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At least 1,549 records · Page 86
All sourcesNASA NTRSDOE OSTI
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 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↗
DOE OSTI2011

The Matrix Metalloproteinase-7 Polymorphism Rs10895304 Is Associated With Increased Recurrence Risk in Patients With Clinically Localized Prostate Cancer

Purpose: To evaluate whether selected high-risk matrix metalloproteinase-7 single nucleotide polymorphisms influence clinicopathologic outcomes in patients with early-stage prostate cancer. Methods and Materials: Two hundred twelve prostate cancer patients treated with radical prostatectomy were evaluated with a median follow-up of 9.8 years. Genotyping was performed using hybridization with custom-designed allele-specific probes. Three single nucleotide polymorphisms within the matrix metalloproteinase-7 gene were assessed with respect to age at diagnosis, margin status, extracapsular extension, lymph node involvement, recurrence-free survival, and overall survival in paraffin-embedded prostate tissue specimens from patients with early-stage prostate cancer who underwent radical prostatectomy. Results: Rs10895304 was the sole significant polymorphism. The A/G genotype of rs10895304 had a statistically significant association with recurrence-free survival in postprostatectomy patients (p = 0.0061, log-rank test). The frequency of the risk-reducing genotype (A/A) was 74%, whereas that of the risk-enhancing genotypes (A/G and G/G) were 20% and 6%, respectively. Multivariable Cox regression analyses detected a significant association between rs10895304 and recurrences after adjustment for known prognostic factors. The G allele of this polymorphism was associated with increased risk of prostate cancer recurrence (adjusted hazards ratio, 3.375; 95% confidence interval 1.567-7.269; p < 0.001). The other assayed polymorphisms were not significant, and no correlations were made to other clinical variables. Conclusions: The A/G genotype of rs10895304 is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer. Our data suggest that for this subset of patients, prostatectomy alone may not be adequate for local control. This is a novel and relevant marker that should be evaluated for improved risk stratification of patients who may be candidates for adjuvant radiation therapy to improve local control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Phase II Study of Oral S-1 and Concurrent Radiotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

Purpose: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m{sup 2}/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Daily Megavoltage Computed Tomography in Lung Cancer Radiotherapy: Correlation Between Volumetric Changes and Local Outcome

Purpose: To assess the predictive or comparative value of volumetric changes, measured on daily megavoltage computed tomography during radiotherapy for lung cancer. Patients and Methods: We included 80 patients with locally advanced non-small-cell lung cancer treated with image-guided intensity-modulated radiotherapy. The radiotherapy was combined with concurrent chemotherapy, combined with induction chemotherapy, or given as primary treatment. Patients entered two parallel studies with moderately hypofractionated radiotherapy. Tumor volume contouring was done on the daily acquired images. A regression coefficient was derived from the volumetric changes on megavoltage computed tomography, and its predictive value was validated. Logarithmic or polynomial fits were applied to the intratreatment changes to compare the different treatment schedules radiobiologically. Results: Regardless of the treatment type, a high regression coefficient during radiotherapy predicted for a significantly prolonged cause-specific local progression free-survival (p = 0.05). Significant differences were found in the response during radiotherapy. The significant difference in volumetric treatment response between radiotherapy with concurrent chemotherapy and radiotherapy plus induction chemotherapy translated to a superior long-term local progression-free survival for concurrent chemotherapy (p = 0.03). An enhancement ratio of 1.3 was measured for the used platinum/taxane doublet in comparison with radiotherapy alone. Conclusion: Contouring on daily megavoltage computed tomography images during radiotherapy enabled us to predict the efficacy of a given treatment. The significant differences in volumetric response between treatment strategies makes it a possible tool for future schedule comparison.

62 RADIOLOGY AND NUCLEAR MEDICINE↗