tbuckley/cabot-search huggingface dataset:
SULT1A1 concordance between whole blood and breast cancer tissue
Authors: J. L. Grabinski, E. Arno, L. S. Smith
Journal: Journal of Clinical Oncology (2007)

14090 Background: The human sulfotransferase (SULT1A1) enzyme is involved in the conjugation of tamoxifen. Studies have demonstrated the significance of polymorphisms within the SULT1A1 gene in relation to breast cancer survival and tamoxifen metabolism (Nowell et al, J Natl Cancer Inst 2002). DNA for genotyping in previous studies was obtained from a number of different biological specimens including whole blood or paraffin-embedded formalin-fixed tissue. The purpose of this study was to evaluate the genotypic concordance of SULT1A1 polymorphisms in whole blood and breast cancer tissue. Methods: Breast cancer patients receiving tamoxifen and previously genotyped for the SULT1A1 gene were consented for enrollment. Samples representing each of the three possible genotypes (*1/*1, *1/*2,*2/*2) were selected for the collection of archived tissue. DNA was extracted from whole blood using the QIAamp Blood Midi Kit (Qiagen Inc., Valencia, CA, USA) and from formalin-fixed paraffin-embedded breast cancer tissue using the QIAamp DNA Mini Kit (Qiagen Inc., Valencia, CA, USA) as per protocol. Genotyping of the SULT1A1 gene was conducted using a validated Pyrosequencing assay. Results: Tissue samples representing each of the three different SULT1A1 genotypes were compared to the whole blood genotypes. Each of the clinical samples demonstrated 100% concordance between the two different specimens. Conclusion: Our data provides evidence to support the genotyping of clinical samples for the SULT1A1 gene utilizing either whole blood or tumor tissue from breast cancer patients. No significant financial relationships to disclose.
ISCHEMIC EVENTS OCCUR EARLY IN PATIENTS UNDERGOING PCI AND ARE REDUCED WITH CANGRELOR: FINDINGS FROM CHAMPION PHOENIX
Authors: Matthew Cavender, Robert Harrington, Gregg Stone, Efthymios Deliargyris, Philippe Steg, C. Michael Gibson, Christian Hamm, Matthew Price, Jayne Prats, Kenneth Mahaffey, Harvey White, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2017)
A phase I study of TPI 287 concurrent with fractionated stereotactic radiotherapy (FSRT) in treatment of brain metastases from advanced breast and non-small cell lung cancer (NSCLC).
Authors: Solmaz Sahebjam, Nam D. Tran, Hatem Hussein Soliman, John Arrington, Tawee Tanvetyanon, Shailaja KS Raj, Dung-Tsa Chen, Jennifer Cooksey, Michael Hayes, Michael E. Montejo, Peter A. J. Forsyth, Nikhil G Rao, George Farmer, Peter A. Johnstone
Journal: Journal of Clinical Oncology (2015)

TPS2076 Background: TPI 287, a member of taxanes diterpenoid (taxoid) family, is a microtubule-inhibitor with significant cytotoxic activity. TPI 287 is not a P-glycoprotein substrate and therefore is able to circumvent resistance associated with the expression of the multidrug-resistance-1 (MDR-1) gene. Preclinical studies have demonstrated that TPI 287 crosses the blood brain barrier and reaches a therapeutic concentration in brain tissue. In vivo models of human breast cancer brain metastasis show that TPI 287 significantly reduces the formation of large brain metastases. The radiosensitizing effect of taxanes is well established. This report describes an ongoing phase I trial of TPI 287 concurrent with FSRT in patients (pts) with 1-3 brain metastases from histologically or cytologically confirmed advanced breast or NSCL cancer. Methods: This phase I study employs a standard 3 + 3 dose escalation design exploring 6 sequential dose escalation cohorts (NCT02187822). Pts with up to 3 untreated brain metastases (maximum diameter of each brain lesion ≤ 5 cm, maximum tumor volume ≤ 120 cc) from breast cancer or NSCLC are eligible. Eligible patients will be treated with FSRT to target brain metastases (25 Gy in 5 daily fractions). TPI 287 is administered intravenously once per week, for total of 3 doses. The first dose of TPI 287 is given concurrently with the first fraction of FSRT. Once the recommended phase II dose (RP2D) is determined, an additional 10 patients will be enrolled in an expansion safety cohort, for a planned total enrollment of 36 patients. The primary study objectives are to determine safety and the RP2D of TPI 287 administered concurrently with FSRT to brain metastases. Secondary endpoints include determination of the pharmacokinetics of TPI 287, preliminary antitumor activity (local control rate, distant intra-cranial control rate, progression-free survival) and evaluating effect of treatment on measures of quality of life. Study Progress: At deadline for abstract submission, 2 patients have been enrolled onto this study. Clinical trial information: NCT02187822.
Gray Zone Lymphoma (GZL) with Features Intermediate Between Diffuse Large B-Cell Lymphoma (DLBCL) and Classical Hodgkin Lymphoma (cHL): Pathologic Classification and Clinical Outcomes from a Multicenter Consensus Study
Authors: Andrew M Evens, Monika Pilichowska, Stefania Pittaluga, Judith Ferry, Jessica Hemminger, Jennifer A. Kanakry, Laurie H. Sehn, Tatyana Feldman, Jeremy S. Abramson, Francisco J. Hernandez-Ilizaliturri, Izidore S Lossos, Oliver W Press, Timothy S. Fenske, Jonathan Friedberg, Julie M Vose, Kristie A. Blum, Deepa Jagadeesh, Gaurav Gupta, Randy D Gascoyne, Elaine Jaffe
Journal: Blood (2016)
Intraperitoneal (IP) port cytology after IP cisplatin therapy for ovarian cancer: A simple test to predict platinum resistance and outcome?
Authors: Maryann Juh Kwa, Franco Muggia
Journal: Journal of Clinical Oncology (2015)

e16537 Background: Disease status at completion of chemotherapy for ovarian cancer is a determinant of recurrence and predictor of survival. PET/CT and CA125 lack sensitivity as predictors of disease-free status. IP therapy via an implantable port allows for drug delivery and analysis of peritoneal fluid cytology. Identifying microscopic evidence of disease by cytology in patients treated with IP platinum may predict for development of platinum resistance, stratify risk recurrence, and lead to new systemic and IP treatments. Our objective is to determine whether IP port cytology is a predictor of outcome. Methods: A retrospective review was performed of patients with ovarian cancer who were treated with IP cisplatin on clinical protocol (conducted by FM) or with IP cisplatin following neoadjuvant chemotherapy/surgical resection. Upon treatment completion, the IP port was sampled for peritoneal cytology. Cytologic findings were correlated with outcome. Recurrence event was defined by RECIST criteria (not port cytology). DFS and OS were calculated using Kaplan-Meier and compared using log rank analysis. Results: From 2004-14, 40 patients who had completed IP therapy had peritoneal cytology analyzed. 7 (17.5%) had positive cytology and 33 were negative (82.5%). Both groups were similar in age, stage, debulking status, and PS. 6/7 (85.7%) in the positive recurred v. 15/33 (45.5%) in the negative. 5/7 (71.4%) in the positive are dead of disease v. 10/33 (30.3%) in the negative. Median time to recurrence was 14 months (m) (95% CI, 10-42) in the positive v. 60 m (95% CI, 50-77) in the negative (p = 0.040). Median OS was 44 m in the positive (95% CI, 25-55) v. 75 m (95% CI, 62-78) in the negative (p = 0.020). Conclusions: Peritoneal cytology after IP treatment can yield prognostic information about development of platinum resistance (leading to earlier recurrence) and survival. It may complement radiologic studies/CA125 in determining risk for relapse, which may guide further treatment including novel IP therapies. Routine analysis of IP cytology up to 6 months (to rule out platinum-resistant recurrence) following therapy (platinum-free interval) should be investigated in a prospective study.
CELL-SPECIFIC DISCRIMINATION OF DESMOSTEROL AND DESMOSTEROL MIMETICS CONFERS SELECTIVE REGULATION OF LXR AND SREBP PATHWAYS IN MACROPHAGES
Authors: Evan Muse, Shan Yu, Chantle Edillor, Jenhan Tao, Nathan Spann, Katherine Ozeki, Jeffrey McDonald, John Bahadorani, Sotirios Tsimikas, Andrew Watt, Lisa Hettrick, Tamar Grossman, Matthew Tremblay, Christopher Glass
Journal: Journal of the American College of Cardiology (2017)
Multicenter prospective phase II trial of bevacizumab (bev) for progressive pancreatic neuroendocrine tumor (PNET).
Authors: Timothy J. Hobday, Jun Yin, Adam Pettinger, Jonathan R. Strosberg, Diane Lauren Reidy, Helen X. Chen, Charles Erlichman
Journal: Journal of Clinical Oncology (2015)

4096 Background: Single agent trials of mTOR inhibitors and VEGF receptor TKIs in PNET yield response rates < 10%. We previously demonstrated a 39% PR rate in PNET with the combination of temsirolimus and bev in patients with progressive PNET. There are no data regarding the efficacy of single agent bev in PNET. Methods: We conducted a multicenter phase II trial of bev at a dose of 10 mg/kg IV q 2 weeks in patients (pts) with well or moderately differentiated PNET, adequate organ function, and ECOG PS of 0-1. Important eligibility criteria included requirement for progression of disease by RECIST within 7 months of study entry. No prior anti-VEGF pathway inhibitor therapy was allowed. Ongoing octreotide was allowed at stable dose if required for symptom control. Primary endpoint was response with null hypothesis of 10% and promising result was defined as 30%. Planned enrollment was 21 pts. Results: : 22 pts enrolled from 10/2012 through 6/2014 were eligible for The primary endpoint of response assessment. 9 patients remain on therapy. Confirmed PR rate is 9% (2/22). 6 month progression free survival (PFS) was 95% (20/22). 15 out of 22 pts have follow-up on study > 12 months. The Kaplan-Meier 12 month PFS was 54% (95% CI: 34-85%). Median PFS is 13.6 months (95% CI 10.6- NA). Therapy was well tolerated with no grade 3-4 AEs except 36% grade 3 hypertension. Conclusions: Bev therapy for PNET is associated with a 9% PR rate in this trial. For a population required to have RECIST criteria progression within 7 months prior to study enrollment, the 6 and 12 month PFS rates of 95% and 54% are promising with minimal systemic toxicity. Clinical trial information: NCT01010126.
A phase 2 single-arm study to assess clinical activity, efficacy and safety of enzalutamide (ENZA) with trastuzumab in HER2+ AR+ metastatic or locally advanced breast cancer.
Authors: Maureen E. Trudeau, Eric P. Winer, Joyce Leta Steinberg, Maggie Liosatos, Srinivasu Poondru, Michael Nicholas Dydo, Amy C. Peterson, William John Gradishar
Journal: Journal of Clinical Oncology (2015)

TPS640 Background: Androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression have been found to correlate, with one series of breast carcinomas demonstrating AR expression in 77% of HER2+ tumors (Barton V et al. Mol Cancer Res. 2013;11:abstr A047). In vitro, ENZA inhibits proliferation of AR+/HER2+ cell lines and enhances the activity of trastuzumab. ENZA also inhibits proliferation of trastuzumab-resistant HER2+ cells (Micello D et al. Virchows Arch. 2010;457:467-476). Methods: Women with metastatic or locally advanced HER2+/ER-/PR- and AR+ (local or central) breast cancer will be enrolled in a phase 2 single-arm study (NCT02091960). Patients will receive daily ENZA (160 mg) continuously and trastuzumab (6 mg/kg) administered every 21 days until disease progression. Patients must have measurable disease per RECIST v1.1 and have received 1–4 prior lines of anti-HER2 therapy in the advanced/metastatic setting. Brain imaging is required to exclude patients with CNS metastases. Patients with a seizure history are excluded. The primary endpoint is clinical benefit rate (CBR), where benefit is defined as complete or partial response or stable disease ≥ 24 weeks according to RECIST v1.1 criteria. Additional endpoints include safety, tolerability, and the relationship between AR expression and ENZA activity. If the CBR is ≥ 3 in 21 evaluable patients, the sample size will increase to 66 patients. The primary endpoint will be analyzed in patients with centrally confirmed AR expression ( ≥ 10% nuclear staining by immunohistochemistry), who have received at least 1 dose of ENZA and have ≥ 1 postbaseline tumor assessment. The null hypothesis, that the true CBR is 10%, will be tested against a 1-sided alternative. This Simon’s 2-stage design yields 90% power when the true response rate is 25% with a 1-sided type 1 error rate of 5%. As of the date of abstract submission, 5 patients have been enrolled; enrollment is expected to continue through 2016. Clinical trial information: NCT02091960.
ICE CREAM: Irinotecan cetuximab evaluation and the cetuximab response evaluation among patients with G13D mutation.
Authors: Eva Segelov, Kate Wilson, Val Gebski, Paul Michael Waring, Josep Tabernero, Harpreet Wasan, Fortunato Ciardiello, Jayesh Desai, Craig Underhill, Christos Stelios Karapetis, Mustafa Khasraw, Louise M. Nott, Warren Lance Joubert, Nick Pavlakis, Guy Van Hazel, Lorraine A. Chantrill, Timothy Jay Price, Michael Jefford, Andrew Mark Haydon, Jeremy David Shapiro
Journal: Journal of Clinical Oncology (2013)

TPS3649 Background: Patients with metastatic colorectal cancer (mCRC) whose disease has progressed despite oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies if the tumor contains no mutations in the KRASgene (i.e. WT). However, it is unknown whether antibodies used in this setting, such as cetuximab, are more efficacious alone or in combination with irinotecan, as suggested by the BOND study which did not select for KRASstatus. This international trial will also evaluate prospectively the activity of cetuximab in the subgroup of patients with mCRC with a specific KRASmutation in codon G13D. In selected retrospective analyses, tumors bearing this mutation appear to derive similar response from cetuximab as WT. Trials involving small molecular subsets (in this case approx. 5% of patients with mCRC, or 18% of patients with KRAS mutations) will provide framework for future collaborations. Methods: This randomised phase II study of cetuximab +/- irinotecan will recruit patients with metastatic colorectal cancer (mCRC) with either KRAS WT (n=50) or G13D mutation (n=50) over 2 years from sites in Australia (12), and three international sites (G13D mutations only): Spain (1), England (1), and Italy (1). The trial will prospectively select the KRAS WT arm for the “quadruple WT" genotype (no mutations also in BRAF, NRAS, PIK3CA exon20). Primary objective is 6 month progression free survival. Secondary objectives are response rate, overall survival, quality of life, and translational research including markers that may predict response such as amphiregulin and epiregulin determined by immunohistochemistry. Eligibility: Patients with histologically confirmed CRC with either “quadruple WT" genotype or KRAS G13D mutation; unresectable metastatic disease; measurable or evaluable disease; ECOG 0-2; life expectancy at least 12 weeks, and disease progression, or intolerance of thymidylate synthase inhibitor and irinotecan and oxaliplatin containing regimens. Status: Opened to accrual November 2012, at 31 Jan 2013 3/100 patients have been enrolled, all with G13D mutations. Clinical trial information: ACTRN12612000901808.
Evidence for rituximab (R) underdosing in subpopulations of elderly patients with DLBC: Results of the RICOVER-60 study of the DSHNHL.
Authors: Michael Pfreundschuh, Carsten Mueller, Samira Zeynalova, Gerhard Held, Viola Poeschel, Carsten Zwick, Marcel Reiser, Eva Lengfelder, Hjalmar B. Steinhauer, Christina Limmroth, Norbert Schmitz, Niels Murawski
Journal: Journal of Clinical Oncology (2012)

8024 Background: Gender and weight independently influence R clearance and R serum elimination half life (Mueller et al., Blood 2012). To investigate whether the differences in R pharmacokinetics translate into different outcomes, we analyzed elderly patients (pts) with different R pharmacokinetics treated in the RICOVER-60 study. Methods: 1222 elderly pts. (61-80 y) were randomized to receive 6 or 8 cycles of CHOP-14 with or without R given on days 1, 15, 29, 43, 57, 71, 85, and 99. For this study, subgroup analyses were performed for pts with faster R clearance: elderly male (vs. female) pts and elderly weighty (upper quartile: &gt;77kg) vs. slim (lower quartile: ≤60 kg) female pts. Results: Elderly females had a slower R clearance (8.21 ml/h vs. 12.68 ml/h; p=0.003) and a prolonged R half life compared to men (t 1/2ß =30.7 vs. t 1/2ß =24.7 d; p=0.003). Female pts had a higher 3-year PFS (68% vs. 61%; p=0.062) and OS (74% vs. 68% p=0.086). The differences in outcome were due to a greater outcome improvement by the addition of R in females: the difference in 3-year PFS between female and male pts was 5.1% (p=0.448) in pts. receiving CHOP-14 only and 7.7% (p=0.053) when R was added. In a multivariate analysis the relative risk for progression in male compared to female patients was not significantly elevated after CHOP-14 (1.1; p=0.348), but was significantly higher after R-CHOP-14 (1.6; p=0.004). With respect to weight, addition of R resulted in a significantly improved 3-year PFS (74% vs. 49%; p=0.006) in female pts with a body weight within the lower quartile (≤60 kg) who have an R serum half life of &gt;38.1 days, while there was no improvement by the addition of R (72% vs. 71%; p=0.816) in female pts. with a body weight within the upper quartile (&gt;77kg), who have a serum half life of &lt;29.3 days. Conclusions: The reduced benefit of adding R to CHOP in elderly DLBCL pts. with a shorter rituximab serum half life (and hence lower serum levels) suggests that the respective subpopulations (males and weighty females) are underdosed when R is dosed based on body surface area at 375 mg/m 2 . Ongoing studies of the DSHNHL investigate whether higher R doses for pts with a shorter R serum half life can improve the outcome of the respective pts.
Direct effects on bone metabolism induced by perioperative anthracycline- and/or taxane-based chemotherapy depend on the menopausal status of patients with primary breast cancer.
Authors: Nadine Rauschenbach, A. Tabea Kurbacher, Susanne Herz, Jutta A. Kurbacher, Katja Monreal, Sandra Sperling, Christian M. Kurbacher
Journal: Journal of Clinical Oncology (2015)

1035 Background: Whereas cancer therapy-induced bone loss (CTIBL) is among the well-known sequelae of adjuvant endocrine therapy in patients (pts) with primary breast cancer (PBC), the knowledge about direct effects of modern perioperative Ctx protocols on bone metabolism is limited. This translational project was initiated to gain detailed insights into the influence of anthracycline (A)- and/or taxane (T)-based Ctx on bone turnover of both pre- and postmenopausal PBC pts in the clinical routine. Methods: Data of 109 pts (premenopausal: 49; postmenopausal: 60) receiving A- and/or-T-based neoadjuvant or adjuvant Ctx were included. Serum bone markers including the C-telopeptide of type I collagen (ICTP) indicating osteoclast activity, the N-propeptide of type I collagen (P1NP) measuring osteoblast activity, and bone alkaline phosphatase (BALP) were determined at baseline and prior to each subsequent Ctx cycle (C) up to C6. Changes of ICTP, P1NP, and BALP over time were analyzed by repeated-measure ANOVA. Results: 600 Ctx cycles were analyzed. Baseline levels of ICTP (p = 0.0027), P1NP (p = 0.0063), and BALP (p = 0.0007) were significantly higher in post- versus premenopausal pts. BALP levels remained largely unchanged during Ctx. Trends showing an increase of ICTP from baseline until C6 in premenopausal pts and a decrease in postmenopausal pts did not reach statistical significance. In contrast, P1NP significantly declined in postmenopausal pts from baseline to C6 (p = 0.0152). In premenopausal pts, P1NP declined from baseline to C3 and thereafter increased to C6. These changes were highly significant (p = 0.0024). Conclusions: Our study represents one of the first systematic evaluations of bone turnover in pts exposed to A- and/or T-based Ctx for PBC in the clinical routine. In postmenopausal pts, Ctx was associated with a sustained suppression of osteoblast activity whereas osteoblast suppression recovered until the end of Ctx in premenopausal pts. Whether these effects will translate into an increased risk of CTIBL remains a matter of further investigations which should clearly focus on the individual menopausal status.
A Phase II Trial Combining Radiolabeled Anti-CD45 Antibody with Fludarabine and Low-Dose Total Body Irradiation (TBI) Followed by Related or Unrelated Hematopoietic Cell Transplantation for Patients Under Age 50 with Advanced Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)
Authors: Raya Mawad, Ted A. Gooley, Joseph G Rajendran, Darrell R. Fisher, Ajay K. Gopal, H. Joachim Deeg, Andrew Shields, Damian J. Green, David G. Maloney, Brenda M. Sandmaier, Rainer Storb, Frederick R. Appelbaum, Oliver W. Press, John M. Pagel
Journal: Blood (2012)
Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014
Authors: Robert S. Rosenson, Michael E. Farkouh, Matthew Mefford, Vera Bittner, Todd M. Brown, Ben Taylor, Keri L. Monda, Hong Zhao, Yuling Dai, Paul Muntner
Journal: Journal of the American College of Cardiology (2017)
COMPREHENSIVE STRATEGY TO REDUCE THE INCIDENCE OF LEAD DISLODGMENT FOR CARDIAC IMPLANTABLE ELECTRONIC DEVICES
Authors: Muhammad Rizwan Afzal, Nancy Matre, Sarah Horner, Dilesh Patel, Mahmoud Houmsse, Emile Daoud, Steven Kalbfleisch, Jaret Tyler, Toshimasa Okabe, John Hummel, Raul Weiss, Ralph Augostini
Journal: Journal of the American College of Cardiology (2017)
Clinical, pharmacokinetic (PK), and pharmacodynamic findings from a phase I trial of an Eg5 inhibitor (AZD4877) in patients with refractory acute myeloid leukemia (AML)
Authors: G. Borthakur, S. Faderl, F. Ravandi, S. Padmanabhan, W. Stock, K. Wu, J. Li, G. Curt, M. Tallman, M. Minden
Journal: Journal of Clinical Oncology (2009)

3580 Background: AZD4877 is a potent, specific inhibitor of Eg5 (kinesin spindle protein). The only known function of Eg5 is to separate the centromeres during mitosis. Eg5 inhibition is thus specific for dividing cells, resulting in monoastral mitotic spindles (monoasters) and apoptotic cell death. Preclinically, hematologic tumor cell lines were generally more sensitive to AZD4877 than those derived from solid tumors. Methods: AZD4877 was administered IV daily x 3 as induction for up to 2 cycles, followed by consolidation (daily x 2) for up to 4 cycles. Eligibility criteria were standard. Results: Cohorts of 3–6 patients (pts) were treated at doses of 2, 4, 7, 10, 13, 16, and 18 mg/day. To date, 24 evaluable pts have received 33 induction and 3 consolidation cycles of treatment. Monoasters were detected at all dose levels evaluated (2, 7, 10, 13, and 18 mg/day). The T 1/2 of AZD4877 ranged from 26 to 42 hr; PK were linear and drug levels non-cumulative. Myelosuppression, the dose limiting toxicity (DLT) in solid tumor studies, was not considered a DLT in this trial. Mucositis was the DLT at 18 mg/day; with 1 pt developing Gr 3 palmar-plantar syndrome at this dose. Bone marrow biopsies were undertaken at screening and as clinically indicated. In pts with evaluable biopsies, marrow blasts decreased by 60–80% in 2 pts, and by 30–50% in 3 pts, with no response in 3 pts. Conclusions: Enrollment is ongoing at 16 mg, the likely Phase 2 dose. Preliminary results suggest possible clinical activity in AML. An expansion phase at the MTD is planned. [Table: see text]