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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2012

Long-Term Outcome of Transcatheter Subsegmental and Segmental Arterial Chemoemobolization Using Lipiodol for Hepatocellular Carcinoma

Purpose: To clarify the efficacy of transcatheter hepatic sub-subsegmental, subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who had been treated using subseg/seg lip-TACE alone were retrospectively examined. Materials and Methods: Subjects comprised 199 patients with HCC (T1/2/{>=}3 = 30/108/61; Child-Pugh A/B/C = 115/52/32; Japan Integrated Staging [JIS] score {<=}1/2/{>=}3 = 88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed with an anticancer drug followed by injection of gelatin sponge particles. Each patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7-, and 10-year cumulative survival rates were calculated. Subgroup analyses were performed by stratifying the population according to T-factor, Child-Pugh classification, and JIS score. Results: Median duration of follow-up was 3.8 years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7- and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS {<=}1, respectively. Significant survival differences were found across two subgroups of staging systems (T2 vs. T3{<=} [P = 0.0012] and JIS score {<=}1 vs. 2 [P = 0.0036]). Conclusion: This study demonstrated that subseg/seg lip-TACE is a feasible treatment for obtaining prolonged survival in patients with localized HCC showing rich vasculature. Outcomes are influenced by both tumor stage and liver function, as seen in the best prolonged survival in patients with JIS score {<=}1.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: >Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. >Atorvastatin administration: >Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. >Reduced the expression of phospho-I{kappa}B >Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

'In vivo' Dose Measurements in High-Dose-Rate Brachytherapy Treatments for Cervical Cancer: A Project Proposal

The aim of this thesis project is to compare doses calculated from the treatment planning system using computed tomography images, with those measured 'in vivo' by using thermoluminescent dosimeters placed at different regions of the rectum and bladder of a patient during high-dose-rate intracavitary brachytherapy treatment of uterine cervical carcinoma. The experimental dosimeters characterisation and calibration have concluded and the protocol to carry out the 'in vivo' measurements has been established. In this work, the calibration curves of two types of thermoluminescent dosimeters (rods and chips) are presented, and the proposed protocol to measure the 'in vivo' dose is fully described.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prevalence and Treatment Management of Oropharyngeal Candidiasis in Cancer Patients: Results of the French Candidoscope Study

Purpose: The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy. Methods and Materials: Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment. Results: Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%-11.0%]in this population. It was most frequent in patients treated with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%). Conclusion: OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice

Microcystins (MCs), the products of blooming algae Microcystis, are waterborne environmental toxins that have been implicated in the development of liver cancer, necrosis, and even fatal intrahepatic bleeding. Alternative protective approaches in addition to complete removal of MCs in drinking water are urgently needed. In our previous work, we found that sulforaphane (SFN) protects against microcystin-LR (MC-LR)-induced cytotoxicity by activating the NF-E2-related factor 2 (Nrf2)-mediated defensive response in human hepatoma (HepG2) and NIH 3T3 cells. The purpose of this study was to investigate and confirm efficacy the SFN-induced multi-mechanistic defense system against MC-induced hepatotoxicity in an animal model. We report that SFN protected against MC-LR-induced liver damage and animal death at a nontoxic and physiologically relevant dose in BALB/c mice. The protection by SFN included activities of anti-cytochrome P450 induction, anti-oxidation, anti-inflammation, and anti-apoptosis. Our results suggest that SFN may protect mice against MC-induced hepatotoxicity. This raises the possibility of a similar protective effect in human populations, particularly in developing countries where freshwaters are polluted by blooming algae. - Graphical abstract: Display Omitted Research Highlights: > SFN protected against MC-LR-induced liver damage and animal death in BALB/c mice. > The dose of SFN is at a nontoxic and physiologically relevant dose. > The protection included activities of anti-oxidation, anti-inflammation, and anti-apoptosis. > SFN may protect mice against MC-induced hepatotoxicity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Induction of Fas receptor and Fas ligand by nodularin is mediated by NF-{kappa}B in HepG2 cells

Nodularin is a natural toxin with multiple features, including inhibitor of protein phosphatases 1 and 2A as well as tumor initiator and promoter. One unique feature of nodularin is that this chemical is a hepatotoxin. It can accumulate into the liver after contact and lead to severe damage to hepatocyte, such as apoptosis. Fas receptor (Fas) and Fas ligand (FasL) system is a critical signaling network triggering apoptosis. In current study, we investigated whether nodularin can induce Fas and FasL expression in HepG2 cell, a well used in vitro model for the study of human hepatocytes. Our data showed nodularin induced Fas and FasL expression, at both mRNA and protein level, in a time- and dose-dependent manner. We also found nodularin induced apoptosis at the concentration and incubation time that Fas and FasL were significantly induced. Neutralizing antibody to FasL reduced nodularin-induced apoptosis. Further studies demonstrated that nodularin promoted nuclear translocation and activation of p65 subunit of NF-{kappa}B. By applying siRNA targeting p65, which knocked down p65 in HepG2 cells, we successfully impaired the activation of NF-{kappa}B by nodularin. In these p65 knockdown cells, we observed that Fas and FasL expression and apoptosis induced by nodularin were significantly reduced. These findings suggest the induction of Fas and FasL expression and thus cell apoptosis in HepG2 cells by nodularin is mediated through NF-{kappa}B pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Dosimetric Comparison of Intensity-Modulated Stereotactic Radiotherapy With Other Stereotactic Techniques for Locally Recurrent Nasopharyngeal Carcinoma

Purpose: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Methods and Materials: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrieved from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. Results: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Conclusion: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Effect of Breathing Motion on Radiotherapy Dose Accumulation in the Abdomen Using Deformable Registration

Purpose: To investigate the effect of breathing motion and dose accumulation on the planned radiotherapy dose to liver tumors and normal tissues using deformable image registration. Methods and Materials: Twenty-one free-breathing stereotactic liver cancer radiotherapy patients, planned on static exhale computed tomography (CT) for 27-60 Gy in six fractions, were included. A biomechanical model-based deformable image registration algorithm retrospectively deformed each exhale CT to inhale CT. This deformation map was combined with exhale and inhale dose grids from the treatment planning system to accumulate dose over the breathing cycle. Accumulation was also investigated using a simple rigid liver-to-liver registration. Changes to tumor and normal tissue dose were quantified. Results: Relative to static plans, mean dose change (range) after deformable dose accumulation (as % of prescription dose) was -1 (-14 to 8) to minimum tumor, -4 (-15 to 0) to maximum bowel, -4 (-25 to 1) to maximum duodenum, 2 (-1 to 9) to maximum esophagus, -2 (-13 to 4) to maximum stomach, 0 (-3 to 4) to mean liver, and -1 (-5 to 1) and -2 (-7 to 1) to mean left and right kidneys. Compared to deformable registration, rigid modeling had changes up to 8% to minimum tumor and 7% to maximum normal tissues. Conclusion: Deformable registration and dose accumulation revealed potentially significant dose changes to either a tumor or normal tissue in the majority of cases as a result of breathing motion. These changes may not be accurately accounted for with rigid motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Impacts of Multileaf Collimators Leaf Width on Intensity-Modulated Radiotherapy Planning for Nasopharyngeal Carcinoma: Analysis of Two Commercial Elekta Devices

We compared the impacts of multileaf collimator (MLC) widths (standard MLC width of 10 mm [SMLC] and micro-MLC width of 4 mm [MMLC]) on intensity-modulated radiotherapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Ten patients with NPC were recruited in this study. In each patient's case, plans were generated with the same machine setup parameter and optimizing methods in a treatment planning system according to 2 commercial Elekta MLC devices. All of the parameters were collected from dose-volume histograms of paired plans and evaluated. The average conformity index (CI) and homogeneous index (HI) for the planning gross target volume in IMRT plans with MMLC were 0.790 {+-} 0.036 and 1.062 {+-} 0.011, respectively. Data in plans with SMLC were 0.754 {+-} 0.038 and 1.070 {+-} 0.010, respectively. The differences were statistically significant (p < 0.05). Compared with CI and HI for planning target volume in paired plans, data with MMLC obviously were better than those with SMLC (CI: 0.858 {+-} 0.026 vs. 0.850 {+-} 0.021, p < 0.05; and HI: 1.185 {+-} 0.011 vs. 1.195 {+-} 0.011, p < 0.05). However, there was no statistical significance between evaluated parameters (Dmean, Dmax, D{sub 5}, gEUD, or NTCP) for organs at risk (OARs) in the 2 paired IMRT plans. According to these two kinds of Elekta MLC devices, IMRT plans with the MMLC have significant advantages in dose coverage for the targets, with more efficiency in treatment for NPC but fail to improve dose sparing of the OARs.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2017

Fluorescence-labeled liposome accumulation in injured colon of a mouse model of T-cell transfer-mediated inflammatory bowel disease

Drug delivery systems maximize the efficacy of drugs by improving their pharmacokinetic profiles, pharmacodynamic effects, or both and reducing their adverse effects. One of the most advanced, clinically available formulations are liposome-encapsulated drugs. In this study, we aimed to determine if liposomes can selectively deliver compounds in gastrointestinal diseases. Initially, we evaluated the correlation between the diarrhea score and accumulation of fluorescence (FL)-labeled liposome using in vivo imaging systems in various disease states of an inflammatory bowel disease mouse model. The result showed that FL-labeled liposome accumulation and colon tissue weight, which reflect the disease state were highly and positively correlated. Then, to confirm the accumulation of liposomes at injured sites of the colon, we administered both FL-labeled liposomes and luminescence probes for detecting reactive oxygen species (ROS) to the mouse model. The imaging data showed that liposome accumulation tended to coincide with ROS detected sites and the correlation coefficient indicated a significantly positive correlation between liposome accumulation and ROS detection levels. Finally, we evaluated the involvement of macrophages in the uptake mechanism of the liposomes by analyzing the relationship between FL-labeled liposome accumulation and macrophage marker gene expression levels. The result showed that the expression of each macrophage marker gene and liposome accumulation showed a significant positive correlation. Therefore, the macrophages considerably contributed to the uptake mechanism of the liposomes. These data suggest that liposomes could be an attractive delivery tool for enhancing the accumulation of drug candidates through macrophages in injured colonic tissues. This approach is expected to provide new treatment options for patients with colitis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Direct Current Combined With Bipolar Radiofrequency Ablation: An Ex Vivo Feasibility Study

The combination of radiofrequency ablation (RFA) with direct current (DC) is a promising strategy to improve the efficiency of RFA. However, DC-enhanced monopolar RFA is limited by electrolytic injury at the positive-electrode site. The aim of this study was to investigate the feasibility of the DC-enhanced bipolar RFA. To obviate the need for the subcutaneous positive electrode, the DC circuit was combined with a commercially available bipolar RFA system, in which both poles of the DC circuit are connected to a single RF probe. DC was applied for 15 min and followed by RFA in bovine livers using the following various DC currents: (1) no DC (control), (2) 3V continued until the end of RFA, (3) 5V continued until the end of RFA, (4) 10V continued until the end of RFA, (5) 5V continued in the circuit with reversed pole, (6) 3V stopped after initiation of RFA, and (7) 5V stopped. Coagulation volume, temperatures at a distance of 5, 10, and 15 mm from the RF probe, mean amperage, ablation duration, applied energy, minimum impedance, and degree of tissue charring were assessed and compared (analysis of variance, Student-Newman-Keuls test). All combined DC and RFA groups did increase coagulation volume. The 10V continued group showed significantly lower applied energy, shortest ablation duration, highest minimum impedance, and highest degree of charring with the lowest coagulation volume (p < 0.05). DC-enhanced bipolar RFA with both poles of the DC circuit on a single probe appears to be ineffective.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Identification of characteristic molecular signature for volatile organic compounds in peripheral blood of rat

In a previous report we demonstrated that the transcriptomic response of liver tissue was specific to toxicants, and a characteristic molecular signature could be used as an early prognostic biomarker in rats. It is necessary to determine the transcriptomic response to toxicants in peripheral blood for application to the human system. Volatile organic compounds (VOCs) comprise a major group of pollutants which significantly affect the chemistry of the atmosphere and human health. In this study we identified and validated the specific molecular signatures of toxicants in rat whole blood as early predictors of environmental toxicants. VOCs (dichloromethane, ethylbenzene, and trichloroethylene) were administered to 11-week-old SD male rats after 48 h of exposure, peripheral whole blood was subjected to expression profiling analysis. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant, and supervised analysis identified 1,217 outlier genes as distinct molecular signatures discerning VOC exposure from healthy controls. Further analysis of multi-classification suggested 337 genes as early detective molecular markers for three VOCs with 100% accuracy. A large-scale gene expression analysis of a different VOC exposure animal model suggested that characteristic expression profiles exist in blood cells and multi-classification of this VOC-specific molecular signature can discriminate each toxicant at an early exposure time. This blood expression signature can thus be used as discernable surrogate marker for detection of biological responses to VOC exposure in an environment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Clinical Outcomes of Intensity-Modulated Pelvic Radiation Therapy for Carcinoma of the Cervix

Purpose: To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). Methods and Materials: We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. Results: The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. Conclusions: Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Intensity-Modulated Radiotherapy for Oral Cavity Squamous Cell Carcinoma: Patterns of Failure and Predictors of Local Control

Purpose: Few studies have evaluated the use of intensity-modulated radiotherapy (IMRT) for squamous cell carcinoma (SCC) of the oral cavity (OC). We report clinical outcomes and failure patterns for these patients. Methods and Materials: Between October 2002 and June 2009, 37 patients with newly diagnosed SCC of the OC underwent postoperative (30) or definitive (7) IMRT. Twenty-five patients (66%) received systemic therapy. The median follow-up was 38 months (range, 10-87 months). The median interval from surgery to RT was 5.9 weeks (range, 2.1-10.7 weeks). Results: Thirteen patients experienced local-regional failure at a median of 8.1 months (range, 2.4-31.9 months), and 2 additional patients experienced local recurrence between surgery and RT. Seven local failures occurred in-field (one with simultaneous nodal and distant disease) and two at the margin. Four regional failures occurred, two in-field and two out-of-field, one with synchronous metastases. Six patients experienced distant failure. The 3-year actuarial estimates of local control, local-regional control, freedom from distant metastasis, and overall survival were 67%, 53%, 81%, and 60% among postoperative patients, respectively, and 60%, 60%, 71%, and 57% among definitive patients. Four patients developed Grade {>=}2 chronic toxicity. Increased surgery to RT interval predicted for decreased LRC (p = 0.04). Conclusions: Local-regional control for SCC of the OC treated with IMRT with or without surgery remains unsatisfactory. Definitive and postoperative IMRT have favorable toxicity profiles. A surgery-to-RT interval of <6 weeks improves local-regional control. The predominant failure pattern was local, suggesting that both improvements in target delineation and radiosensitization and/or dose escalation are needed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Helical Tomotherapy vs. Intensity-Modulated Proton Therapy for Whole Pelvis Irradiation in High-Risk Prostate Cancer Patients: Dosimetric, Normal Tissue Complication Probability, and Generalized Equivalent Uniform Dose Analysis

Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. Methods and Materials: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100{sup o}; 100{sup o}) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normal tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. Results: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving {>=}95% of the prescribed dose (V{sub 95%}) was on average >97% in HT and >99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. Conclusions: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Adjuvant Chemoradiation for Gastric Cancer Using Epirubicin, Cisplatin, and 5-Fluorouracil Before and After Three-Dimensional Conformal Radiotherapy With Concurrent Infusional 5-Fluorouracil: A Multicenter Study of the Trans-Tasman Radiation Oncology Group

Purpose: The INT0116 study has established postoperative chemoradiotherapy as the standard of care for completely resected gastric adenocarcinoma. However, the optimal chemoradiation regimen remains to be defined. We conducted a prospective, multicenter study to evaluate an alternative chemoradiation regimen that combines more current systemic treatment with modern techniques of radiotherapy delivery. Methods and Materials: Patients with adenocarcinoma of the stomach who had undergone an R0 resection were eligible. Adjuvant therapy consisted of one cycle of epirubicin, cisplatin, and 5-FU (ECF), followed by radiotherapy with concurrent infusional 5-FU, and then two additional cycles of ECF. Radiotherapy was delivered using precisely defined, multiple-field, three-dimensional conformal techniques. Results: A total of 54 assessable patients were enrolled from 19 institutions. The proportion of patients commencing Cycles 1, 2, and 3 of ECF chemotherapy were 100%, 81%, and 67% respectively. In all, 94% of patients who received radiotherapy completed treatment as planned. Grade 3/4 neutropenia occurred in 66% of patients with 7.4% developing febrile neutropenia. Most neutropenic episodes (83%) occurred in the post-radiotherapy period during cycles 2 and 3 of ECF. Grade 3/4 gastrointestinal toxicity occurred in 28% of patients. In all, 35% of radiotherapy treatment plans contained protocol deviations that were satisfactorily amended before commencement of treatment. At median follow-up of 36 months, the 3-year overall survival rate was estimated at 61.6%. Conclusions: This adjuvant regimen using ECF before and after three-dimensional conformal chemoradiation is feasible and can be safely delivered in a cooperative group setting. A regimen similar to this is currently being compared with the INT0116 regimen in a National Cancer Institute-sponsored, randomized Phase III trial.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Clinical Evaluation of Spatial Accuracy of a Fusion Imaging Technique Combining Previously Acquired Computed Tomography and Real-Time Ultrasound for Imaging of Liver Metastases

Purpose: This study was designed to evaluate the spatial accuracy of matching volumetric computed tomography (CT) data of hepatic metastases with real-time ultrasound (US) using a fusion imaging system (VNav) according to different clinical settings. Methods: Twenty-four patients with one hepatic tumor identified on enhanced CT and US were prospectively enrolled. A set of three landmarks markers was chosen on CT and US for image registration. US and CT images were then superimposed using the fusion imaging display mode. The difference in spatial location between the tumor visible on the CT and the US on the overlay images (reviewer no. 1, comment no. 2) was measured in the lateral, anterior-posterior, and vertical axis. The maximum difference (Dmax) was evaluated for different predictive factors.CT performed 1-30 days before registration versus immediately before. Use of general anesthesia for CT and US versus no anesthesia.Anatomic landmarks versus landmarks that include at least one nonanatomic structure, such as a cyst or a calcificationResultsOverall, Dmax was 11.53 {+-} 8.38 mm. Dmax was 6.55 {+-} 7.31 mm with CT performed immediately before VNav versus 17.4 {+-} 5.18 with CT performed 1-30 days before (p < 0.0001). Dmax was 7.05 {+-} 6.95 under general anesthesia and 16.81 {+-} 6.77 without anesthesia (p < 0.0015). Landmarks including at least one nonanatomic structure increase Dmax of 5.2 mm (p < 0.0001). The lowest Dmax (1.9 {+-} 1.4 mm) was obtained when CT and VNav were performed under general anesthesia, one immediately after the other. Conclusions: VNav is accurate when adequate clinical setup is carefully selected. Only under these conditions (reviewer no. 2), liver tumors not identified on US can be accurately targeted for biopsy or radiofrequency ablation using fusion imaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Nuclear Factor {kappa}-Light Chain-Enhancer of Activated B Cells is Activated by Radiotherapy and is Prognostic for Overall Survival in Patients With Rectal Cancer Treated With Preoperative Fluorouracil-Based Chemoradiotheraphy

Purpose: Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor {kappa}-light chain-enhancer of activated B cells (NF-{kappa}B) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-{kappa}B activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-{kappa}B activity correlates with the outcome in rectal cancer patients. Methods and Materials: A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-{kappa}B subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-{kappa}B-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-{kappa}B subunit nuclear localization using immunohistochemistry. Results: Several NF-{kappa}B target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-{kappa}B is activated by RT in human rectal tumors. The baseline NF-{kappa}B p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). Conclusion: NF-{kappa}B nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-{kappa}B target gene upregulation on the response to RT. Our results suggest that NF-{kappa}B might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗