tbuckley/cabot-search huggingface dataset:
Treatment of Older Patients with Mantle-Cell Lymphoma
Authors: Yukie Takahashi, Jinichi Mori, Tetsuya Tanimoto
Journal: New England Journal of Medicine (2012)

1. Dawson MA, Kouzarides T, Huntly BJ. Targeting epigenetic readers in cancer. N Engl J Med 2012;367:647-57. 2. Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschlager M. Oct-4-expressing cells in human amniotic f luid: a new source for stem cell research? Hum Reprod 2003;18:148993. 3. De Coppi P, Bartsch G Jr, Siddiqui MM, et al. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007;25:100-6. 4. Valli A, Rosner M, Fuchs C, et al. Embryoid body formation of human amniotic fluid stem cells depends on mTOR. Oncogene 2010;29:966-77. 5. Moschidou D, Mukherjee S, Blundell MP, et al. Valproic acid confers functional pluripotency to human amniotic f luid stem cells in a transgene-free approach. Mol Ther 2012;20: 1953-67. DOI: 10.1056/NEJMc1211175
Abstract 3639: Analytical performance and validation of an enhanced TAm-Seq circulating tumor DNA sequencing assay
Authors: Davina Gale, Vincent Plagnol, Andrew Lawson, Michelle Pugh, Sarah Smalley, Karen Howarth, Mikidache Madi, Bradley Durham, Vasudev Kumanduri, Kitty Lo, James Clark, Emma Green, Nitzan Rosenfeld, Tim Forshew
Journal: Cancer Research (2016)

Abstract Circulating tumor DNA (ctDNA) is becoming established as a tool to supplement conventional biopsies for molecular characterization and monitoring of solid cancers, especially for cancers where tumor tissue is difficult to obtain or is only available at limiting quantity. This requires reliable identification, in patient plasma, of tumor-specific DNA alterations that in some cases may be present as a small fraction of the total cell-free DNA molecules. To overcome these technical challenges, we have developed an enhanced platform for tagged-amplicon deep sequencing (TAm-Seq™). Using a combination of efficient library preparation and statistically-based analysis algorithms, this platform can be used to sequence, identify and quantify cancer mutations across a gene panel including both cancer hotspots, as well as entire coding regions of selected genes. This poster will present validated performance specifications of this multi-gene ctDNA sequencing assay. To perform analytical validation, we used reference standards and plasma DNA controls to demonstrate the sensitivity, specificity and quantitative accuracy of this ctDNA analysis platform. We found that our workflow, using 4 mL input plasma, yields very high sensitivity for variants that are present at allele fraction 0.25% or higher in plasma, and retains substantial sensitivity at allele fractions as low as 0.1%. Using dilution mixtures of well-characterised reference samples, we show that the assay accurately quantifies allele fractions with precision predominantly limited by stochastic sampling. Analysis of plasma samples from control individuals demonstrates a low false positive rate. The assay also detects DNA amplifications (including in ERBB2, MYC, KRAS, EGFR, MET, FGFR1, FGFR2) when the ctDNA are sufficiently high. Together, these data demonstrate the analytical validity and robustness of the TAm-Seq assay and support its use as a basis for clinical applications. Citation Format: Davina Gale, Vincent Plagnol, Andrew Lawson, Michelle Pugh, Sarah Smalley, Karen Howarth, Mikidache Madi, Bradley Durham, Vasudev Kumanduri, Kitty Lo, James Clark, Emma Green, Nitzan Rosenfeld, Tim Forshew. Analytical performance and validation of an enhanced TAm-Seq circulating tumor DNA sequencing assay. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3639.
Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer
Authors: Christof Bernemann, Thomas J. Schnoeller, Manuel Luedeke, Konrad Steinestel, Martin Boegemann, Andres J. Schrader, Julie Steinestel
Journal: European Urology (2016)
Reply
Authors: Jospehine Simonetti, Lisa Bulkow, Brian J. McMahon, Chriss Homan, Mary Snowball, Susan Negus, James Williams, Stephen E. Livingston
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. We share the reader's concern that the error we addressed in our correction changed a key conclusion of our original article.1 For that reason, we felt an urgent need to publish the correction as soon as the error was brought to our attention. However, we disagree with the comment that it might not be meaningful to perform statistical comparisons when the 95% confidence intervals (CIs) are large. Without statistical testing, it would be unknown whether the difference in the incidence of hepatocellular carcinoma (HCC) between persons with and without hepatitis B surface antigen (HBsAg) seroclearance is significant. The CIs were wide because few patients in our cohort developed HCC; however, the occurrence of HCC and HBsAg seroclearance are both relatively rare events. We do not know of another cohort of persons with HBsAg seroclearance of sufficient size that was followed prospectively for as long as our cohort to allow for a more precise estimate of the incidence of HCC after HBsAg seroclearance. Therefore, despite the wide CIs, our study provides valuable population‐based data on the risk for HCC after HBsAg seroclearance. The reader further requested that we provide a more detailed explanation of the corrected data but did not state the specific points requiring clarification. We feel that our correction succinctly but thoroughly explained the methodological error in the original paper and provided an interpretation of the revised results. Additionally, we are preparing a separate manuscript to examine the question of HCC after HBsAg seroclearance by using a case‐control method. That paper will refer to our original article as well as our correction1 and will provide us with another opportunity to raise awareness about the change in our conclusions.
Impact of urologist density and county rurality on the practice of retroperitoneal lymph node dissection and cancer specific death in patients with non seminomatous germ cell tumors.
Authors: Shaheen Riadh Alanee, Joseph Clemons, Whitney Zahnd, Danuta Dynda
Journal: Journal of Clinical Oncology (2016)

e16061 Background: Patient’s access to service providers is strongly associated with treatment choices. We investigated the impact of rural status and urologist density on the practice of retroperitoneal lymph node dissection (RPLND) and cancer specific death (CSD) in patients with NSGCT. Methods: Using 2014-2015 Area Health Resource File data, we calculated the average urologist density per 100,000 by county during the study time (2000-2012). We also considered the 2003 Rural Urban Continuum Codes to categorize counties as rural or urban. We used all cases of NSGCT within SEER 18 with known county code, urologist density value, and disease stage for analysis (n = 9,473). Fisher’s exact test, t-tests, and Cox proportional hazard analysis was used to examine the association between variables of interest and study end points. Results: Overall, 26.7% of NSGCT cases lived in a county with less than the national mean urologist density (3.4 urologists per 100,000), 6.23% lived in counties with no urologists, 9.0% lived in a rural county, and 23.1% (n = 2,208) had RPLND performed. RPLND was performed more in cases who lived in a county with a urologist, and more in cases with urban residence (p < 0.05). The mean number of lymph nodes examined was lower in patients who lived in rural counties and counties with fewer urologists (p < 0.05). There was no difference in the number of positive nodes or cancer specific death dependent upon either urologist density categorization or rurality. Conclusions: Rural residence and low urologist density were associated with decreased RPLND and mean number of lymph nodes examined in patients with NSGCT on the county level. Improving access to RPLND is indicated to provide all possible treatment choices to young patients affected by NSGCT.
Abstract 3878: Proteomic approach to identify biomarkers for invasive cervix cancer: a prospective pilot study
Authors: David P. Mysona, Adam Pyrzak, Jennifer Allen, Ashok Sharma, Paul Weinberger, Bunja Rungruang, Jin-Xiong She, Sharad Ghamande
Journal: Cancer Research (2016)

Abstract Objectives: Cervical cancer is the second most common cancer of women worldwide. In this prospective study, we attempted to identify a set of serum biomarkers, which could identify patients who have invasive cervical cancer and possibly help monitor disease status (recurrence, remission). Methods: Luminex bead array was used to measure serum protein concentrations of 19 different, promising proteins in cervical cancer patients (n = 23) compared to women with precancerous lesions (CIN2-3) (n = 20), and patients with normal cervical cytology (n = 20) in this IRB approved prospective study. Cervical cancer (adenocarcinoma and squamous carcinoma) patients had blood samples drawn within 30 days of diagnosis and repeat blood samples taken on follow up visits after completing therapy. These results were correlated to clinical data and outcomes. Protein expression was confirmed by immunohistochemistry in patient samples. Results: CIN and controls have very similar levels of serum proteins. Six proteins (CA153, OPG, CEA, IGFBP7, IGFBP4, and MMP-7) had significantly different levels in cervical cancer patients compared to controls and CIN (p &amp;lt; 0.05) with Area Under the Curve values of 0.74, 0.77, 0.79, 0.83, 0.84, and 0.98 respectively. IGFBP4 had a sensitivity of 75% at 95% specificity for correctly identifying invasive disease. MMP-7 had a sensitivity of 92% at 95% specificity. MMP-7 was confirmed by IHC in patient specific cervical cancer tissue. ProteinAUCP valueSensitivity at 95% SpecificityMMP70.98 (0.96-0.99)5.29E-1392.11IGFBP40.84 (0.8-0.89)2.36E-0775IGFBP70.83 (0.78-0.87)6.23E-0757.89CEA0.79 (0.74-0.84)1.30E-0542.11OPG0.77 (0.72-0.82)3.80E-0535.14CA1530.74 (0.69-0.8)2.50E-047.89 Conclusions: Several serum proteins are significantly altered in cervical cancer patients compared to controls and CIN, and are worth studying for further clinical utility. MMP-7 may prove to be an important mediator of cervical cancer. Citation Format: David P. Mysona, Adam Pyrzak, Jennifer Allen, Ashok Sharma, Paul Weinberger, Bunja Rungruang, Jin-Xiong She, Sharad Ghamande. Proteomic approach to identify biomarkers for invasive cervix cancer: a prospective pilot study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3878.
Prognostic Significance of the French-American-British (FAB) Morphologic Subclassification of “Acute Myeloid Leukemia, Not Otherwise Specified” in the 2008 WHO Classification: Analysis of 5,848 Newly Diagnosed Patients From HOVON, MRC/NCRI, SWOG, and MD Anderson Cancer Center
Authors: Roland B. Walter, Megan Othus, Alan K. Burnett, Bob Löwenberg, Hagop M. Kantarjian, Gert J. Ossenkoppele, Robert K. Hills, Kees G.M. van Montfort, Farhad Ravandi, Anna Evans, Sherry A. Pierce, Frederick R. Appelbaum, Elihu H. Estey
Journal: Blood (2012)
Margaret McCartney: Can junior doctors feel safe to blow the whistle?
Authors: Margaret McCartney
Journal: BMJ (2016)

In April, NHS England published a national whistleblowing policy.1 “Don’t wait for proof,” it said. “It doesn’t matter if you turn out to be mistaken as long as you are genuinely troubled . . . You will not be at risk of losing your job or suffering any form of reprisal as a result.”

In 2014 a junior doctor, Chris Day, was covering intensive care when two locum doctors booked to work didn’t turn up. Day made a “protected disclosure,” a legal process designed to protect whistleblowers, …
Metastatic breast cancer treated by chemotherapy: Trends in survival and costs in two patient cohorts treated in 1994–1998 and 2003–2006
Authors: G. Galy, S. Labidi, D. Perol, C. Carol, J. Guastalla, B. Favier
Journal: Journal of Clinical Oncology (2009)

6552 Background: Although new chemotherapy agents have been approved during the past decade for the treatment of metastatic breast cancer (MBC), it is unclear whether their use has changed the outcome of patients. This study assessed the clinical and economic impacts of these drugs. Methods: We undertook a retrospective study of women diagnosed with MBC during two periods of time, 1994–1998 and 2003–2006 and compared overall survival data between the two groups. Female patients with MBC were identified from the Centre Léon Bérard (Lyon, France) database. Tumor and treatment characteristics, costs of chemotherapy, and patient outcome were compared using the X 2 test, the log rank test, and Cox regression analysis. Overall survival was calculated from the date of MBC diagnosis to the date of death or last follow-up. Chemotherapy-related costs were calculated according to the 2008 pricelist of French cancer centers. Results: A total of 301 MBC cases were identified. The median follow-up of living patients was 3.87 years. No survival difference was observed between the two periods, with a median overall survival of 2.76 years for the 1994–1998 cohort (149 patients) and 2.68 years for the 2003–2006 cohort (152 patients) (HR 1.04, 95%CI 0.70–1.55; p = 0.83). The median number of lines of chemotherapy was similar in the two groups (=3). The median cost of chemotherapy per MBC patient was 3 times higher in 2003–2006 (25,320 €) than in 1994–1998 (8,865 €; p &lt; 0.001). In multivariate analysis, prognostic factors for overall survival were the number of metastatic sites (HR 2.06; p &lt; 0.0001), bone metastases (HR 0.67; p = 0.007), and hormone receptors (HR 0.56; p = 0.002). Survival was identical in HER-2 positive and HER-2 negative patients (HR 0.99; p = 0.99). Conclusions: Despite the implementation of numerous novel chemotherapeutic agents, the overall survival of patients with metastatic breast cancer has not improved over the last decade on the scale of our institution, whereas the costs of chemotherapy have significantly increased. No significant financial relationships to disclose.
Predictors of treatment outcomes following salvage intravesical chemotherapy in patients with prior BCG treatment.
Authors: Justin T. Matulay, Alexander J. Bandin, Christopher B. Anderson, Guarionex Joel DeCastro, Mitchell C. Benson, James M. McKiernan
Journal: Journal of Clinical Oncology (2016)

e16015 Background: Radical cystectomy is the standard of care for patients who fail intravesical bacillus Calmette-Guérin (BCG) for nonmuscle invasive bladder cancer (NMIBC). For patients unwilling or unable to undergo cystectomy, numerous salvage intravesical chemotherapies (sIVCT) exist. We analyzed our experience in the management of this high-risk population and aim to characterize patient and tumor characteristics predicting treatment outcomes with sIVCT for NMIBC. Methods: We retrospectively identified 94 patients who failed at least one BCG induction cycle and went on to receive sIVCT agents at our institution from 2003-2014. Endpoints of interest included lack of response to initial sIVCT agent and recurrence free survival from first salvage induction course. Univariate and multivariate analyses were used to identify significant patient and disease characteristics. Results: 94 patients with median follow-up of 46 months underwent sIVCT for cT1 (n=31), cTa (n=17), or cTis alone (n=43). There were 5 patients with low-grade, 89 with high-grade, and 62 with multifocal disease. Agents used for sIVCT were docetaxel (44%), nab-paclitaxel (29%), mitomycin C (MMC) (13%), gemcitabine (8%), and valrubicin (6%). Disease recurred in 74 patients (78.7%) at a median of 3.5 months after initial sIVCT induction. Overall mortality was 36% (34 deaths) and disease specific survival was 83% (16/94 dead of disease). We conducted multivariate analyses, controlling for disease stage and grade, for predictors of lack of response to sIVCT and disease recurrence. Results are shown in Table 1. Conclusions: In a population of patients with NMIBC relapsing after prior BCG therapy we have identified tumor characteristics that predict subsequent failure of sIVCT, disease recurrence, and overall survival, as well as outcomes when treated with specific intravesical agents. Multivariate analysis. Variable HR (95% CI) P- value Lack of Initial Response to sIVCT Trigonal involvement 3.37 (1.22- 9.27) 0.019 No response to most recent BCG course 3.09 (1.10- 8.67) 0.032 Disease Recurrence Trigonal involvement 2.55 (1.46- 4.47) 0.001 Variant histology 2.12 (1.03- 4.38) 0.043 Multifocal tumor 0.84 (0.47- 1.51) 0.566
Lung Cancer Screening with Chest Computed Tomography in People Living with HIV: A Review by the Multidisciplinary CANCERVIH Working Group
Authors: Alain Makinson, Vincent Le Moing, Jacques Reynes, Tristan Ferry, Armelle Lavole, Isabelle Poizot-Martin, Jean-Louis Pujol, Jean-Philippe Spano, Bernard Milleron
Journal: Journal of Thoracic Oncology (2016)
First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation
Authors: M Wilhelm, M Smetak, P Reimer, E Geissinger, T Ruediger, B Metzner, N Schmitz, A Engert, K Schaefer-Eckart, J Birkmann
Journal: Blood Cancer Journal (2016)

Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44%, 54% and 39%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible.
States Worse Than Death Among Hospitalized Patients With Serious Illnesses
Authors: Emily B. Rubin, Anna E. Buehler, Scott D. Halpern
Journal: JAMA Internal Medicine (2016)

tegic expansion of evidence-based interventions in geographic areas heavily affected by heroin and fentanyl is needed to reduce demand and stop deaths.The letter by Arens et al 1 demonstrates the importance of public health surveillance of emerging drugs but also conveys the inadequacy of our current approaches: detection requires exposure to drugs at levels that almost cause death.One surveillance strategy to spare lives, detect trends earlier, and influence product safety in illicit drug markets is provision of drug checking services, which conduct forensic analysis of publicly submitted drug samples, the individual results of which are shared anonymously and aggregated for surveillance.In many European countries, drug checking services facilitate clinical and consumer understanding of blackmarket products while providing low-threshold points of contact between supportive services and people who use drugs. 8 New surveillance approaches and rapid expansion of evidencebased interventions are the missing parameters needed to shift the curve of the epidemic of opioid use.The Office of National Drug Control and Policy has provided leadership in supporting closer public health and public safety collaborations to address recent surges in heroin use.Similar oversight, direction, and coordination are needed to expedite implementation of responses and to navigate local, state, and federal opportunities and tensions around these new approaches.
Abstract 2763: DNA methylation profiling unveils TGF-β hyperresponse in tumor associated fibroblasts from lung cancer patients
Authors: Miguel Vizoso, Marta Puig, F. Javier Carmona, María Maqueda, Antonio Gomez, Anna Labernardie, Marta Gabasa, Saioa Mendizuri, Rafael Ikemori, Xavier Trepat, Sebastian Moran, Enrique Vidal, Noemí Reguart, Alexandre Perera, Manel Esteller, Jordi Alcaraz
Journal: Cancer Research (2016)

Abstract There is growing interest in defining the aberrant molecular differences between normal and tumor-associated fibroblasts (TAFs) that support tumor progression. For this purpose, we recently conducted a genome-wide DNA methylation profiling of TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer (NSCLC) patients, and reported a widespread hypomethylation concomitantly with focal gain of DNA methylation; in addition, we found evidence that a fraction of lung TAFs are fibrocytes in origin. Of note, the aberrant epigenome of lung TAFs had a global impact in gene expression and a selective impact on the TGF-β pathway. To get insights on the functional implications of the latter impact, we analyzed the response of lung TAFs to exogenous TGF-β1 in terms of activation and contractility. We found a larger expression of a panel of activation markers including α-SMA and collagen-I in TAFs compared to control fibroblasts. Likewise, TGF-β1 elicited a larger contractility in TAFs than in CFs as assessed by traction force microscopy. These findings reveal that lung TAFs are hyperresponsive to TGF-β1, which may underlie the expansion and/or maintenance of the tumor-promoting desmoplastic stroma in lung cancer. Citation Format: Miguel Vizoso, Marta Puig, F. Javier Carmona, María Maqueda, Antonio Gomez, Anna Labernardie, Marta Gabasa, Saioa Mendizuri, Rafael Ikemori, Xavier Trepat, Sebastian Moran, Enrique Vidal, Noemí Reguart, Alexandre Perera, Manel Esteller, Jordi Alcaraz. DNA methylation profiling unveils TGF-β hyperresponse in tumor associated fibroblasts from lung cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2763.