bluuebunny/crossref_metadata_2025_split huggingface dataset:
High spatial and temporal resolution breast DCE-MRI: A feasibility study.
Authors: Roy N. , Oh K. Y. , Kettler M. D. , Tudorica L. A. , Huang W. 
Published: February 2017

74 Background: The typical 1-2 min low temporal resolution (tRes) of conventional gradient-echo (GRE) breast dynamic contrast-enhanced (DCE) MRI precludes accurate quantitative pharmacokinetic (PK) analysis. The commercially available GRE-based TWIST (time-resolved angiography with stochastic trajectories) sequence employs an alternative k-space sampling scheme to provide high spatial and temporal resolution for dynamic imaging, originally intended for time-resolved MR angiography. Here we sought to evaluate the feasibility of breast DCE-MRI with the TWIST sequence, using both tumor morphology and quantitative PK analyses. Methods: 22 patients with 25 mammography-detected suspicious lesions underwent TWIST DCE-MRI on a 3T Siemens system prior to biopsy. The axial bilateral images were acquired with 20 s tRes and 1.0x1.0x1.4 mm3 spatial resolution (sRes). Immediately after TWIST DCE-MRI, a single DCE image set was acquired in 68 s using a conventional GRE sequence with the same sRes. Blinded to pathology, 3 radiologists compared lesion morphology assessments from the last TWIST DCE and the conventional images, and gave MRI BIRADS scores based on morphology and qualitative kinetic curve analyses. The TWIST DCE lesion signal time-courses were also subjected to Shutter-Speed Model PK analysis. Results: Normal parenchyma S/N ratios were not statistically different between TWIST and conventional GRE images. All readers indicated 88% [95% CI: (68%, 97%)] agreement in morphology evaluation between the TWIST and conventional DCE images. The degree of inter-reader agreement was substantial (κ = 0.75), as was the agreement in BIRADS scores (κ = 0.76). Pathology revealed 8 malignant and 17 benign lesions. Based on MRI BIRADS scores, all 3 readers attained 100% sensitivity and 82% specificity. With PK analysis, a Ktrans (contrast agent plasma/interstitium transfer rate constant) cut-off value of 0.1 min-1 further improved specificity to 94%. Conclusions: TWIST breast DCE-MRI provides both high tRes and sRes for accurate quantitative PK analysis and morphology evaluation, respectively. Utilizing TWIST for clinical breast DCE-MRI with quantitative PK analysis is feasible and may improve MRI interpretation.
Xenotransplantation of surgical specimens of human breast cancer directly into genetically engineered prolactin-humanized immunodeficient mice.
Authors: Yang N. , Utama F. E. , Yanac A. F. , Liu C. , Rosenberg A. L. , Rui H. 
Published: February 2017

76 Background: Prolactin is an important hormone in mammary gland biology and is indispensible for lobulo-alveolar development during pregnancy and homeostasis during lactation. Prolactin has also been implicated in promoting proliferation, survival, and/ or differentiation of breast cancer. Importantly, murine and bovine prolactin, which are the major lactogens in current laboratory experimental conditions in vivo and in vitro, fail to effectively activate human prolactin receptors because of species incompatibility. Therefore, current established human breast cancer cell lines have been selected in the absence of human prolactin and do not represent the potential subgroup of cancers that depends on prolactin for survival or growth. Methods: In an effort to improve in vivo preclinical modeling of human breast cancer and to establish new human breast cancer lines that are prolactin-dependent or prolactin-sensitive, we used genetic-engineering to generate a human prolactin knock-in mouse line, which expresses physiological levels of human prolactin in place of mouse prolactin. We have crossed the prolactin-humanized mouse line into the immunodeficient NSG strain for effective xenotransplantation studies. Fresh surgical specimens from breast cancer patients were directly transplanted orthotopically into female mice within 2 hours of surgery. We then followed the growth of the xenograft tumors over time and retransplanted the tumors if they engrafted. Results: Our initial data suggested about a take rate of ~35% for the xenografted tumors. Estrogen receptor-positive luminal tumors usually have a very low engraftment rate in immunodeficient mice. However, we observed a relatively high rate of engraftment for luminal tumors. Conclusions: This new prolactin-humanized mouse model is highly relevant for in vivo exploration of tumor biology and drug response testing of breast cancer, especially for luminal subtypes.
Low abundance protein enrichment for discovery of plasma protein biomarkers for early detection of breast cancer.
Authors: Quong A. A. , Gormley M. , Meng R. , Bhat V. B. , Rosenberg A. L. 
Published: February 2017

77 Background: Protein biomarkers for breast cancer are desired for early diagnosis, disease prognosis and drug response monitoring. Biomarkers in bodily fluids, such as plasma, allow for non-invasive monitoring and have additional value compared to tissue-based markers. Plasma-based biomarker discovery faces a challenge in that the wide dynamic range of protein concentrations prevents the detection of lower abundance proteins. In this study, we have investigated the use of a novel protein enrichment strategy combined with isobaric label-based LC-MS/MS as well as two experimental designs for the identification of biomarkers of early stage breast cancer. Methods: Plasma from 12 patients with benign breast lesions and 12 with stage I breast cancer were processed using ProteoMiner enrichment followed by on-bead digestion. Two types of standards were investigated: a pooled standard, consisting of equal portions from the 24 plasma digests and a universal standard. The samples were digested, labeled and analyzed using by HPLC-Chip/Q-TOF analysis. Proteins were identified and quantified using Spectrum Mill software. Results: Use of ProteoMiner beads resulted in extraction of sufficient protein for at least 10 technical replicates and cut down preparation time by 80%, as compared to MARS-based immunodepletion. A total of 414 plasma proteins were identified, 89% of which are low abundance plasma proteins and 14 of which were differentially expressed. Expression values normalized using the pooled vs. universal standards were significantly correlated. Conclusions: This study demonstrated use of the ProteoMiner technology for enrichment of low abundance proteins from plasma. Fourteen plasma-based biomarkers of stage I breast cancer were identified with statistical significance. A number of these proteins (e.g., protocadherin FAT2, flightless-1 homolog) have been linked to breast cancer relevant processes, such as cell migration, adhesion, estrogen receptor signaling and proliferation.
Accelerated partial breast irradiation using brachytherapy (APBIb) for breast cancer (bca): Predictors of use and guideline concordance.
Authors: Hattangadi J. A. , Taback N. , Neville B. A. , Harris J. R. , Punglia R. S. 
Published: February 2017

84 Background: APBIb is a novel alternative to whole breast irradiation (WBI). The American Society for Radiation Oncology Guidelines (ASTRO-G) established appropriateness for APBIb use off protocol. Methods: 138,815 bca patients from the Surveillance, Epidemiology, and End Results database underwent WBI or APBIb after lumpectomy from 2000 to 2007. Patients were classified as suitable, cautionary, or unsuitable for APBIb according to ASTRO-G. Logistic regression was applied to study APBIb use overall and within each guideline category. Results: Overall, 2.6% received APBIb and use varied by ASTRO-G: 5% in suitable, 3.4% in cautionary, and 1.6% in unsuitable patients (p<0.0001). APBIb use increased with time (2000: 0.3%, 2007: 7%) and varied widely with region (0% Alaska; 7% Atlanta, Georgia). Independent predictors of APBIb among suitable patients included white (OR 2.0, p<0.001) race, region (OR 2.6-8.6, p<0.0001), later year (2006-7 v 2000-2 OR 20.3, p<0.0001), and lower grade (OR 1.3, p=0.01). Among cautionary patients, white race (OR 1.8, p<0.001), non-Hispanic ethnicity (OR 1.3, p<0.04), region (OR 3.1-10.2, p<0.0001), metropolitan location (OR 1.9, p=0.01), later year (2006-2007 OR 17.6, p<0.0001), and lower grade (OR 1.4, p<0.0001) predicted for APBIb. Among unsuitable patients, race (p<0.0001), region (OR 3.3-21.6, p<0.0001), later year (2006-7 OR 12.7, p<0.0001), estrogen receptor-positive status (OR 1.3, p=0.002), lower grade (OR 1.3, p<0.01), and negative lymph nodes (OR 2.0, p<0.0001) predicted for use. In several regions, odds of APBIb increased as appropriateness decreased (see Table). Conclusions: APBIb has been rapidly adopted in the US. Its use varied by race, ethnicity, and region, especially among patients who may not be suitable candidates for this technique. [Table: see text]
Comparing survival with breast-conservation therapy or mastectomy in the management of young women with early-stage breast cancer.
Authors: Mahmood U. , Morris C. G. , Neuner G. A. , Koshy M. , Kesmodel S. , Buras R. , Chumsri S. , Bao T. , Tkaczuk K. H. , Feigenberg S. J. 
Published: February 2017

85 Background: Previous studies have shown that young women with breast cancer treated with breast-conservation therapy (BCT) experience higher local recurrence rates. Whether such patients are better treated with mastectomy is unclear. The purpose of this study was to evaluate survival outcomes of young women with early-stage breast cancer treated with BCT or mastectomy using a large, population-based database. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients age 20 to 39 diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007 who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable analysis as well as a matched pair analysis were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: 14,760 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range: 0.5 to 17.9 years). Multivariable analysis revealed year of diagnosis, age, race/ethnicity, grade, PR status, tumor size, number of lymph nodes positive, and number of lymph nodes examined were independent predictors of OS and CSS while ER status was of borderline significance. After accounting for all patient and tumor characteristics, multivariable analysis found that BCT resulted in similar OS (HR: 0.93; CI: 0.83-1.04; p = 0.16) and CSS (HR: 0.93, CI: 0.83-1.05; p = 0.26) as mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5/10/15-year OS for BCT and mastectomy were 92.5%/83.5%/77.0% and 91.9%/83.6%/79.1%, respectively (p = 0.99) and the 5/10/15-year CSS for BCT and mastectomy were 93.3%/85.5%/79.9% and 92.5%/85.5%/81.9%, respectively (p = 0.88). Conclusions: Young women with early-stage breast cancer have equivalent survival whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options, and should not choose a mastectomy based on the assumption of improved survival.
Effect of serial sectioning and immunohistochemistry (IHC) on sentinel lymph nodes (SLNs) on the false-negative rate (FNR) of SLN biopsy (SLNB): Results from NSABP B-32.
Authors: Mamounas E. P. , Anderson S. J. , Julian T. B. , Krag D. N. , Weaver D. , Ashikaga T. , Harlow S. P. , Wolmark N. 
Published: February 2017

86 Background: In NSABP B-32 5611 women with invasive breast cancer were randomly assigned to SLNB plus axillary dissection or SLNB alone. Permanent pathologic assessment of SLNs at participating sites was designed to identify all macrometastases >2 mm (slicing SLNs at approximately 2.0 mm intervals, embedding all slices in paraffin tissue blocks, and examining one H&E-stained slide from each block). Routine use of IHC or deeper sectioning was prohibited. SLN paraffin tissue blocks from negative SLNs were later evaluated centrally for occult metastases deeper in the blocks. In this report we examine the effect of this detailed assessment on the FNR of SLNB. Methods: Routine and cytokeratin IHC stains were used at two widely spaced additional levels. Occult metastases were detected in 616 of 3884 pts (15.9%) with initially negative SLNs; 69.8% had isolated tumor-cells, 27.9% micrometastases, and 2.3% macrometastases (Weaver D, et al: N Engl J Med, 2011). Results: Previously reported FNR in B-32 was 9.8% (75 of 766 pts). Information on additional pathologic assessment was available on 72 of these 75 pts and revealed occult metastases in 23 pts (31.9%). Of those 23 pts, 14 had isolated tumor cells (61%), 7 had micrometastases (30%), and 2 had macrometastases (9%) in the SLN. Including the information from the additional pathologic assessment, the FNR of SLNB in B-32 was reduced to 6.4% (49 of 763 cases). This 35% reduction in FNR was statistically significant (p< 0.001). Among the 23 FN SLNs with occult metastases, the number of positive non-SLNs was 1 in 16 pts, 2 in 2 pts, 3 in 2 pts, 4 in 2 pts, and 6 in 1 pt. Conclusions: In the B-32 trial, more detailed assessment of the SLNs with deeper sectioning and IHC staining would have significantly reduced the FNR of SLNB by about one-third. However, this reduction would have come at the expense of a 16% increase in the rate of axillary dissection by taking occult metastases into account. Supported by NCI: U10-CA-12027, U10-CA-37377, U10-CA-69974, U10-CA-69651; and ARRA ROI CA 74137.
Genome-wide copy number analysis of circulating tumor cells from patients (pts) with metastatic breast cancer (MBC).
Authors: Magbanua M. J. M. , Sosa E. , Roy R. , Eisenbud L. , Scott J. , Olshen A. , Pinkel D. , Rugo H. S. , Park J. W. 
Published: February 2017

9 Background: We developed a novel approach to isolate circulating tumor cells (CTCs) via immunomagnetic enrichment followed by fluorescence activated cell sorting (IE/FACS) and examined copy number alterations in these cells. Methods: Magnetic beads coated with EpCAM mAb were added to blood to enrich for tumor cells. Enriched samples were then subjected to FACS analysis using differentially labeled mAbs to distinguish tumor cells (EpCAM+) from leukocytes (CD45+) during sorting. DNA from isolated tumor cells was subjected to whole genome amplification (WGA) and copy number analysis via array comparative genomic hybridization (aCGH). The assay was evaluated in CTCs from 5 MBC pts with matched archival primary tumors and later extended to an additional 176 MBC pts, 97 of which were successfully profiled. Results: Comparison of CTCs with matched archival primary tumors confirmed shared lineage with notable divergence. In addition, serial testing of CTCs confirmed reproducibility, and indicated genomic change over time. Genomic profiling of CTCs from 102 MBC pts revealed a wide range of copy number alterations including those previously reported in breast cancer. Comparison with a published aCGH dataset of primary breast tumors revealed similar frequencies of recurrent genomic copy number aberrations. Conclusions: It is feasible to isolate CTCs away from hematopoietic cells with high purity via IE/FACS and profile them via aCGH analysis following WGA. Our approach may be utilized to explore genomic events involved in cancer progression and to monitor therapeutic efficacy of targeted therapies in clinical trials in a relatively non-invasive manner. This work was supported by grants from the CALGB, BCRF, TBCRC (Avon, Komen), EDRN and U54.
Therapeutic strategy involving endoscopic resection for cN0 superficial carcinoma of the esophagus.
Authors: Iizuka T. , Kikuchi D. , Hoteya S. 
Published: February 2017

1 Background: With the progress in endoscopic submucosal dissection (ESD) which enables en bloc resection irrespective of the size of lesion, a therapeutic strategy has become feasible whereby ESD is undertaken first, followed by considering additional treatment based on the results of histologic exploration. In this study, we attempted to clarify the clinical results in patients who had undergone additional treatment after endoscopic resection (ER) for cN0 superficial carcinoma. Methods: Of 140 patients diagnosed as having T1a-MM-SM2 lesions of squamous cell carcinoma of the esophagus who had undergone ER between January 1998 and March 2010, 83 patients who received additional treatment after ER (surgery, 27 pts; chemoradiotherapy [CRT], 56 pts.) were the subjects of this study. The mean duration of observation was 45.1 months. Results: The en bloc resection rate was 86%. There were 5 patients (6%) who had complications associated with ER, including perforation in 2 patients, secondary hemorrhage in a patient and pneumonia in 2 patients. Complications associated with additional treatment were noted in 13 patients (15.6%), including secondary hemorrhage, recurrent laryngeal nerve paralysis and pulmonary infarction in one patient each, pneumonia in 3, grade ≥ 3 myelosuppression in 5, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and radiation pneumonitis in one patient each. Long-term follow-up revealed no local recurrence and no patients who experienced late toxicity due to CRT. The tumor recurred in 4 patients, the site of recurrent lesion being the mediastinum in 3 patients and the cervical lymph node in one patient, of whom 2 patients died of the primary disease. The 5-year survival rate was 88.4%. Conclusions: Endoscopic resection plus additional treatment for superficial carcinoma of the esophagus did not entail the development of any serious complications; thus, such combined treatment was safe and feasible. The long-term follow-up results were fairly gratifying, and ER with subsequent additional treatment is considered to be valid for patients with cN0 superficial carcinoma of the esophagus. No significant financial relationships to disclose.
Phase II trial report of preoperative chemotherapy (CX) with S-1 plus cisplatin for stage IV gastric cancer (StIV GC).
Authors: Satoh S. , Okabe H. , Teramukai S. , Hasegawa S. , Ozaki N. , Ueda S. , Tsuji A. , Sakabayashi S. , Sakai Y. ,   Kyoto University Surgical Oncology Group
Published: February 2017

107 Background: Prognosis of StIV GC is poor. S-1 plus cisplatin now becomes one of the Japanese standards for unresectable or recurrent GC. We conducted a multicenter phase II study of preoperative S-1 plus cisplatin for StIV GC (KYUH-UHA-GC03-01, NCT00088816 ). In ASCO 2010, we reported early outcomes, indicating that this regimen is feasible and safe. We will report here the results concerning prognosis and recurrence. Methods: Eligibility criteria included histologically proven StIV GC according to Japanese classification. Helical CT and staging laparoscopy were mandatory. Patients (pts) received oral S-1 (80-120 mg/body/day, day 1-21) and intravenous cisplatin (60 mg/m2 on day 8) every 5 weeks for 2 courses. After CX, operation was performed. S-1 (80-120 mg/body/day, day 1-14) was administered every 3 weeks for one year postoperatively. The primary endpoint was 2-year overall survival (OS), and the secondary endpoints were progression free survival (PFS), response, pathologic response, R0 resection, surgical complication, the first recurrence sites and toxicities. Sample size was set at 50. Results: 51 pts were enrolled and all pts were observed more than 2 years after registration. The median age was 63 (range 35-79). PreOp CX was accomplished in 44 cases. Response was 50% (95% CI: 27.2-72.8). 44 (86.3%) pts underwent surgery and R0 resection was done in 26 pts (51%). Adjuvant chemotherarpy was accomplished in 11 cases. Recurrences were observed 14 cases (53.8%). Most frequent recurrence site was peritoneum. 2-Y OS and PFS were 43.1% [96% CI: 29.4-56.1] and 33.3% [20.9-46.2], respectively. R0 in GC with single StIV factor (n = 24) was 79.2% and that in GC with multiple StIV factors (n = 27) was 25.9%, respectively. All pts with only Cy+ (n = 12) showed complete eradication of cancer cell by S-1/CDDP. Pts with only Cy+ showed significantly better prognosis than other pts. Conclusions: As compared to Japanese national StIV control (OS: 20.8%), this induction CX showed promising survival. Especially, pts with only Cy+ was popular and showed significantly better prognosis by S1/CDDP induction CX. No significant financial relationships to disclose.
Gastric adenocarcinoma treated with radiation with or without epirubicin-based chemotherapy: Evaluation of radiation-induced liver disease.
Authors: Schoenfeld J. D. , Mamon H. J. , Blaszkowsky L. S. , Enzinger P. C. , Wo J. Y. , Allen J. N. , Wadlow R. C. , Ryan D. P. , Hong T. S. 
Published: February 2017

110 Background: Anthracycline chemotherapy has been associated with radiation-induced liver disease (RILD). We sought to compare the incidence of liver toxicity among patients with gastric adenocarcinoma treated with radiotherapy (RT) with or without epirubicin-based chemotherapy. Methods: We performed a retrospective analysis of 94 patients with gastric adenocarcinoma treated at Massachusetts General Hospital since November 2005 and the Dana-Farber Cancer Institute since August 1998. All patients underwent definitive surgery and RT (median dose 45 Gray) with a minimum follow up of 6 months. Primary endpoints were development of ascites, radiographic liver change and elevations in liver function tests (LFTs), including alkaline phosphatase (ALP), aspartate transaminase (AST) and alanine transaminase (ALT). Results: In total, 34 patients received epirubicin-based chemotherapy including 9 perioperatively (6 with oxaliplatin and capecitabine [EOX]; 2 with cisplatin and 5-flourouracil [ECF]; 1 with oxaliplatin and 5-flourouracil [EOF]) and 25 postoperatively (2 EOX; 22 ECF; 1 combination). Seven patients were treated with neoadjuvant RT; 87 received adjuvant RT a median of 88 days after surgery (interquartile range 73-108 days). Twenty-one patients developed ascites within 6 months of completing RT, all but one of whom developed peritoneal carcinomatosis or metastatic disease. Among 57 patients that did not develop metastases, maximum elevations in LFTs were similar in patients that received epirubicin-based chemotherapy compared to those who did not (ALP/AST/ALT 150/44/50 vs. 142/41/44, p=0.25/0.36/0.14, respectively), as were rates of radiographic liver change (22% vs. 13%, p=0.44). Conclusions: Epirubicin-based chemotherapy does not significantly increase the risk of RILD in a recent cohort of patients treated with modern RT techniques and dose-constraints. In this setting, treatment of gastric adenocarcinoma with RT and either pre- or postoperative chemotherapy is well tolerated with low rates of liver toxicities. Development of liver toxicity, particularly ascites, within six months of RT may be a harbinger of metastatic disease. No significant financial relationships to disclose.