bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-14-06: Outcomes in 500 patients from a large, retrospective study of APBI with a strut-based breast brachytherapy applicator
Authors: Yashar C , Butler E , Einck JP , Finkelstein SE , Graves YJ , Han B , Hong RL , Komarnicky LT , Lyden M , Mahalingam SB , Mantz CA , Nasr N , Nigh SS , Pollock J , Reiff JE , Scanderbeg D , Snyder MR , Strasser JF , Kuske RR 
Published: August 2014

Abstract
Purpose/Objectives:
The SAVI Collaborative Research Group (SCRG) is a coalition of 14 institutions who have retrospectively compiled a large database of APBI patients treated with a strut-based brachytherapy device (SAVI). This report details the findings of statistical correlations between numerous dosimetric variables and cosmetic outcome.
Materials/Methods:
The SCRG study enrolled 1005 patients. A subset of patients with complete dosimetry and more than 1 year of follow-up by a radiation oncologist were analyzed for toxicity, cosmesis and recurrence/survival. Dosimetric parameters were tabulated for patients, including: V90, V95, V100, V150, V200, skin spacing (skin-bridge), maximum skin dose, tumor size, PTV-Eval volume and applicator size (model). Toxicity (e.g., telangiectasia, fibrosis, fat necrosis, seroma) were graded by physicians for patients with at least 1 year of follow-up (up to 6 years) using the CTCAE v3 Scale and fat necrosis using a simplified CTCAE scale (Grade 1 asymptomatic but seen on imaging, grade 2 symptomatic without intervention, & grade 3 required intervention).
Results:
Median follow up in this cohort was 29.2 months (range 2.4 to 72.2 months). Follow up was &gt;2 yr and &gt;3 yr for 323 and 191 subjects, respectively. Overall, in 500 subjects the late toxicity (grade ≥2) rates were less than 5% during follow up: telangiectasia 1.0%, fibrosis 4.1%, seroma 2.9% and fat necrosis 0.6%. Cosmesis was reported at various post-APBI follow-up visits following treatment completion (6, 12, 24, 36, 48 & 60+ months). For the 6 and 12 month intervals, 98% (n = 122) and 97% (n = 262) were reported excellent or good (E/G), respectively. At 24, 36, 48 and 60 month intervals, the E/G rates were 93% (n = 184), 90% (n = 98), 100% (n = 41) and 94% (n = 15), respectively. The raw rates of ipsilateral breast tumor recurrence (IBTR) and TR/MM were 1.6% (n = 8) and 1.2% (n = 6), respectively, in 500 patients with &gt;1 year of follow up. The 1- and 2-year actuarial rates of overall survival and disease-free survival were: 1-year, 99.6% & 99.4%, resp. and 2-year, 99.2% & 96.7%.
Conclusions:
APBI treatment with the strut-based applicators was well-tolerated, demonstrated low toxicity rates, favorable cosmetic outcomes and excellent local control over the follow-up to date. Patients with challenging breast anatomy were successfully treated with strut-based devices.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-06.
Abstract P5-14-17: Post-lumpectomy tumorbed delineation for breast boost or partial breast irradiation: The influence of additional MRI and CT imaging
Authors: den Hartogh MD , Philippens MEP , van Dam IE , Kleynen CE , Tersteeg RJHA , Kotte ANTJ , van Vulpen M , van Asselen B , van den Bongard DHJG 
Published: August 2014

Abstract
Rationale/Purpose
In early stage breast cancer patients, most recurrences occur in the vicinity of the original tumor location. Therefore, after initial lumpectomy it is important to accurately delineate the tumorbed (TB) area for breast boost and partial breast irradiation on the planning-CT scan. However, consistency in TB delineation among radiation oncologists is low on standard CT imaging.
The purpose of this study was to determine whether additional pre- and postoperative MRI and CT imaging could increase consistency in standard CT-guided target volume delineation among radiation oncologists.
Methods
Fourteen cT1-2 patients underwent MRI and CT imaging in supine radiotherapy position before and after lumpectomy. TBs were delineated by 4 breast radiation oncologists following delineation guidelines on the standard postoperative planning-CT alone, and planning-CT registered to 1) postoperative MRI (T1 (with and without fat suppression) and T2 weighted sequences) 2) preoperative contrast-enhanced (CE) CT, and 3) preoperative CE-MRI (T1 weighted sequence with fat suppression). Consistency was defined by the conformity index (CI), which was calculated by dividing the encompassing volume of each observer pair, by the volume of overlap for each observer pair. Furthermore, volumes and the distance between centres of mass (dCOM) of the delineated TBs were determined. A Wilcoxon signed-rank test was performed to compare variables between different imaging modalities, with a significance level of a = 0.05.
Results
Results of the analysis are shown in Table 1. Addition of a postoperative MRI to the standard postoperative planning CT did not influence the CI (p = 0.176) or dCOM (p = 0.110). However, the TB volumes increased significantly with a median increase of 6 cm3 (p&lt;0.001). Addition of a preoperative CT or MRI increased the CI by 0.01 and 0.02 (both p&lt;0.001). Furthermore, preoperative CT and MRI increased dCOM (p = 0.004 and p = 0.001) and volumes (both p&lt;0.001).
Table 1 medianrange p-valueVolume (cm3) CT224-934 CT + postoperative MRI283-964&lt;0.001CT + preoperative CT266-933&lt;0.001CT + preoperative MRI257-933&lt;0.001 Conformity index CT0.570.00-0.90 CT + postoperative MRI0.610.00-0.890.176CT + preoperative CT0.580.00-0.90&lt;0.001CT + preoperative MRI0.590.00-0.89&lt;0.001 dCOM (mm) CT50-53 CT + postoperative MRI40-520.110CT + preoperative CT31-420.004CT + preoperative MRI50-480.001
Conclusion
Although significant, the addition of postoperative MRI, preoperative CE-CT or preoperative CE-MRI did not result in a clinically relevant improvement of the consistency in postoperative CT-guided TB delineation among radiation oncologists. Furthermore, target volumes increased with all imaging modalities.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-17.
Abstract P6-01-02: Celecoxib alleviates tamoxifen-instigated angiogenic effects by ROS-dependent VEGF/VEGFR2 autocrine signaling
Authors: Mandal M , Prasanth Kumar BN 
Published: August 2014

Abstract
Background
Tamoxifen (TAM) is widely used in the chemotherapy of breast cancer and as a preventive agent against recurrence after surgery. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy. Celecoxib (CXB), a selective COX-2 inhibitor, suppresses VEGF gene expression by targeting the VEGF promoter responsible for its inhibitory effect. For this study, we had selected CXB as non-steroidal anti-inflammatory drug in combination with TAM for suppressing VEGF expression and simultaneously reducing doses of both the drugs.
Methods
The effects of CXB combined with TAM were examined in two human breast cancer cell lines in culture, MCF7 and MDA-MB-231. Assays of proliferation, apoptosis, angiogenesis, metastasis, cell cycle distribution, and receptor signaling were performed.
Results
Here, we elucidated how the combination of TAM and the selective COX-2 inhibitor, celecoxib (CXB) at nontoxic doses exerts anti-angiogenic effects by specifically targeting VEGF/VEGFR2 autocrine signaling through ROS generation. At the molecular level, TAM-CXB suppresses VHL-mediated HIF-1a activation, responsible for expression of COX-2, MMP-2 and VEGF. Besides low VEGF levels, TAM-CXB also suppresses VEGFR2 expression, confirmed through quantifying secreted VEGF levels, luciferase and RT-PCR studies. Interestingly, we observed that TAM-CXB was effective in blocking VEGFR2 promoter induced expression and further 2 fold decrease in VEGF levels was observed in combination than TAM alone in both cell lines. Secondly, TAM-CXB regulated VEGFR2 inhibits Src expression, responsible for tumor progression and metastasis. FACS and in vivo enzymatic studies showed significant increase in the reactive oxygen species upon TAM-CXB treatment.
Conclusions
Taken together, our experimental results indicate that this additive combination shows promising outcome in anti-metastatic and apoptotic studies. In a line, our preclinical studies evidenced that this additive combination of TAM and CXB is a potential drug candidate treatment for breast tumors expressing high levels of VEGF and VEGFR2. This ingenious combination might be a better tailored clinical regimen than TAM alone for breast cancer treatment.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-01-02.
Abstract P6-04-16: TGF-b2, a novel target of CD44-promoted breast cancer invasion
Authors: Al-Riyami H , Madani S , Gupta I , Shanmuganathan S , Abdraboh ME , Al-Farsi Y , Raj MHG , Ouhtit A 
Published: August 2014

Abstract
Hyaluronan (HA) mediates communication between cancer cells and the environment via interactions with the cell surface receptor CD44. We have previously shown that CD44-HA interaction in BC cells promotes adhesion to bone marrow endothelial cells. This suggests that HA/CD44 signalling may be correlated with breast cancer (BC) metastasis. The long-term objective of this study is to increase our understanding of the mechanisms by which CD44-HA interaction promotes BC metastasis, and further identify and validate CD44-downstream transcriptional targets for anti-metastatic therapy.
Pursuant to this goal, we have developed a tetracycline (tet)-regulated expression of CD44 gene in the BC cell line MCF-7 (B5 clone) and identified TGF-beta2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44s-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA for 18, 24, and 48 hr post-tet withdrawal. Expression of TGF-beta 2 was examined using RT-PCR and western-Blot analyses.
Our results showed that TGF-beta2 mRNA levels were significantly elevated following the removal of tet at 18, 24, and 48 h post-HA stimulation compared to the parental cells. Furthermore, the TGF-beta2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tet. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-beta2 expression upon HA-stimulation and in the absence of tet.
Our data strongly support the hypothesis that TGF-beta2 is a potential target of HA/CD44- downstream-signaling mediating BC cell invasion. Ongoing investigation aims to elucidate the signal transduction pathways coupling CD44 to the regulation of TGF-beta2 expression, and further validate CD44/TGF-beta2 axes in breast tumor invasion and metastasis.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-04-16.
Abstract P6-05-21: High standardized uptake value of 18F-fluorodeoxy-glucose positron emission tomography is related with FOXM1 expression, which negatively influences survival in breast cancer patients
Authors: Ahn SG , Lee HM , Lee HW , Lee SA , Leem S-H , Jeong J , Chu I-S 
Published: August 2014

Abstract
Background
Standardized uptake value (SUV), which is an indicator reflecting glucose uptake in 18F-fluorodeoxy-glucose positron emission tomography (18FDG-PET), can be implicated to be a prognostic factor in various malignant tumors. Using a data set with gene expression profiling, we tried to uncover a molecular marker associated with a high SUV, along with an exploration its prognostic value in breast cancer.
Methods
Microarray gene expression profiling was performed in 287 breast tumor samples. Five hundred nanograms of total RNA were used for labeling and hybridization, according to the manufacturer's protocols (Illumina, San Diego, CA). In 66 samples with SUV, genes with expression patterns highly correlated with the value of SUV were selected for cluster analysis. Five hundred thirty tree gene features were selected for analysis. Patients were divided into the following two groups: SUV-high cluster and SUV-low cluster. Hierarchical clustering analysis based on 533 gene features. The prognostic value of the identified gene was validated in 287 samples and the online public set.
Results
Gene network analysis using Ingenuity Pathway Analysis software revealed considerable enrichment of the gene network toward FOXM1 in the SUV-high cluster, suggesting that its activation might be a key determinant associated with SUV level. Also, the expression of many marker genes for cell proliferation, such as AURKA, AURKB, BIRC5, BUB1, and TOP2A, was significantly higher in the SUV-high cluster than in the SUV-low cluster. Next, in the 287 patients with known FOXM1 expression levels, the Kaplan-Meier survival analysis revealed a negative prognostic impact of highly expressed FOXM1 for overall survival (OS), disease-free survival (DFS), and distant-metastasis-free survival (DMFS) (P = 0.002, P = 0.015, P = 0.008, respectively; Table 1). To validate a prognostic impact of FOXM1 in an external data, we performed a survival analysis using online gene-expression array data. There was significant correlation between the FOXM1 expression level and OS, DFS and DMFS.
Conclusion
Here we analyzed FOXM1 as a biomarker associated with a high SUV and demonstrated that FOXM1 is a negative prognostic factor in breast cancer.
Prognostic significance of FOXM1 in 287 patients Overall SurvivalBreast cancer-specific survivalDisease-free survivalDistant metastasis-free survivalFOXM1 high (n = 144)log-rank testlog-rank testlog-rank testlog-rank testFOXM1 low (n = 133)P = 0.002P = 0.001P = 0.015P = 0.008
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-21.
Abstract P6-06-15: Cost impact of oncotype Dx® breast cancer assay use in a fully integrated healthcare delivery system
Authors: Carlson JJ , Watanabe J , Boudreau D 
Published: August 2014

Abstract
Background:
The Oncotype Dx Breast Cancer Assay (ODX) provides relevant information on the risk of distant recurrence and the treatment effect for adjuvant chemotherapy (ACT) in early stage breast cancer. However, no studies to date have evaluated the impact of ODX use on total and oncology specific costs. The objective of this study was to explore the impact of ODX use on total and oncology specific costs within the Group Health Cooperative health plan.
Methods:
Our study sample included women diagnosed between 2004-2012 with ER positive, node negative, early stage (I, IIA, or IIB) breast cancer. Data were collected from SEER and automated health plan data. We used multiple logistic regression to model receipt of adjuvant chemotherapy as a function of OncotypeDx Breast Cancer Assay receipt. Further, we used multiple linear regression to model total and oncology specific one-year costs as a function of OncotypeDx Breast Cancer Assay receipt. In both analyses, we adjusted for key patient, tumor, and health system factors.
Results: The study population consisted of 1510 women, 13% of which received the ODX test. The groups were similar across relevant clinical and demographic characteristics with the exception of age at diagnosis, stage, tumor grade and drug benefits. In the logistic regression analysis, patients who received ODX were 51% less likely to receive adjuvant chemotherapy versus those who did not receive the test. In the multiple linear regression analysis, those who received ODX had fewer total and oncology specific one-year costs (total costs difference: -$9,149 (95% CI: -$13,818, -$4,481, P-Value: &lt;0.001); oncology specific cost difference: -$1,380 (95% CI: -$2,361, -$400, P-Value: &lt;0.006).
Study Results ODX vs. No ODX95% CIP-valueTotal cost difference*-$9,149-$13,818 to -$4,481&lt;0.000Oncology cost difference*-$1,380-$2,361 to -$4000.006Adjuvant chemotherapy use (OR)*0.490.33 to 0.73&lt;0.000* Model covariates: stage, Charlson comorbidity score, age at diagnosis, tumor size, tumor grade, race, and pharmacy benefits
Conclusions: Our results are the first to report on the impact of the ODX test directly on total and oncology specific costs. In accordance with previous studies that used modeled cost estimates, i.e. through cost projections focusing solely on the adjuvant chemotherapy reductions, we found a statistically significant difference in both total and oncology specific costs. These data further bolster the evidence that suggests the ODX lowers total and oncology specific costs. Further evidence is needed to evaluate the impact of ODX on clinical outcomes.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-15.
Abstract P6-07-12: Should adjuvant zoledronic acid be used in early-stage, endocrine-sensitive breast cancer?
Authors: Lamond NWD , Skedgel C , Rayson D , Younis T 
Published: August 2014

Abstract
Introduction: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with endocrine-sensitive breast cancer and low estrogen levels (LEL) including post-menopausal women, and pre-menopausal women treated with LHRH agonists. ZA, however, is also associated with potential adverse events and incremental drug acquisition costs. An overall assessment of the long-term clinical and economic impacts of adjuvant ZA may therefore help guide the decision to adopt this novel therapeutic option. We examined the incremental quality-adjusted life-years (QALY) and costs per QALY associated with adjuvant treatment including ZA relative to treatment without ZA in women with endocrine-sensitive breast cancer and LEL. Methods: A Markov model was developed to compute cumulative costs, from a Canadian perspective, and QALY associated with and without adjuvant ZA over a 25-year horizon. Costs, utilities, DFS and adverse events were derived from relevant clinical trials, the literature and local resources. One-way and probabilistic sensitivity analyses were conducted for key model parameters. Results: Adjuvant ZA was associated with incremental QALY gains of 0.62 and 0.42 and resultant CU estimates of $12,617 and $19,775 per QALY gained in pre- and post-menopausal women, respectively. CU estimates were robust across reasonable uncertainty ranges in all parameters. Conclusions: Adjuvant ZA appears to be associated with long-term QALY gains in women with endocrine-sensitive breast cancer and LEL as well as CU estimates that are below commonly accepted North American thresholds. The favourable long-term clinical and economic impacts observed in this study further support the use of adjuvant ZA in this setting.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-07-12.
Abstract P6-11-03: Follow up of breast cancer patients who underwent gamma knife radiosurgery for a diagnosis of brain metastases: A single institutional experience
Authors: Abu-Khalaf MM , Hatzis C , Chung G , DiGiovanna M , Tara S , Erin H , Lajos P , James YB , Veronica CL 
Published: August 2014

Abstract
Background: Breast cancer (BC) is the second most common cause of brain metastases in the United States. We performed a retrospective analysis of BC patients (pts) in the Yale Gamma Knife Radiosurgery (GKRS) database treated for brain metastases (mets) to report overall survival (OS) from time of GKRS, and to identify factors that predict improved survival outcomes.
Methods: We performed retrospective review of the Yale database of BC pts treated with standard GKRS technique for brain mets from 2000 to May 2013. Treatment doses typically ranged from 16 to 24 Gy prescribed to the 40-85% isodose surfaces. Overall survival (OS) for each patient was calculated from the date of first GKRS treatment of brain metastases. Variables included age, Karnofsky Performance Status (KPS), pre/post whole-brain radiation treatment (WBRT) and/or surgical resection, and # of brain mets treated (1-4 vs ≥5).
Results: A total of 80 BC pts were identified, with a mean age of 56.2 yrs; KPS 40-60 in 8pts (10%), 70-80 in 13 (16%), 90-100 in 41 (51%), unknown in 18 (23%); ER+ in 38 (48%), ER- in 38 (48%), unknown in 4 (5%); HER2 + in 38 (48%), HER2- in 33 (41%), indeterminate in 3 (4%) and unknown in 6 (8%). BC subtypes are Luminal A (ER+/HER2-) in 16 (20%), Luminal B (ER+/HER2+) in 19 (24%), HER-2(ER-/HER2+) in 17 (21%), Basal (ER-/HER2-) in 17 (21%), unknown in 11 (14%). Number of brain mets at time of first GKRS ≥5 in 32 (40%); prior WBRT in 30 (38%); WBRT post GKRS in 9 (11%); surgical resection for brain mets in 13 (16%) prior to GKRS and post GKRS in 9 (11%); 16% had ≥3 GKRS. Median time from primary BC dx to brain mets is 62.8 months (m) (range 46.2-81.6); with no significant difference among subtypes. Median OS from GKRS is 13.1 m (7.6-21.9); median OS from brain mets is 18.8 m (11.7-23.9). On univariate analysis, factors associated with significant improved OS from time of GKRS included HER-2 subtype (p = 0.005), KPS 90-100 (p = 0.008), good control of systemic disease (p = 0.017), pre (p = 0.041) and post GKRS surgical resection (p = 0.02). Age, pre or post WBRT, # of brain mets (1-4 vs. 5) were not significant predictors of OS from time of GKRS. In a multivariate Cox analysis (46 cases), HER-2 subtype remained a significant predictor of improved OS from time of GKRS; (HR) 0.26, 95%CI 0.08 to 0.8, p-value = 0.02. There was a trend in favor of surgical resection of brain mets pre GKRS (HR 0.14, 95% CI 0.02 to 1.15, p-value = 0.067
Conclusion: GKRS offers good local control for BC pts with brain mets, and is a reasonable option for pts with ≥5 brain mets. Our results show no associated survival benefit for administration of WBRT pre/post GKRS. HER-2 subtype is a significant predictor of improved survival in BC pts undergoing GKRS for brain mets.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-03.