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At least 487 records · Page 27
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Breast Imaging of Transgender Individuals: A Review

Purpose: This review will inform radiologists about the evidence base regarding radiographic imaging for transgender individuals and considerations for providing culturally sensitive care for this population. Findings: Transgender individuals are increasingly referred for both screening and diagnostic breast imaging. It is important that the clinic environment is welcoming, the medical staff utilize accepted terminology and patients are able to designate their gender and personal history to ensure appropriate care. Hormone and surgical treatments used for transition by many transgender women and men may change the approach to imaging. Summary: Although not yet evidence-based, screening mammography is currently suggested for transgender women with risk factors, including those receiving hormone treatment over 5 years. The risk for breast cancer in transgender individuals is still being defined.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows

Highlights: Black-Right-Pointing-Pointer Endocrine disrupting chemicals affect adipogenesis in mesenchymal stem cells (MSC). Black-Right-Pointing-Pointer The adipogenic impact depends strongly on the window of exposure. Black-Right-Pointing-Pointer Bisphenol A reduces the potential of MSC to differentiate into adipocytes. Black-Right-Pointing-Pointer DEHP and TBT trigger the adipogenic differentiation of mesenchymal stem cells. Black-Right-Pointing-Pointer BPA, DEHP and TBT did not affect adipogenesis in embryonic stem cells. -- Abstract: Endocrine disrupting chemicals (EDC) like bisphenol A (BPA), bis(2-ethylhexyl)phthalate (DEHP) and tributyltin (TBT) are ubiquitously present in the environment and in human tissues. They bind to nuclear hormone receptors and affect cellular and developmental processes. In this study, we show that BPA, DEHP and TBT affect the adipogenic differentiation of murine mesenchymal stem cells (MSC, C3H/10T1/2) in a concentration-, stage- and compound-specific manner. C3H/10T1/2 cells and embryonic stem cells (CGR8) were exposed to BPA, DEHP or TBT at different stages of cell determination and differentiation (undifferentiated growth, adipogenic induction and terminal adipogenic differentiation). The final amount of differentiated adipocytes, cellular triglyceride content and mRNA expression of adipogenic marker genes (adiponectin, FABP4, PPAR{gamma}2, LPL) were quantified and compared with corresponding unexposed cells. BPA (10 {mu}M) decreased subsequent adipogenic differentiation of MSC, when cells were exposed during undifferentiated growth. In contrast, DEHP (100 {mu}M) during the hormonal induction period, and TBT (100 nM) in all investigated stages, enhanced adipogenesis. Importantly, exposure of undifferentiated murine embryonic stem cells did not show any effect of the investigated EDC on subsequent adipogenic differentiation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

The small GTPase Cdc42 modulates the number of exocytosis-competent dense-core vesicles in PC12 cells

Highlights: Black-Right-Pointing-Pointer Regulation of exocytosis by Rho GTPase Cdc42. Black-Right-Pointing-Pointer Cdc42 increases the number of fusion events from newly recruited vesicles. Black-Right-Pointing-Pointer Cdc42 increases the number of exocytosis-competent dense-core vesicles. -- Abstract: Although the small GTPase Rho family Cdc42 has been shown to facilitate exocytosis through increasing the amount of hormones released, the precise mechanisms regulating the quantity of hormones released on exocytosis are not well understood. Here we show by live cell imaging analysis under TIRF microscope and immunocytochemical analysis under confocal microscope that Cdc42 modulated the number of fusion events and the number of dense-core vesicles produced in the cells. Overexpression of a wild-type or constitutively-active form of Cdc42 strongly facilitated high-KCl-induced exocytosis from the newly recruited plasma membrane vesicles in PC12 cells. By contrast, a dominant-negative form of Cdc42 inhibited exocytosis from both the newly recruited and previously docked plasma membrane vesicles. The number of intracellular dense-core vesicles was increased by the overexpression of both a wild-type and constitutively-active form of Cdc42. Consistently, activation of Cdc42 by overexpression of Tuba, a Golgi-associated guanine nucleotide exchange factor for Cdc42 increased the number of intracellular dense-core vesicles, whereas inhibition of Cdc42 by overexpression of the Cdc42/Rac interactive binding domain of neuronal Wiskott-Aldrich syndrome protein decreased the number of them. These findings suggest that Cdc42 facilitates exocytosis by modulating both the number of exocytosis-competent dense-core vesicles and the production of dense-core vesicles in PC12 cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells

Highlights: Black-Right-Pointing-Pointer We evaluated the effect of ANXA1 on promoting migration and invasion in MDA-MB-231 cells. Black-Right-Pointing-Pointer ANXA1 siRNA inhibits invasion and migration. Black-Right-Pointing-Pointer ANXA1 regulates MMP-9 expression and activity. Black-Right-Pointing-Pointer ANX-1 siRNA inhibits the activation of NF-{kappa}B in MDA-MB-231 cells. -- Abstract: Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-{kappa}B) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-{kappa}B signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

c-Met inhibitor SU11274 enhances the response of the prostate cancer cell line DU145 to ionizing radiation

Highlights: Black-Right-Pointing-Pointer c-Met inhibition could significantly enhance the radiosensitivity of DU145 cells. Black-Right-Pointing-Pointer The mechanisms of the radiosensitization effect of c-Met inhibition on DU145 cells were also presented in this paper. Black-Right-Pointing-Pointer This is the first study demonstrating the effectiveness of c-Met inhibition on treating HRPC cells with radiotherapy. -- Abstract: Hormone-refractory prostate cancer shows substantial resistance to most conventional therapies including radiotherapy, constitutes a key impediment to curing patients with the disease. c-Met overexpression plays a key role in prostate cancer tumorigenesis and disease progression. Here, we demonstrate that c-Met inhibition by SU11274 could significantly suppress cell survival and proliferation as well as enhance the radiosensitivity of DU145 cells. The underlying mechanisms of the effects of SU11274 on DU145 cells may include the inhibition of c-Met signaling, depolarization of the mitochondrial membrane potential, impairment of DNA repair function, abrogation of cell cycle arrest, and enhancement of cell death. Our study is the first to show the effectiveness of combining c-Met inhibition with ionizing radiation to cure hormone-refractory prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the homeostasis of these lipids in TNBC. Together, our results uncover an unexpected role for Sac3 phosphatase in TNBC cell proliferation. Database analyses, discussed herein, reinforce the involvement of Sac3 in breast cancer pathogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Calcium and actin in the saga of awakening oocytes

The interaction of the spermatozoon with the egg at fertilization remains one of the most fascinating mysteries of life. Much of our scientific knowledge on fertilization comes from studies on sea urchin and starfish, which provide plenty of gametes. Large and transparent, these eggs have served as excellent model systems for studying egg activation and embryo development in seawater, a plain natural medium. Starfish oocytes allow the study of the cortical, cytoplasmic and nuclear changes during the meiotic maturation process, which can also be triggered in vitro by hormonal stimulation. These morphological and biochemical changes ensure successful fertilization of the eggs at the first metaphase. On the other hand, sea urchin eggs are fertilized after the completion of meiosis, and are particularly suitable for the study of sperm–egg interaction, early events of egg activation, and embryonic development, as a large number of mature eggs can be fertilized synchronously. Starfish and sea urchin eggs undergo abrupt changes in the cytoskeleton and ion fluxes in response to the fertilizing spermatozoon. The plasma membrane and cortex of an egg thus represent “excitable media” that quickly respond to the stimulus with the Ca{sup 2+} swings and structural changes. In this article, we review some of the key findings on the rapid dynamic rearrangements of the actin cytoskeleton in the oocyte/egg cortex upon hormonal or sperm stimulation and their roles in the modulation of the Ca{sup 2+} signals and in the control of monospermic fertilization. - Highlights: • Besides microtubules, microfilaments may anchor the nucleus to oocyte surface. • The cortical Ca{sup 2+} flash and wave at fertilization mirror electrical membrane change. • Artificial egg activation lacks microvilli extension in the perivitelline space. • Calcium is necessary but not sufficient for cortical granules exocytosis. • Actin cytoskeleton modulates Ca{sup 2+} release at oocyte maturation and fertilization.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

1-α,25-dihydroxyvitamin D3 potentiates avian osteoclast activation by increasing the formation of zipper-like structure via Src/Rac1 signaling

Highlights: • 1α,25-(OH){sub 2}D{sub 3} potentiates the formation and activation of avian osteoclasts. • 1α,25-(OH){sub 2}D{sub 3} promotes the formation of the zipper-like structure in OC precursors. • 1α,25-(OH){sub 2}D{sub 3} stimulates zipper-like structure formation via Src/Rac1 signaling. Avian bone metabolism diseases affect the development and production of chickens, and many of these diseases can be prevented and controlled by balanced nutrition and hormone medicine. The steroid hormone 1α,25-dihydroxyvitamin D{sub 3} plays a key role in maintaining the balance of avian bone metabolism. Clinically, 1α,25-(OH){sub 2}D{sub 3} has been used to treat several bone diseases. Although several previous studies have investigated the effects of 1α,25-(OH){sub 2}D{sub 3} on osteoclastogenesis, the mechanisms underpinning osteoclast (OC) activity remain largely unknown. Herein, we used molecular and cell biology approaches to demonstrate that 1α,25-(OH){sub 2}D{sub 3} increases avian OC formation and activity, and upregulates bone resorption-related genes. Moreover, 1α,25-(OH){sub 2}D{sub 3} regulates the OC cytoskeleton by increasing the formation of zipper-like structure in OC precursor cells to potentiate OC activity via the Src/Rac1 signaling pathway. These findings provide new insight into the role of 1α,25-(OH){sub 2}D{sub 3} in OC activity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Target identification of hepcidin production inhibitors by a combination of chemical proteomics and radioactive compound binding assay

Highlights: • Hepcidin, a peptide hormone, regulates systemic iron homeostasis. • Hepcidin inhibition could be a strategy for treating anemia of chronic disease. • Molecular target of DS79182026, a hepcidin production inhibitor, must be identified. • Affinity purification-based chemical proteomics identified its target candidates. • Radioactive binding assay and siRNA experiments indicated ALK2 as primary target. Hepcidin is a peptide hormone and has emerged as the central molecule regulating systemic iron homeostasis. Hepcidin inhibition could be a strategy for treating anemia of chronic disease. We previously reported the discovery of DS79182026, a new inhibitor of hepcidin production, from phenotypic screening using the human hepatocyte HepG2 cell line. In this study, we utilized a combination of affinity purification-based chemical proteomics and radioactive compound binding assay, and identified several candidate proteins. Purified recombinant proteins were subjected to radioactive compound binding assays for validation, and ALK2 and ALK3 demonstrated specific binding to the compound. Since ALK2 is known to be related to hepcidin production, we focused on ALK2 and found that its knockdown decreased hepcidin expression; we also found a strong correlation (R = 0.920) between pharmacological activity and compound affinity to ALK2. These results indicate that ALK2 is the primary target protein of our new hepcidin production inhibitors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Brassinosteroid reduces ABA accumulation leading to the inhibition of ABA-induced stomatal closure

Highlights: • ABA strengthened BL-induced stomatal closure. • Expression of OST1 was induced by BL, and BL-induced stomatal closure required OST1. • Inhibition of ABA-induced stomatal closure by BR was due to reduced ABA accumulation. Proper regulation of stomatal movement in response to various environmental stresses or developmental status is critical for the adaptation of many plant species to land. In plants, abscisic acid (ABA)-induced stomatal closure is a well-adapted method of regulating water status. In addition to ABA, we previously showed that plant-specific steroidal hormone, brassinosteroid (BR), also induces stomatal closure; however, BR modulates ABA-induced stomatal closure negatively at high concentrations. In this study, we further investigated the cross-talk between ABA and BR in relation to stomatal movement. In contrast to previous reports that ABA-induced stomatal closure was inhibited by brassinolide (BL), the most active BR, we showed that BL-induced stomatal closure was enhanced by ABA, indicating that the sequence of ABA or BL treatments led to different results. We found that this phenomenon occurred because the guard cells still had the capacity to be closed further by ABA, as the degree of stomatal closure by BL was always less than that by ABA. We also found that BL-induced stomatal closure required Open Stomata 1 (OST1) activity and the induced expression of OST1 was indifferent to the sequence of ABA and/or BL treatments. In addition, we examined the underlying mechanism by which inhibition of ABA-induced stomatal closure by BL occurred. We revealed that the downregulation of ABA-biosynthetic genes by BL resulted in a lower accumulation of ABA. These results suggested that the regulation of stomatal movement is finely controlled by the combined effects of plant hormones, ABA and BR.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2011

Outcomes of Node-Negative Breast Cancer 5 Centimeters and Larger Treated With and Without Postmastectomy Radiotherapy

Purpose: The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.0-cm tumors treated with mastectomy, stratified by PMRT use. Materials and Methods: Between January 1, 1989 and December 31, 2000, the British Columbia provincial database yielded 100 node-negative patients with tumors {>=}5 cm of 19,846 nonmetastatic breast cancer patients (0.5%). Of these 100 patients, 44 (44%) had received adjuvant PMRT. Results: The PMRT group contained significantly more pT3 >5-cm cases (p = 0.001) and margin-positive cases (p = .03). With a median follow-up of 10 years, the cumulative 10-year LRR rate was 2.3% (95% confidence interval, 0.2-10.5) in the PMRT group vs. 8.9% (95% confidence interval, 3.2-18.2) in the no-PMRT group (p = .2). Regarding LRR in the no-PMRT group, all patients had Grade 3 histologic features (LRR 17%, 5 of 29) and had not received hormonal therapy (LRR 15%, 5 of 34). The 10-year breast cancer-specific survival rate was 85.8% (95% confidence interval 71.0-93.4) in the PMRT group vs. 74.6% (95% confidence interval 59.9-84.5) in the no-PMRT group (p = .2). On multivariate analysis, adjusted for the prognostic and predictive variables, PMRT did not significantly improve the LRR or breast cancer-specific survival rates. Conclusion: The present study demonstrated a low LRR rate for node-negative breast cancer {>=}5 cm. Our results indicate that PMRT should be considered for Grade 3 histologic features and patients not undergoing hormonal therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Pretreatment Nomogram to Predict the Risk of Acute Urinary Retention After I-125 Prostate Brachytherapy

Purpose: Acute urinary retention (AUR) after iodine-125 (I-125) prostate brachytherapy negatively influences long-term quality of life and therefore should be prevented. We aimed to develop a nomogram to preoperatively predict the risk of AUR. Methods: Using the preoperative data of 714 consecutive patients who underwent I-125 prostate brachytherapy between 2005 and 2008 at our department, we modeled the probability of AUR. Multivariate logistic regression analysis was used to assess the predictive ability of a set of pretreatment predictors and the additional value of a new risk factor (the extent of prostate protrusion into the bladder). The performance of the final model was assessed with calibration and discrimination measures. Results: Of the 714 patients, 57 patients (8.0%) developed AUR after implantation. Multivariate analysis showed that the combination of prostate volume, IPSS score, neoadjuvant hormonal treatment and the extent of prostate protrusion contribute to the prediction of AUR. The discriminative value (receiver operator characteristic area, ROC) of the basic model (including prostate volume, International Prostate Symptom Score, and neoadjuvant hormonal treatment) to predict the development of AUR was 0.70. The addition of prostate protrusion significantly increased the discriminative power of the model (ROC 0.82). Calibration of this final model was good. The nomogram showed that among patients with a low sum score (<18 points), the risk of AUR was only 0%-5%. However, in patients with a high sum score (>35 points), the risk of AUR was more than 20%. Conclusion: This nomogram is a useful tool for physicians to predict the risk of AUR after I-125 prostate brachytherapy. The nomogram can aid in individualized treatment decision-making and patient counseling.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Use of the Charlson Combined Comorbidity Index To Predict Postradiotherapy Quality of Life for Prostate Cancer Patients

Purpose: To determine the impact of pretreatment comorbidity on late health-related quality of life (HRQoL) scores after patients have undergone combined radiotherapy for prostate cancer, including high-dose rate brachytherapy boost and hormonal deprivation therapy. Methods and Materials: Results from the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire survey of 158 patients 5 years or more after completion of therapy were used from consecutively accrued subjects treated with curative radiotherapy at our institution, with no signs of disease at the time of questionnaire completion. HRQoL scores were compared with the Charlson combined comorbidity index (CCI), using analysis of covariance and multivariate regression models together with pretreatment factors including tumor stage, tumor grade, pretreatment prostate-specific antigen level, neoadjuvant hormonal treatment, diabetes status, cardiovascular status, and age and Charlson score as separate variables or the composite CCI. Results: An inverse correlation between the two HRQoL domains, long-term global health (QL) and physical function (PF) scores, and the CCI score was observed, indicating an impact of comorbidity in these function areas. Selected pretreatment factors poorly explained the variation in functional HRQoL in the multivariate models; however, a statistically significant impact was found for the CCI (with QL and PF scores) and the presence of diabetes (with QL and emotional function). Cognitive function and social function were not statistically significantly predicted by any of the pretreatment factors. Conclusions: The CCI proved to be valid in this context, but it seems useful mainly in predicting long-term QL and PF scores. Of the other variables investigated, diabetes had more impact than cardiovascular morbidity on HRQoL outcomes in prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Locoregional Recurrence of Breast Cancer in Patients Treated With Breast Conservation Surgery and Radiotherapy Following Neoadjuvant Chemotherapy

Purpose: Breast conservation surgery (BCS) and radiotherapy (RT) following neoadjuvant chemotherapy (NCT) have been linked with high locoregional recurrence (LRR) rates and ipsilateral breast tumor recurrence (IBTR) rates. The purpose of this study was to analyze clinical outcomes in patients who exhibited LRR and IBTR after being treated by BCS and RT following NCT. Methods and Materials: In total, 251 breast cancer patients treated with BCS and RT following NCT between 2001 and 2006 were included. All patients had been shown to be clinically node-positive. Clinical stage at diagnosis (2003 AJCC) was II in 68% of patients and III in 32% of patients. Of those, 50%, 35%, and 15% of patients received anthracycline-based, taxane-based, and combined anthracycline-taxane NCT, respectively. All patients received RT. Results: During follow-up (median, 55 months), 26 (10%) patients had LRR, 19 of these patients had IBTR. Five-year actuarial rates of IBTR-free and LRR-free survival were 91% and 89%, respectively. In multivariate analyses, lack of hormone suppression therapy was found to increase both LRR and IBTR rates. Hazard ratios were 7.99 (p < 0.0001) and 4.22 (p = 0.004), respectively. Additionally, pathology stage N2 to N3 increased LRR rate (hazard ratio, 4.22; p = 0.004), and clinical AJCC stage III IBTR rate (hazard ratio, 9.05; p = 0.034). Achievement of pathological complete response and presence of multifocal tumors did not affect LRR or IBTR. Conclusions: In patients with locally advanced disease, who were clinically node-positive at presentation, BCS after NCT resulted in acceptably low rates of IBTR and LRR. Mastectomy should be considered as an option in patients who present with clinical stage III tumors or who are not treated with adjuvant hormone suppression therapy, because they exhibit high IBTR rates after NCT and BCS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Clinical Outcomes Using Accelerated Partial Breast Irradiation in Patients With Invasive Lobular Carcinoma

Purpose: We compared clinical outcomes of women diagnosed with either invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC) treated with accelerated partial breast irradiation (APBI). Methods and Materials: A total of 16 patients with ILC received APBI as part of their breast-conservation therapy (BCT) and were compared with 410 patients with IDC that received APBI as part of their BCT. Clinical, pathologic, and treatment related variables were analyzed including age, tumor size, hormone receptor status, surgical margins, lymph node status, adjuvant hormonal therapy, adjuvant chemotherapy, and APBI modality. Clinical outcomes including local recurrence (LR), regional recurrence (RR), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed. Results: Median follow-up was 3.8 years for the ILC patients and 6.0 years for the IDC patients. ILC patients were more likely to have positive margins (20.0% vs. 3.9%, p = 0.006), larger tumors (14.1 mm vs. 10.9 mm, p = 0.03) and less likely to be node positive (0% vs. 9.5%, p < 0.001) when compared with patients diagnosed with IDC. The 5-year rate of LR was 0% for the ILC cohort and 2.5% for the IDC cohort (p = 0.59). No differences were seen in the rates of RR (0% vs. 0.7%, p = 0.80), distant metastases (0% vs. 3.5%, p = 0.54), DFS (100% vs. 94%, p = 0.43), CSS (100% vs. 97%, p = 0.59), or OS (92% vs. 89%, p = 0.88) between the ILC and IDC patients, respectively. Additionally, when node-positive patients were excluded from the IDC cohort, no differences in the rates of LR (0% vs. 2.2%, p = 0.62), RR (0% vs. 0%), DFS (100% vs. 95%, p = 0.46), CSS (100% vs. 98%, p = 0.63), or OS (92% vs. 89%, p = 0.91) were noted between the ILC and IDC patients. Conclusion: Women with ILC had excellent clinical outcomes after APBI. No difference in local control was seen between patients with invasive lobular versus invasive ductal histology.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients

Purpose: To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Methods and Materials: Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. Results: One hundred patients were enrolled in this institutional review board-approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation, and another patient elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients were evaluable for toxicity, and, in 1 case, both breasts were treated with partial breast irradiation. Median patient age was 68 years (range, 53-88 years); in 55% of patients the tumor size was <1 cm. All patients had hormone receptor-positive cancers: 87% of patients underwent adjuvant antihormone therapy. At a median follow-up of 64 months (range, 2-125 months), there was one local recurrence (1% ipsilateral breast failure) and one contralateral breast cancer (1% contralateral breast failure). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (one breast edema, one transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36 months follow-up. Conclusions: Five-year efficacy and toxicity of 3D-CRT delivered in prone partial breast irradiation are comparable to other experiences with similar follow-up.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Hypofractionated High-Dose Radiation Therapy for Prostate Cancer: Long-Term Results of a Multi-Institutional Phase II Trial

Purpose: To report late gastrointestinal (GI) and genitourinary (GU) toxicity, biochemical and clinical outcomes, and overall survival after hypofractionated radiation therapy for prostate cancer (PC). Methods and Materials: Three institutions included 113 patients with T1 to T3N0M0 PC in a phase II study. Patients were treated with 56 Gy in 16 fractions over 4 weeks. Late toxicity was scored using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria extended with additional symptoms. Biochemical outcome was reported according to the Phoenix definition for biochemical failure. Results: The incidence of late GI and GU toxicity was low. The 3-year actuarial risk of developing late GU and GI toxicity of grade {>=}2 was 13% and 8% respectively. Five-year biochemical non-evidence of disease (bNED) was 94%. Risk group, T stage, and deviation from planned hormone treatment were significant predictive factors for bNED. Deviation from hormone treatment remained significant in multivariate analysis. Five-year clinical non evidence of disease and overall survival was 95% and 91% respectively. No patient died from PC. Conclusions: Hypofractionated high-dose radiation therapy is a valuable treatment option for patients with PC, with excellent biochemical and clinical outcome and low toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗