tbuckley/cabot-search huggingface dataset:
Association of decreased carboplatin dosage and obesity in women with papillary serous endometrial cancer.
Authors: Nicole Nevadunsky, Anne R. Van Arsdale, Merieme Klobocista, Gurpreet Kaur, Dennis Yi-Shin Kuo, Malte Renz, Gary L. Goldberg
Journal: Journal of Clinical Oncology (2015)

e16529 Background: Undertreatment with chemotherapy has been reported for obese women with breast cancer. Patients with uterine papillary serous carcinoma, at high risk for recurrence, are treated with carboplatin. Obesity is a risk factor for uterine papillary serous carcinoma. Current standard of care defines maximum dosages of carboplatin regardless of actual body mass index (BMI) calculated dosages. The objective of our study was to evaluate actual verses calculated dosages of carboplatin in obese women verses normal and overweight women, as well as prevalence of Grade 3/4 toxicities and recurrent disease. Methods: A retrospective cohort study was conducted of 34 women treated at a single institution for papillary serous endometrial cancer with carboplatin and paclitaxel from January 1999-2009. Patients with BMI of less then 29, and greater or equal to 30 were grouped as normal/overweight and obese respectively. Ideal chemotherapy dosages were calculated using actual patient BMI and the Cockroft Gault equation. Data were abstracted from medical records and National Death Index. Chi-square and Student's t-testing was performed using SPSS software, all tests were two-sided, significance of 0.05. Results: 68% (n = 23) of patients were obese with a mean BMI of 36 kg/m2. 35% (n = 8) of obese patients versus 0% of normal/overweight patients had actual carboplatin doses that deviated at least 20% below calculated dosages, P < 0.05. There were no differences in mean age, 68 versus 70 years, stage of cancer, or grade 3/4 toxicities of anemia, thrombocytopenia, and neutropenia between normal/overweight and obese women. 82% of obese women verses 50% of normal/overweight women were of self identified non-white race, P < 0.05. There were no differences in recurrence/death between normal/overweight and obese patients. Conclusions: There is an association between obesity and deviation of chemotherapy dosages of 20% or more from doses based on actual BMI for women with uterine papillary serous cancers. Further investigation of the clinical impact of chemotherapy dose reduction on toxicity and efficacy for recurrence free and overall survival, as well as pharmacokinetics of chemotherapy in obese women is warranted.
Is there an additional health-related quality of life (HRQL) benefit with abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC) beyond that mediated by clinical endpoints?
Authors: David Cella, Arturo Molina, Dennis D. Gagnon, Derek Espindle, Yanni Hao, Ethan M. Basch
Journal: Journal of Clinical Oncology (2013)

9617 Background: HRQL was evaluated as part of COU-AA-301, a randomized phase 3 trial of AA + prednisone (P) vs placebo + P in mCRPC patients (pts) post-docetaxel, where AA + P demonstrated significant benefits over P in numerous HRQL measures. Here we report post hoc analyses investigating the role of disease progression (px) in mediating the HRQL benefits of AA. Methods: Intensity of pain and fatigue and their interference with daily activities were assessed with the BPI-SF and BFI questionnaires and multiple domains of HRQL with the FACT-P questionnaire. Mediation analyses were conducted using a series of 3 models (Baron &amp; Kenny J Pers Soc Psychol 1986), to assess whether presence and timing of disease px mediated treatment effects of AA + P vs P on HRQL changes: in Model 1, HRQL (i.e. the outcome variable) is predicted by treatment, in Model 2, px (i.e. the mediator variable) is predicted by treatment, and in Model 3, HRQL is predicted by both treatment and px. Three different disease px indicators (ie, PSA px, radiographic px, and a composite px variable) were used. Results: Treatment predicted the change in FACT-P total score from baseline (Model 1; p = 0.011). Treatment (as sole predictor) was significantly (p ≤ 0.001) predictive of both PSA px and radiographic px (Model 2). Some of the treatment benefit of AA + P on the FACT-P total score was not explained as the result of the effect of treatment on PSA and radiographic px (Model 3; p = 0.030). In Model 3, pts with late (&gt; 250 d post-randomization) or no px had better FACT-P scores than those with early px for PSA px (p = 0.019, no px; p = 0.008, late px) and radiographic px (p = 0.054, no px; p = 0.017, late px). Models evaluating the mediating role of the composite px variable showed the same pattern of results. Identical sets of mediation analyses conducted for the BPI and BFI also exhibited very similar outcomes. Conclusions: In post-docetaxel mCRPC pts, the benefits of AA to HRQL appear to be related to both treatment assignment and the mediating effects of disease px. HRQL end points expand understanding of treatment benefit beyond clinical disease px end points. Clinical trial information: NCT00638690.
TP53 Mutations and Outcome After Fludarabine and Cyclophosphamide (FC) or FC Plus Rituximab (FCR) in the CLL8 Trial of the GCLLSG.
Authors: Thorsten Zenz, Patrick Hoth, Raymonde Busch, Hanne Helfrich, Dirk Winkler, Andreas Bühler, Nancy Patten, Sim Truong, Lin Wu, Günther Fingerle-Rowson, Kirsten Fischer, Anna-Maria Fink, Ulrich Jäger, Sebastian Böttcher, Michael Kneba, Michael K. Wenger, Myriam Mendila, Michael Hallek, Hartmut Döhner, Stephan Stilgenbauer
Journal: Blood (2009)
Heritability of Iron Status Phenotype in the Hemochromatosis and Iron Overload Screening (HEIRS) Family Study
Authors: C. E. McLaren, J. C. Barton, G. D. McLaren, R. T. Acton, P. C. Adams, L. F. Henkin, V. R. Gordeuk, J. H. Eckfeldt, C. D. Vulpe, B. W. Harrison, J. A. Reiss, B. M. Snively
Journal: Blood (2008)
Addition of upfront whole-brain radiotherapy to surgery or stereotactic radiosurgery versus surgery or stereotactic radiosurgery alone for treatment of brain metastases: A systematic review and meta-analysis.
Authors: Yu Yang Soon, Ivan Weng Keong Tham, Keith Hsiu Chin Lim, Wee Yao Koh, Jiade Jay Lu
Journal: Journal of Clinical Oncology (2012)

2016 Background: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. We performed a systematic review and meta-analysis of published randomized controlled trials (RCT) to determine the efficacy and safety of additional upfront WBRT. Methods: We searched MEDLINE, EMBASE, CENTRAL from date of inception and annual meeting proceedings of ASCO and ASTRO from 1999 to September 2011 for RCTs comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), quality of life (Qol) and neurological toxicity. Hazard ratios (HR), confidence intervals (CI), p values (p) were estimated with random effects models using Revman 5.1. Results: We found five RCTs including 663 patients with one to four brain metastases. Adding upfront WBRT decreased the one-year incidence of any intracranial disease progression from 73-76% to 22 - 47% but did not improve OS (HR 1.11, 95%CI 0.83 - 1.48, p = 0.47) and PFS (HR 0.76, 95%CI 0.53 - 1.10, p = 0.14). Subgroup analyses showed that the effects on overall survival are similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The effects of upfront WBRT on NF, Qol and neurological toxicity were variable. Conclusions: Adding upfront WBRT to surgery or SRS significantly decreased any intracranial disease progression at one year but did not improve overall and progression free survival and produced variable effects on neurocognitive function, quality of life and neurological toxicity when compared with surgery or SRS alone. Future research should focus on developing more effective approaches to characterize and ameliorate the potential neurological toxicity of WBRT.
A first-in-human phase I study to evaluate the fully human monoclonal antibody OMP-59R5 (anti-Notch2/3) administered intravenously to patients with advanced solid tumors.
Authors: Anthony W. Tolcher, Rashmi Chugh, Glenda Chambers, Villette Thorpe, Jakob Dupont, Dawn Hill, Lu Xu, Ann Kapoun, David C. Smith
Journal: Journal of Clinical Oncology (2012)

3025 Background: The Notch pathway plays a central role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many human cancers. OMP-59R5 is a fully human IgG2 originally identified by binding to Notch2. It inhibits the signaling of both Notch2 and Notch3 receptors. Mouse xenograft studies using minimally-passaged, patient-derived xenografts show that OMP-59R5 impedes tumor growth and eliminates cancer stem cells (CSCs) in many tumor types. OMP-59R5 modulates the expression of stromal genes and genes associated with the function of tumor vascular pericytes. As such, OMP-59R5 is a novel anti-cancer agent that inhibits tumor growth through direct actions on tumor cells, including CSCs, and effects the stroma and vasculature. Methods: A phase I dose escalation study (3+3 design) was initiated in solid tumor patients. OMP-59R5 was administered to study safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy, and to determine the maximum tolerated dose (MTD). Results: Twenty-four patients have been enrolled in 5 dose-escalation cohorts at doses of 0.5, 1, 2.5, and 5mg/kg administered weekly (QW) and 5mg/kg administered every other week (QOW). The most frequently reported drug-related adverse events were: mild to moderate diarrhea, fatigue, nausea, vomiting, decreased appetite, and constipation. Diarrhea was dose related and occurred at doses ≥2.5mg/kg weekly and appears less pronounced with every other week dosing. Two dose-limiting toxicities (grade 3 diarrhea and grade 3 hypokalemia) occurred at 5mg/kg QW and 2.5mg/kg was established as an MTD for QW dosing. A QOW dosing schedule is currently under investigation. The PK of OMP-59R5 was characterized by fast and dose-dependent clearance. Two patients (Kaposi’s sarcoma at 5mg/kg and adenoid cystic carcinoma at 2.5mg/kg) had prolonged stable disease for ≥110 days. PD analyses for Notch pathway modulation are ongoing. Conclusions: OMP-59R5 is generally well tolerated. An MTD of 2.5mg/kg QW has been established and a QOW schedule is currently under study. Updated results will be presented.
Comparison of efficacy and toxicity of bevacizumab in combination with chemotherapy in the first, second, and third or higher line of treatment for metastatic colorectal carcinoma (mCRC): Data from the Czech multi-institutional registry.
Authors: Igor Kiss, Zbynek Bortlicek, Bohuslav Melichar, Alexandr Poprach, Jana Halamkova, Rostislav Vyzula, Ladislav Dusek, Tomas Buchler
Journal: Journal of Clinical Oncology (2013)

e14622 Background: Data from the Czech national registry of patients treated with targeted therapies for mCRC were analyzed retrospectively to compare treatment outcomes for bevacizumab in combination with chemotherapy in the 1st, 2nd and 3rd line of treatment. Methods: The database was launched in 2005 as a clinical registry of patients with mCRC treated with bevacizumab. Epidemiological and clinical data are entered by all Czech comprehensive cancer centers administering targeted therapy. In total, 4487 mCRC patients who received bevacizumab combined with chemotherapy in either 1st line (n=3990, 88.9%), 2nd line (n=386, 8.6%), or 3rd and higher line (n=111, 2.5%) had evaluable data and were included in the present analysis. Survival was calculated using the Kaplan-Meier method, and the differences were assessed using the log-rank test. Results: Statistically significant differences were observed in the efficacy of combination chemotherapy with bevacizumab between the treatment lines. The objective response rate (ORR) in the 1st, 2nd, and 3rd/higher line was 42.9%, 34.0% and 8.3%; (p&lt;0.001) respectively. Similarly, in the 1st, 2nd, and 3rd/higher line median progression free survival (mPFS) was 11.3 months (95% CI 11.0-11.7 months), 9.5 months (95% CI 8.2-10.9 months) , and 7.3 months (95% CI 5.9-8.7 months; p&lt;0.001), and median overall survival (mOS) was 28.4 months (95% CI 27.1-29.8 months), 25.9 months (95% CI 19.4-32.4 months), and 15.0 months (95% CI 10.7-19.3 months; p&lt;0.001), respectively. The spectrum of the most common adverse events was comparable in the 1st, 2nd, or 3rd/higher line, and incidence of adverse events was similar at 11.6%, 8.8% and 8.1%, respectively. Conclusions: The efficacy of bevacizumab in combination with chemotherapy decreased when administered in later lines of treatment for mCRC while the incidence and spectrum of toxicities remains unchanged.
Demystifying cancer and engaging patients through information technology.
Authors: Simone Lehwess Mozzilli, Lisandra Panzoldo dos Santos, Andre Leme Fleury, Rodrigo Franco Gonçalves
Journal: Journal of Clinical Oncology (2015)

e17550 Background: Technological evolution, equipment modernization and internet accessibility are contributing to the increase of Information Technology, especially in the oncology area, where patients and family members are eager for information. However, the exponential growth in the amount of information does not guarantee the quality and responsiveness of it, highlighting the inadequacy and inappropriateness of information as a cause of fear, insecurity and even lack of commitment to treatment. Methods: Websites (10) of renowned oncology world hospitals were analyzed in Normative Descriptive Model. The Descriptive Model contemplates the existence and specificity of the areas: Lexi-Visual Content, Organic Search, Advanced Search (Yes/No). The Normative Model was based on principles and heuristics proposed by Ergonomics Areas, Human-Computer Interaction and Information Design: Information Structure, Simplicity Clarity, Unity, Usability, Acessibility (Appropriate/Partially Appropriate/Inappropriate). Results: See table. Conclusions: The appropriate production of information facilitates learning, providing greater identification, understanding, and ensuring the message quality. All Information Technology resources should have as its main goal to assist the understanding of treatment, which is assumed to be humanized and effective, meeting the needs, providing relief and improving the patient and family quality of life. Institution Lexi-Visual Content Organic Search Advanced Search Text Content Text Design Image Content Image Design Video Content Video Design Usability Acessibility H1 Y N N PA PA A A - - A I H2 Y N N A PA A A - - A I H3 N N Y A PA - - - - A I H4 N N N A A - - PA PA A I H5 N N N I I - - - - I I H6 N N N PA I - - - - I I H7 N N N I I - - - - A I H8 N N N PA I - - - - I I H9 N N N I I - - - - I I H10 N N N PA I - - - - A I *100% of the analyzed websites are inappropriate for accessibility, even excluding patients who became disabled by cancer.
Phase II study of individualized sunitinib (SUN) as first-line therapy for metastatic renal cell cancer.
Authors: Georg A. Bjarnason, Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Pawel Zalewski, Christina M. Canil, Eric Winquist, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn Jane Macfarlane, Peter M. Venner, Anil Kapoor, Aaron Richard Hansen, Bernhard J. Eigl, Piotr Czaykowski, Ben Boyd, Lisa Wang, Naveen S. Basappa
Journal: Journal of Clinical Oncology (2017)

4514 Background: Higher SUN exposure is associated with better outcomes. Patients (pts) with minimum toxicity on the standard schedule do worse than pts needing dosing changes for toxicity. Methods: It was hypothesized that toxicity-driven dose/schedule individualization would improve the primary endpoint (PFS) from 8.5 (EFFECT trial) to 14 months (mo), with 99 pts required to detect this with 90% power and 2-sided alpha = 0.05. In a prospective phase II study (eligibility as EFFECT) pts start on 50 mg/day (d) for 28 d with treatment (Rx) breaks reduced to 7 d. If grade-2 toxicity develops before d 28, pts stay on a 50 mg on the next cycle with the number of d on Rx individualized aiming for ≤ grade-2 toxicity. Dose is reduced to 37.5 mg and then 25 mg if pts do not tolerate a 50 mg or 37.5 mg dose respectively for at least 7 d. Pts with minimum toxicity on d 28 are escalated to 62.5 mg and then 75 mg. Results: 117 pts were enrolled in 12 centers. Nine non-evaluable pts came off early due to toxicity (5), non-compliance (2) and global deterioration (2). Of 108 pts evaluable for response (IMDC favorable 31.5%, intermediate 58.3%, poor 10.2%. Bone mets 19%, Nephrect 83%), 10 are still on Rx. Dose was escalated in 20 pts (18.5%) to 62.5 mg (12 pts) and then to 75 mg (8 pts). In 49 pts (45.4%) eligible for dose reduction by standard criteria, a 50 mg dose was maintained but for 7 - 24 d, while 7 pts (6.5%) stayed on a 28 d schedule. Dose was reduced to 37.5 mg in 22 pts (20.4% vs. 36 - 63% in 4 large SUN trials) and to 25 mg in 10 pts (9.3% vs. 27 - 43% in 4 trials). Rx was stopped due to toxicity in 10/117 pts (9.3% vs. 15 - 19% in 4 trials). See table for response (ORR, 108 pts) and survival (117 pts) data vs. EFFECT (146 pts). The median followup is 15.5 mo (0.6 -37.9) for PFS and 24.5 mo (4.4 - 47.7) for OS. Conclusions: The null hypothesis of the PFS being 8.5 mo can be rejected with a p &lt; 0.001. Individualized dosing is safe and feasible in a multicenter setting and associated with improved dose intensity and one of the best ORR, PFS and OS reported for a TKI. Clinical trial information: NCT01499121. [Table: see text]
Investigations on non-small cell lung cancer screening.
Authors: Xuedong Du, Jiasong Ji, Jingjing Song, Zhongwei Zhao, Jianfei Tu, Xiaoxi Fan, Xing Tang, Da Lou, Hongmei Tao, Yue Lin, Chris Chang Yu
Journal: Journal of Clinical Oncology (2015)

e12587 Background: Non-small cell lung cancer (NSCLC) is one of the most common cancers in the world. The high mortality rate of lung cancer is partly due to that current image-based technologies are not sensitive enough to screen early lung cancer incidences. A new cancer diagnostics method, named Cancer Differentiation Analysis Technology (CDA hereafter), was developed for diagnosis of lung cancer. In CDA technology, multi-level and multi-parameter data information including protein fragments and cellular information are collected while most existing technologies are single parameter technology, e.g. bio-marker and gene test. Methods: Three groups of samples were investigated, NSCLC group (383 samples), non-cancerous lung disease group (103 samples) and control group (149 samples). Samples used in this investigation were whole blood collected via syringe containing EDTA anticoagulant. CDA data were then collected and the differences in CDA data distribution among NSCLC group, non-cancerous lung disease group and control group were investigated. Results: Test results are shown in Table 1, which exhibited significant statistical difference with P value < 0.05 between any 2 groups in T test. Based on initial data, the sensitivity and specificity of CDA technology for lung cancer test appears to be higher than that of existing technologies, reaching 87.7% and 79.9% respectively. Conclusions: CDA technology is a promising technology for lung cancer diagnostics. It is able to distinguish control group, non-cancerous disease group and NSCLC group, with sensitivity and specificity higher than existing technologies. CDA Test Results of Three Groups of Samples Sample Group Sample Size CDA Mean(Rel. Units) CDA Stdev Control Group 149 34.09 5.23 Non-Cancerous Disease 103 44.77 9.44 NSCLC Group 383 48.93 7.41
Single agent trabectedin in heavily pretreated patients with recurrent ovarian cancer (ROC).
Authors: Feriel Boumedien, Jean-Philippe Adam, Khalid Akkour, Nathalie LeTarte, Diane M. Provencher
Journal: Journal of Clinical Oncology (2015)

5553 Background: Trabectedin is approved in Canada since 2010 in combination with liposomal doxorubicin for platinum-sensitive ROC in patients who are not expected to benefit, are ineligible or not willing to receive retreatment with platinum-based chemotherapy. In 2012, due to a shortage of liposomal doxorubicin, single agent trabectedin was proposed to patients with ROC. The aim of this study was to evaluate the efficacy and tolerability of trabectedin in this context. Methods: This retrospective IRB approved study included all patients who received trabectedin for ROC between January 1st 2012 and June 30th 2014 at the CHUM. This study was not funded.The primary outcome was progression free survival (PFS) based on CA-125 and clinical exam. We also evaluated overall survival (OS), response rate and toxicities (CTCAE v4.0). PFS and OS were estimated by Kaplan-Meier method. Results: A total of 25 evaluable patients with a median age of 59 years received trabectedin 1.3 mg/m2 I.V. in 3 hours every 3 weeks in 3rd or 4th line (36%), 5th or 6th line (36%) and ≥ 7 lines (28%). Among the patients, 60% were platinum-sensitive and 40% platinum-resistant. The median number of cycles received was 5 (range 1-16 cycles) for a total of 130 cycles. Complete response (CR), partial response (PR), stable disease (SD) and progression occurred in 16%, 20%, 24% and 40% of patients respectively. The median PFS was 3.7 months (95% CI 1.9-5.6). In patients with a response (CR, PR, SD), the median PFS was 4.9 vs 0.8 months (p < 0.001). Death occurred in 15 patients (60%). The median OS was 16.2 months. The Cox model reported that response to treatment is the only variable influencing the PFS and the OS (p < 0.001), but not the platinum status or the number of previous lines received. Grade 3 or 4 toxicities include: neutropenia (8%), febrile neutropenia (4%) and muscle weakness (4%). Dose reduction was required in 4 patients for hepatic and hematologic toxicities. No death was attributable to toxicities. Conclusions: Our results demonstrate that trabectedin has an interesting efficacy as a single agent in heavily treated ROC patients. At a dose of 1.3 mg/m2 every 3 weeks, trabectedin is well tolerated with few adverse events.