bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prone versus supine breast irradiation in early stage breast cancer patients.
Authors: Trela K , Eberhardt B , Bereza I , Misztal L , Gabrys D 
Published: December 2010

Abstract
Abstract #5130
Introduction&#x2028; External beam radiotherapy for breast cancer patients is necessary after breast conserving therapy. Volume of breast tissue which needs to be irradiated is close to critical structures such as lung, heart; therefore an alternative prone position could be used to improve dose homogeneity during radiotherapy. The purpose of this study was to compare dose distribution within target and normal tissue volumes between two radiotherapy plans in prone and supine position in women with large and also with small breasts.&#x2028; Material and methods&#x2028; 36 early breast cancer patients (15 – right side and 21 left side, 7 – small, 9 - median, and 20 – large breast size) in clinical stage T1-2N0 were treated with breast conserving therapy and were dedicated for further radiotherapy. Planning CT was performed in a prone and supine position and two treatment plans for each patient were developed using conventional tangents technique. Dose volume histograms were produced and plans were compared with regard to dose volumes parameters. Comparison of the different techniques was statistically analyzed using the Wilcoxon signed rank test.&#x2028; Results&#x2028; The mean doses to the target volume were (50.9 Gy ± 0.59 for supine position and 50.3 Gy ± 0.81 for prone position, p=0.005), minimum dose (39.9 Gy ± 3.7 vs. 38.7 Gy ± 7.7, p=0.6) and maximum dose (54.9 Gy ± 0.5 vs. 54.4 Gy ± 0.9, p=0.02), the dose in 95 % of PTV was significantly higher in supine compare to prone position (48.0 Gy ± 1.3 vs. 46.7 Gy ± 1.8, p=0.0002). The percentage of ipsilateral lung receiving specified dose were significantly higher in supine position compare to prone position: V5 Gy was 26.8% ± 9.5 for supine position and 7.7% ± 6.4 for prone position (p&lt;0.0001), V10 Gy was 18% ± 7.9 vs. 4.8% ± 4.6 (p&lt;0.0001) and V20 Gy was 12.1 ± 4.9 vs. 2.7% ± 2.8 (p=0.0001). Furthermore, the maximum and mean dose to the ipsilateral lung and heart was lower in prone position (max/mean lung 44.4/2.2 Gy, max/mean heart 27.9/2.4 Gy) compare to supine position (max/mean lung 51.4/7.8 Gy, max/mean heart 30.8/3.4 Gy).&#x2028; In the last part we precisely evaluated dose to the heart in left side breast patients. In this case there was significant decrease in maximum, mean and dose to the heart in prone position (max/mean heart 42.9/3.3 Gy, for prone position and max/mean heart 48.1/5 Gy for supine position). There was also smaller heart volume which received 5 Gy (10% ± 5.7 vs. 15.5 ± 11.1). Decrease in dose to the organ at risk was seen not only in large breast size patients but also in patients with smaller breasts.&#x2028; Conclusion&#x2028; Irradiation of patients in prone positions compare to supine positions did not improved dose distribution within target volume. Using plans generated in prone position we were able to reduce the dose to the organ at risk especially ipsilateral lung and heart.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5130.
Radiotherapeutic management of isolated local-regional recurrence following mastectomy.
Authors: Chen J , Guo X , Pan Z , Feng Y , Jiang G 
Published: December 2010

Abstract
Abstract #5135
Background: Postmastectomy isolated local-regional recurrence(ILRR) remains a therapeutic challenge. This retrospective study aims to evaluate the role of radiotherapy(RT) in these patients and to analyze factors that influence local-regional control and survival.&#x2028; Methods: 255 pts with chest-wall(CW) and/or regional nodes recurrence(supraclavicular SC, axillary AXI and internal mammary nodes IMN) as first failure and received RT during 1990 and 2005 were analyzed, included 109 CW recurrence only, 114 regional nodes only and 32 pts with both, resulted in 304 recurrent sites. The median dose was 60Gy(47-74). Systemic treatment was give to 190 pts, including chemotherapy in 171, endocrine therapy(ET) in 69, and both in 41 pts.&#x2028; Results: The median disease-free interval(DFI) was 22 mo(2-260 mo), which were 37 and 17 mo in pts with positive hormonal receptor (HR) and negative HR respectively. Median follow-up was 45 mo (9 mo -15.5 yrs). The 2, 5 and 8-yr overall survival rate was 86.4%, 56.5% and 35% respectively. Median survival time after recurrence was 79 mo. The 2, 5 and 8-yr local control rate was 56.1%, 36.3% and 27.6% respectively. 79 second recurrence in the initial recurrent region and 83 subsequent recurrence in other local-regional sites were found.&#x2028; &#x2028; CW is the most common site of second recurrence. Multivariate analysis showed that no CW involvement, non-diffuse recurrence and radiation to the entire recurrent region were independent prognostic factors on local control of initial recurrent sites. ET proved to be the only independent prognostic factors on subsequent recurrence in other sites. In pts with CW recurrence, small field(67 pts) resulted in significantly lower 5-yrs local control compared to entire CW irradiation(74 pts) (33.6% vs 55.6%, p=0.023). Cox regression model found that DFI≥1yr, positive HR, solitary CW or non-supraclavicular nodal recurrence were independent favorable prognostic factors on overall survival .&#x2028; Conclusions: RT is an effective approach for ILRR after mastectomy. Radiation fields should cover the entire recurrent region. Elective irradiation to the CW in pts with nodal recurrence is recommended. Prognostic Index based on the positive multivariate analysis could be established as to stratify different prognostic sub-groups.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5135.
Local recurrence rates in the conserved breast after MRI targeted radiotherapy.
Authors: Beresford MJ , Whipp E , Sawyer E , Halliwell M 
Published: December 2010

Abstract
Abstract #5143
Background: To optimise the effects of whole breast irradiation after breast conservation surgery, precise identification and delineation of clinical target volumes is essential. If the site of the “post-operative cavity” (POCx) is inaccurately located, any target miss of residual cancer cells may lead to underdosing and thus impact on local recurrence rates and survival. Studies with surgical clips have shown rates of geographical miss of the POCx to be worryingly high for radiotherapy boost doses (up to 87%). Of even more concern is that the whole breast tangential fields frequently miss the tumour bed even though the fields appear adequate based on external landmarks (in approximately a quarter of cases). MRI has subtle breast tissue characterisation that may demonstrate post-operative detail more clearly than CT and more accurately than surgical clips.&#x2028; Methods and Materials: Simple opposed tangential fields were defined by surface anatomy in the conventional manner in 221 consecutive patients. Following MR imaging, fields were modified by a single radiation oncologist (EW) to encompass the POCx with a 10mm margin. Patients were treated to a dose of 45Gy in 20 fractions or 50Gy in 25 fractions, with or without an electron boost to the tumour bed (usually 12.5Gy in 5 fractions). Genetic analysis, using genome wide single nucleotide polymorphism (SNP) arrays and loss of heterozygosity (LOH), was performed on all local relapses to distinguish true recurrences (TRs) from new primaries (NPs)&#x2028; Results: This cohort was at relatively high risk, with only 9.8% classified as low risk by St Gallen criteria. 43.4% were grade 3 and 19.9% had surgical margins &lt;1mm. 62.4% of patients received boosts to the tumour bed. After a median follow-up of 5 years there were 3 local recurrences. This is an actuarial 5-year local relapse rate of 1.3%. Genetic analysis showed that 2 local relapses had identical genetic profiles to the initial primaries; they were TRs. The other was genetically distinct; it was an NP.&#x2028; Conclusions: In this cohort of relatively high risk patients, the TR rate was 0.9% at 5 years. These figures compare favourably with the EORTC boost trial and the START results, although both of these studies had different inclusion criteria, particularly with regard to surgical margins. Theoretically, TRs should be the type of relapse most likely to be avoided by accurate coverage of the post-operative complex. Radiotherapy planned with guidance from MR images may cover the clinical target volume more accurately than treatment guided by anatomical landmarks alone.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5143.
Utilization of tomotherapy-based topotherapy for emerging breast radiation techniques: boost integration and accelerated partial breast irradiation.
Authors: McIntosh A , Sheng K , Khandelwal SR , Arthur DW , Ruchala KJ , Olivera GH , Jeswani S , Read PW 
Published: December 2010

Abstract
Abstract #5148
Background: Helical Tomotherapy-based intensity modulated radiation therapy (IMRT) can be delivered using fixed gantry angles, known as Topotherapy, with daily image guidance. With the advent of accelerated or hypofractionated treatment schemes to shorten courses of radiation, conformality and accuracy is imperative for breast radiotherapy techniques since high doses of targeted radiation are used. The purpose of this study was to characterize the dosimetry of Topotherapy for delivery of Accelerated Partial Breast Irradiation (APBI) and hypofractionated Simultaneous Integrated Boost (SIB) breast irradiation in comparison with conventional techniques.&#x2028; Materials and Methods: Ten patients with early stage left sided breast cancer were evaluated for this study using Topotherapy planning. The planning target volume (PTV) was contoured as the lumpectomy cavity with a 1.5cm margin, and the breast was defined by the tissue encompassed by tangent fields minus the PTV and 5mm of skin. To evaluate SIB, nine patients were comparatively planned using a standard sequential treatment of 50Gy tangents to the whole breast with a 10Gy electron boost in 30 fractions versus Topotherapy integrated boost with the same cumulative dose in 25 fractions versus hypofractionated Topotherapy with 42.4Gy to the breast and 51.2Gy to the PTV in 16 fractions. For evaluation of APBI, 3cm hypothetical lumpectomy cavities were contoured in the four breast quadrants of a single patient, with a similar 1.5cm expansion and breast volume. Plans to deliver 38.5Gy in 10 fractions were generated for each lesion using Topotherapy and compared to 3-dimensional conformal radiation therapy (3DCRT) and IMRT using the dosimetric guidelines from the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol.&#x2028; Results: Target coverage and dose to heart and lung were clinically equivalent when comparing Topotherapy APBI and SIB to conventional techniques. For ABPI, the Topotherapy conformality index was superior to 3DCRT for all breast quadrants, but inferior to IMRT for lesions located in the medial quadrants of the breast. For SIB, Topotherapy provided an improvement in conformality over conventional sequential techniques, however there was no intensity modulated comparison. Equivalent target uniformity was observed in all APBI techniques however for SIB, Topotherapy provided a superior uniformity index for the whole breast target.&#x2028; Discussion: Topotherapy is capable of delivering clinically acceptable dosimetry for accelerated or hypofractionated breast radiation without compromising dose to structures at risk. This treatment modality will be utilized in the near future pending FDA approval.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5148.
Radiofrequency ablation treatment for small breast cancer.
Authors: Noguchi M , Earashi M , Motoyoshi A 
Published: December 2010

Abstract
Abstract #5155
Aims: There is increasing demand for minimally invasive and non-surgical treatment in breast cancer. Although radiofrequency (RF) ablation seems the most promising non-surgical treatment for small breast cancer, its relevance has been controversial. This study was performed to determine the feasibility and the safety of treating small breast cancer with RF ablation. Methods: In this study, all patients had a localized breast cancer of 2.0 cm or less in greatest diameter. The tumors were confirmed to be localized lesions by ultrasonography, mammography, and enhanced MRI or CT. Before treatment, core needle or mammotome biopsy was performed to obtain the tumor tissue for establishing the histological diagnosis and the status of hormonal receptors and HER-2 expression. A model 15000 generator with a seven-array Starbusrt XL needle-electrode Model 70 (RITA Medical System) was used for RF ablation. In the first series, 17 patients underwent RF ablation and sentinel lymph node (SLN) biopsy followed immediately by wide resection (n=13) or total mastectomy (n=4). Axillary dissection was performed in 5 patients with positive SLN. On the other hand, 15 patients underwent RF ablation and SLN biopsy in the second series. Axillary dissection was performed in 3 patients with positive SLN. The ablated lesion was excised by mammotome after several months later. The ablated tumor tissue was examined histologically with H&E staining and NADH-diaphorase staining to assess tumor cell viability. Patients who underwent wide resection or RF ablation alone received breast irradiation, and all of the patients were treated with systemic therapy according to the St. Gallen recommendation. Results: Histological examination with H&E staining revealed a spectrum of changes ranging from complete coagulation necrosis to normal-appearing tumor cells, but NADH-diaphorase staining revealed no viable tumor cells in the either series. No patient developed to local or breast recurrence in the first series with a median follow-up period of 46 months (range: 34-61 months), and in the second series with a median follow-up period of 23 months (range: 12-32 months). However, one patient in the first series and another in the second series developed to the distant metastases, although they are alive with systemic treatment. The cosmesis of conserved breast was excellent in the second series more than in the first series, and no adverse effect such as skin burn or persistent hard lump was observed in the second series. Conclusions: RF ablation is feasible for small breast cancer. To achieve wide acceptance, however, further studies are needed to determine whether the use of RF ablation for small breast cancer can provide local control and survival rates equivalent to those of conventional breast-conserving treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5155.
Evaluation of microtubule associated protein tau expression as prognostic and predictive marker in the NSABP-B 28 randomized clinical trial.
Authors: Pusztai L , Jeong J , Gong Y , Ross JS , Kim C , Hortobagyi GN , Paik S , Symmans WF 
Published: December 2010

Abstract
Abstract #54
Objective: We assessed Tau protein expression in patients who participated in the National Surgical Breast and Bowel Project (NSABP)-B28 clinical trial using immunohistochemistry. Expression levels were correlated with disease-free (DFS) and overall survival (OS) and we also examined if there is interaction between this marker and paclitaxel efficacy. Patients and Methods: Tissue microarrays were available for 1942 patients (63 % of all trial participants) who were included in the NSABP-B28 clinical trial and were randomized to receive either 4 courses of doxorubicin/cyclophosphamide (AC) or AC followed by 4 additional courses of paclitaxel (ACT) adjuvant chemotherapy. All patients with hormone receptor positive tumors also received adjuvant endocrine treatment. Immunohistochemistry for Tau was performed at MD Anderson Cancer Center blinded to clinical outcome. Correlation with survival was performed by the NSABP Statistical Center. Results: Forty-three percent of tumors were Tau-positive defined as equal or greateer staining than in normal breast epithelium. Tau expression correlated strongly with estrogen receptor (ER)-positive status (p&lt;0.0001). In univariate analyses, Tau, ER and HER-2 expression as well as grade, tumor size and nodal status were each independently and significantly associated with DFS and OS (p&lt;0.003). In multivariate analysis, the same variables except HER2 remained significant. However, there was no significant interaction between Tau expression and benefit from paclitaxel in the entire population or among the ER-positive or ER-negative subsets, respectively. Conclusion: High Tau protein expression is associated with better prognosis including longer disease-free and overall survival in patients treated with adjuvant anthracyline and paclitaxel chemotherapy and endocrine therapy. However, we could not detect a statistically significant interaction between Tau expression and paclitaxel benefit.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 54.
Surface functionalized nanoparticles for proximity-activated detection and imaging of breast cancer.
Authors: Sewell SL , Giorgio TD 
Published: December 2010

Abstract
Abstract #6002
Site directed therapy of metastatic and primary breast cancer promises to minimize systemic toxicity associated with chemotherapy agents that have no specificity for pathologic tissues. We have developed a multifunctionalized nanoparticle specifically designed to target breast cancer, including metastases.&#x2028; Quantum dots (QDs) were functionalized with a matrilysin (MMP-7) cleavable, proximity activated substrate, PEG-peptide-PEG (PA construct), where cleavage occurs at the peptide bridge. The QDs were further functionalized with folic acid, a strong breast cancer cell targeting ligand with well-known binding to some normal tissues. The construct initially conceals the folate ligand and reduces binding to non-target tissues. MMP-7 activated cleavage of the PA construct and subsequent unmasking of the folate ligand occurs only at the site of the breast tumor, resulting in a proximity activated targeting (PAT) system. The activity of QDs functionalized with both the PA construct and folic acid (FA-QD-PA) was compared to QDs functionalized with only folic acid (QD-FA).&#x2028; Cellular association of QD-FA nanoparticles with the human breast cancer cell line MDA-MB-231 revealed that 61.9 ± 6.5% of the cells were fluorescently labeled. Addition of the PA construct reduced QD-FA recognition by MDA-MB-231 cells to 2.1 ± 0.4%. MMP-7 cleavage of the protected FA-QD-PA construct restored MDA-MB-231 recognition to 21.9 ± 5.4 %, a significant increase compare to the uncleaved multifunctional nanoparticle construct (one-way ANOVA, p*&lt;0.001, n=3). This in vitro data suggests that the PAT nanoparticle model could function effectively in vivo for specific targeting of breast cancer and metastasis. In the next phase of research, the ability of the FA-QD-PA and FA-QD nanoparticles to detect breast cancer in vivo will be tested using murine models of human breast cancer.&#x2028; This work was funded by the US Army Medical Research and Material Command CDMRP under award BC043908.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6002.
Multifunctional and multiplexed nanoparticles for molecular imaging and treatment of breast cancer.
Authors: Yang L , Sajja H , Cao Z , Wang AY , Smith MQ , Bender L , Mao H , Nie S , Wood WC 
Published: December 2010

Abstract
Abstract #6003
Multifunctional nanoparticles with the ability to target tumors, provide molecular imaging and to deliver therapeutic agents hold great promise for improving the survival of cancer patients. We have developed multifunctional nanoparticles targeted to cellular receptors that are highly expressed in breast cancer and tumor stromal cells. Fluorescent quantum dot (QD) or magnetic iron oxide (IO) nanoparticles are conjugated to either the amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA) or to a single chain antibody against the epidermal growth factor receptor (ScFvEGFR), resulting in uPAR or EGFR targeted nanoparticles. Since the binding of ATF peptides or ScFvEGFR to their receptors results in blocking receptor function and internalization of the receptor-ligand complex, these targeted imaging probes can also inhibit tumor growth and deliver drugs. Using near infrared fluorescence (NIR) dye-labeled targeting peptides, we demonstrate specificity of these targeting ligands in an orthotopic human breast cancer model in nude mice. We found that tail vein injection of a mixture of Cy5.5 dye-ATF and IRDye 800-ScFvEGFR peptides leads to the selective accumulation of both probes in human breast cancer xenografts and NIR optical imaging of the tumors in the mammary fat pad of nude mice (Fig. A).&#x2028; &#x2028; We show that uPAR- and EGFR-targeted nanoprobes display different patterns of intratumoral distribution with EGFR probes in the central area and uPAR probes in the peripheral and central regions of the tumor, which may be the results of expressing uPAR in the invasive edge of tumor cells and tumor stromal cells and EGFR only in tumor cells. In vivo optical imaging using ATF-nanoparticles is also demonstrated in human breast cancer xenograft (Fig. B) and in mouse mammary tumor lung metastatic models. Furthermore, magnetic Cy5.5-ATF IO nanoparticles are multimodality imaging probes for both optical and MR tumor imaging. Since magnetic IO nanoparticles are biodegradable and relatively safe for human use, we have developed a therapeutic imaging nanoparticle by encapsulating doxorubicin into the polymer coating of the nanoparticles and have shown selective delivery of the drug and cytotoxic effect in breast cancer cells in vitro. Results of our study show that multifunctional and multiplexed nanoparticles have great potential for the development of novel tumor imaging and therapeutic approaches.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6003.