tbuckley/cabot-search huggingface dataset:
Strategies to overcome barriers to accrual (BtA) to NCI-sponsored clinical trials: A project of the NCI-Myeloma Steering Committee Accrual Working Group (NCI-MYSC AWG).
Authors: Matthias Weiss, Morie A. Gertz, Richard F. Little, Vincent Rajkumar, Susanna J. Jacobus, Rafat Abonour, Kenneth Carl Anderson, Bart Barlogie, Natalie Scott Callander, Edward J. Gorak, Jeffrey Matous, Glenn Morris Mills, Robert C. Kane, Michael S. Katz, LeeAnn Jensen, James Omel, Robert Z. Orlowski, Paul Gerard Guy Richardson, Nikhil C. Munshi
Journal: Journal of Clinical Oncology (2013)

8592 Background: Accrual to NCI clinical trials(CT)is often slower than planned at times mandating premature closure resulting in loss of valuable resources and delay of scientific progress. Methods: The NCI-MYSC AWG identified 10 potential BtA. SWOG, ECOG and Alliance investigators were queried and agreed that these barriers impede accrual (results stratified for academic and community sites). The MYSC AWG developed in collaboration with NCI and FDA strategies to overcome these barriers. Results: Strategies listed for the 3 most often cited BtA: 1. Reimbursement for CT related expenses:increase awareness of improved reimbursement for phase II CT; tailor reimbursement according to CT complexity; request funds from industry and other sources ( http://biqsfp.cancer.gov ) for qualifying ancillary CT components. 2. Spectrum of available treatment options influences CT participation: educate patients and providers about the significance of a new CT using social media, presentations at national meetings and by adding educational material to CT protocol; encourage opinion leaders and advocacy groups not to promote a new therapy as “standard” in the absence of phase III data. 3. Requirement of CT specific therapy at NCI designated sites only: “MYSC AWG Drug Administration Table” describes NCI/FDA approved rules for CT specific drug administration; CT protocol will outline which standard treatment components of a CT can be administered at any site as long as protocol specific guidelines are followed and conduct is supervised by enrolling investigator. Examples of additional strategies to overcome identified BtA: determine feasibility, indication and insurance coverage of CT specific tests during protocol development; discourage narrow eligibility criteria; avoid competing CT; allow up to 1 cycle of commercially available therapy prior to enrollment; CIRB support for phase II CT. Conclusions: The MYSC Accrual Working Group developed in collaboration with NCI and FDA strategies to overcome barriers to myeloma clinical trial accrual. These strategies may be applicable to NCI-sponsored clinical trials evaluating interventions in other diseases.
Abiraterone Acetate for Metastatic Prostate Cancer in Patients With Suboptimal Biochemical Response to Hormone Induction
Authors: Thomas W. Flaig, Melissa Plets, Maha H. A. Hussain, Neeraj Agarwal, Nicholas Mitsiades, Hari A. Deshpande, Ulka N. Vaishampayan, Ian M. Thompson
Journal: JAMA Oncology (2017)

Men with metastatic prostate cancer who have a poor response to initial androgen-deprivation therapy (ADT), as reflected by a prostate-specific antigen (PSA) level higher than 4.0 ng/mL after 7 months of ADT, have a poor prognosis, based on historical controls.To determine the efficacy of abiraterone acetate with prednisone in these high-risk patients with a suboptimal response to hormonal induction.A phase 2 single-arm study was conducted through the National Clinical Trials Network-Southwest Oncology Group. Eligible patients had metastatic prostate cancer and a PSA level higher than 4.0 ng/mL between 6 and 12 months after starting ADT. The PSA level could be rising or falling at the time of enrollment, but had to be higher than 4.0 ng/mL. No previous chemotherapy or secondary hormonal therapies were allowed, except in patients receiving a standard, first-generation antiandrogen agent with a falling PSA level at the time of enrollment; this therapy was continued in this cohort. Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily was administered to all participants. A total of 41 men were enrolled between the trial's activation on August 9, 2011, and closure on August 1, 2013. Data analysis was conducted from March 21 to November 29, 2016.Abiraterone acetate, 1000 mg, once daily by mouth with prednisone, 5 mg, by mouth twice daily.The primary end point was a PSA level of 0.2 ng/mL or lower within 12 months of starting abiraterone acetate plus prednisone. A partial response (PR) was a secondary end point, defined as a PSA level reduction to lower than 4.0 ng/mL but higher than 0.2 ng/mL.Of the 41 men enrolled, 1 did not receive any protocol treatment and was excluded from analysis. The median (range) age of the 40 participants was 66 (39-85) years. Five (13%) patients achieved a PSA level of 0.2 ng/mL or lower (95% CI, 4%-27%). Thirteen (33%) additional patients achieved a partial response, with a reduction in the PSA level to lower than 4.0 ng/mL but higher than 0.2 ng/mL. Sixteen (40%) patients had no PSA response and 6 (15%) were not assessable and assumed to be nonresponders. The median progression-free survival was 17.5 months (95% CI, 8.6-25.0 months) and the median overall survival was 25.8 months (95% CI, 15.7-25.8 months). There was 1 incident each of grade 4 adverse events of alanine aminotransferase level elevation and rectal hemorrhage. Eleven patients reported grade 3 adverse events.This study did not reach its prescribed level of 6 PSA responses of 0.2 ng/mL or lower, although 5 responses were observed. The overall survival and progression-free survival rates observed in this trial are encouraging compared with historical controls. The therapy was generally well tolerated, without any clear signal of any unexpected adverse effects.
A phase I study of cabozantinib (Cabo) plus docetaxel (D) and prednisone (P) in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Fatima H. Karzai, Ravi Amrit Madan, Andrea Borghese Apolo, Howard L. Parnes, John Joseph Wright, Jane B. Trepel, Melony A. Beatson, Nancy Harold, Anna Couvillon, Seth M Steinberg, Douglas K. Price, James L. Gulley, William Douglas Figg, William L. Dahut
Journal: Journal of Clinical Oncology (2013)

TPS5095 Background: In mCRPC, two randomized trials demonstrated an overall survival (OS) benefit with the chemotherapeutic agent D. However, the survival improvement is modest and new strategies are needed to enhance clinical response. D-based combinations have been evaluated as one alternative strategy. Cabo targets multiple tyrosine kinases including c-Met, vascular endothelial growth factor receptor 2 (VEGFR2) and RET. Cabo has shown activity in mCRPC, with resolution of bone lesions on bone scan, regression of soft tissue/visceral disease, and reductions in circulating tumor cells and bone biomarkers (Smith, et al, J Clin Oncol 30, 2012 [suppl; abstr 4513]). We hypothesize the addition of Cabo to D and P, in patients (pts) with mCRPC, will have an acceptable toxicity profile and could lead to improved survival by targeting different cellular pathways simultaneously. This combination therapy may represent a safe and effective strategy to improve the outcome of mCRPC pts treated with D-based chemotherapy. Methods: This is a phase I trial to determine the safety profile and the recommended phase II dose of Cabo in combination with D and P. Pts receive a fixed dose of D (75 mg/m2 IV day 1 of each 21 day cycle) and P (5 mg po q12 hours) in combination with Cabo at three escalating doses: dose level 1 is 20 mg, level 2 is 40 mg, and level 3 is 60 mg (all po qdaily). Using a standard 3 + 3 design, three patients will initially be treated at each dose level until the maximum tolerated dose (MTD) has been defined. An expansion cohort will then be enrolled at the MTD. The accrual ceiling for the study, including both the dose escalation and the expansion phases, is set at 24 pts. Secondary objectives include assessments of pharmacokinetics of each agent, evaluation of antitumor activity of the combination therapy, and assessment of changes in molecular biomarkers for receptor tyrosine kinase and angiogenesis pathways, as well as biomarkers for bone metabolism. Restaging with bone and CT scan will be undertaken every 3 cycles. Enrollment at dose level 1 has been completed without dose-limiting toxicity. Accrual is ongoing at the second dose level. Clinical trial information: NCT01683994.
Abstract P219: Dairy Consumption and Body Mass Index: Mendelian Randomization Analysis of 184,802 Participants and Systematic Review of 37 Randomized Controlled Trials
Authors: Tao Huang, Ming Ding, Helle K Bergholdt, Tiange Wang, Yoriko Heianza, Dianjianyi Sun, Børge Nordestgaard, Christina Ellervik, Lu Qi
Journal: Circulation (2017)

Objective: Using the Mendelian randomization (MR) approach and meta-analysis of selected randomized controlled trials (RCTs), we aimed to assess whether dairy intake was causally related to BMI. Methods: We used a genetic polymorphism in MCM6 ( LCT -13910 C/T, rs4988235), located upstream of the lactase gene ( LCT), as an instrumental variable (IV) for dairy intake in a MR design. The causal effect of dairy intake on BMI was quantified by IV estimators among 184,802 participants from 25 studies. We further conducted a new meta-analysis of RCTs on the effect of dairy consumption on changes in body composition among 3,007 participants in 37 RCTs. Results: Higher dairy intake was associated with higher BMI (multivariable-adjusted β = 0.03 kg/m 2 per serving/day; 95% CI, 0.00, 0.06; p=0.04), while the LCT -13910 C/T CT+TT genotype was significantly associated with higher dairy intake (β = 0.20 serving/day; 95% CI, 0.14, 0.25; p=3.15х10 -12 ) and higher BMI (β = 0.12 kg/m 2 ; 95% CI, 0.06, 0.17; p=2.11х10 -5 ). The IV analysis showed that higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m 2 per serving/day; 95% CI, 0.27, 0.92; p=3.0х10 -4 ). In addition, our systematic review of 37 RCTs indicated that higher dairy intervention significantly increased body weight (0.36 kg, 95% CI: 0.01, 0.70) and marginally increased lean mass (0.14 kg, 95% CI: -0.06, 0.33) in trials without energy restriction. Conclusions: The present study provides evidence to support a causal effect of higher dairy intake in the absence of caloric restriction on increased BMI.
Night work and cancer: A systematic review and meta-analysis.
Authors: Lanhua Tang, Meizuo Zhong, Jin Huang, Shushan Zhao
Journal: Journal of Clinical Oncology (2013)

1604 Background: The association between night work (or shift work) and cancers has been studied for decades. However, researches investigating the association have yielded inconsistent results. Methods: A systematic review and meta-analysis was performed to investigate whether night work is a risk factor for different kinds of cancer. PubMed and Cochrane library search were independently conducted by two authors from January 1960 to January 2013 using keywords related to night work and cancer. According to between-studies heterogeneity, pooled risk ratios (RR) were estimated with fixed or random effects models by STATA 12.0 software. Sensitivity analysis and publication bias were also analyzed. Results: A total of 33 studies were identified according to the inclusion criteria. The aggregate estimate for all cancers combined was [1.35, (1.24-1.47)] with a similar signiﬁcant elevation of breast cancer [1.36, (1.21-1.52)], ovary cancer [1.24, (1.08-1.43)] risk among female, and malignant melanoma [1.58, (1.03-2.44)]. No significant risks were observed as regard to patients with prostate cancer, colorectal cancer, cervix cancer and non-Hodgkin lymphoma. Sensitivity analyses indicated no change in all results but malignant melanoma and colorectal cancer. The RRs became significant differences after removing one study from the colorectal cancer [1.60, (1.70-2.18)]. No publication bias was observed in this meta-analysis. Conclusions: The current meta-analysis suggested that night work played an important role in breast cancer, ovary cancer, and malignant melanoma. However, it might be premature to consider night work as a risk factor for prostate cancer, colorectal cancer, cervix cancer and non-Hodgkin lymphoma. [Table: see text]
Health state preferences associated with subcutaneous injections and intravenous infusions for treatment of bone metastases.
Authors: Louis S. Matza, Ze Cong, Karen Chung, Alison Stopeck, Katia Sonia Tonkin, Janet Elizabeth Brown, Ada H. Braun, Kate Van Brunt, Kelly McDaniel
Journal: Journal of Clinical Oncology (2012)

e16528 Background: Although cost utility models are often used to estimate the value of treatments for metastatic cancer, limited information is available on the utility of common treatment modalities. Bisphosphonate treatment for bone metastases (BM) is frequently administered via intravenous (IV) infusion, while a recently approved treatment to prevent skeletal-related events (SREs) of BM is administered as a subcutaneous (SC) injection. This study estimated the impact of these treatment modalities on health state (HS) preference. Methods: Participants from the UK general population completed time trade-off interviews to assess the utility of HS vignettes. Respondents first rated a HS representing cancer with BM. Subsequent HSs added descriptions of treatment modalities (ie, injection or infusion) to this basic HS. To represent a range of possible treatment experiences, the two treatment modalities were presented with and without chemotherapy (chemotx), and infusion characteristics were varied by duration (30 minutes or 2 hours) and renal monitoring. Results: A total of 121 participants completed the interviews (47.9% male, 76.9% white). Cancer with BM had a mean utility of 0.40 on a standard utility scale (1 = full health; 0 = death). Adding an injection resulted in a mean utility decrease (ie, disutility) of -0.004. The 30 minute and 2 hour infusions had mean disutilities of -0.02 and -0.04, respectively. Mean disutility of the 30 minute infusion was greater with renal monitoring (-0.05 with same-day blood draw; -0.07 with blood draw 2 days prior). Chemotx was associated with substantial disutility (-0.17). For the HS of BM with chemotx, the mean disutilities of injection, 30 minute infusion, and 2 hour infusion, were -0.02, -0.03, and -0.04, respectively. Disutility associated with injection was significantly smaller than the disutility of both the 30 minute and 2 hour infusions (p &lt; 0.05), regardless of chemotx status. Conclusions: Respondents perceived an inconvenience with each type of BM treatment, but injections were preferred over infusions. The resulting utilities may be used in cost utility models examining the value of treatments for the prevention of SREs in patients with BM.
Poly(GP) proteins are a useful pharmacodynamic marker for <i>C9ORF72</i> -associated amyotrophic lateral sclerosis
Authors: Tania F. Gendron, Jeannie Chew, Jeannette N. Stankowski, Lindsey R. Hayes, Yong-Jie Zhang, Mercedes Prudencio, Yari Carlomagno, Lillian M. Daughrity, Karen Jansen-West, Emilie A. Perkerson, Aliesha O’Raw, Casey Cook, Luc Pregent, Veronique Belzil, Marka van Blitterswijk, Lilia J. Tabassian, Chris W. Lee, Mei Yue, Jimei Tong, Yuping Song, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W. Dickson, Rosa Rademakers, John D. Fryer, Beth K. Rush, Otto Pedraza, Ana M. Caputo, Pamela Desaro, Carla Palmucci, Amelia Robertson, Michael G. Heckman, Nancy N. Diehl, Edythe Wiggs, Michael Tierney, Laura Braun, Jennifer Farren, David Lacomis, Shafeeq Ladha, Christina N. Fournier, Leo F. McCluskey, Lauren B. Elman, Jon B. Toledo, Jennifer D. McBride, Cinzia Tiloca, Claudia Morelli, Barbara Poletti, Federica Solca, Alessandro Prelle, Joanne Wuu, Jennifer Jockel-Balsarotti, Frank Rigo, Christine Ambrose, Abhishek Datta, Weixing Yang, Denitza Raitcheva, Giovanna Antognetti, Alexander McCampbell, John C. Van Swieten, Bruce L. Miller, Adam L. Boxer, Robert H. Brown, Robert Bowser, Timothy M. Miller, John Q. Trojanowski, Murray Grossman, James D. Berry, William T. Hu, Antonia Ratti, Bryan J. Traynor, Matthew D. Disney, Michael Benatar, Vincenzo Silani, Jonathan D. Glass, Mary Kay Floeter, Jeffrey D. Rothstein, Kevin B. Boylan, Leonard Petrucelli
Journal: Science Translational Medicine (2017)

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.
Resection margin and locoregional control in vulvar cancer: A subset analysis of the AGO CARE-1 multicenter study.
Authors: Linn Lena Woelber, Jalid Sehouli, Anika Habermann, Peter Hillemanns, Petra Neuser, Sophie Fuerst, Hans-Georg Strauss, Klaus H. Baumann, Falk Clemens Thiel, Alexander Mustea, Werner Meier, Philipp Harter, Pauline Wimberger, Lars Christian Hanker, Barbara Schmalfeldt, Ulrich Canzler, Tanja N. Fehm, Alexander Luyten, Martin Hellriegel, Sven Mahner
Journal: Journal of Clinical Oncology (2014)

5608 Background: Recently, the standard of minimal pathological resection margin distance of 8mm in surgery for primary vulvar cancer has been challenged since several single center analyses failed to show impact of smaller margins for disease control. Methods: The AGO CaRE-1 study is a retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Patients with primary squamous-cell vulvar cancer FIGO stage 1B and higher (UICC-TNM version 6) treated at 29 gynecologic cancer centers in Germany 1998-2008 were included in a centralized database. While a total of 1,618 patients were documented, this subgroup analysis focuses only on surgically staged node-negative patients with complete tumor resection and known margin distance without radio/chemotherapy (n=289). Results: Median age of the 289 analyzed patients was 66 years (22-94); 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumors. 125 (43.3%) underwent complete, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1mm–33mm); median follow-up was 38.8 months. 46 patients (15.9%) developed disease recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in the group of patients with a resection margin <8mm and 10.2% in patients with a margin ≥8mm. Other sites of recurrent disease were groins (8 cases; 2.8%), pelvis (1 case; 0.3%) and distant (3 cases; 1.0%). When analyzed as a continuous variable, margin distance had no significant impact on disease-free survival (HR per mm increase 0.945, 95% CI 0.886 – 1.009, p=0.090). Similarly, neither uni- nor multivariate analysis adjusted for age, tumor stage, tumor grade, depth of invasion and tumor diameter could reveal a significant difference in disease-free survival between the subgroup of patients with a margin ≥8 or <8mm (multivariate HR 0.642, 95% CI 0.355 – 1.162, p=0.143). Results were consistent when looking at vulvar recurrences only. Conclusions: Tumor-free resection margins are crucial for loco-regional control in vulvar cancer. The need for a minimal margin of 8mm could, however, not be observed in the large cohort of the AGO-CaRE database.
Evaluations of health economics in radiation oncology: A systematic review.
Authors: Timothy K. Nguyen, Chris D Goodman, Gabriel Boldt, Andrew Warner, George Rodrigues, David Palma, Gregory S Zaric, Alexander V. Louie
Journal: Journal of Clinical Oncology (2015)

e17780 Background: Despite the rising costs in Radiation Oncology, the impact of health economics research on radiotherapy practice is unclear. The aim of this study was to perform a systematic review of cost-utility/effectiveness analyses (CUA/CEA), to identify trends in the Radiation Oncology literature quality over time. Methods: A systematic review of Radiation Oncology economic evaluations published in the English language up to 2014 was performed using the Medline and EMBASE databases. Letters, editorials, reviews and stand-alone cost-analyses were excluded. Two reviewers abstracted data independently, with discrepancies settled by a third. The CHEERS guideline for health economic evaluations informed study demographics, methodological details, and economic parameters abstraction. Tufts CEA registry quality scores (TUFTS) and reports in the National Health Sciences (NHS) economic evaluation database were obtained. Studies were stratified into 3 time periods (pre-2005, 2005-2009, 2010-2014). The Chi-Square Trend test and the equivalent linear trend test were used to determine significant changes over time, with a p < 0.05 considered statistically significant. Results: Of 726 abstracts identified, 102 were eligible for inclusion. Most studies were North American (70%) and were based on a model (62%) or clinical trial (26%). Many studies lacked a conflict of interest (COI) statement (66%), a sponsorship statement (51%), a study time horizon (38%), or the use of discounting (31%). Over time, there was a significant increase in the reporting of a COI statement (p < 0.01), study healthcare vs. society payer perspective (p < 0.01), study time horizon (p = 0.01), incremental cost-effectiveness threshold (p < 0.01), and cost effectiveness acceptability curves (p = 0.04). While there was a borderline trend in increased reporting of sensitivity analyses (p = 0.07) and utility derivations (p = 0.07) over time, TUFTS (p = 0.35) and NHS reporting (p = 0.39) remained constant. Conclusions: Economic evaluations in Radiation Oncology have increased over time, and more recent reports are of a higher quality, which may lead to better-informed decision making. Further research is needed to evaluate the impact of this research on clinical practice.