tbuckley/cabot-search huggingface dataset:
A critical evaluation of regulatory guidance on patient reported outcomes (PROs) addressing the use of PRO measures and endpoints in clinical trials
Authors: L. Claassens, D. Jones, A. Bottomley
Journal: Journal of Clinical Oncology (2008)

9590 Background: PROs are frequently used within industry-sponsored clinical trials and phase III registration trials. Recently, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) have produced draft PRO guidance. The aim of this study was to evaluate this regulatory guidance with reference to the current expert and literature evidence base on the use of PROs in cancer trials and existing QoL tools (EORTC QLQ C30 and LC13). Methods: We conducted a systematic evaluation of both FDA and EMEA guidance and undertook quantitative analyses of 47 leading world key cancer research organizations that provided a formal response to the FDA guidance. In addition, we evaluated grey literature, 25 websites, and consulted over 20 key opinion leaders. Finally, we undertook a systematic literature review (medline 1990–2007) to evaluate conformity between regulatory positions and the scientific literature. Results: In comparison with the EMEA, the FDA has a more prescriptive approach, requiring tools with robust conceptual frameworks and psychometric studies. Current state assessment, advocated by the FDA, was contradicted by 88% of 25 reviewers addressing this issue (p < 0.001). Most expert reviewers (79 % of 14 non-significant) challenged the EMEA’ s and FDA’ s views that a general QOL claim requires improvement in all domains. Minor modifications or translations triggering full re-validation, was not considered realistic by nearly all organizations (97% of 32 p < 0.0001). In addition, substantial disagreement with FDA and EMEA exists on the subject of blinding (100% of 17 p < 0.0001). However, the Minimum Important Difference (MID) is in general agreed with by organizations (86% of 28 p < 0.05). Limited literature exists to support the debatable issues of the PRO guidance. On the whole, existing instruments (e.g. EORTC QLQ-LC13, MDASI) appear to meet FDA and EMEA requirements sufficiently. Conclusions: The regulatory PRO guidance were appreciated by the research community. However, differences on philosophical and design topics are evident. While this guidance is already impacting on trial design, we hope our evaluation will encourage dialogue between all parties, bringing harmony to such positions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca
Abstract P392: Eating Frequency and Snacking and Risk of Incident Type 2 Diabetes among French Women
Authors: Martin Lajous, Anne Bijon, Guy Fagherazzi, Beverley Balkau, Marie-Christine Boutron-Ruault, Francoise Clavel-Chapelon
Journal: Circulation (2013)

Background—Increased eating frequency has been suggested to improve the metabolic profile among individuals with and without diabetes. However, a recent study found that both a decreased and an inc...
NT-pro-BNP and CA 125 as potential markers of mortality during long-term immunetherapy with trastuzumab in HER-2-positive metastatic breast cancer
Authors: D. Rossner, K. Knobloch, R. Lichtinghagen, A. Lichtenberg, H. Kuehnle, H. J. Lueck
Journal: Journal of Clinical Oncology (2004)

804 Background: Immunetherapy with trastuzumab (TR, herceptin, Roche), a selective HER-2(ErbB2)-antibody, is approved in women with metastatic breast cancer (MBC). During TR monotherapy cardiotoxicity is noted in 7% of patients (pts). Both, nt-pro-BNP (brain natriuretic peptide) and CA 125 are reported to be associated with the degree of clinical heart failure. The aim of this study is to determine pro-nt-BNP and CA 125 during longterm immunetherapy regarding mortality. Methods: In 28 female patients with metastatic HER-2-positive breast cancer blood samples before and 30min after intravenous TR infusion were drawn. Depending on the nt-pro-BNP-levels <155pg/ml (group A, n=16, age 57±13 years) vs. nt-pro-BNP >155pg/ml (group B, n=12, age 62±9 years, n.s.) two groups have been defined. Median time to initial TR-dosis was 93±86 weeks (A) vs. 117±38 weeks (B, n.s.), respectively. Results: The echocardiographic determined ejection fraction (EF%) before immunetherapy initiation was 68±3% (A) vs. 72±4% (B), lowest EF% during the TR-therapy 57±10% (A, p<0.05) vs. 48±11% (B, p<0.05), EF% at blood sampling 62±7%(A, n.s.) vs. 58±6% (B, p<0.05). Levels of nt-pro-BNP before and after TR-therapy were 65±36pg/ml vs. 66±33pg/ml (n.s.) in group A vs. 520±443pg/ml vs. 498±411pg/ml in group B (n.s.). Corresponding CA 125 levels were 25±29U/ml vs. 24±28U/ml in group A and 230±466U/ml vs. 236±484U/ml in group B (p<0.05). CA15–3 was 47±34U/ml (A) vs. 150±162U/ml (B, p<0.05). All myocardial ischemic markers (CK,CK-MB,troponine T) remained in normal ranges. Median three-months-mortality after nt-pro-BNP-measurement was 10% in group A vs. 40% in group B. Conclusions: Elevated levels of nt-pro-BNP, CA125 and CA15–3 indicate a higher median three-months-mortality in trastuzumab-treated patients on longterm immunetherapy. Therefore, elevated levels of nt-pro-BNP, CA 125 and CA 15–3 may further support clinical decisions in these patient group regarding their limited prognosis . No significant financial relationships to disclose.
Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Societe Francaise de Greffe de Moelle
Authors: L Sutton, C Chastang, P Ribaud, JP Jouet, M Kuentz, M Attal, J Reiffers, JM Tigaud, B Rio, C Dauriac, M Legros, F Dreyfus, B Lioure, X Troussard, N Milpied, F Witz, P Oriol, JY Cahn, M Michallet, E Gluckman, N Ifrah, JL Pico, E Vilmer, V Leblond
Journal: Blood (1996)
Long term survival in stage IIIb non-small cell lung cancer (NSCLC) treated with consolidation docetaxel following concurrent chemoradiotherapy (SWOG S9504)
Authors: D. R. Gandara, K. Chansky, L. E. Gaspar, K. S. Albain, P. N. Lara, J. Crowley
Journal: Journal of Clinical Oncology (2005)

7059 Background: The optimal approach to chemoradiotherapy for unresectable stage III NSCLC remains unclear. We have previously reported the efficacy of consolidation docetaxel (D) following concurrent cisplatin-etoposide (PE) and thoracic radiotherapy (RT) in stage IIIb NSCLC in which documentation of T4 (non-effusion) or N3 status was required (S9504). Methods: Here we update results in regard to survival at 5 years in 83 patients (pts) treated with P: 50 mg/m2 days 1, 8, 29 and 36, E: 50 mg/m2 days 1–5 and 29–33 and concurrent thoracic RT starting day 1: 61 Gy (1.8–2.0 Gy/day), followed by consolidation docetaxel 75–100 mg/m2 every 21 days for 3 cycles. Results: Median age 60 (34–80), male/female: 61/22, performance status: 0–1/2:78/5, TNM: T4N0–1: 31, T4N2: 22, N3: 30. Median follow-up: 71 months (mos). Median progression-free survival (PFS): 16 mos. Median survival (MST): 26 mos. 5 year survival: 29%. MST and 5 year survival for Stage IIIb subsets: T4N0–1: 32 mos and 29%: T4N2: 26 mos and 37%; N3: 16 mos and 20%. Survival data are compared below to SWOG 9019, which treated a similarly staged IIIb cohort of 50 pts with identical concurrent chemoradiotherapy, differing only in substitution of consolidation docetaxel for continued PE. Conclusions: 1) Long term survival endpoints achieved in S9504 in documented Stage IIIb NSCLC compare favorably with the SWOG historical control (S9019) and other published series in this pt population. 2) 5 year survival of stage IIIb subsets ranges from 20–37%. 3) Ongoing intergroup trial S0023 is further evaluating the S9504 regimen followed by maintenance therapy with the EGFR inhibitor gefitinib or placebo (Supported by CA 30102). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Understanding Asian American awareness of and experience with cancer clinical trials (CCTs): A mixed methods approach
Authors: D. A. Paterniti, M. S. Chen, L. A. Beckett, C. Chiechi, N. M. Horan, C. Turrell, J. Darr, J. Gonzalez, S. Davis, P. N. Lara
Journal: Journal of Clinical Oncology (2005)

6052 Background: Barriers to recruitment of minority populations affect generalizability, impact, and use of CCT findings for those populations. Methods: We undertook a mixed-methods approach to understand awareness of and experiences with CCTs. A self-administered survey using convenience sampling was provided in English to new cancer patients and their support persons at outpatient oncology clinics within a 9-county area of an NCI-designated cancer center. Observations of accrual processes to CCTs were conducted using the grounded theory approach. Results: 1006 surveys were completed and 59 unique patients observed. Comparison of survey results for Asian and non-Asian respondents showed Asians less likely to have heard the term “clinical trial” (59% Asian versus 69% all others) and more likely to define a clinical trial as “an experiment” or “a test procedure in a clinic” (n=45, 75%) than Whites (n=570, 61%) or persons of other ethnicities (n=107, 60%). Asians were more likely to have employer-based insurance (n=35, 60% versus n=448, 47%) and to report an understanding of issues related to CCT cost reimbursement (n=22, 37% versus n=310, 33%). Asians were the least likely to have been involved in or to know someone who was in a CCT (n=7, 12% versus n=171, 18%) and reported less willingness than Whites (n=38, 64% versus 747, 84%) to consider participation in a trial. Our limited observations of four Asian patients (15% of all observations) suggest that Asians presenting for CCT are younger, inquire more about the availability of a novel therapy, and have more advanced disease. Conclusions: Multiple strategies are necessary to enhance awareness of and experience with accrual to CCTs for Asians, including richer description of Asian understandings of CCTs and their contexts; optimal involvement of Asians in the process of development, implementation, and participation in CCTs; and greater attention to location and diversity of Asian populations in structuring study centers and evaluating trial Results: (ACS IRG 95–125-04; R21CA10172; VANCHCS; ACS-CRTG to PNL.) No significant financial relationships to disclose.
Abstract #2380: Curcumin overcomes the proliferative effect of estradiol in HPV positive cervical carcinoma cells by inducing apoptosis
Authors: mayank singh, Neeta Singh
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Back ground: Cervical cancer is the most common cancer in Indian females and is associated with infection with high risk Human papillomaviruses (HPVs). Prolonged use of oral contraceptives has been established as a risk factor for cervical cancer which is mediated by elevated estradiol level. Curcumin (Diferuloyl methane), a chemopreventive agent induces apoptosis in cervical cancer cells. The present study investigated whether curcumin could protect against the proliferative effect of estradiol in cervical cancer cell lines SiHa, HeLa, CaSki and C33A. Methods: HPV positive cervical cancer cell lines SiHa, HeLa, CaSki and HPV negative C33A cells were cultured in DMEM/RPMI/MEM media respectively, supplemented with 10% FBS in a humidified atmosphere of 5% CO2 at 37oC. They were treated with 10 and 30 nM estradiol for 24 hrs followed by 25 and 50\#956;M curcumin treatment for 24 hrs. Apoptosis was measured by flow cytometery. Telomerase activity was studied using PCR ELISA. The expression of various proteins like PCNA, p16 was assessed by ICC and confocal microscopy. Expression of viral oncoproteins E6 and E7, cyclin D1, p53 and p73 was assessed by western blotting. Results: Treatment of cervical cancer cells with estradiol resulted in two fold increase in proliferation after 24 hrs in HPV positive cell lines HeLa, SiHa and CaSki but not in HPV negative cell line C33A. Treatment with curcumin of these estradiol pretreated cell lines inhibited proliferation by inducing apoptosis in HPV positive cell lines. An increase in Telomerase activity, protein expression of viral oncoproteins E6 and E7, PCNA, p16 and cyclin D1 was seen in HPV positive cell lines on treatment with estradiol, but after treatment with curcumin the levels of E7, PCNA and Cyclin D1 were reduced, thereby demonstrating the antiproliferative effect of curcumin, by inducing apoptosis. However, the HPV negative cell line C33A remained unaffected on estradiol treatment, but showed increased apoptosis on treatment with curcumin. This was accompanied with a decrease in Telomerase activity, PCNA, p16 levels and an increase in p53 and p73 proteins. Conclusion: Curcumin appears to act as an antagonist to estradiol by inhibiting its proliferative effect in HPV positive cervical cancer cell lines.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2380.
Impact of ifosfamide-based chemotherapy on survival in patients with primary extremity synovial sarcoma
Authors: F. C. Eilber, F. R. Eilber, J. J. Eckardt, G. Rosen, C. Forscher, R. G. Maki, S. R. Grobmyer, M. F. Brennan, S. Singer
Journal: Journal of Clinical Oncology (2004)

9017 Background: The impact of adjuvant chemotherapy on the survival of patients with soft tissue sarcoma is controversial. Although ifosfamide based chemotherapy (IF) has generated significant responses in the treatment of metastatic synovial sarcoma, its effect on the survival of patients with primary disease remains unclear. The objective of this study is to determine if IF offers a survival benefit to patients with primary extremity synovial sarcoma. Methods: Two prospectively collected sarcoma databases were used to identify a contemporary cohort of 101 adult (≥16yrs) patients with primary, extremity, ≥5cm, deep, synovial sarcomas that underwent surgical treatment for cure from 1990 to 2002. 68 patients were treated with IF and 33 received no chemotherapy (NoC). Clinical, pathologic and treatment variables were analyzed for disease specific survival (DSS) and distant recurrence free survival (DRFS). Results: Median follow-up for the 101 patients was 58 months. 90%(91/101) underwent limb-sparing surgery and 97%(88/91) of these patients received radiation therapy. The 68 IF treated patients received a median of four cycles of ifosfamide at a median dose of 10gm/m2/cycle. The characteristics of the 68 IF treated patients [median age=34, median size=7.2cm, monophasic n=47(69%)] were very similar to the 33 NoC patients [median age=37, median size=7, monophasic n=24(72%)]. The 4 year DSS of the IF treated patients was 88%(±8%) compared to 67(±17%) for the the NoC patients(p=0.01). The significant independent prognostic factors for DSS were size (HR=3.2,p=0.0001) and IF (HR=0.3,p=0.007)(table). The 4 year DRFS of the IF treated patients was 83%(±5%) compared to 64%(±8%) for the the NoC patients(p=0.019). Conclusions: Ifosfamide based chemotherapy is associated with improved DRFS and DSS in patients with large, primary, extremity synovial sarcoma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer; Eli Lilly
Study of isocentric variation of 2-dimensional and 3-dimensional treatment planning in clinical radiotherapy
Authors: R. C. Joshi, T. Ganesh, R. Prabhakar, M. B. Pandey, P. S. Sridhar, P. K. Julka, G. K. Rath, A. K. Bansal
Journal: Journal of Clinical Oncology (2005)

864 Background: The placement of isocenter plays a very crucial role in tumor coverage as well as the dose delivery. In routine radiotherapy, most of the cancer sites are treated with 2 dimensional treatment planning in developing countries. In 2-D treatment planning, the image slice which lies in the center of the tumor is selected for planning and the tumor volume which are maximum in other slices are super-imposed onto the central cut in which the 3D shape of the tumor is not taken into account. The aim is to study the shift in planning isocenter between 2D and 3D treatment planning for various treatment sites in radiation therapy. The main purpose of this study is to segregate those sites that are routinely used for 2D planning and which badly require 3D treatment planning. Materials and Methods: In this study, a group of 50 patient of varied diagnosis like cancer of breast, maxilla, lung, cervix, retinoblastoma, oesophagus, bladder, parotid, thymoma, prostate, rectum etc., were selected and CT scans were performed for all the cases for 3D planning. A single CT cut is selected at the center of the tumor for 2D planning onto which tumor volume which are maximum in other slices were superimposed. The target volume is marked on all the CT slices for 3D treatment planning and the planning was done based on the Beams Eye View. The isocenter is placed at the center of mass of gravity for the 3D treatment planning. Separate 2D planning were done on the selected central cut. The shift in isocenter was quantified based on the X,Y and Z coordinates Results and Conclusion: The study revealed that the maximum 3D shift in the isocenter between 2D and 3D planning were 2.7 cm for Ca. Breast followed by 1.5 cm for maxilla and less than 0.7cm for rest of the sites. The study clearly showed that for cancer of breast, 3D treatment plan is necessary. No significant financial relationships to disclose.
Weather scientists cite Bob Dylan too
Authors: Sally Brown, Karen L Aplin, Katie Jenkins, Sarah Mander, Claire Walsh, Paul D Williams
Journal: BMJ (2016)

Congratulations to those who squeezed Bob Dylan songs into their papers and those involved in the analysis. 1 Medical scientists are not the only Bob Dylan fans with a sense of humour-meteorologists and climate impact scientists have one too. [2]3][4] To our knowledge, Bob Dylan has sung
A phase 3 study of ibrutinib in combination with either bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously treated follicular lymphoma or marginal zone lymphoma.
Authors: Nathan Hale Fowler, Wolfgang Hiddemann, John Leonard, Esther Rose, Tahamtan Ahmadi, Jessica Vermeulen, Julie S. Larsen, Steven Sun, Lisa Mentzer, Shean-Sheng Wang, Tzu-Min Yeh, Gilles A. Salles
Journal: Journal of Clinical Oncology (2014)

TPS8611^ Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL) and account for approximately 22% and 10%, respectively, of all NHLs. Although patients often respond to initial therapy, most will relapse and suffer substantial morbidity and mortality related to persistence/recurrence of disease. For patients with relapsed iNHL, the most common chemoimmunotherapy regimens are BR and R-CHOP; however, outcomes in the relapsed setting remain suboptimal. Ibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor that has demonstrated activity in a phase 1 study in patients with various B-cell malignancies, including iNHL. A phase 2 monotherapy study in chemoimmunotherapy-resistant FL is ongoing. Other completed and ongoing studies have demonstrated that ibrutinib can be safely combined with BR or R-CHOP. Based on these observations, this phase 3 trial has been designed to investigate the combination of ibrutinib with BR or R-CHOP in patients with iNHL. Methods: The SELENE study, PCI32765FLR3001, is a randomized, double-blind, placebo-controlled, multicenter, phase 3 study of ibrutinib combined with either BR or R-CHOP for previously treated FL or MZL. The study aims to enroll approximately 400 patients with disease that has relapsed after, or was refractory to, prior chemoimmunotherapy. All patients will receive 6 cycles of BR or R-CHOP (based on prior treatment) and either a daily oral dose of 560 mg ibrutinib or placebo continued up to progression. The primary objective is to evaluate whether the addition of ibrutinib to BR or R-CHOP will prolong progression-free survival, with secondary objectives of evaluation of overall survival, CR rate, ORR, patient-reported lymphoma symptoms, and safety. Exploratory objectives include the minimal residual disease negative rate in FL patients, patient-reported outcomes related to general health status, and the pharmacokinetics of ibrutinib. Approximately 145 sites in Europe, Asia, Australia, USA and South America will participate. Enrollment began in Q1 2014. Clinical trial information: NCT01974440.
Abstract 2241: Direct Visualization Of The Fossa Ovalis For Transeptal Puncture: <i>In Vivo</i> Evaluation Of The IRIS Catheter In A Porcine Model
Authors: Aravinda Thiagalingam, Andre d’Avila, Lori Foley, David Miller, Chris Rothe, Vahid Saadat, Jeremy N Ruskin, Vivek Y Reddy
Journal: Circulation (2007)

Introduction: Transeptal puncture is required for many interventional procedures but has a serious complication rate of ~1%. The primary risk of the procedure is related to mis-identification of the interatrial septum resulting in inadvertant puncture of the aorta or the atrial wall into the pericardium. We have investigated the utility of a catheter that allows direct visualization of the fossa ovalis to correctly position the transseptal needle at the interatrial septum. Methods: This study included 6 swine. The IRIS catheter (Voyage Medical, Campbell, CA) enables direct visualization using a cone-shaped hood into which saline is infused to exclude blood. In 4/6 animals, intracardiac echocardiography was used to visualize, but not guide, the transeptal puncture; there was no visible tenting of the septum. After transeptal puncture was performed the IRIS catheter was used to directly visualize and cannulate the puncture sites. Results: In 5 animals, transeptal puncture was successfully performed repeatedly (2–4 punctures/animal), and a .035 guidwire passed into the left atrium. IRIS could also guide cannulation of previous puncture in these animals. In 1 animal, visualization could not be performed because the atrial septum was lacerated during an attempt at left atrial visualization via a patent foramen ovale. Pericardial effusion was only observed in this latter animal on post-mortem exam. IRIS visualization of the atrial septum correlated well with the pathological specimen (see Figure ). Conclusion: The IRIS catheter allows direct in vivo visualization of the interatrial septum to guide de novo transeptal puncture or cannulation of previous punctures. Top: A cascade of in vivo IRIS images of transeptal puncture holes (arrows) and a PFO Bottom: Corresponding post mortem speciman
IDENTIFICATION OF BIOMARKERS PREDICTING STEROID RESPONSE IN ACUTE SEVERE ULCERATIVE COLITIS USING SURFACE-ENHANCED LASER DESORPTION/IONISATION TIME OF FLIGHT MASS SPECTROMETRY
Authors: N. C. Hare, M. Imrie, Austin Smith, K. Soo, L. Smith, Robert Gray, Gwo-Tzer Ho, I. D. Arnott, Jack Satsangi
Journal: Gut (2009)