tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of CT colonography (CT-C) as a screening (Scr) tool for colorectal cancer (CRC).
Authors: Vinay Duddalwar, David I. Quinn, Heinz-Josef Lenz, Afsaneh Barzi, Sarmad Sadeghi
Journal: Journal of Clinical Oncology (2016)

e13049 Background: CT-C is not recommended by the US Preventive Services Task Force and Centers for Medicare and Medicaid. It is thought that the incidence reduction (IR) and cancer mortality reduction (CMR) associated with Scr with CS (CS) and flexible sigmoidoscopy (FS) are derived from their role in detection of adenomas as opposed to invasive cancer and down-staging. CT-C is able to detect adenomas but data for its efficacy in IR and CMR are unavailable. Methods: A Markov model was built to represent the CRC incidence and its natural history in the US general population. Individual level simulation was used to compare the benefits of CRC Scr from a societal perspective. Costs and effects were discounted (Dis) at 3%. 13 Scr strategies (ST) were compared to No Scr. The sensitivity of CT-C for detection of adenoma was set at .8 relative to CS. Dis Life Years (LY), IR, CMR, and Dis costs of Scr and total costs of care were measured. Incremental cost effectiveness ratios (ICERs) were calculated. Results: CS emerged as the most effective Scr ST. CT-C is the second most effective strategy and has an ICER of $1000/LYG. Conclusions: Although CT-C was dominated by CS, it would be next most cost effective ST among the remaining STs. While further research into the efficacy of CT-C and its ability to reduce the CRC incidence and mortality is warranted, it can be seen from these results that it potentially can find a place in the CRC Scr. Strategy Comparative Effectiveness Costs Cost Effectiveness Status (Rank-ICER $) Dis LY CRC IR (%) CMR (%) Total Scr With CS Without CS No Scr 15.205 0 0 3415 0 D D ST 1: FOBT 15.215 12 17 3164 86 D D ST 2: FIT 15.211 6 12 3303 123 D D ST 3: FOBT + FS 15.217 14 19 3170 158 D D ST 4: FIT + FS 15.214 8 14 3338 232 D D ST 5: CS 15.227 23 34 2861 526 U (1- 0) ST 6: FS 15.221 11 21 3145 270 D D ST 7: FOBT 2 15.218 12 20 3054 75 D U (1-0) ST 8: FIT 2 15.215 5 14 3186 93 D D ST 9: FOBT 2 + FS 15.219 13 21 3128 178 D D ST 10: FIT 2 + FS 15.217 7 17 3256 230 D D ST 11: DNA 15.216 14 18 4296 1255 D D ST 12: DNA 3 15.219 14 21 4161 1232 D D ST 13: CT-C 15.225 20 30 3062 494 D U (2- 1,089) FOBT: Fecal Occult Blood Test, FIT: Fecal Immunochemical Test, DNA: Stool DNA Test. Stool tests are done annually or at the interval listed. D: Dominated. U: Undominated.
Oncologists’ use of tumor sequencing findings and patient derived benefit.
Authors: Michele Caroline Gornick, Erin Frances Cobain, Lan Q. Le, Elena Martinez Stoffel, Arul M. Chinnaiyan, J. Scott Roberts
Journal: Journal of Clinical Oncology (2017)

e13016 Background: Despite increasing use of tumor genomic sequencing in clinical oncology, there is currently limited understanding of how oncologists interpret and apply this information to a patient’s clinical management. Methods: We surveyed oncologists who referred patients with refractory cancers to the Michigan Oncology Sequencing (MI-ONCOSEQ) program which uses integrative clinical sequencing to detect multiple classes of somatic and germline molecular aberrations including point mutations, amplifications, insertions/deletions, gene fusions, and outlier gene expression from June 2014-February 2015. Patients were also surveyed approximately 2 weeks after notification of completion of sequencing. In addition, we conducted chart reviews to ascertain how many patients’ clinical management was changed or derived clinical benefit as a result of sequencing. Results: Forty-three oncologists (37% female, 98% academic medical center practice), referring 112 patients ( M = 2, range: 1-9) completed the survey (response rate = 93%). Oncologists reported an intention to change 22% of patients’ treatment plans on the basis of sequencing results, with referral to a clinical trial (N = 12; 50%) as the most frequently endorsed intended change. However, few patients (N = 9, 38%) had an actual change in clinical management. Barriers identified included patient factors, ineligibility for identified treatment, and loss to follow-up/deceased. Of the 57 patients who completed post-sequencing surveys, 34 (60%) reported that results of sequencing had not been disclosed. However, patient records had documentation that results disclosure had indeed taken place in 41% of cases. Conclusions: Although expectation of enrollment in clinical trials is frequently proposed as the indication for genomic sequencing, practice barriers remain. These include lack of access to studies, severity of patient illness and challenges to effective communication of results.
Development of a nationwide genomic screening network for squamous cell lung cancer in Japan (LC-SCRUM-Japan).
Authors: Tadasuke Shimokawaji, Eri Sugiyama, Shingo Matsumoto, Kiyotaka Yoh, Masato Shingyoji, Kadoaki Ohashi, Terufumi Kato, Hiromi Aono, Yuichiro Ohe, Shunichi Sugawara, Naoki Furuya, Hirofumi Nakazaki, Kageaki Taima, Hiroshi Watanabe, Taishi Harada, Tomohiro Sakamoto, Shinnosuke Ikemura, Katsuya Tsuchihara, Koichi Goto
Journal: Journal of Clinical Oncology (2016)

9097 Background: Potentially targetable genes have been identified in squamous cell lung cancer (SqLC), but effective molecular-targeted therapies against SqLC have not yet been established. To select appropriate patients for clinical trials of targeted therapies, we have analyzed advanced SqLCs for genetic alterations in our nationwide genomic screening system (LC-SCRUM-Japan). Methods: LC-SCRUM-Japan was established in February 2013, and a genomic screening of advanced SqLCs has been operated since March 2015. As of December 2015, 155 institutions across Japan were participating and 105 SqLCs patients had been enrolled in this study. Submitted tumor samples were analyzed for genetic alterations using a next-generation sequencing system, Oncomin Comprehensive Assay, enabling the simultaneous analysis of 143 cancer-related genes. Results: The median age of the 105 patients was 69 years (range, 27-84 years). Eighty-eight (84%) were male and most patients (95%) were smokers. Among 88 available samples, potentially targetable gene alterations were detected in 47 (53%), including 21 (24%) with PIK3CA alterations, 2 (2%) with AKT1 mutations and 2 (2%) with PTEN mutations as candidate targets for clinical trials of PI3K or AKT inhibitors. There were also 9 patients (10%) with FGFR1 copy number gains and 1 case (1%) with a FGFR3 fusion as candidates for clinical trials of FGFR inhibitors. Other genetic alterations were mutations of NFE2L2 (16 cases, 18%) and KRAS (12, 14%), and copy number gains of SOX2 (14, 16%), DCUN1D1 (13, 15%), MYC (6, 7%) and EGFR (3, 3%). An ALK fusion was also detected in 1 case (1%). Conclusions: A series of potentially targetable gene alterations were detected in Japanese advanced SqLC patients, indicating that our nationwide screening project is able to contribute to the development of novel effective targeted therapies against advanced SqLC. This project is now ongoing with a total of 600 SqLC patients for inclusion. We will present updated data in the 2016 ASCO Annual Meeting.
Treating Specialty and Outcomes in Newly Diagnosed Atrial Fibrillation
Authors: Alexander C. Perino, Jun Fan, Susan K. Schmitt, Mariam Askari, Daniel W. Kaiser, Abhishek Deshmukh, Paul A. Heidenreich, Christopher Swan, Sanjiv M. Narayan, Paul J. Wang, Mintu P. Turakhia
Journal: Journal of the American College of Cardiology (2017)
A trail of neoadjuvant recombinant human endostatin in combination with docetaxel, epirubicin, and cyclophosphamide in breast cancer patients.
Authors: Yunjiang Liu, Miao Cao, Yueping Liu, Xiangmei Zhang
Journal: Journal of Clinical Oncology (2016)

e12033 Background: Endostar (EN), recombinant human endostatin, is available to increase apoptosis of tumor cells due to its antiangiogenesis. It also has synergy with chemotherapy medicine. EN or combined with chemotherapy drugs show efficiency in lung cancer, colon cancer or other solid tumors treatments. Here, we evaluated the effect of EN combined with Docetaxel, Epirubicin and Cyclophosphamide (EN+TEC) as a neoadjuvant in treating breast cancer patients. Methods: One hundred and two breast cancer patients confirmed by core biopsy randomly received four cycles neoadjuvant of EN+TEC or TEC only. The clinical complete and partial response rate, pathological complete response rate, Miller & Payne classification (MP score), safety and quality of life were analyzed. Vascular endothelial growth factor (VEGF) and microvessel density (MVD) expressed in tumor tissue were evaluated by immunohistochemistry staining pre- and post-operation. Results: The clinical complete and partial response rate showed no differences between EN+TEC and TEC group. No significant difference of pathological complete response rate was found between those two treatments. Compared with TEC only, treatment with EN+TEC significantly increased MP score and enhanced the tumor response rate (P < 0.05). Meanwhile, the safety and quality of life showed no difference between EN+TEC and TEC therapy. Furthermore, EN+TEC group significantly decreased the tissue VEGF and MVD expression compare to TEC only group detected in tumor tissue (P < 0.05). Post-operation follow-up displayed a better overall survival rate at both 3-year and 5-year in EN+TEC treatment compared to TEC only. Conclusions: our study show EN combined with TEC neoadjuvant effectively improved the MP score, enhance tumor response rate and prolong the overall survival, suggesting a selective way in breast cancer therapy. Clinical trial information: ChiCTR-TRC-11001424.
Knowledge outcomes in a randomized trial of telephone vs. in-person disclosure of genetic testing: The COGENT study.
Authors: Nina Beri, Linda J. Patrick-Miller, Brian L. Egleston, Olufunmilayo I. Olopade, Michael J. Hall, Mary Beryl Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Susan M. Domchek, Angela R. Bradbury
Journal: Journal of Clinical Oncology (2017)

1534 Background: Telephone disclosure (TD) of genetic testing is non-inferior to in-person disclosure (IPD) for most outcomes but did not meet non-inferiority for knowledge change. We sought to understand which concepts patients don’t understand and factors associated with lower knowledge. Methods: Patients were recruited to a multi-center, randomized trial (NCT01736345) comparing TD to IPD of genetic test results. 819 patients were randomized (IPD = 418; TD = 401); 165 declined randomization and requested IPD. Knowledge was assessed after pre-test counseling (V1) and test disclosure (V2). Results: There were no significant differences in genetic or multi-gene (MG) knowledge between disclosure groups after V1 and V2. On average, patients answered 73% (SD 1.19) of genetic knowledge and 57% (SD 1.78) of mg knowledge items correctly.After V1, most understood implications of a positive result (87%), that results are not deterministic (84%) and risks for their children (91%). Understanding of uninformative negative, true negative and variant of uncertain significance (VUS) results was lower (post-V1: 33%, 65%, 29%; post-V2 : 37%, 65%, 25%). In multivariable analyses, lower genetic knowledge after V1 was associated with study site, being older (p &lt; 0.01), single (p &lt; 0.01), non-white (p &lt; 0.01), not Ashkenazi Jewish (p = 0.01), and not having a mutation in the family (p = 0.03), having more relatives with cancer (p &lt; 0.01) and not graduating college (p &lt; 0.01). Lower mg knowledge after V1 was associated with site and being non-white (p = 0.01). Lower genetic knowledge after V2 was not associated with disclosure method but associated with study site, being older (p &lt; 0.01), not graduating college (p &lt; 0.01) and being non-white (p &lt; 0.01). Lower mg knowledge after V2 was only associated with not graduating college (p = 0.02). Conclusions: While there were no significant differences in genetic knowledge by disclosure method, understanding of several concepts (e.g. VUS and negative results) were lower regardless of arm. Several factors, including age, education and race/ethnicity were associated with lower knowledge. Interventions to improve genetic knowledge in real-world and diverse populations are needed. Clinical trial information: NCT07136345.
Time to definitive deterioration in patients with metastatic breast cancer subjected to second-line monochemotherapy.
Authors: Miguel Angel Seguí-Palmer, Noelia Martinez Janez, Esperanza Blanco, J. Norberto Batista, Montserrat Munoz, Cesar Augusto Rodriguez, Isaura Fernandez, Yolanda Jerez, Isabel Garau, Kepa Amillano, Carlos Garcia, Antonia Perello, Ana Santaballa, Pablo Borrega, Javier Salvador, Andres Garcia, Manuel Ruiz, Lorena Pellin, Raquel Andres
Journal: Journal of Clinical Oncology (2016)

e12504 Background: Since metastatic breast cancer (MBC) is incurable, main goals of chemotherapy (CT) are the recovery and maintenance of patient health-related quality of life (HRQOL), the reduction of symptoms related with the disease and prolonging life. In this context, time to definitive deterioration (TDD) has been proposed as a modality of longitudinal HRQOL analysis for cancer patients. To date, few studies have focused in the analysis of TDD in patients with MBC treated with 2nd-line CT in a context of normal medical practice. Methods: A prospective observational study performed in 87 MBC patients (100 patients recruited; 50% of total planned) who initiated 2nd-line monoCT in 30 Spanish hospitals. Using the EORTC-QLQ-C30 questionnaire, the breast module QLQ-BR23 and the CT-induced peripheral neuropathy (CIPN) module, HRQOL was assessed at the beginning of CT and every three months thereafter until disease progression and/or treatment (TX) discontinuation. TDD was considered when HRQOL decrease 5% versus baseline. Kaplan–Meier method was used to estimate TDD. Results: Median age was 60 years. 20% of patients presented with de novo metastatic disease. 76% were hormone-receptor-positive. 85% had a baseline ECOG performance status of 0-1. Definitive deterioration (DD) of HRQOL was detected in 56% of patients after 3.4 (95%CI, 3.0-6.0) months. Disease progression occurred in 55% of patients after 6.2 (95%CI, 5.4-8.3) months and time to progression (TTP) was not affected by TDD (p= 0.529). TDD was not affected by age (p= 0.476), comorbidities (p= 0.158), CIPN (p= 0.166) or response to TX (p = 0.357). TDD increased with TX duration (p< 0.0001). Conclusions: DD was reported in 56% of patients. In 50% of them, DD occurred before the 3rd month of CT regardless of patient´s age, comorbidities or CIPN. TDD was not affected by the response to CT and DD events did not modify TTP.
A phase Ib study of lapatinib plus pegylated liposomal doxorubicin in patients with advanced HER2-positive breast cancer.
Authors: Andrea Rocca, Lorenzo Cecconetto, Alessandro Passardi, Elisabetta Melegari, Daniele Andreis, Manuela Monti, Roberta Maltoni, Samanta Sarti, Elisabetta Pietri, Alessio Schirone, Anna Fedeli, Caterina Donati, Oriana Nanni, Dino Amadori
Journal: Journal of Clinical Oncology (2016)

600 Background: Conventional anthracyclines are particularly active in HER2-positive breast cancer (BC), but their use concomitantly with anti-HER2 agents is limited by cardiotoxicity. Pegylated liposomal doxorubicin (PLD) and lapatinib (L) offer a safer alternative for combining these two classes of agents. Methods: This is an open label phase Ib study, with 3+3 dose escalation design. Patients with HER2-positive (FISH amplified or immunohistochemistry 3+) advanced BC, progressing after trastuzumab with a cumulative dose of doxorubicin ≤ 240 mg/m2 or equivalent, received PLD 30 mg/m2 intravenously on day 1 plus escalating doses of L orally on days 1-21 of each 21-day cycle (L dose levels 1 / 2: 1250 / 1500 mg/m2). The primary endpoint was to define the maximum tolerated dose (MTD) at first cycle, and secondary endpoints were the activity and safety profile with multiple cycles. Results: Nine patients out of 11 enrolled were evaluable (1 excluded for allergic reaction at first PLD dose, 1 withdrew consent): 3 at dose level 1 and 6 at level 2. Median age was 65 years (range 43-77), ECOG PS 0 or 1, median number of prior systemic therapies for advanced BC 2 (range 0-3). Median number of cycles were 7 for PLD (range 3-13), 6 for L (range 3-26). No dose-limiting toxicities (DLTs) occurred at dose level 1, while a DLT (G3 diarrhea) occurred at dose level 2, leading to the expansion of this cohort to 6 patients, with no further DLTs. Main grade 1-2 toxicities at first cycle were diarrhea (5 patients), mucositis (2), liver toxicity (2), nausea (1) and anorexia (1). Two episodes of G3 toxicity occurred at cycle 2 (colitis level 1, anorexia level 2) and 1 at cycle 3 (stomatitis + hand-foot syndrome level 2), leading to treatment interruption or dose reduction. No case of left ventricular systolic dysfunction occurred. Although a formal MTD was not reached, given the long-term intent of treatment, level 2 was considered as the recommended phase 2 dose. Best responses were: 1 partial response (PR), 1 stable disease (SD) and 1 disease progression (PD) at level 1; 2 PR, 1 SD and 3 PD at level 2. Conclusions: The combination of PLD and L is sufficiently well tolerated and shows potential activity in pretreated HER2-positive advanced BC patients. Clinical trial information: 2009-012996-82.
Стеатоз підшлункової залози у дітей. Частина 2. Фактори ризику, можливості діагностики та лікування
Authors: Yu.M. Stepanov, N.Yu. Zavgorodnyaya, N.Yu. Zavgorodnyaya
Journal: GASTROENTEROLOGY (2017)

Стаття присвячена стеатозу підшлункової залози (ПЗ) у дітей — патологічному стану, що характеризується акумуляцією жиру в ПЗ. В огляді проаналізовані дані, що стосуються факторів ризику, можливостей діагностики і терапії стеатозу ПЗ. Продемонстровано, що провідними чинниками, асоційованими з розвитком стеатозу ПЗ, вважаються ожиріння і метаболічний синдром. Охарактеризовані переваги неінвазивних візуалізаційних методів, таких як трансабдомінальне ультразвукове дослідження, комп’ютерна томографія, магнітно-резонансна томографія та ендоскопічне ультразвукове дослідження в діагностиці стеатозу ПЗ у дітей. Представлені й обґрунтовані основні напрямки терапії стеатозу ПЗ: модифікація способу життя, корекція дисліпідемії та порушень вуглеводного обміну, екзокринної недостатності. Для написання огляду здійснювався пошук інформації з використанням баз даних Scopus, Web of Science, MedLine, PubMed, Google Scholar, CyberLeninka, РІНЦ за ключовими словами: «стеатоз підшлункової залози», «неалкогольна жирова хвороба підшлункової залози», «діти».
Janus-like monocytes regulate postoperative ileus
Authors: Allan McI Mowat
Journal: Gut (2017)

In Gut , Farro et al and Pohl et al present new findings on the role of myeloid cells in postoperative ileus (POI).1 2

POI is a frequent consequence of abdominal surgery that can lead to costly delays in patient recovery.3 The failure of peristalsis reflects paralysis of the smooth muscles of the intestine and several studies have suggested that this is dependent on macrophages in the muscularis externa (ME) layer of the gut wall that produce nitric oxide (NO).4

The intestine contains one of the largest pools of macrophages in the body, the majority of which is located in the lamina propria (LP) of the mucosa, near the epithelium. However macrophages are also present between the longitudinal and circular muscle layers of the ME, where they are in close proximity to the myenteric plexus.5 6 Recent studies indicate that LP and ME macrophages are phenotypically and functionally distinct under steady-state conditions.6 In particular, ME macrophages appear to have specialised tissue protection functions, including the production of factors such as bone morphogenic protein-2 (BMP2) that promote neuronal growth. In return, β2-adrenergic receptors on ME macrophages allow them to be sustained by sympathetic neurons and these two-way interactions are at least partly dependent on the local microbiota.6 …
A randomized double-blind, comparative study of ARN-509 plus androgen deprivation therapy (ADT) versus ADT alone in nonmetastatic castration-resistant prostate cancer (M0-CRPC): The SPARTAN trial.
Authors: Matthew Raymond Smith, Glenn Liu, S. Martin Shreeve, Shannon Matheny, Antonieta Sosa, Thian San Kheoh, Margaret K. Yu, Eric Jay Small
Journal: Journal of Clinical Oncology (2014)

TPS5100 Background: ADT is the standard of care for patients (pts) with metastatic prostate cancer and is frequently used in pts with non-metastatic prostate cancer. Initial ADT achieves responses in nearly all pts, but most progress to castration-resistant disease within a few years. Among men with M0-CRPC, a rising prostate-specific antigen (PSA) heralds the development of metastases and associated morbidity and mortality. Prevention of metastases is a major unmet medical need in M0-CRPC. ARN-509 (ARN) is a potent and selective androgen receptor (AR) antagonist that inhibits AR nuclear translocation and DNA binding without significant AR agonist properties (Clegg N et al. Cancer Res.2012). ARN demonstrates a 12- and 24-week PSA response rate of 91% in M0-CRPC pts and an excellent safety profile (Smith MR et al. ASCO GU 2013; Smith MR et al. ESMO 2013). Methods: This is a multicenter, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy and safety of ARN in pts with M0-CRPC at high risk for progression (PSA doubling time [PSADT] ≤ 10 months). Continuous ADT is mandatory in order to maintain castrate concentrations of testosterone (< 50 ng/dL). Pts are stratified based on PSADT (≤ 6 vs > 6 months), baseline use of bone-sparing agents for osteoporosis, and presence of locoregional disease, and randomized (2:1) to ARN + ADT or placebo + ADT. The absence of distant metastasis at screening is documented by central radiographic review. The primary end point is metastasis-free survival. Secondary end points include overall survival and other clinically relevant end points. Approximately 1200 pts will be randomized to provide appropriate statistical rigor to detect the hypothesized risk reduction in metastasis or death. This study uses group sequential design, including an interim analysis. The stratified log rank test will be used for the analysis. An independent data monitoring committee is commissioned to conduct reviews of the safety and efficacy data. Approximately 300 sites in 24 countries will participate. Pts are being screened and enrolled as of September 2013. Clinical trial information: NCT01946204.
Abstract 267: Preserved Cardiac Contractility and Venous Return in Beta-arrestin2 Transgenic Mice During Sepsis With Insufficient Resuscitation
Authors: Hui Yan, James Denney, Hui Li, Christopher Daniels, Krishna Singh, Balvin Chua, Yi Caudle, Gene LeSage, Deling Yin
Journal: Circulation Research (2015)

β-arrestin 2 is a negative regulator of inflammation and a protective signaling transducer in acute heart injury. In this study, using echocardiography and Millar Pressure-Volume systems, we found that heart dysfunction accompanied with hemodynamic instability occurred rapidly after experimental sepsis with insufficient resuscitation in wild type and β-arrestin 2 knock out mice but not in β-arrestin 2 transgenic mice. β-arrestin 2 overexpression is associated with preserved preload, cardiac output, systolic contractility and diastolic elasticity after cecal ligation and puncture (CLP). Furthermore, β-arrestin 2 overexpression up-regulated IL-6/IL-6R/gp130/STAT3 anti-apoptotic signaling through suppressing p38 activation and subsequently inhibiting phosphorylation of membrane bound gp130, the signal transducer part of IL-6 receptor complex. In conclusion, β-arrestin 2 is a crucial cardiac function regulator in sepsis.