bluuebunny/crossref_metadata_2025_split huggingface dataset:
N0539 Phase II Trial of Fulvstrant and Bevacizumab in Patients with Metastatic Breast Cancer Previously Treated with an Aromatase Inhibitor: A North Central Cancer Treatment Group Trial.
Authors: Tan W. , Dueck A. , Flynn P. , Steen P. , Anderson D. , Rowland K. , Nothfeldt D. , Lingle W. , Copland J. , Perez E. 
Published: December 2010

Abstract
Background: Treatment of aromatase refractory metastatic breast cancer (MBC) is difficult and challenging. Estrogen receptor (ER) resistance causes enhanced expression of the vascular endothelial growth factor (VEGF).Several studies have shown that the ER interacts with the VEGF pathway and is an important mechanism of resistance. Therefore we embarked on a phase II study of fulvestrant, a complete ER suppressor and bevacizumab, a well studied VEGF monoclonal antibody in aromatase refractory MBC patients. Methods: A single stage phase II study with an interim analysis of fulvestrant and bevacizumab was conducted with these objectives: 6 month progression-free survival rate (PFS), tumor response, toxicity, and overall survival. Regimen: fulvestrant 250 mg day1 and 15 (cycle 1) then day 1 (cycle 2 and beyond) and bevacizumab 10mg/kg days 1 and 15 of each 4 weeks is a cycle. Results: At the time of interim analysis, 11/20 evaluable patients achieved 3-month progression-free survival status while remaining on treatment for at least 3 months, not meeting the protocol specified efficacy requirements and thus halting accrual. 36 patients were enrolled from September 2007-December 2008; 33 patients were evaluable. Number of prior metastatic chemotherapy regimens: 0 in 26 patients and 1 in 7 patients. 22 (67%) patients received prior hormonal therapy in the metastatic setting. 18 (55%) had measurable disease. A median of 6 cycles (range 1-19) were administered. 12/33 evaluable patients (95% CI:20-55%) achieved 6-month progression-free survival status while remaining on treatment for a least 6 months. Among 18 patients with measurable disease, 2 (11%) patients CI:1.4-35%) had a confirmed tumor reponse (both PR). Additionally, 2 patients had stable disease for greater than 6 months, for a clinical benefit rate of 22%. Median follow up was 8.5 months (range 1.7-17.5 months). Median progression-free survival was 6.2 months (95% CI:5.4-10.1 months). The 6 -month overall survival rate was 84.8% (95% CI 73.5-98%). The median dose level administered was 250 mg for fulvestrant and 10 mg/kg for bevacizumab for cycles 1-19. The most common grade 3/4 adverse events (AEs) were hypertension 2 (6%), headache pain 2 (6%), and confusion 2 (6%). There was 1 grade 5 central nervous system hemorrhage. 13 (39%) patients experienced a grade 3 non-hematologic AE and 4 (12%) experience a grade 4+ non-hematologic AE. Conclusion: Fulvestrant/bevacizumab is safe and tolerable. Although this regimen did not meet its statistical endpoint, 22% of evaluable patients with aromatase refractory diesease achieved clinical benefit with minimal toxicity.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4096.
Pentoxifylline and Vitamin E Treatment for Prevention of Radiation Induced Side Effects in Women with Breast Cancer: A Phase Two, Double Blind, Placebo Controlled Randomised Clinical Trial (Ptx-5).
Authors: Malmström P. 
Published: December 2010

Abstract
Background: A previous study has shown that pentoxifylline in combination with vitamin E can reverse radiation induced fibrosis. Our aim in the present study was to investigate if the same drugs could prevent radiation induced side effects in women with breast cancer.Patients and Methods: A randomised, placebo-controlled, double blind, parallel group trial was performed. Women with breast cancer were treated for 12 months with pentoxifylline 400 mg t.i.d. or placebo, in combination with vitamin E 100 mg t.i.d. starting 1-3 months after the completion of radiotherapy. The primary endpoint was passive abduction of the shoulder, and the secondary endpoint was difference in arm volumes. The trial is registered on the ISRCTN.org website, number ISRCTN39143623.Results: 83 patients were included in the study; 42 in the pentoxifylline + vitamine E group and 41 in the placebo + vitamine E group. Both treatments were generally well tolerated. Seven patients were withdrawn from treatment due to disease progression; four in the pentoxifylline group and three in the placebo group. At inclusion patients had impaired passive abduction of the shoulder. During treatment both groups improved significantly. With one year of follow-up median improvement from baseline was 3.7° (p=0.0035) in the pentoxifylline group and 9.4° (p= 0.0041) in the placebo group, but no difference between the groups was detected (p=0.20). Arm volumes increased over time in the placebo group (1.04%), but not in the pentoxifylline group (0.50%). This difference between the groups was statistically significantl(p=0.0172).Conclusions: The combination of pentoxifylline and vitamin E was safe and may be used for prevention of some radiation induced side effects. We found that pentoxifylline in combination with vitamin E diminished development of lymphoedema.(Accepted for publication in European Journal of Cancer)Updated results with longer follow-up will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4100.
Feasibility of Preoperative Single Fraction Partial Breast Radiotherapy for Early Stage Breast Cancer.
Authors: Palta M. , Yoo S. , Horton J. 
Published: December 2010

Abstract
Introduction: Preliminary data supports the efficacy of partial breast irradiation (PBI) in carefully selected patients. However, in 2008, several series evaluating external beam PBI reported negative toxicity outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses.We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume, as defined by magnetic resonance imaging (MRI), would be dosimetrically feasible and result in decreased dose to the ipsilateral breast as compared to institutional historical controls.Methods: Ten patients with unifocal T1 breast cancer who had undergone a preoperative MRI were identified. Contrast-enhanced subtraction MR images were loaded into Eclipse treatment planning software and used to define the gross tumor volume (GTV). A 1.5cm uniform expansion (minus first 5mm of skin) was used to generate the clinical target volume (CTV) for dose-volume analysis. An additional 2-3 mm margin was included for penumbra.The first 3mm of skin/subcutaneous tissue was defined as an avoidance structure. Bilateral lungs and heart were segmented. A prospective “virtual plan” was created using four photon beams in a non-coplanar beam arrangement and optimized to deliver 15Gray (Gy) to the CTV.Specific dosimetric data was extracted including dose conformity (breast volume receiving 100% of the dose/CTV) and dose to the ipsilateral breast, ipsilateral lung, and heart.Results: The median breast volume was 1713cc's (range 1014 – 2140cc's) and the median target volume only 41cc's (26-62cc's). In all cases, 95% of the prescription dose covered 100% of the CTV volume. Median dose conformity was 1.2 (range 1.1-1.6). Maximum dose for all plans was not greater than 110%. Doses to the heart and lung were negligible.Median maximum skin dose was 9.3Gy or 62% of the prescription dose. Median maximum dose to 1cc of skin was reduced to 7.0Gy and at 10cc's skin volume, the median maximum was only 4.9Gy.Median percent of the ipsilateral breast volume receiving 100% of the dose (V100) was only 3.5% (range 2.4-4.7%). The median percent volume receiving 50% of the dose (V50) was 13% (range 7.5-20.8%), substantially less than institutional experience with post-operative PBI. Pre-operative PBIPost-operative PBI n=10n=27 Median (range)Median (range)V1003.5% (2.4-4.7)20% (3-42)V5013% (7.5-20.8)43% (24-65) Conclusion: Pre-operative radiotherapy is dosimetrically feasible in women with small breast tumors. Excellent target coverage with negligible dose to normal tissue can be achieved. Skin dose appears reasonable given the small volumes.Median V100 and V50 compare favorably to institutional experience with post-operative PBI. A prospective Phase I trial evaluating this technique is undergoing institutional review.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4105.
Guideline Compliant Irradiation Following Breast Conserving Surgery or Mastectomy Improves Recurrence Free Survival.
Authors: Kurzeder C. , Wolters R. , Wischnewsky M. , Woeckel A. , Atassi Z. , Wiegel T. , Kreienberg R. 
Published: December 2010

Abstract
Purpose: Two pivotal studies by Veronesi and Fisher have established the concept of breast conserving surgery for small breast cancers stage T1 or with size less than 4 cm respectively. The aim of this retrospective study was to validate the current practice of BCS in an unselected cohort of patients within the network of 16 regional breast cancer centres in germany and to quantify the detrimental effect of guideline non-compliant locoregional therapy on recurrence free survival.Methods: 4507 patients who received primary therapy between 1992 and 2005 were recorded. Data on surgery, axillary dissection and postoperative irradiation were used to categorize patients according to adherence to guidelines. The effect of guideline compliant locoregional therapy on recurrence free survival was calculated.Results: Out of 3579 patients (79.4%) who were treated by BCS 3036 (84.8%) received postoperative irradiation as mandated by the guideline. A total of 928 (20.6%) patients underwent mastectomy, out of these a fraction of 344 patients received postoperative irradiation as required by the guideline. No significant difference in recurrence free survival was found between patients who underwent BCS plus postoperative irradiation and those patients who underwent mastectomy (T1: HR=1.08 (95%-CI: 0.70-1.67), p=0.281; T2: HR=1.21 (95%-CI: 0.61 - 2.39), p=0.577). Guideline compliant locoregional therapy resulted in a significant improvement in RFS as shown for patients receiving guideline compliant BCS plus irradiation or guideline compliant mastectomy without irradiation versus patients with any type of non-compliant locoregional therapy (HR=3.53, 95%-CI: 2.97-4.18, p&lt;0.001).Conclusion: Our findings support current clinical practice of BCS in small tumors as initially indicated and also in tumors of stage T2. Violations of guidelines for locoregional therapy were clearly associated with a poorer prognosis.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4106.
Is Exclusive Radiotherapy an Option for Early Breast Cancers with Complete Clinical Response after Neoadjuvant Chemotherapy?
Authors: Daveau C. , Savignoni A. , Abrous-Anane S. , Pierga J. , Reyal F. , Gautier C. , Kirova Y. , Dendale R. , Campana F. , Fourquet A. , Bollet M. 
Published: December 2010

Abstract
Purpose: To determine whether exclusive radiotherapy (ERT) could be an option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC).Patients and methods: Between 1985 and 1999, 1477 patients received NCT for EBC considered to be too large for primary conservative surgery. Of 165 patients with cCR, 65 were treated by breast surgery (with radiotherapy) and 100 by ERT.Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91% and 77% in the no surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities.Conclusion: Omission of breast surgery in patients who achieved cCR to NCT was not associated with an increased risk of distant metastases or death. However a trend towards an increased risk of locoregional recurrence was observed in the ERT group. Imaging modalities appear to be essential to monitor chemotherapy response and possibly select patients in whom ERT can be proposed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4108.
Postmastectomy Radiotherapy in Intermediate-Risk Patients: Long Term Carcinologic and Quality of Life Results of the Montpellier Cancer Center.
Authors: Azria D. , Lemanski C. , Rat F. , Huguet H. , Llacer Moscardo C. , Gutowski M. , Dubois J. 
Published: December 2010

Abstract
Background:The impact of postmastectomy radiotherapy (PMRT) on survival has been controversial for decade in intermediate-risk patients.We present here our monocentric long-term carcinologic and quality of life results in the subset of patients classified at intermediate risk and treated with PMRT.Material and Methods: From 1990 to 2000, 1622 patients received adjuvant radiotherapy after mastectomy. Among them, 421 were defined at intermediate risk of local recurrence i.e. (i) one to 3 positive nodes (ii) negative node but younger than 35 years old and/or pT3-T4 and/or grade 3 and/or invasive multifocality and/or lymphovascular invasion. PMRT consisted in a 50 Gy-electron therapy to the chest wall with node irradiation if indicated. Adjuvant chemotherapy and/or hormonotherapy were administered according to our local guideline. Patients were visited every 6 months for at least 10 years. Quality of life questionnaires (EORTC QLQC30/BR23) were filled in at the last medical visit.Results: Median age was 57 years (range, 27-80). One-hundred thirty five patients (32%) and 286 (68%) were premenopausal and menopausal, respectively. Seventy-five percent of the patients presented a ductal invasive carcinoma and 55% one to three positive axillary nodes. The median number of nodes was 13 (range, 3-27). 77% of the patients presented an axillary dissection with more than 10 nodes. 32% of the nodes were associated with capsular effraction. In the node negative subgroups, grade 3, lymphovascular invasion, multifocality, pT3-4, and age &lt; 35 were found in 57%, 19%, 33%, and 4%, respectively. Extensive DCIS was found in 227 patients (54%). Hormonal receptors (ER and/or PR) were positive in 321 patients (76%) and therefore treated with postoperative tamoxifen for 5 years. Adjuvant chemotherapy was delivered in 126 patients and mainly included anthracyclin. HER2 status was not available at that time in our center. Chest wall RT was delivered in all patients to a median total dose of 50 Gy (range, 43-62). Sus-clavicular and internal mammary chain were irradiated in 294 and 346 patients, respectively. With a 10-y median follow-up, 12 (2.8%) and 74 (17.6%) patients presented locoregional and metastatic recurrences, respectively. Locoregional-free survival (LRFS) was 98.3% and 97.1% at 5 and 10 years, respectively. None of the 12 patients presented metastasis before local recurrence. Multifactorial analysis showed a significant impact of LRFS on metastatic-free survival (p&lt;0.001). Quality of life was good to excellent.Conclusion: In this study, only 2.8% recurrences were observed with a very long-term follow-up. Local recurrence is one of the main prognostic factors for metastatic progression. RT in this population seems to be clearly indicated.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4112.
In Vivo Tracking of Expression Levels of Human Growth Factors Secreted by Human ADRCs in a Murine Fat Graft Model.
Authors: Zhu M. , Eguchi M. , Xu S. , Eguchi C. , Fraser J. , Pinkernell K. 
Published: December 2010

Abstract
Background: Our previously published data show that Adipose-derived regenerative cells (ADRCs) enhance the long term retention of autologous fat grafting compared to non-cell-enhanced grafts. To further understand the time course of growth factor expression of ADRCs, we developed an in vivo xenogenic fat graft model.Materials and Methods: Male NCR nude mice were used as recipients to avoid immune rejection of human ADRCs. Inguinal fat pads from male C57Bl6 mice were minced and used as donor fat for transplantation. Human ADRCs from three healthy donors were isolated using the automated Celution® 800/CRS System (Cytori Therapeutics, San Diego, USA) and mixed with minced mouse fat at a concentration of 5x10E5/ml. The mixture was grafted into the dorsal subcutaneous space of nude mice. Grafted samples were harvested at day 0, day 1, day 7, day 14, day 28, day 56 and day 84, for a total of seven different time points (N=4 per time point). DNA and RNA was isolated for further human-specific detection of IGF-1 and VEGF-A and human-specific single copy DNA using real time RT-PCR. All data were normalized to time 0 samples as 100%.Results: Both of human IGF-1 and VEGF-A expression were detected in the first two weeks after fat grafting, and each of the human growth factor showed its unique pattern. For IGF-1, the highest expression level of 100±7.5% was detected at time 0 with a decline to 0.9±0.7% that was maintained for two weeks. By day 14 only 0.22% of the original signal was detected and no more signal could be detected after day 28. In contrast, on day 1 VEGF-A expression showed an increase to 212±82.6% of the time 0 value. It further declined to 30±23% on day 7 and 8.7±11.7% on day 14. After day 28 no more VEGF-A expression could be detected. The engraftment of ADRCs, measured by DNA content, declined to 12±10.7% on day 1 and remained at around 1% until day 14. By day 28, only 0.14% of human DNA signal could be detected and no more signal could be found after day 56.Conclusion: These findings demonstrate that this xenogenic approach allows the evaluation of single growth factor expression of human ADRCs in vivo using a mouse background when studying cell-enhanced fat grafting. It also allows quantitative assessment of cell survival. By using this model we find that human ADRCs secrete several growth factors within the grafts and that each growth factor has its own unique profile. Furthermore, it becomes evident that ADRCs are active for several days after implantation before growth factor expression subsides. This is an important safety feature of this adult cell therapy source since continued, high level expression of growth factors would not be desirable in cases of reconstruction after breast cancer removal, when concerns of residual tumor cells exist.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4124.
Magnetic Resonance Image Guided Focused Ultrasound Surgery of Early Breast Cancer: Efficacy and Safety in Excisionless Study.
Authors: Furusawa H. , Yasuda Y. , Shidooka J. , Nakahara H. , Hirabara E. , Inomata M. , Machida E. , Maeda Y. , Komaki K. 
Published: December 2010

Abstract
Background: The prognosis of the breast cancer patient doesn't depend on the local treatment, but on the systemic treatment. Breast conserving therapy, lumpectomy following radiotherapy, has been proved to be as good as mastectomy in several clinical trials. When focused ultrasound waves propagate in tissue, the energy is absorbed and converted to heat, resulting in tissue coagulation. MRI is the best modality in spatial resolution for the detection of breast cancer spread. Two phase II clinical studies (excision studies) to investigate pathological efficacy and clinical safety of MR guided focused ultrasound surgery (MRgFUS) were conducted and their outcome has been published.Purpose: The purpose of this study is to inspect the efficacy and safety of MRgFUS as a local treatment for early breast cancer followed by radiotherapy in a phase III study.Methods: The inclusion criteria include 1) tumor diagnosis by core needle biopsy under ultrasound 2) HER-2,HR status confirmation 3) tumor size is less than 15mm in diameter, 4) well demarcated mass in contrast enhanced MRI. The exclusion criteria include 1) pure type mucinous carcinoma, 2) invasive micropapillary carcinoma, 3)skin dimple or dimpling sign, previous surgical scar of the skin above the tumor, 4) location of the tumor requires a high sonication angle. Core needle biopsy was performed again within three weeks after ablation and no residual viable cancer cells were identified by HE stain and single strand DNA immunohistochemical stein. The following radiotherapy is whole breast(50Gy) and boost(10Gy). Results: Fifty patients entered this study and forty-one lesions were completely treated from April 2005 to June 2009. The median age was 57 years old (37 - 72). The average tumor size was 11.0mm (6 - 15). The median follow up period was 29 months (1 - 48). Thirty five cases were followed up for more than 12 months. There were no severe adverse events and no local recurrence cases.Conclusions: Although the number of cases is still small and the follow-up period is short, MRgFUS has the potential of replacing usual breast conserving surgery. Strict selection of cases is essential.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4126.
Targeting Pleural Carcinoma Cells with the Anti-EpCAM BiTE Antibody MT110 by Stimulating Microenvironment T Cells.
Authors: Mayer B. , Witthauer J. , Winter H. , Funke I. , Baeuerle P. , Jauch K. 
Published: December 2010

Abstract
Rationale: Despite therapy, most patients with advanced breast cancer develop malignant pleural effusion (MPE) associated with short survival. Strikingly, the metastatic cancer cells are frequently hormon receptor negative and show a reduced Her2/neu expression compared to the corresponding primary tumors. Thus, new treatment strategies are urgently needed.Objectives: In the present study, the efficacy of the bispecific single-chain antibody MT110 targeting both the epithelial antigen EpCAM (CD326) and the T cell antigen CD3 was investigated ex vivo with MPE samples of breast cancer patients.Methods: Target antigen expression of MPE cells was analyzed by immunohistochemistry. Percentage of redirected target cell lysis by MT110 was determined by double staining of cells with 7-amino actinomycin and an anti-EpCAM antibody using FACS analysis. Activation of autologous CD4+ and CD8+ cells in response to MT110 was studied by expression of CD25 and granzyme B using FACS staining and different cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) using ELISA analysis.Results: EpCAM+ cells were found in 14 out of 18 (78%) MPE samples from metastatic breast cancer patients. The fraction of EpCAM+ pleural carcinoma cells varied between 30% and 100% (mean 78%). CD3-positive cells were detected in all MPE samples ranging from 60% to 93% (mean 80%). Seven effusion samples were analyzed for MT110 treatment and revealed a dose-dependent and specific redirected lysis of EpCAM+ cells after 48h and 72h with 10 ng/ml (48h, 72h: p=0.03, respectively) and 1000 ng/ml (48h, p=0.03; 72h, p=0.016). After 72 h, 57% ± 29.5% (mean ± SD) of EpCAM+ cells were killed using 1000 ng/ml MT110. The ratio between effector (E) and target (T) cells revealed no influence on the extent of the redircted specific lysis. Antibody treatment increased the fraction of CD25/CD4 cells after 48h (p=0.03) and 72h (p=0.016). Similar, CD25 expression on CD8 cells was stimulated after 48h (p=0.03) and 72h (p=0.016) using 1000 ng/ml MT110. Cytokine analysis revealed a strong TH1 immune response detecting an increased TNFα (p=0.016) and IFNγ (p=0.03) secretion. Conclusion: Single-agent therapy with MT110 is capable of activating unstimulated autologous T cells for efficient and specific redirected lysis of EpCAM+ tumor cells in MPE from breast cancer patients. MPE revealed interindividual differences regarding the extent of specific lysis and the stimulation of the microenvironmental T cells. Thus, treatment with the bispecific antibody MT110 might by an option in the management of a subcohort of metastatic breast cancer patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4133.