tbuckley/cabot-search huggingface dataset:
Randomized phase II study of panitumumab (Pmab) + irinotecan (CPT-11) versus cetuximab (Cmab) + CPT-11 in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) after fluoropyrimidine (FU), CPT-11, and oxaliplatin (L-OHP) failure: WJOG6510G.
Authors: Naotoshi Sugimoto, Daisuke Sakai, Takao Tamura, Hiroki Hara, Tomohiro Nishina, Taito Esaki, Hiroyuki Okuda, Tadamichi Denda, Masahiro Tsuda, Taroh Satoh, Akitaka Makiyama, Kentaro Yamazaki, Hidekazu Kuramochi, Ayumu Hosokawa, Takashi Tsuda, Hiroya Taniguchi, Junji Kishimoto, Narikazu Boku, Ichinosuke Hyodo, Kei Muro
Journal: Journal of Clinical Oncology (2017)

661 Background: Continuation of CPT-11 in combination with Cmab after CPT-11 failure has a survival benefit over Cmab alone. However, it is not clear whether CPT-11 with Pmab shows similar benefits. Methods: Pts with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies were randomized 1:1 to either Cmab + CPT-11(Cmab arm), or Pmab + CPT-11(Pmab arm). Primary objective was progression free survival (PFS), with an expected hazard ratio (HR) of 1.0 with non-inferiority margin of 1.3 (80% CI) using cox proportional hazards model. Median PFS with both arms were assumed to be 6.0 months. Secondary objectives were overall survival (OS), response rate (RR), disease control rate (DCR), and safety. Results: From December 2011 to September 2014, 121 pts were enrolled from 31 sites in Japan. Because 1 patient declined before treatment, totally, 120 (Cmab arm: 59, Pmab arm 61) pts were eligible for efficacy analysis. Baseline characteristics were well balanced between the two arms. 116 pts (96.7 %) were previously treated with bevacizumab. Efficacy results are shown in the table. The common grade 3 or 4 adverse events in Cmab/Pmab arm were leukopenia 19.0/3.3%, neutropenia 27.6/8.3%, hypomagnesaemia 6.9/16.7%, and rash 5.2/13.3 %, respectively. Conclusions: Non-inferiority of Pmab to Cmab in combination with CPT-11 was suggested for patients with KRAS WT mCRC previously treated with FU-, L-OHP-, and CPT-11- based chemotherapies, associated with favorable PFS and OS. Clinical trial information: UMIN000006643. [Table: see text]
Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis
Authors: Paola Guglielmelli, Annalisa Pacilli, Giada Rotunno, Elisa Rumi, Vittorio Rosti, Federica Delaini, Margherita Maffioli, Tiziana Fanelli, Alessandro Pancrazzi, Daniela Pietra, Silvia Salmoiraghi, Carmela Mannarelli, Annalisa Franci, Chiara Paoli, Alessandro Rambaldi, Francesco Passamonti, Giovanni Barosi, Tiziano Barbui, Mario Cazzola, Alessandro M. Vannucchi
Journal: Blood (2017)
Characterization of DNA methylation of the promoters <i>CTCF</i> and BORIS (<i>CTCFL</i>) in breast and ovarian cancer.
Authors: Ernesto Soto Reyes Solis, Daniela Morales-Espinosa, David Cantu, Gabriela Alvarado-luna, Dan Green, Clementina Castro Hernandez, Iliana Alcala-Moreno, Fernanda Cisneros-Soberanis, Daniel Motola, Jeronimo Rodriguez-Cid, Luis A. Herrera
Journal: Journal of Clinical Oncology (2013)

e22151 Background: Genetic and epigenetic alterations may promote the initiation or development of cancer. Global DNA hypomethylation and local hypermethylation have been observed, particularly in cell cycle control-associated genes, such as tumor suppressor genes like CTCF. The dissociation of CTCF is associated with hypermethylation of several promoters; its paralogue gene (BORIS) is normally expressed in testicular tissue during spermatogenesis. BORIS over-expression has been identified in multiple neoplasms such as melanoma, gynecological cancer, glioblastoma and – recently – breast cancer. The aim of this study was to characterize the methylation status of the promoter regions of CTCF and BORIS in samples from breast and ovarian cancer compared to non-neoplastic tissue, and correlate it to its expression. Methods: Tissue samples from breast and ovarian cancer, as well as healthy controls were analyzed by MS-PCR for CTCF and BORIS. BorismRNA expression was also analyzed by RT-PCR. Results: A total of 8 ovarian and 16 breast tumors, as well as 10 tumor-adjacent breast tissue samples were prospectively obtained. In non-neoplastic tissue, BORIS was found to be hypermethylated, while in ovarian tumors a loss of methylation was identified in 75% of the samples. The same phenomenon was observed in 68% of breast cancer samples when compared to non-neoplastic tissue. A correlation between loss of DNA methylation of the promoter and gene over-expression was found by RT-PCR, thus suggesting that methylation is an epigenetic phenomenon associated to the over-expression of the oncogene BORIS. The methylation analysis of CTCF did not show any differences between neoplastic and non-neoplastic tissue, suggesting that epigenetic changes mainly affect BORIS. Conclusions: Loss of methylation of the promoter region of BORIS is associated with the over-expression of the gene. No differences were found in the methylation status between healthy and neoplastic tissue for CTCF.
Comprehensive reassessment of plasma VEGFA (pVEGFA) as a candidate predictive biomarker for bevacizumab (Bv) in 13 pivotal trials (seven indications).
Authors: Carlos Bais, Christina Rabe, Norbert Wild, Magdalena Swiatek-de Lange, David Chen, Kyu Hong, Lukas Amler, Nicola Moore, Priti S. Hegde
Journal: Journal of Clinical Oncology (2014)

3040 Background: Baseline (BL) pVEGFA level has been investigated as a predictive biomarker for the clinical efficacy of anti-VEGF therapy with Bv in 13 trials (7 indications).Three studies, AVADO (breast cancer [BC]), AVAGAST (gastric cancer), and AVITA (pancreatic cancer [PC]), reported that a high BL pVEGFA level was associated with prolonged PFS or OS, but contrasting data were obtained in other Bv clinical trials. Therefore, pVEGFA as a potential predictive factor of Bv activity in specific oncological indications and individual pts remains poorly understood. Methods: To investigate the potential value of BL pVEGFA level (from EDTA-plasma) as a predictive biomarker for Bv activity, sensitivity analyses were carried out on pVEGFA assay data from 13 pivotal Bv trials. In all trials, a VEGFA assay with preferred sensitivity toward the short VEGFA isoforms was used (IMPACT platform, currently used for pt stratification in the MERiDiAN BC trial). Results: In the AVADO study, a high BL pVEGFA level was associated with improved PFS in pts treated with Bv 7.5mg/kg but not Bv 15mg/kg. Additionally, while BL pVEGFA levels were predictive of OS and PFS in the AVITA trial, these results were not replicated in a second PC trial (CALGB 80303). Parallel sensitivity analyses of the IMPACT VEGFA assay and assays that recognize all VEGFA isoforms similarly, suggested that preferential detection of the short isoform of VEGFA was not required to assess outcome correlations (AVADO trial). Sensitivity analysis of pVEGFA data from the AVADO trial also indicated an 11% difference in Spearman's rank correlation between different VEGFA assays, which resulted in a loss of the interaction p-value. Finally, longitudinal analysis of VEGFA level in plasma samples from healthy donors showed substantial intra-pt variability in pVEGFA concentration over time. Conclusions: These data suggest that pVEGFA level is not a robust predictive biomarker for Bv activity; stratification of pts based on a single BL measurement of pVEGFA is unlikely to be successfully implemented in clinical practice. Further assessment of this hypothesis awaits the prospective analysis of pVEGFA data from MERiDiAN.
Phase I/II study of biweekly pemetrexed plus cisplatin in patients with locally advanced, nonresectable or metastatic urothelial cancer: Safety and efficacy results from phase II.
Authors: Ana Lopez Martin, Joaquim Bellmunt, José Pablo Maroto, Enrique Gallardo, Marta Lopez Brea, Jose Luis Perez-Gracia, Daniel E. Castellano, Claudia María Valverde, Susana Bezares, Emiliano Calvo, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2013)

4550 Background: Pemetrexed (P) plus cisplatin (C) combination is effective against several malignant tumors. Single-agent P has shown antitumor activity in advanced urothelial cancer; we performed a phase I/II study to define the maximum tolerated dose of biweekly P plus C combination. Here, we report the final results of the phase II study. Methods: Eligible patients (pts) had locally advanced or metastatic transitional cell carcinoma of the urothelium not suitable for curative therapy, performance status (PS) 0-2, estimated life expectancy of at least 12 weeks, and adequate organ function. P and C were administered on days 1 and 15 of each 28-day cycle, up to a maximum of 6 cycles. Pts received the recommended dose from phase I, with P at 400 mg/m 2 plus C at 50 mg/m 2 (folic acid and vitamin B 12 supplementation were also administered). Primary objective was overall response rate (ORR) according to RECIST 1.0. Results: Thirty-eight pts were recruited, 32 (84.2%) pts had bladder cancer with a mean diagnosis time of 1 (range 0-7) year and 30 (78.9%) had metastatic disease; 19 (50%) pts had visceral metastasis and 2 (5.3%) pts had a PS 2. Only 2 pts did receive adjuvant systemic therapy. Median number of cycles was 3 (range 0-7). Twelve (31.6%) pts discontinued the study treatment due to toxicity. The most common treatment-related AEs (&gt; 20%) were asthenia (n=27 pts), nausea and vomiting (n=21, respectively), diarrhea (n=18), anorexia (n=17), mucosal inflammation (n=14), and constipation (n=8). Most treatment-related AEs were of mild or moderate severity. Neutropenia (n=5) and asthenia (n=3) were the most frequent Grade 3 or 4 treatment-related AEs. Serious related AEs were observed in 8 (21.1%) pts. ORR was 39.5% (95% CI 24.0-56.6): 2 (5.3%) pts achieved complete response and 13 (34.2%) pts, partial response. Median progression free survival was 6.7 months, and median overall survival was 10.5 months. Conclusions: In this study, biweekly P (400 mg/m 2 ) plus C (50 mg/m 2 ) combination showed anti-tumor activity in pts with advanced urothelial cancer, with an acceptable safety profile. Clinical trial information: NCT00374868.
Prospectively collected baseline erectile function (EF) in 1,173 consecutive newly diagnosed prostate cancer patients referred for radiotherapy.
Authors: Jill Nicholson, Paul J. Kelly
Journal: Journal of Clinical Oncology (2017)

89 Background: Preservation of EF is a goal of care for many men with newly diagnosed prostate cancer. In order to accurately counsel patients regarding their likely treatment outcome, an assessment of baseline EF, and screening for known risk factors, should form part of the assessment of all prostate cancer patients. Methods: We performed a retrospective review of prospectively-collected data regarding baseline EF in men with prostate cancer referred for a radiotherapy opinion. 1173 consecutive patients referred over a 5.5 year period from 2011-16 were included. All patients were offered the opportunity to complete the International Index of Erectile Function (IIEF-5) questionnaire in privacy. Information on known risk factors such as age, vascular comorbidity, smoking and alcohol history, and cardiovascular risk factors was recorded. Results: Of the 1173 patients, 233 were excluded due to metastatic disease at referral. Of the remaining 940 with localised disease, 812 (86%) completed the questionnaire. 561 (69%) successfully filled the questionnaire yielding a score. A further 251 (31%) commented on the questionnaire without completing the score (see table). Median age was 66years (IQR 62-71). 574(61%) had known risk factors for erectile dysfunction such as hypertension or diabetes. 173 (18.5%) had a history of peripheral, cardiovascular, or cerebrovascular disease. Smoking and alcohol history was available for 645 patients, 353(60%) had a smoking history, and 450(70%) had a history of alcohol use. Conclusions: In this population, there is a high prevalence of baseline erectile dysfunction (IIEF-5 ≤16), 242/561 (43%). Additionally, significant numbers of patients were sexually inactive or unconcerned regarding ED. Known risk factors for erectile dysfunction were common in this population, many of which are modifiable. [Table: see text]
A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.
Authors: Nozomi Minagawa, Hideyasu Sakihama, Nozomi Kobayashi, Kenji Wakayama, Tatsuhiko Kakisaka, Yousuke Tsuruga, Tatsushi Shimokuni, Shigenori Homma, Hideki Yokoo, Hirofumi Kamachi, Norihiko Takahashi, Toshiya Kamiyama, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2013)

e15038 Background: Circulating tumor cells (CTC) in peripheral blood (PB) and disseminated tumor cells (DTC) in bone marrow (BM) have been recently focused as predictive and prognostic markers in solid tumors. But hepatocellular carcinoma (HCC) usually lacks epithelial antigens, only a few reports described CTC or DTC at a cellular level. The aim of this study is to establish methodology for detecting CTC and DTC in HCC at a cellular level, and to determine to what degree DTC match the phenotype criterion of putative cancer stem cells. Methods: PB (n-17) and BM samples (n-12) were preoperatively collected from patients with HCC between October 2011 and December 2012. Mononuclear cells were collected by Ficoll gradient separation. CD45+ cell population was deleted through magnetic activated cell sorting system. Subsequently, double immunofluorescence for AFP, Arginase-1 or Hep-Par1 and CD45 was performed. PB samples from 20 healthy volunteers and BM samples from 3 patients with benign disease were used as controls. Our protocol has been approved by the ethical committee of Hokkaido University Hospital and written informed consent was obtained from all enrolled patients. Results: Positive rates of CTC and DTC were 70.5% (12/17) and 75.0% (9/12), respectively. No CTC or DTC was found in the control groups. Poorly differentiated HCC were found in 50.0% of CTC+ patients and 66.6% of DTC+ patients, whereas, 20% in CTC- patients and 0% of DTC- patients. There’re higher risk of recurrence in CTC+ or DTC+ patients, compared with that of CTC- or DTC- patients (33.3%, 55.5% vs 20%, 0%). Over 40% of DTC expressed putative stem cell marker CD133, although the median positive rate of CD133 in primary HCC was reported to be less than 1%. Conclusions: Our protocol might provide highly specific detection of CTC, DTC from HCC patients. Detection of CTC and DTC might closely correlate with histological grade of differentiation and recurrence rate.
Tuberculosis Among Foreign-Born Persons Diagnosed ≥10 Years After Arrival in the United States, 2010–2015
Authors: Clarisse A. Tsang, Adam J. Langer, Thomas R. Navin, Lori R. Armstrong
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

The majority of tuberculosis (TB) cases in the United States are attributable to reactivation of latent TB infection (LTBI) (1). LTBI refers to the condition when a person is infected with Mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of TB disease. CDC and the U.S. Preventive Services Task Force (USPSTF) recommend screening populations at increased risk for LTBI, including persons who have lived in congregate settings at high risk and persons who were born in, or are former residents of countries with TB incidence ≥20 cases per 100,000 population (2-4). In 2015, foreign-born persons constituted 66.2% of U.S. TB cases (5). During the past 30 years, screening of persons from countries with high TB rates has focused on overseas screening for immigrants and refugees, and domestic screening for persons who have newly arrived in the United States (6,7). However, since 2007, an increasing number and proportion of foreign-born patients receiving a diagnosis of TB first arrived in the United States ≥10 years before the development and diagnosis of TB disease. To better understand how this group of patients differs from persons who developed TB disease and received a diagnosis <10 years after U.S. arrival, CDC analyzed data for all reported TB cases in the United States since 1993 in the National TB Surveillance System (NTSS). After adjusting for age and other characteristics, foreign-born persons who arrived in the United States ≥10 years before diagnosis were more likely to be residents of a long-term care facility or to have immunocompromising conditions other than human immunodeficiency virus (HIV) infection. These findings support using the existing CDC and USPSTF recommendations for TB screening of persons born in countries with high TB rates regardless of time since arrival in the United States (2,3).
Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2-negative locally advanced breast cancer (LABC): A phase II trial of the NSABP Foundation Research Group
Authors: P. Rastogi, M. Buyse, S. Swain, S. Jacobs, A. Robidoux, M. Liepman, P. Dy, C. Geyer, N. Wolmark
Journal: Journal of Clinical Oncology (2009)

584 Background: Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer. The purpose of this trial was to determine the activity and safety profile of bevacizumab with chemotherapy in women with LABC. Methods: Between November 2006 and August 2007, 45 women with HER-2 negative LABC initiated preoperative standard AC x 4 followed by docetaxel 75 mg/m 2 IV and capecitabine 825 mg/m 2 BID days 1–14 (TX) every 21 days for 4 cycles. Bevacizumab 15 mg/kg IV was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively, bevacizumab was resumed for a total of 10 doses. Primary endpoint was pathologic complete response rate (pCR) in the breast. The secondary endpoints include clinical response rates and toxicity. Results: The median age was 50 yrs (range 30–78). 30 patients had stage IIIA (67%), 12 stage IIIB (27%), and 3 stage IIIC (7%) disease. Of these, 10 (22%) had inflammatory breast cancer. 27 patients (60%) had ER-positive disease. A pCR in the breast was documented in 4/44 (9%) patients, which included negative axillary nodes. A complete clinical response was noted in 14/45 (31%). One patient did not have surgery due to progression. Toxicities included hand-foot (grade 2/3–33%/22%), mucositis (grade 2/3–49%/27%), and febrile neutropenia (grade 3–24%). Conclusions: This regimen demonstrated only modest activity with substantial toxicity, and does not appear to warrant further evaluation. This clinical trial is being conducted through the support of Genentech and Roche. [Table: see text]
Asthma management: A new phenotype‐based approach using presence of eosinophilia and allergy
Authors: M. Terl, V. Sedlák, P. Cap, R. Dvořáková, V. Kašák, T. Kočí, B. Novotna, E. Seberova, P. Panzner, V. Zindr
Journal: Allergy (2017)

Abstract Asthma is a heterogeneous disease. The Czech Pneumology and Allergology Societies commissioned 10 experts to review the literature and create joint national guidelines for managing asthma, reflecting this heterogeneity. The aim was to develop an easy‐to‐use diagnostic strategy as a rational approach to the widening opportunities for the use of phenotype‐targeted therapy. The guidelines were presented on websites for public comments by members of both the societies. The reviewers’ comments contributed to creating the final version of the guidelines. The key hallmark of the diagnostic approach is the pragmatic concept, which assesses the presence of allergy and eosinophilia in each asthmatic patient. The guidelines define three clinically relevant asthma phenotypes: eosinophilic allergic asthma, eosinophilic nonallergic asthma and noneosinophilic nonallergic asthma. The resulting multifunctional classification describing the severity, level of control and phenotype is the starting point for a comprehensive treatment strategy. The level of control is constantly confronted with the intensity of the common stepwise pharmacotherapy, and the concurrently included phenotyping is essential for phenotype‐specific therapy. The concept of the asthma approach with assessing the presence of eosinophilia and allergy provides a way for more precise diagnosis, which is a prerequisite for using widening options of personalized therapy.
Treatment utilization patterns for prostate cancer (PCa): An analysis from the National Cancer Database (NCDB).
Authors: Jeanny B. Aragon-Ching, Heather M. Hussey, Hong Nguyen, Dechang Chen, Donald Henson, Samuel J. Simmens
Journal: Journal of Clinical Oncology (2017)

99 Background: We previously reported the effects of the PSA screening guidelines on the patterns of diagnosis and treatment for PCa based on analyses from the NCDB dataset (Aragon-Ching et al., ASCO GU 2016). Given increasing use and advocacy for active surveillance, we now report on the treatment utilization patterns for PCa by facility type and overall incidence of active treatment (surgery or radiation), no treatment, or active surveillance by PCa stage using the NCDB dataset. Methods: Using a de-identified dataset acquired from NCDB from 1998 to 2012, treatment status of all 337,568 men for which information was available was tabulated according to whether active treatment, no treatment, or active surveillance (i.e. watchful waiting) was performed. Patient characteristics, stage, and treatment status by facility type was determined. Results: There were 1,802,596 patients diagnosed with prostate cancer between 1998 and 2012 in the NCDB. Of the 337,568 men for which treatment status was available, 92% received treatment, nearly 4% were under active surveillance, and another 4% did not receive any form of treatment or active surveillance. Of patients diagnosed with TNM Stage I and II PCa, only 7.5% and 2.22%, respectively, were followed under active surveillance. Overall, active surveillance was most utilized (n = 7,524; 5.7% of men) in academic research programs compared to other treatment facilities. Of the 310,898 men who received any form of active treatment, 193,889 men (62.3%) received surgery and 108,925 men (35%) received radiation. Conclusions: Active surveillance as a treatment modality comprised only a minority of patients who underwent treatment for PCa from 1998–2012, even among men with early Stage I and II Pca. Interestingly, the majority of the men who did receive active surveillance as their treatment option were treated at academic research programs, perhaps alluding to increased recognition and adherence to the PSA screening and active surveillance guidelines compared to other treatment facility types. Datasets including PCa patients beyond 2012 will be explored to further evaluate these changes in treatment modalities.