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At least 1,567 records · Page 87
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms

SIRT5 is one of the seven mammalian sirtuins which are NAD{sup +}-dependent deacylases. In human beings, SIRT5 gene encodes for four SIRT5 protein isoforms, namely SIRT5{sup iso1}, SIRT5{sup iso2}, SIRT5{sup iso3}, and SIRT5{sup iso4}. Previous studies have focused mostly on SIRT5{sup iso1}. Characteristics regarding localization, activity and tissue distribution of the other three SIRT5 isoforms remain unclear. In the present study, we characterized these properties of these SIRT5 isoforms. We found that SIRT5{sup iso1−3} were mitochondria-localized, while SIRT5{sup iso4} localized mainly in cytoplasm. SIRT5{sup iso2−4} had little deacylase activity comparing with SIRT5{sup iso1}. Although cDNAs of all SIRT5 isoforms were readily detected in multiply tissues according to EST database, proteins of SIRT5{sup iso2−4} were seldom observed in human cell lines. Altogether, we dissected the four isoforms of human SIRT5 protein.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Nucleolar localization signal and histone methylation reader function is required for SPIN1 to promote rRNA gene expression

Highlights: • A NoLS in the N-terminus of SPIN1 mediates its nucleolar localization and function. • The H3R8me2a-recognizing capacity of SPIN1 is indispensable for its promotion of rRNA expression. • SPIN1 is involved the formation of SL1 complex on rDNA loci. Spindlin1 (SPIN1), a histone modification reader protein, was enriched in the cell nucleolus and facilitated rRNA expression. However, how SPIN1 localizes to the nucleolus and its functional role in rRNA gene expression remain unresolved. Here, we identified a nucleolar localization signal in the N-terminal region of SPIN1 that is essential for its enrichment and function in the nucleolus. We also discovered that, in addition to its H3K4me3 recognizing activity, the H3R8me2a-recognizing capacity of SPIN1 is also indispensable for stimulating rRNA expression. Chromatin immunoprecipitation results indicated that SPIN1 is required for the association or assembly of selective factor 1 (SL1) complex, probably facilitating the initiation of rDNA transcription through its H3 K4me3-R8me2a reader function.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

On the use of peak-force tapping atomic force microscopy for quantification of the local elastic modulus in hardened cement paste

A surface of epoxy-impregnated hardened cement paste was investigated using a novel atomic force microscopy (AFM) imaging mode that allows for the quantitative mapping of the local elastic modulus. The analyzed surface was previously prepared using focussed ion beam milling. The same surface was also characterized by electron microscopy and energy-dispersive X-ray spectroscopy. We demonstrate the capability of this quantitative nanomechanical mapping to provide information on the local distribution of the elastic modulus (from about 1 to about 100 GPa) with a spatial resolution in the range of decananometers, that corresponds to that of low-keV back-scattered electron imaging. Despite some surface roughness which affects the measured nanomechanical properties it is shown that topography, adhesion and Young's modulus can be clearly distinguished. The quantitative mapping of the local elastic modulus is able to discriminate between phases in the cement paste microstructure that cannot be distinguished from the corresponding back-scattered electron images.

36 MATERIALS SCIENCE↗
DOE OSTI2021

A finite element formulation for deformation twinning induced strain localization in polycrystal magnesium alloys

Deformation twinning induces shear strain localization in hexagonal close-packed crystals and is critical for the material’s ductility and failure. Cracks often occur at twin-twin or twin-grain boundary intersections and propagate along twin bands. However, most crystal plasticity models for deformation twinning are based on a “pseudo-slip” approach and do not capture the localized deformation associated with the formation of each discrete twin band. The few exceptions are discrete twin models that involve very complex numerical algorithms and are often compromised in accuracy due to the numerical convergence. These factors make the discrete twin models hard to adopt. This paper proposes a modification to the conventional finite element weak form, to fully incorporate a twin-induced heterogeneous deformation that does not depend on the “pseudo-slip” assumption. The model starts by splitting the deformation gradient into elastic-slip-twinning components. The twin-induced deformation gradient component is computed separately by solving a microstructural evolution problem and then implemented into finite element weak form by constructing a global “twin-force” vector. The constitutive update (e.g., in the user-defined material subroutine, or UMAT, for ABAQUS) therefore avoids dealing with the twinning and recovers to the form of a regular slip-based crystal plasticity model. The results presented here indicate that the twin-induced strain localization and the associated stress-reversal phenomena near the twin band were naturally captured in the model, which was validated against an in-situ synchrotron X-ray micro-diffraction experiment.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Explainable machine learning reveals that local structural motifs encode the thermodynamic state across the CuZr metallic glass-forming range

Metallic glasses derive their properties from the statistics of local atomic motifs rather than from long-range order, yet a quantitative, chemistry-specific link between motif populations and the underlying glassy state has remained elusive. In this work we combine large-scale molecular dynamics, Voronoi tessellation, deep neural networks, and SHapley Additive exPlanations (SHAP) to identify which local structural motifs define the glassy state of Cu—Zr metallic glasses. A dataset of 17,180 atomistic configurations spanning ten compositions (Cu 20 Zr 80 –Cu 80 Zr 20 ) and four quench rates (10 9 –10 12 K/s) is used to train a feed-forward neural network that regresses temperature across the 50–2000 K liquid–supercooled–glass range, achieving a mean absolute error of 19.89 K and R 2 = 0.9974, confirming that the local structural state is faithfully encoded in motif-level structure. SHAP analysis then reveals that a tightly coupled near-icosahedral family of motifs (coordination numbers (CN) 11–13, including the full icosahedron 001200 and its single-atom-perturbation sibling 10930) collectively encodes the thermodynamic state of the system across the full glass-forming range. The CN = 11–13 ordered members carry negative SHAP values at high populations, tracking the most deeply-quenched configurations, while 10930 shows the reversed signature consistent with its role as a soft-spot host whose population shrinks as the icosahedral network deepens. The analysis demonstrates that explainable machine learning can isolate the minimal motif vocabulary defining the glassy state and recovers the near-icosahedral building blocks previously identified by data-driven analyses of Cu—Zr. The approach provides a general, chemistry-specific route for characterizing the structural state of disordered materials.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Mining project's economic impact on local communities, as a social determinant of health: A documentary analysis of environmental impact statements

Australian mining developments cause indirect economic impacts on nearby communities leading to poor health and wellbeing of local residents. Economic instability is a recognised social determinant of health (SDoH); however, SDoHs are rarely considered adequately in Environmental Impact Assessments (EIAs). This research aimed to determine the extent economic impacts as a SDoH are considered in three Environmental Impact Statements (EISs) of mining projects in the New South Wales, Australia. We adopted an exploratory case study design following Yin (2012). Three cases in New South Wales, Australia, were purposively sampled as being of concern to the local community who had sought legal advice about the content of the EIS (although not necessarily for health reasons). Two were open cut mines: Watermark located in the Liverpool Plains and Warkworth Continuation in the Hunter Valley Region. The third is a comparative case – the underground Mandalong Southern Extension located in Lake Macquarie. We adapted a health-focused EIA coding framework to investigate how economic indicators as SDoH were explicitly mentioned in EISs and applied this to the three cases. Economic indicators as SDoH were rarely considered. There was a greater focus on population characteristics rather than the potential economic impacts of the mining projects on the communities. Causal association of economic determinants and health outcomes were insufficiently reported compared to best practice, and health data were not used to inform assessments. Despite two EISs – Warkworth Continuation and Watermark – associating some economic indicators to health outcomes, impacts were not adequately discussed when compared to the known literature on economic impacts of mines. Our findings show that the three EISs were inadequately utilised to determine economic impacts of mining projects on the health and wellbeing of local communities. The evidence base linking economic impacts of mines to health is underdeveloped, which compromises assessing the quality of economic coverage in EISs. EIA scoping should enable sufficient inclusion of broader determinants of health using appropriate methodology, and the economic-focused content of EISs should be subject to rigorous peer-review process to fully inform government approvals for projects. Our methods lend themselves to research in other contexts to investigate the quality of EIAs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2020

Locally developed electronic conduction in a yttria stabilized zirconia (YSZ) electrolyte for durable solid oxide fuel cells

In the present work, anode supported solid oxide fuel cells (SOFCs) based on a YSZ single layer electrolyte with locally developed electronic conduction near the anode side is fabricated to improve the cell durability under negative voltage conditions. A ceria added Ni/YSZ anode functional layer is utilized and co-sintered with the YSZ electrolyte at 1460 °C. Cerium ions are diffused into a limited region of the YSZ layer (~6 μm), establishing a ceria doped YSZ region. We successfully demonstrate that this YSZ single layer cell can operate stably for ~100 h without anode/electrolyte interface delamination, even under a negative voltage. The embedded probe technique and theoretical calculation reveal that the internal oxygen partial pressure (near the anode) is substantially reduced (stabilized) by means of local electronic conduction of ceria doped YSZ. Thus, we propose an SOFC electrolyte design comprising a YSZ single layer with a ceria added anode functional layer (locally formed ceria doped YSZ in the electrolyte) as a protection method against fuel cell stack degradation caused by negative voltage operation.

25 ENERGY STORAGE↗
DOE OSTI2020

Localized Corrosion Behavior of Non-Equiatomic NiFeCrMnCo Multi-Principal Element Alloys

A series of single phase Ni 38 Fe 20 Cr x Mn 21–0.5x Co 21–0.5x multi-principal element alloys (MPEAs) were fabricated and their localized corrosion behavior was tested in 0.6 M NaCl solution. These MPEAs were found to be susceptible to localized corrosion, exhibiting pitting at room temperature, as indicated by positive hysteresis loops and low repassivation potentials observed in cyclic potentiodynamic polarization experiments. The pitting resistance increased with increasing Cr content. Interestingly, even the MPEAs with low chromium content, Ni 38 Fe 20 Cr 6 Mn 18 Co 18 and Ni 38 Fe 20 Cr 10 Mn 16 Co 16 , exhibited passivity and localized corrosion. Here, the passivity observed in these low chromium MPEAs is likely derived from their relatively high nickel content. Crystallographic pit morphology was observed in most of these MPEAs, suggesting the absence of a salt film on the dissolving pit surface. Such crystallographic pit morphology indicates that the pit growth in most of these MPEAs was under charge-transfer/ohmic control.

36 MATERIALS SCIENCE↗
DOE OSTI2018

Localized real-time information on outdoor air quality at kindergartens in Oslo, Norway using low-cost sensor nodes

Highlights: • We show that low-cost sensors can provide an indication of outdoor air quality. • We employed a data fusion method to provide real-time air quality maps. • Localized real-time air quality information can help parents and kindergarten staff. In Norway, children in kindergartens spend significant time outdoors under all weather conditions, and there is thus a natural concern about the quality of outdoor air. It is well known that air pollution is associated with a wide variety of adverse health impacts for children, with greater impact on children with asthma. Especially during winter and spring, kindergartens in Oslo that are situated close to streets with busy traffic, or in areas where wood burning is used for house heating, can experience many days with bad air quality. During these periods, updated information on air quality levels can help the kindergarten teachers to plan appropriate outdoor activities and thus protect children's health. We have installed 17 low-cost air quality nodes in kindergartens in Oslo. These nodes are smaller, cheaper and less complex to use than traditional equipment. Performance evaluation shows that while they are less accurate and suffer from higher uncertainty than reference equipment, they still can provide reliable coarse information about local pollution. The main challenge when using this technology is that calibration parameters might change with time depending on the atmospheric conditions. Thus, even if the sensors are calibrated a priori, once deployed, and especially if they are deployed for a long time, it is not possible to determine if a node is over- or under-estimating the concentration levels. To enhance the data from the sensors, we employed a data fusion technique that allows generating a detailed air quality map merging the data from the sensors and the data from an urban model, thus being able to offer air quality information to any location within Oslo. We arranged a focus group with the participation of local administration, kindergarten staff and parents to understand their opinion and needs related to the air quality information that was provided to the participant kindergartens. They expressed concern about the data quality but agree that having updated information on the air quality in the surroundings of kindergartens can help them to reduce children's exposure to air pollution.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2026

Predicting critical heat flux using localized sensing at invisible vapor-liquid interfaces

Predicting critical heat flux (CHF) in two-phase electronics cooling systems remains a significant challenge due to the sudden onset of boiling crisis and the difficulty in directly visualizing vapor-liquid interfaces. Existing sensing methods rely on lagging temperature measurements, optically accessible systems, or spatially averaged signals that cannot pinpoint CHF initiation at localized high-heat-flux regions. Here, we report a planar capacitive sensing approach that enables real-time, localized detection of vapor-liquid interface dynamics for CHF prediction in boiling heat transfer. The capacitive sensor exploits the dielectric constant difference between liquid and vapor phases to capture bubble nucleation, growth, and departure dynamics with a temporal resolution down to 2 ms. The capacitive sensing reveals distinct signals across boiling regimes: from high-frequency fluctuations during strong nucleate boiling to low-frequency fluctuations with increased amplitudes when approaching CHF. The multi-sensor array experiments demonstrate real-time localized sensing, where each sensor responds exclusively to boiling in its immediate vicinity without crosstalk from neighboring regions. This non-intrusive sensing approach provides predictive rather than lagging sensing signals of CHF occurrence, offering predictive diagnosis of two-phase liquid cooling for the thermal management of high-power-density electronics.

CHF↗
DOE OSTI2020

Localization of deformation in fluid-saturated sandstone

Herein we discuss a laboratory study of inelastic deformation and localization was conducted to evaluate microseismicity and fracture in fluid-saturated rock. Plane strain compression experiments were performed on oil- and water-saturated Berea sandstone under dry, drained, undrained, and quasi-unjacketed conditions. Parameters associated with the elastic and inelastic material response were accurately measured and used in a constitutive model to predict localization of deformation under the drained and undrained conditions. Acoustic emission (AE) activity was recorded and the onset of inelastic response in fluid-saturated rock, similar to dry rock, coincided with an increase in AE rate. Fracture initiation and propagation were successfully monitored by AE locations. Clustering of AE events and the start of inhomogeneous deformation inferred from displacement measurements are shown to be well correlated with the model prediction of the onset of localized deformation under various rock-fluid interaction conditions.

42 ENGINEERING↗
DOE OSTI2010

Is Local Radiotherapy Still Valuable for Patients With Multiple Intrahepatic Hepatocellular Carcinomas?

Purpose: To investigate whether local radiotherapy (RT) is valuable for patients with multiple hepatocellular carcinomas (HCCs). Methods and Materials: From July 1992 to August 2006, 107 patients with unresectable HCC were treated with local RT after incomplete transcatheter arterial chemoembolization (TACE). The RT field included a main tumor with or without other tumor nodules, depending on the effectiveness of TACE. The median RT dose was 50.4Gy in conventional fractionation. Patients were categorized into four groups: Group 1, single tumor (39 patients); Group 2, multiple tumors within the RT field (25 patients); Group 3, controlled tumors out of the RT field (19 patients); and Group 4, tumors that remained viable out of the RT field (24 patients). Results: Group 1 showed the best survival rate (MST, 35 months; 2-year OS, 60%) and Group 4 the worst (MST, 5 months; 2-year OS, 16%). Group 2 and Group 3 showed similar survival (MST, 13 vs. 19 months; 2-year OS, 35% vs. 46%; p = 0.698). Significantly worse intrahepatic control in Group 4 was observed. The survival in Groups 2 and 3 (MST, 16 months) was significantly different from that in Group 4 (p = 0.004), and was marginally significant compared with that in Group 1 (p = 0.051). Conclusions: Local RT to the main tumor could be applicable in well-controlled intrahepatic tumors out of the RT field. Patients with viable intrahepatic tumors out of the RT field showed worse survival. In future clinical trials, these patients need to be excluded.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Combined Modality Therapy Including Intraoperative Electron Irradiation for Locally Recurrent Colorectal Cancer

Purpose: To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). Methods and Materials: From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Results: Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Conclusions: Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Pelvic Lymph Node Status Assessed by 18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Low-Risk Group for Distant Recurrence in Locally Advanced Cervical Cancer: A Prospective Study

Purpose: To develop a prediction model to identify a low-risk group for distant recurrence in patients with locally advanced cervical cancer treated by concurrent chemoradiation. Methods and Materials: Prospectively, 62 patients with locally advanced cervical cancer were recruited as a training cohort. Clinical variables and parameters obtained from positron emission tomography (PET) and magnetic resonance imaging were analyzed by logistic regression. For the test set, 54 patients were recruited independently. To identify the low-risk group, negative likelihood ratio (LR) less than 0.2 was set to be a cutoff. Results: Among the training cohort, multivariate logistic analysis revealed that advanced International Federation of Gynecology and Obstetrics (FIGO) stage and a high serum squamous cancer cell (SCC) antigen level were significant risk factors (p = 0.015 and 0.025, respectively). Using the two parameters, criteria to determine a low-risk subset for distant recurrence were postulated: (1) FIGO Stage IIB or less and (2) pretreatment SCC < 2.4 (Model A). Positive pelvic node on PET completely predicted all cases with distant recurrence and thus was considered as another prediction model (Model B). In the test cohort, although Model A did not showed diagnostic performance, Model B completely predicted all cases with distant recurrence and showed a sensitivity of 100% with negative LR of 0. Across the training and test cohort (n = 116), the false negative rate was 0 (95% confidence interval 0%-7.6%). Conclusions: Positive pelvic node on PET is a useful marker in prediction of distant recurrence in patients with locally advanced cervical cancer who are treated with concurrent chemoradiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Feasibility Study of Moderately Accelerated Intensity-Modulated Radiotherapy Plus Concurrent Weekly Cisplatin After Induction Chemotherapy in Locally Advanced Head-and Neck Cancer

Purpose: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). Methods and Materials: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m{sup 2} plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. Results: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. Conclusions: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Preoperative Chemoradiation With Irinotecan and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: Long-Term Results of a Phase II Study

Purpose: Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer has shown benefit over postoperative CRT; however, a standard CRT regimen has yet to be defined. We performed a prospective concurrent CRT Phase II study with irinotecan and capecitabine in patients with locally advanced rectal cancer to investigate the efficacy and safety of this regimen. Methods and Materials: Patients with locally advanced, nonmetastatic, and mid-to-lower rectal cancer were enrolled. Radiotherapy was delivered in 1.8-Gy daily fractions for a total of 45 Gy in 25 fractions, followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of 40 mg/m{sup 2} of irinotecan per week for 5 consecutive weeks and 1,650 mg/m{sup 2} of capecitabine per day for 5 days per week (weekdays only) from the first day of radiotherapy. Total mesorectal excision was performed within 6 {+-} 2 weeks. The pathologic responses and survival outcomes were included for the study endpoints. Results: In total, 48 patients were enrolled; 33 (68.7%) were men and 15 (31.3%) were women, and the median age was 59 years (range, 32-72 years). The pathologic complete response rate was 25.0% (11 of 44; 95% confidence interval, 12.2-37.8) and 8 patients (18.2% [8 of 44]) showed near-total tumor regression. The 5-year disease-free and overall survival rates were 75.0% and 93.6%, respectively. Grade 3 toxicities included leukopenia (3 [6.3%]), neutropenia (1 [2.1%]), infection (1 [2.1%]), alanine aminotransferase elevation (1 [2.1%]), and diarrhea (1 [2.1%]). There was no Grade 4 toxicity or treatment-related death. Conclusions: Preoperative CRT with irinotecan and capecitabine with treatment-free weekends showed very mild toxicity profiles and promising results in terms of survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗