tbuckley/cabot-search huggingface dataset:
Assessment of BRCA testing uptake in ovarian cancer patients during the implementation of an oncologist-led genetic counseling model at an urban and suburban teaching hospital.
Authors: Jennifer Jorgensen, Kimberley Chiu, Kristin Gotimer, Eva Chalas, Dennis Yi-Shin Kuo, Gloria S. Huang
Journal: Journal of Clinical Oncology (2017)

1589 Background: BRCA testing has become an integral component of ovarian cancer management; however, low testing uptake remains an obstacle. This study evaluated the impact of an oncologist-led counseling and testing model on BRCA testing uptake. Methods: The ENGAGE study (NCT02406235) is a prospective study of an oncologist-led BRCA counseling and testing model in patients with epithelial ovarian, primary peritoneal and fallopian tube cancer (EOC). The United States lead accruing gynecologic oncology sites were Montefiore, an urban academic medical center; and Winthrop, a suburban teaching hospital. Oncologists were trained in BRCA counseling prior to site activation, and directly submitted patients’ samples for BRCA testing. Prior to the ENGAGE study, EOC patients were referred to genetics professionals for counseling and testing. We determined the number of BRCA tests performed, and simple descriptive statistics were used to summarize the data. Results: A combined total of 141 EOC patients underwent BRCA testing during the 20 consecutive months analyzed. In the 10 months pre-ENGAGE, 8 Montefiore patients had BRCA testing, all submitted through the genetics division. Nineteen Winthrop patients had BRCA testing, 16 from their oncologist’s office and 3 from an external genetics office. During the 10-month ENGAGE trial, 64 Montefiore patients and 50 Winthrop patients had BRCA testing. This represents a four-fold increase in BRCA testing uptake, with 114 patients tested during ENGAGE versus 27 patients tested pre-ENGAGE. Of these 114, 99 had BRCA counseling and testing through their oncologist’s office. Conclusions: Implementation of an oncologist-led genetic counseling and testing model was associated with increased BRCA testing among ovarian cancer patients in both the urban and suburban hospitals. Increased BRCA testing could be related to increased patient convenience and standardized training of the clinical team. These findings may guide other institutions as they implement streamlined genetic counseling and testing protocols.
Strategies to Sustain Success in Childhood Immunizations
Authors: None The National Vaccine Advisory Committee
Journal: JAMA (1999)

Following an outbreak of measles in 1989-1991, a blueprint for change was developed to improve immunization coverage by addressing deficiencies in the immunization delivery system. A review was undertaken by the National Vaccine Advisory Committee (NVAC) to assess progress in improving immunization coverage, decreasing disease incidence, and developing an immunization delivery system to serve children in the United States. Based on this review, strategies were recommended to sustain success in immunization coverage.A Subcommittee on Immunization Coverage was appointed by the chairman of the NVAC in 1995 and included representatives from federal agencies, professional organizations, vaccine manufacturers, state and regional health departments, and academic centers.Presentations on immunization programs, strategies, and financing were made to the subcommittee by representatives from federal, state, and local agencies; professional organizations; insurers; businesses; and public and private health care providers. Evidence from the published literature also was reviewed.After review and discussion of evidence presented, conclusions and recommendations were crafted and endorsed by members of the subcommittee. The subcommittee's report was submitted to the NVAC for review, comment, and approval.Although incidence rates of traditional vaccine-preventable diseases are at all-time low levels and corresponding vaccination coverage rates are at all-time high levels, a system to ensure timely vaccination of the 11000 US infants born each day that also incorporates newly recommended vaccines is incomplete. Key barriers include lack of financing of vaccination in many insurance programs and the lack of implementation of evidence-based interventions to raise coverage levels. The NVAC makes 15 recommendations to achieve a sustainable childhood immunization delivery system organized around (1) vaccination financing to ensure full insurance coverage of recommended vaccines and to support the Vaccines for Children program; (2) provider practices to ensure the implementation of recall/reminder systems and office-based assessment of coverage levels; (3) information systems for monitoring disease, vaccination coverage, and performance on immunization delivery; and (4) support for communities and families to ensure that the public is aware of the importance of vaccination, that resources are focused to help underserved children, that immunization linkages with WIC (the Special Supplemental Nutrition Program for Women, Infants, and Children) are enhanced, and that citizen coalitions can advocate improvements in the immunization delivery system.
Combination of Selective Inhibitor of Nuclear Export (SINE) Compounds, Selinexor and KPT-8602, with Venetoclax (ABT-199) Displays Enhanced Activity in Leukemia and Large Cell Lymphoma
Authors: Melissa A. Fischer, Sharon Friedlander, Leah Hogdal, Pia Arrate, Hua Chang, Trinayan Kashyap, Christian Argueta, Boris Klebanov, William Senapedis, Erkan Baloglu, Margaret S. Lee, Sharon Shacham, Michael R. Savona
Journal: Blood (2016)
A multicenter phase I trial of the DNA-dependent protein kinase (DNA-PK) inhibitor M3814 in patients with solid tumors.
Authors: Mark van Bussel, Morten Mau-Soerensen, Lars Damstrup, Dorte Nielsen, Henk M.W. Verheul, Philippe Georges Aftimos, Maja J. De Jonge, Karin Berghoff, Jan H.M. Schellens
Journal: Journal of Clinical Oncology (2017)

2556 Background: Agents that generate breaks in DNA are frequently used as cancer therapeutics. These agents induce different forms of DNA damage including double-strand breaks (DSBs), which are the most lethal if left unrepaired. M3814 targets tumor cell growth and survival by inhibiting DNA-PK, which is part of a critical DSB DNA damage repair mechanism. The purpose of the phase I, first in man trial was to evaluate the dose-limiting toxicity (DLT), establish a recommended phase II dose (RP2D), and assess the pharmacokinetic (PK) profile and single-agent clinical activity of M3814. Methods: Patients (pts) with potential aberrations in the DNA-damage and repair systemwere included. A standard 3+3 design was implemented with a starting dose of M3814 of 100 mg once daily, determined based on non-clinical safety. M3814 was given continuously and DLT was evaluated after 3 weeks. Throughout the trial rich PK sampling was taken. Tumor evaluation was performed every second cycle and treatment continued until progression, unacceptable toxicity, pt wish, or physician decision. Results: A total of 25 pts were enrolled at 6 dose levels (DL). Three pts were enrolled per DL, except at 300 and 400 mg BID where 9 and 4 pts were enrolled, respectively. At 300 mg BID one DLT (several low grade adverse events [AEs] lasting &gt; 1 week) was seen. No DLTs were observed at 400 mg BID, which was declared as the RP2D; further dose escalation was not possible due to an impurity in the drug. An additional 6 pts were included at the RP2D. The most frequent AEs were nausea, vomiting, decreased appetite, constipation, diarrhea, pyrexia, fatigue, and rash, all seen in &gt; 20% of pts. No pts discontinued due to AE and no grade 4 AEs were reported. Six pts (20%) had stable disease for at least 18 weeks; no pt had a partial remission. PK analysis demonstrated high variability of exposure with a tendency for skin rash in pts with the highest exposure. Conclusions: M3814 was found to be safe and tolerable at doses up to 400 mg BID, with limited single-agent activity in the studied population. Clinical evaluation of M3814 is ongoing in combination with radiotherapy as well as chemo-radiotherapy and planned in combination with chemotherapy. Clinical trial information: NCT02316197.
Peripheral blood cells are predominantly chimeric of affected and normal cells in patients with paroxysmal nocturnal hemoglobinuria: simultaneous investigation on clonality and expression of glycophosphatidylinositol-anchored proteins
Authors: H Ohashi, T Hotta, A Ichikawa, T Kinoshita, R Taguchi, T Kiguchi, H Ikezawa, H Saito
Journal: Blood (1994)
Phase 1, open-label, dose-escalation and expansion study of ABBV-399, an antibody drug conjugate (ADC) targeting c-Met, in patients (pts) with advanced solid tumors.
Authors: John H. Strickler, John J. Nemunaitis, Colin D. Weekes, Ramesh K. Ramanathan, Eric Angevin, Daniel Morgensztern, Rebecca Suk Heist, Todd Michael Bauer, Patrick Kaminker, Xiaolin Fan, Sara Siggelkow, Shekman Wong, Edward B. Reilly, Daniel E. Afar, Louie Naumovski, Karen Kelly
Journal: Journal of Clinical Oncology (2016)

2510 Background: The c-Met receptor is overexpressed in multiple tumors. ABBV-399 is a first-in-class antibody-drug conjugate (ADC) comprised of the anti-c-Met antibody, ABT-700, and monomethyl auristatin E. Although prior efforts at targeting c-Met overexpression have met with limited clinical success, an ADC directed against c-Met represents a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells. Methods: In a 3+3 dose escalation design, ABBV-399 was administered at doses ranging from 0.15 to 3.3 mg/kg once every 21 days to pts with metastatic solid tumors (NCT02099058). The recommended single-agent phase 2 dose (RPTD) of ABBV-399 was then studied in a dose-expansion cohort in pts with c-Met+ (immunohistochemistry (IHC) ≥2+) non-small cell lung cancer (NSCLC). c-Met overexpression was assessed by an IHC assay utilizing the SP44 antibody (Ventana). Results: As of January 4, 2016, 45 pts received at least 1 dose of ABBV-399. Dose-proportional increases of area under the curve (AUC) for ABBV-399 and total antibody were observed after single dose administration. Half-lives for ABBV-399 and total antibody were approximately 2-4 days. Dose-limiting toxicity (DLT) of febrile neutropenia occurred in 1 pt at 3 mg/kg and 1 pt (with septic shock) at 3.3 mg/kg. The RPTD of 2.7 mg/kg was chosen based primarily on safety and tolerability. There were no toxic deaths. Treatment-related adverse events occurring in ≥10% of pts (including all dose levels and all grades) were fatigue (20%), nausea (17.8%), neuropathy (13.3%), decreased appetite (13.3%), hypoalbuminemia (11.1%), and vomiting (11%). 3/10 evaluable c-Met+ NSCLC pts had a partial response; the duration of response ranged from 1+ to 5 months. There were no responses among 9 pts with c-Met negative tumors. Conclusions: ABBV-399 is well tolerated at the RPTD of 2.7 mg/kg and has demonstrated promising anti-tumor activity in pts with cMet+ NSCLC. The study will continue to assess the anti-tumor activity and safety of ABBV-399 in c-Met+ pts both as monotherapy and in combination with standard of care. Clinical trial information: NCT02099058.
Platelet counts in women with normal pregnancies: A systematic review
Authors: Jessica A. Reese, Jennifer D. Peck, Jennifer J. McIntosh, Sara K. Vesely, James N. George
Journal: American Journal of Hematology (2017)

The occurrence of thrombocytopenia in 5% of pregnant women at delivery, described as gestational thrombocytopenia, is well documented. A commonly believed concept is that gestational thrombocytopenia is the result of gradually decreasing platelet counts in all women during pregnancy. The goal of our study was to evaluate the data supporting this concept. To learn what is known about platelet counts throughout normal pregnancies, we systematically reviewed all publications describing platelet counts during pregnancy. We identified 3,039 studies; 46 reporting ≥30 women with normal pregnancies were included in our analyses. The combined mean platelet counts from all studies supported the concept that platelet counts decrease during pregnancy and increase postpartum: first trimester, 251,000/µL (95% CI, 238,000-264,000/µL); second trimester, 238,000/µL (95% CI, 222,000-253,000/µL); third trimester, 224,000/µL (95% CI, 213,000-235,000/µL); delivery, 237,000/µL (95% CI, 209,000-264,000/µL); 4-8 weeks postpartum, 247,000/µL (95% CI, 207,000-287,000/µL). However, individual studies were inconsistent. Eleven longitudinal studies compared platelet counts on the same women at different times during gestation: seven reported a decrease; four reported no change. Ten cross-sectional studies compared platelet counts of different women at different times during gestation: five reported a decrease; five reported no change. Five studies compared platelet counts of pregnant to nonpregnant women: three reported that platelet counts were lower in pregnant women; one reported no difference; one reported that platelet counts were higher in pregnant women. These inconsistent data emphasize the need to accurately describe platelet counts throughout normal pregnancies. Accurate data are essential for evaluating the clinical importance of thrombocytopenia during pregnancy.
Knowledge, Attitudes, and Beliefs Regarding Cardiovascular Disease in Women
Authors: C. Noel Bairey Merz, Holly Andersen, Emily Sprague, Adam Burns, Mark Keida, Mary Norine Walsh, Phyllis Greenberger, Susan Campbell, Irene Pollin, Cassandra McCullough, Nancy Brown, Marjorie Jenkins, Rita Redberg, Paula Johnson, British Robinson
Journal: Journal of the American College of Cardiology (2017)
Tissue trauma and the subsequent risk of soft tissue sarcoma of the extremity: A population based case-control study in Sweden.
Authors: Hakan Lars Olsson, Philippe Wagner
Journal: Journal of Clinical Oncology (2017)

e13088 Background: Soft tissue sarcomas (STS) are a rare group of heterogeneous tumors that may occur in the extremities. Little is known of their etiologies and only a handful putative risk factors have been identified. Studies as well as case reports have connected soft tissue tumors to events of physical trauma. There is mounting evidence of inflammation as both an initiator and promotor of tumorigenesis, as well progression. Moreover, as the physiological response of tissue repair and regeneration is mediated through inflammation, it is not unlikely that physical injury may cause and/or contribute to tumor initiation, promotion and/or progression, not least when the subsequent inflammation becomes chronic. Methods: We conducted a matched case control study in a total population in the South of Sweden 1988-2009, collecting 249 cases to examine the risk of STS of the extremities (STSE) following exposure to physical trauma such as accidental injury and/or surgery. Results: Having been exposed to surgery or injury from accidents to any part of the body both increased the risk of STSE, OR 2.1 (1.5 – 3) and 1.5 (1.1 – 2.1), respectively. Adjusting for potential confounders yielded ORs of 2.4 (1.6 – 3.6) and 1.4 (1.00 – 2.00). Surgery related odds ratios (SOR) varied with STSE histological subtype, from 1.2 to 4.2. UPS/MFH, Leiomyosarcoma and Liposarcoma showed significantly elevated SORs that were significantly greater than for remaining subtypes (P = 0.029). The accident related odds ratio (AOR) varied from 0.8 to 3.5, being significantly elevated for Leiomyo- and Liposarcoma, and the AOR of the two combined was significantly greater than remaining subtypes (P = 0.045). Analyzing surgery or accidental injury to a given part of the body and the subsequent STSE risk in the same location showed the SOR to be 4.13 (1.87 – 9.15) and the AOR was 2.29 (1.21 – 4.32). Conclusions: The population attributable risk of having had surgery was 37% (20 – 53%) and accidental injury was 13% (2 – 24%). Combined, the PAR was 43% (25 – 57%), indicating that tissue trauma may be an important contributing factor in sarcomagenesis of the extremities.
Survival outcomes of screening with breast MRI in high-risk women.
Authors: Min Sun Bae, Janice S. Sung, Wonshik Han, Blanca Bernard-Davila, Filipe R. Bara, Elizabeth J. Sutton, Christopher Comstock, Maxine S. Jochelson, Elizabeth Ann Morris
Journal: Journal of Clinical Oncology (2017)

1508 Background: Mammography is the only imaging modality proven to reduce mortality from breast cancer. Over the past decade, magnetic resonance imaging (MRI) screening of women with increased risk of breast cancer ( &gt; 20% cumulative life time risk) has been recommended. However, there is little evidence that supplemental screening with MRI improves survival. The purpose of this study was to compare survival outcomes of combined screening with MRI and mammography to screening mammography alone in women at increased risk for breast cancer. Methods: A total of 3,002 women at increased risk underwent at least two screening rounds between 2001 and 2005, with at least 5 years of follow-up. 1,534 women had combined screening (MRI and mammography), and 1,468 had screening mammography alone. Cancer detection yield and survival were determined in the two groups. Results: 60 women were diagnosed with breast cancer, 38 patients in the combined screening group and 22 in the mammography-only group. Cancer yield was 24.8 per 1000 (95% CI, 17.6-33.8) combined screening and 15.0 per 1000 (95% CI, 9.4-22.6) mammography-only. No interval cancers occurred in women undergoing combined screening, while 9 interval cancers were found in women undergoing only mammography screening. During a median follow-up of 10.8 years (range, 0.7-15.2), a total of 11 recurrences and 5 deaths (4 breast cancer cause and 1 unknown cause) were found. Of the 11 recurrences, 6 were in the combined screening group and 5 were in the mammography-only group. All deaths were in the mammography-only group. The Kaplan-Meier estimate for disease-free survival showed no statistically significant difference between the two groups ( P = .325). However, patients in the combined screening group had a significantly better overall survival compared with patients in the mammography-only group ( P = .002). Conclusions: Combined screening with MRI and mammography in women with increased risk of breast cancer resulted in not only a higher cancer detection yield but also better overall survival.
Nab-paclitaxel in clinical practice: Preliminary data from the mantel study.
Authors: Ornella Garrone, Chiara Saggia, Paola Bergnolo, Alessandra Beano, Federico Castiglione, Paola Vanella, Anna Turletti, Enrico De Conciliis, Giorgio Vellani, Nerina Denaro, Elisa Bellini, Emanuela Miraglio, Marco Carlo Merlano
Journal: Journal of Clinical Oncology (2017)

e12561 Background: Metastatic breast cancer (MBC) is an incurable disease. The main goals of treatment are palliation, symptoms control, preserving QoL and prolonging survival. New drugs have contributed to ameliorate the outcome of MBC patients (pts) by increasing response rates (RR) progression free survival (PFS) and, in some setting, overall survival (OS). Taxanes are the most effective drugs in the management of MBC. Nab-Paclitaxel (Nab-P), a solvent-free albumin-bound taxane with high tumor retention, showed antitumor efficacy, and limited toxicity in MBC pts. Aim of the present study is to evaluate the activity and safety of Nab-P in clinical practice. Methods: MANTEL is a retrospective, multicenter, observational study, designed to collect biological and clinical data of MBC treated with Nab-P, from its availability in Italy. Objectives of the study are PFS, correlation between response and tumor biological characteristics and safety. Results: Up to date 137 cases were collected from 9 centers. Main patients’ characteristics were: median age 58 y (32-82) including 40 pts over 65, median ECOG PS 0 (0-2), ER/PgR positive 118 pts (86.1%), Triple Negative 11 pts (8%), most common metastatic sites: bone 100 pts (73%), liver 77 pts (56.2%), soft-tissues 72 pts (52.5%), lung 38 pts (27.7%), CNS 7 (5.1%) median number of organs involved: 2 (1-5), median number of previous chemotherapy regimens for advanced disease: 2 (0-9). Preliminary results were: 4 CR (3%), 34 PR (24.8), 35 SD (25.5%), 54 PD (39.4%) and 10 NE (7.3%), CB was observed in 52 pts (37.9%). Median number of cycles administered was 5 (1-15). Six pts are still on treatment. Median PFS is 4.2+ months (0.3+ - 34). G3-4 leucopenia and neutropenia were observed in 6 (4.3%) and 11 pts (8%) respectively, anemia (all grades) in 51 pts (37.2%). 65 pts (47.4%) experienced neuropathy (G3 in 6 pts), 87 (63.5%) fatigue (G3 in 4) and 20 pts (14.6%) G1-2 arthro-myalgia. 99 pts (72.2%) received standard every 3-weeks schedule. 34 pts (24.8%) required dose reduction due to toxicity. Conclusions: Nab-P is feasible in unselected MBC pts. No concerns about toxicity in this real life population including large number of elderly and heavily pretreated pts. The study is ongoing.
Personalized Prognostic Prediction Models for Breast Cancer Recurrence and Survival Incorporating Multidimensional Data
Authors: Xifeng Wu, Yuanqing Ye, Carlos H. Barcenas, Wong-Ho Chow, Qing H. Meng, Mariana Chavez-MacGregor, Michelle A. T. Hildebrandt, Hua Zhao, Xiangjun Gu, Yang Deng, Elizabeth Wagar, Francisco J. Esteva, Debu Tripathy, Gabriel N. Hortobagyi
Journal: JNCI Journal of the National Cancer Institute (2016)

In this study, we developed integrative, personalized prognostic models for breast cancer recurrence and overall survival (OS) that consider receptor subtypes, epidemiological data, quality of life (QoL), and treatment.A total of 15 314 women with stage I to III invasive primary breast cancer treated at The University of Texas MD Anderson Cancer Center between 1997 and 2012 were used to generate prognostic models by Cox regression analysis in a two-stage study. Model performance was assessed by calculating the area under the curve (AUC) and calibration analysis and compared with Nottingham Prognostic Index (NPI) and PREDICT.Host characteristics were assessed for 10 809 women as the discovery population (median follow-up = 6.09 years, 1144 recurrence and 1627 deaths) and 4505 women as the validation population (median follow-up = 7.95 years, 684 recurrence and 1095 deaths). In addition to the known clinical/pathological variables, the model for recurrence included alcohol consumption while the model for OS included smoking status and physical component summary score. The AUCs for recurrence and OS were 0.813 and 0.810 in the discovery and 0.807 and 0.803 in the validation, respectively, compared with AUCs of 0.761 and 0.753 in discovery and 0.777 and 0.751 in validation for NPI. Our model further showed better calibration compared with PREDICT. We also developed race-specific and receptor subtype-specific models with comparable AUCs. Racial disparity was evident in the distributions of many risk factors and clinical presentation of the disease.Our integrative prognostic models for breast cancer exhibit high discriminatory accuracy and excellent calibration and are the first to incorporate receptor subtype and epidemiological and QoL data.