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At least 181 records · Page 10

Neurovestibular Effects of Long-Duration Spaceflight: A Summary of Mir-Phase 1 Experiences

Space motion sickness and associated neurovestibular dysfunction though not completely understood - have been relatively well clinically and operationally characterized on short-duration (1-2 week) Space Shuttle missions (Oman, et al, 1984, 1986; Thornton, et al, 1987; Reschke, et al, 1994). Between March 1995 and June 1998, seven NASA astronauts flew on the Russian Mir space station, as "Phase 1" of the joint effort to build the International Space Station, and provided NASA with invaluable experience on the operational and biomedical problems associated with flights of up to six months in duration. The goal of this paper is to provide a summary of the available information on neurovestibular dysfunction, space motion sickness, and readaptation to Earth's gravity on the NASA Mir flights, based on a set of medical questionnaire data, transcripts, and interviews which are available from the NASA-Mir Phase I program. Records were incomplete and anecdotal. All references to specific crewmembers have been removed, to respect their individual privacy. Material was excerpted from multiple sources of information relating to neurologic function, sensory illusions and motion sickness of NASA-Mir Phase I Program crewmembers. Data were compiled by epoch (in-flight vs landing/postflight) and grouped by neurovestibular topic. The information was recorded either contemporaneously during or within days after landing, or retrospectively weeks to months later. Space motion sickness symptoms are more intense and longer in duration. Sense of spatial orientation takes at least a month to become "natural and instinctive" in space station structures, but mental survey knowledge is apparently not completely developed even after 3 months in some cases. Visual reorientation illusions (VRI) are more easily induced after long exposure to weightlessness. Head movements can cause illusory spinning sensations for up to 7 days postflight. Postural and balance control does not fully recover for at least a month postflight.

Richards, Jason T.↗

A Phase 1 Study of Everolimus + Weekly Cisplatin + Intensity Modulated Radiation Therapy in Head-and-Neck Cancer

Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neck cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A cognitive operating system (COGNOSYS) for JPL's robot, phase 1 report

The most important software requirement for any robot development is the COGNitive Operating SYStem (COGNOSYS). This report describes the Stanford University Artificial Intelligence Laboratory's hand eye software system from the point of view of developing a cognitive operating system for JPL's robot. In this, the Phase 1 of the JPL robot COGNOSYS task the installation of a SAIL compiler and a FAIL assembler on Caltech's PDP-10 have been accomplished and guidelines have been prepared for the implementation of a Stanford University type hand eye software system on JPL-Caltech's computing facility. The alternatives offered by using RAND-USC's PDP-10 Tenex operating sytem are also considered.

Mathur, F. P.↗

Technology Transfer at Edgar Mine: Phase 1; October 2016

The objective of this project is to study the flow of fluid through the fractures and to characterize the efficiency of heat extraction (heat transfer) from the test rock mass in the Edgar Mine, managed by Colorado School of Mines in Idaho Springs, CO. The experiment consists of drilling into the wall of the mine and fracturing the rock, characterizing the size and nature of the fracture network, circulating fluid through the network, and measuring the efficiency of heat extraction from the 'reservoir' by monitoring the temperature of the 'produced' fluid with time. This is a multi-year project performed as a collaboration between the National Renewable Energy Laboratory, Colorado School of Mines and Sandia National Laboratories and carried out in phases. This report summarizes Phase 1: Selection and characterization of the location for the experiment, and outlines the steps for Phase 2: Circulation Experiments.

15 GEOTHERMAL ENERGY↗

Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planning target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Combination of Olaparib and Radiation Therapy for Triple Negative Breast Cancer: Preliminary Results of the RADIOPARP Phase 1 Trial

Preclinical studies have evidenced that triple-negative breast cancer (TNBC) cell lines are more sensitive to poly (ADP-ribose) polymerase inhibitors. This provides a strong rationale for developing a new therapeutic approach for TNBC management based on poly (ADP-ribose) polymerase inhibition. The primary goal of the RADIOPARP phase 1 trial was to evaluate the dose-limiting toxicities (DLT) and the maximum tolerated dose of olaparib combined with locoregional radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Controls-structures interaction guest investigator program: Overview and phase 1 experimental results and future plans

The NASA Controls-Structures Interaction (CSI) Guest Investigator program is described in terms of its support of the development of CSI technologies. The program is based on the introduction of CSI researchers from industry and academia to available test facilities for experimental validation of technologies and methods. Phase 1 experimental results are reviewed with attention given to their use of the Mini-MAST test facility and the facility for the Advance Control Evaluation of Structures. Experiments were conducted regarding the following topics: collocated/noncollocated controllers, nonlinear math modeling, controller design, passive/active suspension systems design, and system identification and fault isolation. The results demonstrate that significantly enhanced performance from the control techniques can be achieved by integrating knowledge of the structural dynamics under consideration into the approaches.

Smith-Taylor, Rudeen↗

Phase 1 Study of Dose Escalation in Hypofractionated Proton Beam Therapy for Non-Small Cell Lung Cancer

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectiveness [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Long-Term Update of NRG Oncology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3-Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy Cavity for Stage I and II Breast Carcinoma

Purpose: NRG Oncology RTOG 0319 was the first cooperative group trial in the United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT) accelerated partial breast irradiation (APBI). This report updates secondary endpoints of toxicity and efficacy. Methods and Materials: Patients with stage I or II invasive breast cancer (tumor size ≤3 cm, ≤3 positive lymph nodes, negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily fractions. Patient characteristics and treatment details have previously been reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0). This analysis updates the rates of ipsilateral breast recurrence (IBR), contralateral breast recurrence, ipsilateral node recurrence (INR), metastatic sites (distant metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival, and overall survival. Results: Of 58 enrolled patients, 52 were eligible, with a median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7-9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and 7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within the planning target volume. The patterns of failure were as follows: 3 IBRs, 1 INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of mastectomy-free survival, disease-free survival, and overall survival were 71.2%, 71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10 of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4 patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported. Conclusions: This phase 1 and 2 trial of 3D-CRT APBI continues to show durable tumor control and minimal G3 toxicity, comparable to other APBI techniques. Mature phase 3 results will determine the appropriateness and limitations of this noninvasive APBI technique.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Large deployable antenna program. Phase 1: Technology assessment and mission architecture

The program was initiated to investigate the availability of critical large deployable antenna technologies which would enable microwave remote sensing missions from geostationary orbits as required for Mission to Planet Earth. Program goals for the large antenna were: 40-meter diameter, offset-fed paraboloid, and surface precision of 0.1 mm rms. Phase 1 goals were: to review the state-of-the-art for large, precise, wide-scanning radiometers up to 60 GHz; to assess critical technologies necessary for selected concepts; to develop mission architecture for these concepts; and to evaluate generic technologies to support the large deployable reflectors necessary for these missions. Selected results of the study show that deployable reflectors using furlable segments are limited by surface precision goals to 12 meters in diameter, current launch vehicles can place in geostationary only a 20-meter class antenna, and conceptual designs using stiff reflectors are possible with areal densities of 2.4 deg/sq m.

Rogers, Craig A.↗

Chemoradiation of Hepatic Malignancies: Prospective, Phase 1 Study of Full-Dose Capecitabine With Escalating Doses of Yttrium-90 Radioembolization

Purpose: Radiosensitizing chemotherapy improves the outcomes in comparison with radiation alone for gastrointestinal cancers. The delivery of radiation therapy with yttrium90 ({sup 90}Y) radioembolization, in combination with the radiosensitizing chemotherapeutic agent capecitabine, provides the opportunity to enhance the effects of radiation on hepatic malignancies. This phase 1 study sought to determine the maximum tolerated dose (MTD) of {sup 90}Y plus capecitabine in patients with cholangiocarcinoma or liver metastases confined to the liver. Methods and Materials: Patients were given initial treatment at full-dose capecitabine during days 1 to 14 of a 21-day cycle. At days 1 to 7 of the second cycle, whole-liver {sup 90}Y was given at the test dose, after which time capecitabine was continued. Dose-limiting toxicity (DLT) was determined 6 weeks after {sup 90}Y infusion. If a DLT was not observed, the {sup 90}Y dose was escalated. The planned dose cohorts were 110, 130, 150, and 170 Gy. The primary endpoint was to determine the MTD of {sup 90}Y with full-dose capecitabine. Results: Sixteen patients were treated according to the study protocol. Two patients experienced DLTs. Nine patients required capecitabine dose reduction as a result of toxicities attributable to capecitabine alone. The criteria for establishing {sup 90}Y MTD were not met, indicating an MTD of >170 Gy. Conclusion: The MTD of {sup 90}Y delivered in conjunction with capecitabine in the setting of intrahepatic cholangiocarcinoma or metastatic disease confined to the liver exceeds 170 Gy. This is the highest {sup 90}Y dose reported to date and has important implications on combined therapy with the radiosensitizing oral chemotherapeutic capecitabine. Further studies are under way.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Phase 1 results from the Stirling-powered vehicle project

The NASA Technology Utilization (TU) Office is sponsoring a multiyear, multiphase demonstration program to assess the technology developed under the DOE/NASA automotive Stirling engine (ASE) program with engines installed in various Air Force vehicles while being evaluated by independent third parties under realistic conditions. This paper reviews the operational history of Phase 1 with a Mod 1 Stirling engine installed in an Air Force multistop van in a variety of missions. Ten months of operation were with Air Force personnel at Langley Air Force Base, Virginia, where over 1100 hr and 4000 mi were logged on the Langley flight line. The Stirling-powered van operated on unleaded gasoline, JP-4 aircraft fuel, and diesel fuel at Langley Air Force Base. Two months of operation were completed with Deere and Company personnel in the Moline, Illinois area where over 175 hr and 2650 mi were logged on a Deere mail delivery route.

Shaltens, Richard K.↗

Requirements and concept for an on-orbit construction facility for phase 1 Space Station Freedom

A construction facility attached to NASA's Space Station Freedom (SSF) will be required for the accommodation of assembly activities for large payloads, as well as demonstration of the on-orbit construction of future spacecraft. This facility's capabilities must be sufficiently flexible to address the wide variety of future spacecraft needs without compromising the SSF's phase 1 configuration. The proposed construction facility concept will incorporate a storage module, a construction turntable, equipment-attachment platforms, a surrogate payload bay structure, and a portable workstation. Attention is given to this configuration's resulting mass properties and control characteristics.

Buchan, Robert W.↗

A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial

Purpose: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. Methods and Materials: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. Results: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. Conclusions: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Space-Shielding Radiation Dosage Code Evaluation - Phase 1: SHIELDOSE-2 Radiation-Assessment Code

Radiation-transport codes or radiation-analysis tools are used in the spacecraft-design community to define and assess the local radiation levels. Among various radiation-transport/analysis tools available, SHIELDOSE-2 is commonly used in the early spacecraft-design phases because it has been established that it provides reasonably reliable results with relatively rapid computation time. The NASA Engineering and Safety Center initiated a two-phased study: (1) to better understand and document the SHIELDOSE-2 code capabilities and limitations, and (2) to recommend alternative tools to use for cases where SHIELDOSE-2 is not applicable. This report provides a summary of the Phase 1 study.

SHIELDOSE-2↗

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.

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