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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 1,009 records · Page 56
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Phosphoproteomic analysis reveals PAK2 as a therapeutic target for lapatinib resistance in HER2-positive breast cancer cells

Highlights: • Phosphoproteomic analysis identified PAK2 as a drug target for lapatinib resistance. • PAK2 knockdown restores lapatinib sensitivity of lapatinib-resistant SKBR-LR cells. • Cotreatment of lapatinib with PAK inhibitor restores the sensitivity to lapatinib. The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of breast cancer. Lapatinib has been widely used as a HER2-targeted therapy, however, a number of patients develop lapatinib resistance and still suffer from poor prognosis. Therefore, it is essential to identify novel therapeutic targets that could overcome lapatinib resistance. In this study, we carried out phosphoproteomic analysis of lapatinib sensitive and resistant cell lines (SKBR3 and SKBR3-LR) using stable isotope labeling with amino acids in cell culture (SILAC). We identified 3808 phosphopeptides from 1807 proteins and then analyzed signaling pathways, Gene Ontology, and protein-protein interaction networks. Finally, we identified PAK2 as a therapeutic target from the network analysis and validated that PAK2 knockdown and PAK inhibitor treatment resensitize the lapatinib resistant cells to lapatinib. This results suggest that PAK2 is a potent therapeutic target to overcome acquired lapatinib resistance in HER2-positive breast cancer cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

SpWRKY6 acts as a positive regulator during tomato resistance to Phytophthora infestans infection

Highlights: • SpWRKY6 acts as a positive regulator of tomato resistance to P. infestans infection. • Over-expressing SpWRKY6 tomato increased resistance to P. infestans by scavenging reactive oxygen species. • SpWRKY6-mediated tomato resistance to P. infestans through regulating the expression level of PR genes. WRKY transcription factors have been widely known to play key regulatory roles in plant disease resistance. In our previous study, characteristics of SpWRKY6 and its role in response to biotic and abiotic stress was studied. To further investigate the function of SpWRKY6 in tomato resistance to Phytophthora infestans (P. infestans), we studied the effects of loss and gain of function of SpWRKY6. Inhibition of SpWRKY6 mRNA accumulation in tomato leaves, using virus-induced gene silencing (VIGS), greatly reduced SpWRKY6 mRNA levels, and compromised tomato resistance to P. infestans. In contrast, overexpressing- SpWRKY6 tomato plants showed enhanced resistance to P. infestans, accompanied by decreased number of necrotic cells, lesion sizes and disease index. Furthermore, after P. infestans infection, the expression levels of pathogenesis related (PR) genes in transgenic tomato plants overexpressed SpWRKY6 were significantly higher than those in wild type plants, while the number of necrotic cells and the reactive oxygen species (ROS) accumulation were fewer and lower. Taken together, these results indicating that SpWRKY6 acts as a positive regulator of tomato resistance to P. infestans infection through regulating the ROS level and the expression level of PR genes along with alleviating cell membrane injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Crystal structure of the 65-kilodalton amino-terminal fragment of DNA topoisomerase I from the gram-positive model organism Streptococcus mutans

Here, we report the first structure of topoisomerase I determined from the gram-positive bacterium, S. mutans. Bacterial topoisomerase I is an ATP-independent type 1A topoisomerase that uses the inherent torsional strain within hyper-negatively supercoiled DNA as an energy source for its critical function of DNA relaxation. Interest in the enzyme has gained momentum as it has proven to be essential in various bacterial organisms. In order to aid in further biochemical characterization, the apo 65-kDa amino-terminal fragment of DNA topoisomerase I from the gram-positive model organism Streptococcus mutans was crystalized and a three-dimensional structure was determined to 2.06 Å resolution via x-ray crystallography. The overall structure illustrates the four classic major domains that create the traditional topoisomerase I “lock” formation comprised of a sizable toroidal aperture atop what is considered to be a highly dynamic body. A catalytic tyrosine residue resides at the interface between two domains and is known to form a 5’ phosphotyrosine DNA-enzyme intermediate during transient single-stranded cleavage required for enzymatic relaxation of hyper negative DNA supercoils. Surrounding the catalytic tyrosine residue is the remainder of the highly conserved active site. Within 5 Å from the catalytic center, only one dissimilar residue is observed between topoisomerase I from S. mutans and the gram-negative model organism E. coli. Immediately adjacent to the conserved active site, however, S. mutans topoisomerase I displays a somewhat unique nine residue loop extension not present in any bacterial topoisomerase I structures previously determined other than that of an extremophile.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

An a priori DNS study of the shadow-position mixing model

In this study, the modeling of mixing by molecular diffusion is a central aspect for transported probability density function (tPDF) methods. In this paper, the newly-proposed shadow position mixing model (SPMM) is examined, using a DNS database for a temporally evolving di-methyl ether slot jet flame. Two methods that invoke different levels of approximation are proposed to extract the shadow displacement (equivalent to shadow position) from the DNS database. An approach for a priori analysis of the mixing-model performance is developed. The shadow displacement is highly correlated with both mixture fraction and velocity, and the peak correlation coefficient of the shadow displacement and mixture fraction is higher than that of the shadow displacement and velocity. This suggests that the composition-space localness is reasonably well enforced by the model, with appropriate choices of model constants. The conditional diffusion of mixture fraction and major species from DNS and from SPMM are then compared, using mixing rates that are derived by matching the mixture fraction scalar dissipation rates. Good qualitative agreement is found, for the prediction of the locations of zero and maximum/minimum conditional diffusion locations for mixture fraction and individual species. Similar comparisons are performed for DNS and the IECM (interaction by exchange with the conditional mean) model. The agreement between SPMM and DNS is better than that between IECM and DNS, in terms of conditional diffusion iso-contour similarities and global normalized residual levels. It is found that a suitable value for the model constant c that controls the mixing frequency can be derived using the local normalized scalar variance, and that the model constant a controls the localness of the model. A higher-Reynolds-number test case is anticipated to be more appropriate to evaluate the mixing models, and stand-alone transported PDF simulations are required to more fully enforce localness and to assess model performance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Analyzing impact of $\mathrm{DER}$ on $\mathrm{FIDVR}$ - comparison of $\mathrm{EMT}$ simulation of a combined transmission and distribution grid with aggregated positive sequence models

The increase in percentage of distributed energy resources (DERs) brings in a degree of uncertainty in bulk power system planning and operations. Further, the presence of 1 - φ induction motors introduces the possibility of motor stalling and fault induced delayed voltage recovery (FIDVR). With newer versions of IEEE Std 1547™ there can be the opportunity to obtain dynamic voltage support from DERs. In this report, the impact of DERs providing dynamic voltage on the dynamic behavior of 1 - φ induction motors is examined in detail along with an exploration of the need for simulation platforms that go beyond positive sequence. The studies discussed here are carried out both in detailed electromagnetic time domain and in positive sequence domain for comparison.

24 POWER TRANSMISSION AND DISTRIBUTION↗
DOE OSTI2025

Uplifting winds: The surprisingly positive community-wide impact of wind energy installations on property values

A primary concern of stakeholders when considering a new wind project is the potential negative effects wind turbines may have on home values. Yet, what has been surprisingly overlooked in the literature and general discourse around wind energy is that the well-researched positive economic development and fiscal and amenity benefits of wind energy (e.g., increased tax base, tax revenue, better public services and employment gains) might positively affect jurisdiction-wide housing values. With a focus on school districts in the United States, we compare home values in school districts with wind energy installations, before and after a wind energy installation becomes operational, to home values in other school districts located in the same county but without a wind energy installation to provide some of the first causal evidence on the relationship between wind energy projects and district-wide property values. We find that wind projects lead to economically meaningful increases in district-wide housing values of approximately 3 %, when those values are compared to similar homes located in school districts in same-county without wind energy. The effect is strongly correlated with wind project size. The mechanisms, our research suggests, are likely related to relatively large increases in school district per-pupil revenues and expenditures, which are also correlated with wind project size. We suggest other possible mechanisms for the increased values as well.

Attitudes↗
DOE OSTI2023

Position-specific carbon isotopes of Murchison amino acids elucidate extraterrestrial abiotic organic synthesis networks

The Murchison meteorite is a well-studied carbonaceous chondrite with relatively high concentrations of amino acids thought to be endogenous to the meteorite, in part because they are characterized by carbon isotope (δ 13 C) values higher than those typical of terrestrial amino acids. Past studies have proposed that extraterrestrial amino acids in the Murchison meteorite could have formed by Strecker synthesis (for α-amino acids), Michael addition (for β-amino acids), or reductive amination, but a lack of constraints have prevented confident discrimination among these possibilities, or assignment of specific formation pathways to each of several specific amino acids. Position-specific carbon isotope analysis differentiates amongst these mechanisms by relating molecular sites to isotopically distinct carbon sources and by constraining isotope effects associated with elementary chemical reactions. Prior measurements of the position-specific carbon isotopic composition of α-alanine from the Murchison CM chondrite demonstrated that alanine’s high δ 13 C VPDB value is attributable to the amine carbon (δ 13 C VPDB = +142 ± 20‰), consistent with Strecker synthesis drawing on 13 C-rich carbonyl groups in precursors (Chimiak et al., 2021). Here, we measured the δ 13 C composition of fragment ions generated by electron impact ionization of derivatized α-alanine, β-alanine, and aspartic acid from Murchison via gas chromatography-Fourier transform mass spectrometry. α-Alanine’s amine carbon yielded δ 13 C VPDB = +109 ± 21‰, which is consistent with the previously measured value and with formation from 13 C-rich precursors. β-Alanine’s amine carbon presents a lower δ 13 C VPDB = +33 ± 24‰, which supports formation from 13 C-rich precursors but potentially via a Michael addition mechanism rather than Strecker synthesis. Aspartic acid’s amine carbon has δ 13 C VPDB = -14 ± 5‰, suggesting synthesis from precursors distinct from those that generated the alanine isomers. Further, these measurements indicate that Murchison amino acids are a mixture of compounds made from different synthesis mechanisms, though some subsets likely drew on the same substrates; this conclusion highlights the complexity of extraterrestrial organic synthesis networks and the potential of emerging methods of isotope ratio analysis to elucidate the details of those networks.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2011

Comparison of Treatment Outcome Between Breast-Conservation Surgery With Radiation and Total Mastectomy Without Radiation in Patients With One to Three Positive Axillary Lymph Nodes

Purpose: To test the difference in treatment outcome between breast-conservation surgery with radiation and total mastectomy without radiation, to evaluate the benefits of adjuvant radiotherapy in patients with one to three positive axillary lymph nodes. Methods and Materials: Using the Severance Hospital Breast Cancer Registry, we divided the study population of T1, T2 and one to three axillary node-positive patients into two groups: breast-conservation surgery with radiation (BCS/RT) and total mastectomy without radiation (TM/no-RT). Data related to locoregional recurrence, distant recurrence, and death were collected, and survival rates were calculated. Results: The study population consisted of 125 patients treated with BCS/RT and 365 patients treated with TM/no-RT. With a median follow-up of 68.4 months, the 10-year locoregional recurrence-free survival rate with BCS/RT and TM/no-RT was 90.5% and 79.2%, respectively (p = 0.056). The 10-year distant recurrence-free survival rate was 78.8% for patients treated with BCS/RT vs. 68.0% for those treated with TM/no-RT (p = 0.012). The 10-years overall survival rate for patients treated with BCT/RT and TM/no-RT was 87.5% and 73.9%, respectively (p = 0.035). After multivariate analysis, patients treated with BCT/RT had better distant recurrence-free survival (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.297-0.934; p = 0.028), with improving locoregional recurrence-free survival (HR, 0.491; 95% CI, 0.231-1.041; p = 0.064) and overall survival trend (HR, 0.544; 95% CI, 0.277-1.067; p = 0.076). Conclusions: This study provides additional evidence that adjuvant radiation substantially reduces local recurrence, distant recurrence, and mortality for patients with one to three involved nodes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

A Phase II Study of Radiotherapy and Concurrent Paclitaxel Chemotherapy in Breast-Conserving Treatment for Node-Positive Breast Cancer

Purpose: Administering adjuvant chemotherapy before breast radiotherapy decreases the risk of systemic recurrence, but delays in radiotherapy could yield higher local failure. We assessed the feasibility and efficacy of placing radiotherapy earlier in the breast-conserving treatment course for lymph node-positive breast cancer. Methods and Materials: Between June 2000 and December 2004, 44 women with node-positive Stage II and III breast cancer were entered into this trial. Breast-conserving surgery and 4 cycles of doxorubicin (60 mg/m{sup 2})/cyclophosphamide (600 mg/m{sup 2}) were followed by 4 cycles of paclitaxel (175 mg/m{sup 2}) delivered every 3 weeks. Radiotherapy was concurrent with the first 2 cycles of paclitaxel. The breast received 39.6 Gy in 22 fractions with a tumor bed boost of 14 Gy in 7 fractions. Regional lymphatics were included when indicated. Functional lung volume was assessed by use of the diffusing capacity for carbon monoxide as a proxy. Breast cosmesis was evaluated with the Harvard criteria. Results: The 5-year actuarial rate of disease-free survival is 88%, and overall survival is 93%. There have been no local failures. Median follow-up is 75 months. No cases of radiation pneumonitis developed. There was no significant change in the diffusing capacity for carbon monoxide either immediately after radiotherapy (p = 0.51) or with extended follow-up (p = 0.63). Volume of irradiated breast tissue correlated with acute cosmesis, and acute Grade 3 skin toxicity developed in 2 patients. Late cosmesis was not adversely affected. Conclusions: Concurrent paclitaxel chemotherapy and radiotherapy after breast-conserving surgery shortened total treatment time, provided excellent local control, and was well tolerated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Intrafraction Variation of Mean Tumor Position During Image-Guided Hypofractionated Stereotactic Body Radiotherapy for Lung Cancer

Purpose: Prolonged delivery times during daily cone-beam computed tomography (CBCT)-guided lung stereotactic body radiotherapy (SBRT) introduce concerns regarding intrafraction variation (IFV) of the mean target position (MTP). The purpose of this study was to evaluate the magnitude of the IFV-MTP and to assess target margins required to compensate for IFV and postonline CBCT correction residuals. Patient, treatment, and tumor characteristics were analyzed with respect to their impact on IFV-MTP. Methods and Materials: A total of 126 patients with 140 tumors underwent 659 fractions of lung SBRT. Dose prescribed was 48 or 60 Gy in 12 Gy fractions. Translational target position correction of the MTP was performed via onboard CBCT. IFV-MTP was measured as the difference in MTP between the postcorrection CBCT and the posttreatment CBCT excluding residual error. Results: IFV-MTP was 0.2 {+-} 1.8 mm, 0.1 {+-} 1.9 mm, and 0.01 {+-} 1.5 mm in the craniocaudal, anteroposterior, and mediolateral dimensions and the IFV-MTP vector was 2.3 {+-} 2.1 mm. Treatment time and excursion were found to be significant predictors of IFV-MTP. An IFV-MTP vector greater than 2 and 5 mm was seen in 40.8% and 7.2% of fractions, respectively. IFV-MTP greater than 2 mm was seen in heavier patients with larger excursions and longer treatment times. Significant differences in IFV-MTP were seen between immobilization devices. The stereotactic frame immobilization device was found to be significantly less likely to have an IFV-MTP vector greater than 2 mm compared with the alpha cradle, BodyFIX, and hybrid immobilization devices. Conclusions: Treatment time and respiratory excursion are significantly associated with IFV-MTP. Significant differences in IFV-MTP were found between immobilization devices. Target margins for IFV-MTP plus post-correction residuals are dependent on immobilization device with 5-mm uniform margins being acceptable for the frame immobilization device.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

The Number of Pathologically Positive Lymph Nodes and Pathological Tumor Depth Predicts Prognosis in Patients With Poorly Differentiated Squamous Cell Carcinoma of the Oral Cavity

Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%), neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes ({>=}4 vs. {<=}3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of {>=}11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth {>=}11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

MRI- Versus CT-Based Volume Delineation of Lumpectomy Cavity in Supine Position in Breast-Conserving Therapy: An Exploratory Study

Purpose: To examine magnetic resonance imaging (MRI) and computed tomography (CT) for lumpectomy cavity (LC) volume delineation in supine radiotherapy treatment position and to assess the interobserver variability. Methods and Materials: A total of 15 breast cancer patients underwent a planning CT and directly afterward MRI in supine radiotherapy treatment position. Then, 4 observers (2 radiation oncologists and 2 radiologists) delineated the LC on the CT and MRI scans and assessed the cavity visualization score (CVS). The CVS, LC volume, conformity index (CI), mean shift of the center of mass (COM), with the standard deviation, were quantified for both CT and MRI. Results: The CVS showed that MRI and CT provide about equal optimal visibility of the LC. If the CVS was high, magnetic resonance imaging provided more detail of the interfaces of the LC seroma with the unaffected GBT. MRI also pictured in more detail the interfaces of axillary seromas (if present) with their surroundings and their relationship to the LC. Three observers delineated smaller, and one observer larger, LC volumes comparing the MRI- and CT-derived delineations. The mean {+-} standard deviation CI was 32% {+-} 25% for MRI and 52% {+-} 21% for CT. The mean {+-} standard deviation COM shift was 11 {+-} 10 mm (range 1-36) for MRI and 4 {+-} 3 mm (range 1-10) for CT. Conclusions: MRI does not add additional information to CT in cases in which the CVS is assessed as low. The conformity (CI) is lower for MRI than for CT, especially at a low CVS owing to greater COM shifts for MRI, probably caused by inadequate visibility of the surgical clips on magnetic resonance (MR) images. The COM shifts seriously dictate a decline in the CI more than the variability of the LC volumes does. In cases in which MRI provides additional information, MRI must be combined with the CT/surgical clip data.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Metabolic Response of Lymph Nodes Immediately After RT Is Related With Survival Outcome of Patients With Pelvic Node-Positive Cervical Cancer Using Consecutive [{sup 18}F]fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Purpose: To evaluate the metabolic response of uterine cervix and pelvic lymph nodes (LNs) using consecutive {sup 18}F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) immediately after RT and to correlate survival outcome with the metabolic response. Methods and Materials: We retrospectively reviewed 48 patients with cervical cancer who had positive pelvic LNs by preradiation therapy (pre-RT) PET/CT. All patients underwent PET/CT scans immediately after RT (inter-RT PET/CT) after median 63 Gy to the gross LNs. The metabolic response of the LNs was assessed quantitatively and semiquantitatively by measurement of the maximal standardized uptake value (SUV{sub max}). Results: Classifying the metabolic response of all nodal lesions, 37 patients (77%) had LNs with complete metabolic response on the inter-RT PET/CT (LNCMRi), and 11 patients had a non-LNCMRi, including 4 patients with progressive metabolic disease. The overall 3-year survival rates were 83% for the patients with LNCMRi and 73% for the non-LNCMRi group (P=.038). The disease-free survival for patients with LNCMRi were significantly better than that for the non-LNCMRi group (71% vs 18%, respectively, P<.001). The 3-year distant metastasis-free survival rates were 79% for the patients with LNCMRi and 27% for the non-LNCMRi group (P<.001). There were no statistically significant differences in overall survival (76% vs 86%, respectively, P=.954) and disease-free survival rates (58% vs 61%, respectively, P=.818) between the CMR of primary cervical tumor and the non-CMR groups. Conclusions: The results showed a significant correlation between survival outcome and the interim metabolic response of pelvic LNs. CMR of nodal lesion on inter-RT PET/CT had excellent overall survival, disease-free survival and distant metastasis-free survival rates. This suggested that PET/CT immediately after RT can be a useful tool for the evaluation of the interim response of the LNs and identify a subset of patients with a high risk of recurrence and poor survival in patients with cervical cancer with initial positive LNs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Postoperative Radiation Therapy With or Without Concurrent Chemotherapy for Node-Positive Thoracic Esophageal Squamous Cell Carcinoma

Purpose: To retrospectively compare the efficacy of radiation therapy (RT) and chemotherapy plus RT (CRT) for the postoperative treatment of node-positive thoracic esophageal squamous cell carcinoma (TESCC) and to determine the incidence and severity of toxic reactions. Methods and Materials: We retrospectively reviewed data from 304 patients who had undergone esophagectomy with 3-field lymph node dissection for TESCC and were determined by postoperative pathology to have lymph node metastasis without distant hematogenous metastasis. Of these patients, 164 underwent postoperative chemotherapy (cisplatin 80 mg/m{sup 2}, average days 1-3, plus paclitaxel 135 mg/m{sup 2}, day 1; 21-day cycle) plus RT (50 Gy), and 140 underwent postoperative RT alone. Results: The 5-year overall survival rates for the CRT and RT groups were 47.4% and 38.6%, respectively (P=.030). The distant metastasis rate, the mixed (regional lymph node and distant) metastasis rate, and the overall recurrence rate were significantly lower in the CRT group than in the RT group (P<.05). However, mild and severe early toxic reactions, including neutropenia, radiation esophagitis, and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P<.05). No significant differences in incidence of late toxic reactions were found between the 2 groups. Conclusions: Our results show that in node-positive TESCC patients, postoperative CRT is significantly more effective than RT alone at increasing the overall survival and decreasing the rates of distant metastasis, mixed metastasis, and overall recurrence. Severe early toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Radiation Therapy in Primary Mediastinal B-Cell Lymphoma With Positron Emission Tomography Positivity After Rituximab Chemotherapy

Purpose: To investigate the role of radiation therapy (RT) in patients affected with primary mediastinal B-cell lymphoma (PMBCL) with residual {sup 18}fluorodeoxyglucose positron emission tomography ({sup 18}FDG-PET)-positive disease after rituximab chemotherapy (R-CT). Methods and Materials: Thirty-seven patients treated with R-CT and RT, all with {sup 18}FDG-PET scan at diagnosis and before RT, were included. All {sup 18}FDG-PET scans were reviewed, and responses were classified according to the Deauville 5-point scoring system. Outcomes measures were overall survival (OS) and progression-free survival (PFS), estimated for the whole cohort and for subgroups according to {sup 18}FDG-PET score after R-CT. Results: The median follow-up time was 40.9 months. Three patients were assigned to Deauville score 1 (8.1%), 9 to score 2 (24.3%), 7 to score 3 (19%), 14 to score 4 (37.8%), and 4 to score 5 (10.8%). After RT, all patients with score 3-4 experienced a complete response (CR). Among patients with score 5, 1 was in CR (25%), 2 had persistent positivity (50%), and 1 showed progressive disease (25%). A total of 4 patients experienced progression or relapse: 1 of 33 (3%) with scores 1-4, and 3 of 4 (75%) with score 5. The 3-year OS and PFS of the whole cohort were 89.8% and 88.7%, respectively. OS was significantly different between scores 1-3 and scores 4-5 (100% vs 77% at 3 years, P<.05). Patients with a score of 5 had a significantly worse outcome than did all other patients (OS at 2 years, 33.3% vs 100%). Conclusions: Approximately 50% of PMBCL patients show residual disease at {sup 18}FDG-PET scan after R-CT. RT is able to convert to CR approximately 85% of these patients, but those with a Deauville score of 5 (10%) appear at high risk of progression and death, and they might be candidates for intensified programs.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Dose Escalated Liver Stereotactic Body Radiation Therapy at the Mean Respiratory Position

Purpose: The dosimetric impact of dose probability based planning target volume (PTV) margins for liver cancer patients receiving stereotactic body radiation therapy (SBRT) was compared with standard PTV based on the internal target volume (ITV). Plan robustness was evaluated by accumulating the treatment dose to ensure delivery of the intended plan. Methods and Materials: Twenty patients planned on exhale CT for 27 to 50 Gy in 6 fractions using an ITV-based PTV and treated free-breathing were retrospectively evaluated. Isotoxic, dose escalated plans were created on midposition computed tomography (CT), representing the mean breathing position, using a dose probability PTV. The delivered doses were accumulated using biomechanical deformable registration of the daily cone beam CT based on liver targeting at the exhale or mean breathing position, for the exhale and midposition CT plans, respectively. Results: The dose probability PTVs were on average 38% smaller than the ITV-based PTV, enabling an average ± standard deviation increase in the planned dose to 95% of the PTV of 4.0 ± 2.8 Gy (9 ± 5%) on the midposition CT (P<.01). For both plans, the delivered minimum gross tumor volume (GTV) doses were greater than the planned nominal prescribed dose in all 20 patients and greater than the planned dose to 95% of the PTV in 18 (90%) patients. Nine patients (45%) had 1 or more GTVs with a delivered minimum dose more than 5 Gy higher with the midposition CT plan using dose probability PTV, compared with the delivered dose with the exhale CT plan using ITV-based PTV. Conclusions: For isotoxic liver SBRT planned and delivered at the mean respiratory, reduced dose probability PTV enables a mean escalation of 4 Gy (9%) in 6 fractions over ITV-based PTV. This may potentially improve local control without increasing the risk of tumor underdosing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Contouring and Constraining Bowel on a Full-Bladder Computed Tomography Scan May Not Reflect Treatment Bowel Position and Dose Certainty in Gynecologic External Beam Radiation Therapy

Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined. Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm{sup 3}. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm{sup 3} (range, 74.3-251.4 cm{sup 3}). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm{sup 3}; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV{sub B}owel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

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

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

62 RADIOLOGY AND NUCLEAR MEDICINE↗