaken by the UAS in the NAS project's Human-Systems Integration team during during it's first phase. The technical activites are discussed in terms of the project's stated mission, research themes and technical challenges. The talk also covers the simulation research that has been performed by the HSI in Phase 1. The end of the presentation lays out the group's plans for Phase 2.

Fern, Lisa↗

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01)

Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC).

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study

Purpose: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). Methods and Materials: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. Results: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. Conclusions: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase 1 Study of Ipilimumab Combined With Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients With Brain Metastases

Purpose: We performed a phase 1 study to determine the maximum tolerable dose and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) in patients with brain metastases from melanoma. Methods and Materials: Based on the intracranial disease burden, patients underwent WBRT (arm A) or SRS (arm B). The ipilimumab starting dose was 3 mg/kg every 3 weeks, starting on day 3 of WBRT or 2 days after SRS. The ipilimumab dose was escalated to 10 mg/kg using a 2-stage, 3+3 design. The primary endpoint was to determine the maximum tolerable dose of ipilimumab combined with radiation therapy. The secondary endpoints were overall survival, intracranial and extracranial control, progression-free survival, and toxicity. The (ClinicalTrials.gov) registration number is (NCT01703507). Results: The characteristics of the 16 patients enrolled between 2011 and 2014 were mean age, 60 years; median number of brain metastases, 2 (range 1->10); and number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), and ipilimumab 3 mg/kg (n=7) or 10 mg/kg (n=9). The median follow-up was 8 months (arm A) and 10.5 months (arm B). A total of 21 grade 1 to 2 neurotoxic effects occurred, with no dose-limiting toxicities. One patient experienced grade 3 neurotoxicity before ipilimumab administration. Ten additional grade 3 toxicities were reported, with gastrointestinal toxicities (n=5; 31%) the most common. No patient developed grade 4 or 5 toxicity. The median progression-free survival and overall survival in arm A was 2.5 months and 8 months and in arm B was 2.1 months and not reached, respectively. Conclusions: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early because of slow accrual but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced dose-limiting toxicity. Larger studies, including those with combination checkpoint inhibitor therapy and SRS, are warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

NAR/NASA CSM 101 Delta critical design review phase 1

The supplemental CSM 101 Delta Critical Design Review (CDR), as associated with the Block II redefinition changes, will be conducted in two phases. Phase 1 is a software review of the drawings, SCN's, and other appropriate documentation. A mockup review of the crew interfaces (only) related to the redefinition changes will follow the software review.

E. M. Clauser↗

ATD-2 Phase 1 New Features Training

This document is a compilation of the New Releases/New Features training materials accompanying various software releases during ATD-2 Phase 1.

training↗

Phase 1 Final Report: Titan Submarine

The conceptual design of a submarine for Saturn's moon Titan was a funded NASA Innovative Advanced Concepts (NIAC) Phase 1 for 2014. The proposal stated the desire to investigate what science a submarine for Titan's liquid hydrocarbon seas might accomplish and what that submarine might look like. Focusing on a flagship class science system (100 kg), it was found that a submersible platform can accomplish extensive science both above and below the surface of the Kraken Mare. Submerged science includes mapping using side-looking sonar, imaging and spectroscopy of the lake, as well as sampling of the lake's bottom and shallow shoreline. While surfaced, the submarine will not only sense weather conditions (including the interaction between the liquid and atmosphere) but also image the shoreline, as much as 2 km inland. This imaging requirement pushed the landing date to Titan's next summer period (2047) to allow for lighted conditions, as well as direct-to-Earth communication, avoiding the need for a separate relay orbiter spacecraft. Submerged and surfaced investigation are key to understanding both the hydrological cycle of Titan as well as gather hints to how life may have begun on Earth using liquid, sediment, and chemical interactions. An estimated 25 Mb of data per day would be generated by the various science packages. Most of the science packages (electronics at least) can be safely kept inside the submarine pressure vessel and warmed by the isotope power system.The baseline 90-day mission would be to sail submerged and surfaced around and through Kraken Mare investigating the shoreline and inlets to evaluate the sedimentary interaction both on the surface and then below. Depths of Kraken have yet to be sensed (Ligeia to the north is thought to be 200 m (656 ft) deep), but a maximum depth of 1,000 m (3,281 ft) for Kraken Mare was assumed for the design). The sub would spend 20 d at the interface between Kraken Mare and Ligeia Mare for clues to the drainage of liquid methane into the currently predicted predominantly ethane Kraken Mare. During an extended ninety-day mission, it would transit the throat of Kraken (now Seldon Fretum) and perform similar explorations in other areas of Kraken Mare. Once this half year of exploration is completed the submarine could be tasked to revisit points of interest and perhaps do a complete sonar mapping of the seas. All in all, the submarine could explore over 3,000 km (1,864 mi) in its primary mission at an average speed of 0.3 meters per second.

Titan↗

Hubble Space Telescope cycle 5. Phase 1: Proposal instructions, version 4.0

This document has the following purposes: it describes the information that must be submitted to the Space Telescope Science Institute by Phase 1 proposers, both electronically and on paper, and describes how to submit it; it describes how to fill out the proposal LATEX templates; it describes how to estimate the number of spacecraft orbits that the proposed observations will require; it provides detailed information about the parameters that are used in the forms to describe the requested observations; and it provides information about the preparation and electronic submission of proposal files. Examples of completed proposal forms are included.

Madau, Piero↗

Phase 1 Free Air CO2 Enrichment Model-Data Synthesis (FACE-MDS): Meteorological Data

These datasets comprise the meteorological, CO2 and N deposition data used to run models for the Duke and Oak Ridge FACE experiments. Phase 1 datasets are reproduced here for posterity and reproducibility although these meteorological datasets are superseded by the Phase 2 datasets. If you would like to use the meteorological datasets to run your own model or for any other purpose please use the Phase 2 datasets.

54 ENVIRONMENTAL SCIENCES↗