tbuckley/cabot-search huggingface dataset:
The comparison of the evaluation of axillary lymph node metastasis in breast cancer among PET, chest CT, and ultrasound sonography.
Authors: H. Kim, W. Han, H. Moon, S. K. Ahn, C. K. Yom, H. Shin, D. Noh
Journal: Journal of Clinical Oncology (2011)

e11567 Background:The evaluation of axillary lymph node metastasis is important in the plan for advanced breast cancer. A neoadjuvant chemotherapy can be recommended when the positive lymph node metastasis is expected. Until now, the accuracy of PET as a preoperative evaluation of axillary lymph node metastasis in breast cancer has been measured about 65-75 percent of sensitivity and 95–99% of specificity since the application of PET in breast cancer. We compared the accuracy of a chest CT and a ultrasonography with a PET for axillary lymph node evaluation of the same breast cancer patients. Methods:We retrospectively studied 229 breast cancer patients who were preoperatively evaluated by an enhanced chest CT, a PET and a ultrasound sonography from June, 2006 to May, 2010. These 229 patients were diagnosed as an infiltrating breast cancer by a gun biopsy, then evaluated with an enhanced chest CT, a PET and an axillary ultrasound sonography followed by the surgery within one month from the last evaluation without another treatment. All evaluations were accomplished in one month. All patients’ axillary lymph node status was examined by an sentinel lymphnode biopsy during the operation and followed by the level 2 or 3 axillary lymph node dissection in case of the positive result. Results: The positive results of axillary lymph node metastasis were 44 patients. A PET predicted 31 patients of axilary lymph node metastasis in the 44 patients, whereas a chest CT, 40 patients. A PET predicted 171 patients in the 185 negative results of axilly lymph node metastaiss, wheareas a chest CT, 177 patients.The sensitivity, The specificity, The false positive rate and the false negative rate of a PET were 71 percent, 92percent, 39 percent and 8 percent. Whereas a chest CT were 91 percent, 95percent, 5 percent and 9 percent. Conclusions: Our retrospective research show that the chest CT is superior to the PET in the evaluation of axillary lymph node metastasis in breast cancer. And the result for a sonography in comparison with a chest CT and a PET will be published in the conference afterwards.
Prospective determination of long-term toxicity and quality of life (QoL) of patients with prostate cancer after intensity-modulated radiotherapy (IMRT).
Authors: Aurore Goineau, Virginie Marchand, Sylvain Bourdin, Emmanuel Rio, Loic Campion, Albert Lisbona, Marc-Andre Mahe, Stephane Supiot
Journal: Journal of Clinical Oncology (2012)

151 Background: To determine prospectively long-term toxicity and quality of life (QoL) of prostate cancer patients after intensity-modulated radiotherapy (IMRT). Methods: 55 patients with localized prostate adenocarcinoma were treated by IMRT (76 Gy) between February and November 2006. Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events version 3.0. Patients assessed general and prostate-specific QoL before IMRT (baseline) and at 2, 18 and 54 months using European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-PR25. Results: Median age was 73 years (range 54-80 years). Risk categories were 18% low risk, 60% intermediate risk, and 32% high risk. The incidence of urinary and bowel toxicity immediately after IMRT (n=55) was, respectively, 36.8% and 23.7% (grade 1), 5.3% and 5.3% (grade 2), 2.6% and none (grade 3). At 18 months (n=55), it was 23.7% and 10.3% (grade 1), 26.3% and 13.2% (grade 2) and none and 2.6% (grade 3). At 54 months (n=38), it was, 34.2 and 23.7% (grade 1), 5.3% and 15.8% (grade 2) and 5.3% and none (grade 3). After 54 months, there was a statistically significant worsening of QoL with regards to 11 items among the 19 studied. However, the scores were clinically relevant (decrease &gt; 10 points) only for physical functioning, role functioning, social functioning, fatigue, pain, dyspnea and constipation. No statistical differences were shown between 54 months and baseline for general health, bowel symptom, treatment related symptoms and sexual activity. Concerning urinary symptoms, there was a statistically significant deterioration but not clinically relevant (difference &lt; 10 points). Conclusions: High-dose IMRT to the prostate with accurate positioning does not induce any clinically relevant deterioration in long-term urinary and gastrointestinal QoL. Deterioration in functioning items may also be related to age and comorbidities. To our knowledge, our study is the only prospective study regarding quality of life following prostate IMRT with a very long follow-up of 54 months.
Nucleoside Diphosphate Kinase-C Suppresses cAMP Formation in Human Heart Failure
Authors: Issam H. Abu-Taha, Jordi Heijman, Hans-Jörg Hippe, Nadine M. Wolf, Ali El-Armouche, Viacheslav O. Nikolaev, Marina Schäfer, Christina M. Würtz, Stefan Neef, Niels Voigt, István Baczkó, András Varró, Marion Müller, Benjamin Meder, Hugo A. Katus, Katharina Spiger, Christiane Vettel, Lorenz H. Lehmann, Johannes Backs, Edward Y. Skolnik, Susanne Lutz, Dobromir Dobrev, Thomas Wieland
Journal: Circulation (2016)

Background: Chronic heart failure (HF) is associated with altered signal transduction via β-adrenoceptors and G proteins and with reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of patients with end-stage HF, but the functional consequences of this are largely unknown, particularly for NDPK-C. Here, we investigated the potential role of NDPK-C in cardiac cAMP formation and contractility. Methods: Real-time polymerase chain reaction, (far) Western blot, immunoprecipitation, and immunocytochemistry were used to study the expression, interaction with G proteins, and localization of NDPKs. cAMP levels were determined with immunoassays or fluorescent resonance energy transfer, and contractility was determined in cardiomyocytes (cell shortening) and in vivo (fractional shortening). Results: NDPK-C was essential for the formation of an NDPK-B/G protein complex. Protein and mRNA levels of NDPK-C were upregulated in end-stage human HF, in rats after long-term isoprenaline stimulation through osmotic minipumps, and after incubation of rat neonatal cardiomyocytes with isoprenaline. Isoprenaline also promoted translocation of NDPK-C to the plasma membrane. Overexpression of NDPK-C in cardiomyocytes increased cAMP levels and sensitized cardiomyocytes to isoprenaline-induced augmentation of contractility, whereas NDPK-C knockdown decreased cAMP levels. In vivo, depletion of NDPK-C in zebrafish embryos caused cardiac edema and ventricular dysfunction. NDPK-B knockout mice had unaltered NDPK-C expression but showed contractile dysfunction and exacerbated cardiac remodeling during long-term isoprenaline stimulation. In human end-stage HF, the complex formation between NDPK-C and Gα i2 was increased whereas the NDPK-C/Gα s interaction was decreased, producing a switch that may contribute to an NDPK-C–dependent cAMP reduction in HF. Conclusions: Our findings identify NDPK-C as an essential requirement for both the interaction between NDPK isoforms and between NDPK isoforms and G proteins. NDPK-C is a novel critical regulator of β-adrenoceptor/cAMP signaling and cardiac contractility. By switching from Gα s to Gα i2 activation, NDPK-C may contribute to lower cAMP levels and the related contractile dysfunction in HF.
Phase I study of irinotecan and temsirolimus in patients with refractory sarcomas.
Authors: S. Movva, T. Bocklage, B. Schmit, R. Quinn, B. J. Liem, C. F. Verschraegen
Journal: Journal of Clinical Oncology (2011)

10027 Background: Topoisomerase I inhibitors have some activity in refractory sarcomas, such as rhabdomyosarcoma and other round cell tumors, with responses between 70-20% depending on the histologic type. mTOR inhibitors have also a modest activity against sarcomas. I and T have different mechanisms of actions. This Phase IB study evaluates the combination of I and T for refractory metastatic sarcomas. The aims were to determine (1) the maximum tolerated dose and toxicity profile, (2) the antitumor activity in an expanded cohort. Aim 1 is reported. Methods: Pts with metastatic sarcomas who failed at least one chemotherapy regimen were eligible if they had signed a consent form, and had good performance status and normal organ functions. Treatment was administered weekly x 3 every 4 weeks and clinical response evaluated every 2 courses by RECIST criteria. A 2 arm crossing design was used (Lee SJ, et al. Invest New Drugs. 2008). In arm 1, I dose was fixed at 80 mg/m2/dose and T was escalated by 5 mg starting at 15 mg/dose. In arm 2, T dose was fixed at 25 mg/dose and I was escalated by1 5 mg starting at 50 mg/m2/dose. AEs were recorded using NCI-CTCAE v3. DLTs were defined as grade 3 neutropenia on retreatment day, a grade 4 febrile neutropenia, a drug-related grade >3 non-hematologic toxicity (except fatigue, nausea, vomiting or grade 3 hypersensitivity reaction), and incapacity to retreat on a weekly basis. Results: Fourteen pts were enrolled. Arm 2: Two/3 pts had DLT and could not be retreated weekly. This arm was closed. Arm1: The first cohort was expanded to 6 pts because one pt could not be retreated weekly. Grade 2 & 3 hematologic side effects observed were neutropenia (2 & 1pts) with one neutropenic fever and thrombocytopenia (1 & 2pts). Non-hematological side effects were grade 2 nausea, vomiting and diarrhea in 1, 1, and 2 pts and mucositis in 1 pt. Two patients have received 11 (leiomyosarcoma) and 6+ courses (sarcoma NOS) each with stable disease. All other patients progressed after 2 courses. Conclusions: The recommended Phase II dose of the weekly combination of I and T is I 80 mg/m2 with T 20 mg. We are now expanding this Phase II dosing to better evaluate this regimen.
FLT3-Kinase Inhibitors Quizartinib and Midostaurin Do Not Impair T-Cell Reactivity and Activation
Authors: Denise Wolleschak, Thomas S. Mack, Florian Perner, Tina M Schnoeder, Marie-Christine Wagner, Stefanie Kliche, Burkhart Schraven, Satish Ranjan, Berend H. Isermann, Daniel B. Lipka, Thomas Fischer, Florian H Heidel
Journal: Blood (2012)
Low Transplant Related Toxicity and Mortality after Transplantation of CD3/CD19 Depleted Haploidentical Stem Cells with Reduced Intensity Conditioning in Children.
Authors: Peter J. Lang, Ingo Mueller, Heiko Teltschik, Matthias Pfeiffer, Martin Ebinger, Michael Schumm, Rupert Handgretinger
Journal: Blood (2007)
Precision of Multi-Echo CMR for Myocardial Iron Overload Evaluation Is Dependent From MR Sequence Design
Authors: Antonella Meloni, incenzo Positano, Alessia Pepe, Dell'Amico Maria Chiara, Luca Menichetti, Daniele De Marchi, Brunella Favilli, Angelo Peluso, Anna Spasiano, Luigi Landini, Aurelio Maggio, Massimo Lombardi
Journal: Blood (2010)
Assessment of gastric cancer malignancy based on CD133 and thrombospondin1 (THBS1) expression and the role of histone acetylation.
Authors: Hirohiko Sato, Mitsuo Shimada, Nobuhiro Kurita, Takashi Iwata, Masanori Nishioka, Shinya Morimoto, Kozo Yoshikawa, Tomohiko Miyatani, Masakazu Goto, Hideya Kashihara, Chie Mikami
Journal: Journal of Clinical Oncology (2012)

31 Background: Epigenetic modification by HDAC (histone deacetylase) plays important roles in the development and progression of cancer. It has been reported that CD133 positive cancer stem cells were induced through the HDAC → HIF-1α (Hypoxia Inducible Factor-1α) pathway, and Thrombospondin1 (THBS1) is associated with tumor angiogenesis. The aim of this study is to evaluate relationship between the HDAC, CD133, THBS1 and prognosis in gastric cancer. Methods: 65 patients of gastric cancer were enrolled in this study. HDAC1, CD133 and THBS1 expressions were evaluated in immunohistochemical (IHC) staining of surgical specimens. Relationship between the expressions of HDAC1, CD133, THBS1 and clinicopathological factors was investigated. Results: HDAC1-positive patients were 52% and had significantly poor prognosis compared with negative patients. There were more frequent liver metastasis and lymphatic invasion in positive patients. CD133-positive patients were 23.1% and had significantly poor prognosis compared with negative patients. There were more frequent depth wall invasion, distant metastasis, peritoneal recurrence. THBS1-positive patients were 26% and had significantly better prognosis compared with negative patients. In THBS1 positive patients, there was less lymph node metastasis, positive peritoneal cytology in ascites, distant metastasis and lymphatic invasion. CD133 expression is positively correlated with HDAC1. THBS1 expression revealed negative correlation with HDAC1. The survival rate of HDAC1 (+) / CD133 (+) group was significantly poor prognosis compared to the other group (HDAC1 (+) / CD133 (-), HDAC1 (-) / CD133 (+), HDAC1 (-) / CD133 (-)). HDAC1 (-) / THBS1 (+) group revealed significantly higher survival rate compared to the other group (HDAC1 (-) / THBS1 (+), HDAC1 (+) / THBS1 (+), HDAC1 (+) / THBS1 (-)). Conclusions: It was suggested that HDAC1 promoted CD133, suppressed THBS1 in gastric cancer and their interaction were increased the degree of malignancy.
Improved Outcome After Allogeneic Stem-Cell Transplantation (SCT) As Compared to Non-Allogeneic SCT Therapies in Patients with High-Risk Peripheral T-Cell Lymphomas in First Response.
Authors: Margot Robles, Loic Ysebaert, Stephane Vigouroux, Anne Huynh, Marie Parrens, Krimo Bouabdallah, Reza Tabrizi, Thibaut Leguay, Marie-Sarah Dilhuydy, Arnaud Pigneux, Axelle Lascaux, Cedric Duclos, Gerald Marit, Noel Milpied
Journal: Blood (2012)
An update on the dosimetric analysis of concurrent radiation therapy and trastuzumab on early cardiac events.
Authors: K. S. Keene, L. C. Klepczyk, R. Meredith, A. Forero-Torres, J. T. Carpenter, H. Krontiras, M. Hyatt, Y. Li, J. F. De Los Santos
Journal: Journal of Clinical Oncology (2011)

121 Background: The impact of radiation therapy (RT) with concurrent trastuzumab on early cardiac morbidity is relatively unknown. Trastuzumab’s radiosensitizing properties may augment both early and late effects of RT. This retrospective review update provides an analysis of cardiac event (CE) development in patients treated with concurrent RT and trastuzumab with a focus on RT heart dose. Methods: Sixty-five patients treated with concurrent RT (30 left, 33 right, 2 bilateral) and trastuzumab at the University of Alabama at Birmingham were identified. Patient data for pre-existing heart disease, cardiac risk factors, drug regimen, and CEs were recorded. Dosimetric parameters of maximum heart dose, mean heart dose, heart volume receiving 5, 10, 15, 20 and 30Gy (V5, V10, V15, V20, V30) were also analyzed. Endpoints include the occurrence of CEs at any time in relation to RT and those specifically after the start of RT. Results: In addition to receiving trastuzumab, 80% of patients received doxorubicin. 15.4% had preexisting heart disease. The mean heart dose for all patients was 248cGy. With a median follow-up of 24.5 months, six patients developed CEs (9.2%), and three of these cases occurred after RT initiation (4, 4, and 0.5 months post-RT). All six CEs occurred during treatment with trastuzumab and consisted of congestive heart failure. Analysis of the heart dose maximum, mean, V5, V10, V15, and V20, V30 were similar in patients with and without CEs, and small differences between groups did not reach statistical significance. CE incidence was significantly associated with smoking (p=0.0037) but not hypertension, diabetes or pre-existing heart disease. Conclusions: This updated retrospective dosimetric analysis did not find a correlation between concurrent trastuzumab and RT on the development of early cardiac events. Modern era RT with 3D conformal planning, the use of heart blocks, and breath hold techniques will continue to decrease the dose to the heart. Longer follow-up will be needed for analysis of the impact of modern technologic advances and late cardiac morbidity.
A nomogram to predict nonsentinel lymph node involvement in breast cancer patients with sentinel lymph node metastases.
Authors: Y. Kojima, K. Tsugawa, K. Enokido, H. Iwata, S. Ohno, F. Akiyama, K. Motomura, C. Watanabe, S. Nakamura
Journal: Journal of Clinical Oncology (2011)

14 Background: Several nomograms have been described as predictors of non-sentinel axially lymph node (non-SN) metastases in breast cancer with positive sentinel nodes (SN). However, all these predicting models were based on data from western countries. The purpose of this study was to examine predictive factors of non-SN status among SN metastatic patients, in order to develop a nomogram based on Japanese large data set. Methods: This research was analyzed by using a clinical database of 11,228 Japanese breast cancer patients who registerd to cohort study as SN biopsy between March 2008 and Octover 2009 in Japan. We reviewed data retrospectively to extract patients with SN metastases who underwent complementary axillary lymph node dissection. In this cohort, we examined predictive factors of non-SN metastases. All clinical and pathologic features were analyzed to predict the non-SN status, by using univariate and multivariate logistic regression model. A receiver operating characteristic curve was constructed and the area under the curve (AUC) was calculated. Results: Among the database, SN metastases were found in 1,029 patients, and 345 (33.5%) were non-SN positive. Univariate analysis showed a significant association between non-SN involvement and primary tumor size (p&lt;0.001), histologic grade (p=0.011), lymphatic invasion (p&lt;0.001), venous invasion (p=0.005) and the number of involved SNs among all identified SNs (p&lt;0.001). Tumor size (p&lt;0.001), lymphatic invasion (p&lt;0.001), and the size of SN metastasis (p&lt;0.001) were associated with non-SN metastasis in multivariate analysis. Based on the multivariate analysis, we developed a scoring system to predict the likelihood of non-SN metastases in breast cancer patients with SN involvement. The discriminatory ability of our nomogram, as measured by the AUC, was 0.752. Conclusions: In patients with invasive breast cancer and a positive SN, primary tumor size, lymphatic invasion, and the size of SN metastases among all identified SNs were independently predictive of non-SN involvement, and used for a nomogram. Validation study will be performed in the future investigation.
Expression of Toll-Like Receptors on Peripheral Blood Cells After Allogeneic Stem Cell Transplantation: Ongoing Results of a Prospective Study
Authors: Cristina Skert, Emirena Garrafa, Manuela Fogli, Simona Fiorentini, Doris Ricotta, Luigi Caimi, Carla Filì, Annalisa Peli, Cesare Bergonzi, Michele Malagola, Martinelli Giovanni, Ilaria Iacobucci, Alessandro Turra, Mario Arpinati, Federica Cattina, Arnaldo Caruso, Domenico Russo
Journal: Blood (2010)
A phase II pharmacokinetic/pharmacogenetic (PK/PG) study using fixed-dose capecitabine in metastatic breast cancer (MBC).
Authors: R. M. Connolly, M. A. Rudek, H. L. Mc Leod, E. Garrett-Mayer, S. C. Jeter, L. A. Wright, V. Stearns, D. K. Armstrong, J. H. Fetting, S. P. Watkins, N. E. Davidson, A. C. Wolff
Journal: Journal of Clinical Oncology (2011)

1067 Background: The pro-drug capecitabine is approved in anthracycline- and paclitaxel-resistant MBC. However, GI/skin toxicity and wide interpatient PK variability occur despite body surface area (BSA)-dosing schedule. We hypothesized that a fixed-dose schedule would simplify drug administration and provide an effective and safe alternative to BSA-based dosing. Methods: We conducted an open label, single-arm, two-stage study of oral capecitabine with fixed starting dose (1.5 g PO bid x 14d q21d) in patients treated with max 3 prior MBC cytotoxic regimens. Blood samples obtained were PG at baseline and PK during cycle 1. We correlated pharmacodynamic (PD) endpoints (e.g., efficacy [response] per RECIST and toxicity, adherence (MEMS caps) and PK/PG. Sample size: 45 patients to detect 25% response rate from null response rate of 10% using Simon two-stage design with 80% power and 5% type I error rate. Three responses were required in 1st stage to proceed to 2nd. Results: Twenty six patients were enrolled in the first-stage and 21 were evaluable (57% ER+, 43% ER-; 14% also HER2+); median BSA 1.89 m2; median # prior chemo = 0, range 0-2) after a median of 4 cycles of capecitabine (range 2-16). Median ratio of fixed administered dose vs BSA-dosing was 79% (range 68-92%). Eight patients had stable disease but progressed after median of 7 cycles (range 2-16). Despite clinical benefit rate of 19% (4 patients with SD ≥ 24 weeks), no partial or complete responses were observed following the 1st stage and study was closed. No unexpected related toxicities were seen except for grade 2 hand-foot syndrome (28%) and vomiting (5%) requiring dose-reduction. We observed a significant variability of the active metabolite 5-fluorouracil (5FU) Cmax and AUC (154% vs 85% in historical controls), which was not explained by BSA (P>0.05). Conclusions: Fixed-dose capecitabine is feasible, simplifies drug administration, and is associated with PK variability of 5FU not explained by BSA. Single agent activity of capecitabine was modest in our patients with ER- or ER+ endocrine-resistant disease and comparable to recent studies. Final PK/PD/PG analyses will be reported. (Funding from Roche and Susan G. Komen for the Cure.)
Factors impacting survival after diagnosis of breast cancer (BC) brain metastases (BM).
Authors: J. Aicardi, D. H. Moore, H. S. Rugo, A. J. Chien, J. W. Park, M. M. Moasser, P. N. Munster, M. E. Melisko
Journal: Journal of Clinical Oncology (2011)

31 Background: With improvements in control of systemic disease, subsets of breast cancer patients (pts) including those with HER2+ and triple negative (TN) BC appear to have an increased risk of BM. We sought to evaluate factors influencing outcomes after diagnosis of BM. Methods: We collected treatment information and outcomes for pts diagnosed with BM who received ongoing care at our center from 1997 to 2011. We correlated clinical, treatment, and pathologic characteristics including age, hormone receptor (HR) and HER2 status, Karnofsky Performance Score (KPS) and number of BM (#BM) at diagnosis with outcomes. Patients were characterized as one of three subtypes: HR+/HER2+, HER2+, or TN. Results: 184 patients are included in this analysis. Median time to BM diagnosis (TTBM) was 38.8 months (mo) (range, 0–274); median survival (OS) after diagnosis of BM was 14.9 mo. Both varied by tumor subtype. Multivariate analysis revealed that TN disease, age &gt;50 and KPS &lt;90 were associated with decreased OS after diagnosis of BM. Progression of systemic disease and &gt;3 BM at diagnosis were univariate predictors of decreased OS (P=0.0005 and P=0.02 respectively) but were not significant in multivariate analysis. Pts treated with gamma knife (GK) as initial therapy followed by whole brain radiation therapy (WBRT) as salvage had similar OS to patients who received WBRT first then had GK as salvage (31.8 vs. 28 mo). Patients who received WBRT or GK only had worse OS (7.7 and 16.3 mo respectively). Since the year 2000, OS after diagnosis of BM remained relatively constant. Conclusions: Underlying tumor biology appears to drive outcomes, and patients with TN BC continue to have a poor prognosis after BM diagnosis. Despite the reported improvement in OS following BM diagnosis compared to previous decades, we did not observe a reduction in risk of death based on calendar year of diagnosis of BM. [Table: see text]