tbuckley/cabot-search huggingface dataset:
Prediction of late relapse in patients with estrogen-receptor–positive breast cancer.
Authors: Steven Buechler, Sunil S. Badve
Journal: Journal of Clinical Oncology (2014)

11065 Background: Proliferation plays an important role in the prediction of early relapse of ER+ breast cancer. This constitutes the basis of almost all of the currently available prognostic tools including gene expression based signatures (e.g. OncotypeDX, Mammaprint, and ProSigna). However, these tools are poor predictors of late relapses (greater than 8 years from initial diagnosis) and there is a dire need for a classifier that can accurately identify patients who remain at high risk of long-term relapse in spite of standard therapy. A better understanding of the mechanisms leading to late relapse could lead to improved strategies for management of these patients. Methods: Gene expression of 1,518 primary tumors from the METABRIC dataset, which contains long-term follow up for breast cancer specific survival (BCSS), was divided into training and validation sets balanced for late relapse cases. An innovative multistate gene methodology was used to identify predictors of late relapse in the training set and confirmed in validation set. Results: Analysis of the training set (n=382; 48 late relapse cases) identified 20 genes that were most predictive of late relapse. Late Relapse Score (LateR) was developed using these genes to optimally separate patients into low and high risk groups (P=0.002). In the validation set (n= 367; 47 late relapse cases), the LateR risk stratification (61% low risk) predicted late relapse (low LateR 0.87 (95%CI 0.80-0.95); high LateR 0.70 (95%CI 0.60-0.81); p=0.03). Furthermore, the combination of INDUCT score and LateR lead to more accurate prediction (p=0.002). In the LateR high risk group, pro-inflammatory cytokines are significantly up-regulated and genes involved in immune response are significantly down-regulated. Conclusions: Immune system plays a major role in the development of late relapse. LateR accurately predicts the likelihood of late relapse for patients with ER+ breast cancer. Together with the INDUCT test for early relapse, LateR provides a valuable tool for assessing the likelihood of relapse and might help the patient and their physicians make appropriate long-term treatment decisions.
A Phase II Study of Curcumin and Vitamin D in Previously Untreated Patients with Early Stage Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Authors: Basem M. William, Kaylee Brillhart, Manuel Afable, Kristen Bakalarz, Brenda Cooper, Hillard M Lazarus, Stanton L. Gerson, Richard Creger, Kalyanam Nagabhushanam, James Grote, Pingfu Fu, Sandeep Kunati, Shuming Yang, Yan Xu, Philip Woost, James Jacobberger, Marcos de Lima, Paolo Caimi
Journal: Blood (2018)
Preoperative neutrophil-lymphocyte ratio and prediction of survival after resection for pancreas cancer patients.
Authors: Koichiro Uchida, Koji Imai, Kenji Watanabe, Masashi Miyamoto, Daisuke Ishii, Masahiko Taniguchi, Hiroyuki Furukawa
Journal: Journal of Clinical Oncology (2014)

e15247 Background: To select the candidates for resection for pancreas cancer (PC) via radiographic appearances, response to chemotherapy or biomarker provide favorable outcome due to their aggressive biological behavior and high perioperative mortality. Recently inflammatory response to cancer progression and recurrence had been reported in several cancer but few in PC. Aim of this study is to evaluate the impact of preoperative neutrophil-lymphocyte ratio (NLR) on outcome after resection for PC. Methods: From 2000 to 2010, 84 consecutive curative resection were performed for PC. Follow up is until DEC 2012. The date were retrospectively corrected and analyzed. Results: With median follow-up of 24 months, 54 patients had cancer recurrence and 44 died from the disease. The 5-year overall survival (OS) and disease free survival (DFS) rate are 32.6% and 24.5% respectively. Lymphatic invasion, lymph node metastasis, portal vein invasion (PVI) and preoperative NLR³a5 (n=8) were associated with both poor OS and recurrence in univariate analysis. Multivariate analysis showed that PVI was independent factor associated with recurrence. NLR was also independent factor associated with survival (Hazard ratio 0.328) in addition to PVI. The median OS of those with a NLR ³a 5 was 6.5 months compared with 24 months for those with a NLR < 5. Conclusions: High inflammatory circumstance, such as NLR³a5, have significant impact on survival for resected PC patients. Preoperative NLR measurement provides simple method of identifying patients with the high biological activity of PC.
Functional results of nephron-sparing approach for tumors larger than 7cm in patients with RCC.
Authors: Oleksandr Stakhovskyi, Iuriy Vitruk, Oleg Voylenko, Volodymyr Kotov, Eduard Stakhovsky
Journal: Journal of Clinical Oncology (2014)

e15578 Background: Radical nephrectomy remains the mainstream approach for tumors larger than 7cm. Organ sparing approach and evolution of surgical technique pushes the limits of partial nephrectomy (PN) over the range of 7cm nowadays. Objective of the study was to evaluate functional and oncological results of PN and to determine indications in tumors >7cm. Methods: 56 patients with RCC lesions more than 7cm treated with PN from 2008 to 2013 were included in the study. Mean age of the patients was 52.9±13.0 years. Mean size of the tumor was 93.6 ± 25.6mm. Mean functional renal parenchyma volume (FRPV) calculated on CT imaging was 68.0±9.7%. Mean R.E.N.A.L. nephrometry score was 9.5±1,8, with 55.4% of patients with scores 10-12. Baseline mean GFR was evaluated with nephroscintigraphy and was 86.9±18.8ml/min (40.0±11.7 on side with the lesion). Results: Surgeries were done through subcostal transabdominal approach. In 15(26.8%) cases were performed with central ischemia (mean duration 15.7±5.3) and 41 (73.2%) cases were done with no ischemia. Mean intraoperative blood loss was 483 ± 365cc and in 3(5.4%) cases blood transfusions were needed. There were 2(3.6%) intraoperative spleen injuries, followed by splenectomy. 5(8.9%) postoperative complications were recorded: 3(5.4%)cases of urinary fistula and 2(3.6%) cases of pyelonephritis. Mean follow up was 21.8±4.5. Local reccurence was diagnosed in 3 (5.4%) patients at 12, 13 and 24 months postop respectively. Overall kidney function decreased to 77.5±19.0 ml/min (10,8%) at 3 months and to mean 72.7±30.2 ml/min (16.3%) at 12 months (p=0.06). There was a 37% decline in function of operated kidney (25.2±8,1ml/min) at 3 months and 36% (25.6±13.4ml/min) at 12 months respectively (p<0.05), showing the contralateral kidney effect on overall function. Conclusions: FRPV more than 55% is an indication for PN in tumors more than 7cm, resulting in safe procedure with acceptable intraoperative and postoperative complication rates and low recurrence rate of 5.4%. Disregard large kidney injury, kidney was preserved. Further observations needed to evaluate safety and oncological outcomes of PN in tumors more than 7cm.
Burden of high-risk HPV infection in the United States: NHANES (1999-2012).
Authors: Erin Dunn, Kevin J. Moore, Qingyun Liu, Stacey L. Tannenbaum, Tulay Koru-Sengul
Journal: Journal of Clinical Oncology (2014)

e12517 Background: Certain Human Papilloma Viruses (HPVs) have been implicated in causing cancer of the cervix, penis, anus, vagina, vulva, and oropharynx. Other HPV types can cause non-cancerous tumors such as warts or papillomas. National population-based surveys provide estimates of population-specific prevalence, trend, and determinants to identify the burden of high-risk HPV. Notably, the varying distribution of gender, ethnicity, and marital status among the high-risk types of HPVs has important implications in public health interventions. Methods: We looked at the prevalence of HPV infections by DNA (female only) and oral testing (females and males) in the US from the 1999-2012 National Health and Nutrition Examination Survey (NHANES) to obtain a representative sample of the US non-institutionalized civilian population. NHANES performs in-person interviews and physical examinations and collects biological samples at the household and at mobile examination centers. We provided epidemiology of HPV infection for both females and males. Analysis was performed by SAS v9.3 (SAS Institute Inc., Cary, NC, USA) with survey procedures to take into account the multistage complex sampling design. Results: Among HPV positive persons, orally-measured high-risk HPV infection was more prevalent for men (79.4%) than for women (20.6%). Among high-risk HPV infections, men had the highest prevalence for every type tested (HPV 16, 18, 26, 31, 33, 35, 39, IS39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68, 69, 70, 73, and 82). Non-Hispanic Whites had the highest prevalence of high-risk HPV for all types except HPV 26, 58, 59, 73, and 82. Non-Hispanic Blacks had the highest prevalence of HPV 58, 59, and 73, while Mexican Americans had the highest prevalence of HPV 82. Among those who tested positive for high-risk HPV, those who were married had the highest burden in each case except for HPV 26, 45, 73, and 82. Conclusions: Using a large population-based survey,our results show the variation of high-risk HPV infection by gender, ethnicity and marital status. Understanding the burden of these infections may provide a base for future culturally competent cancer prevention programs via screening, vaccination, health promotion and literacy.
The Impact of Clonal Hematopoiesis of Indeterminate Potential on Survival in Patients with Newly Diagnosed Acute Myeloid Leukemia
Authors: Koji Sasaki, Rashmi Kanagal-Shamanna, Guillermo Montalban-Bravo, Rita Assi, Kiran Naqvi, Ana Alfonso Pierola, Musa Yilmaz, Nicholas J Short, Elias J. Jabbour, Farhad Ravandi, Tapan M. Kadia, Sherry A. Pierce, Koichi Takahashi, Courtney D. DiNardo, Graciela M. Nogueras González, Yasmin Abaza, KC Devendra, Kamal Chamoun, Kenichi Sakurai, Keyur P. Patel, Jorge E. Cortes, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2018)
Use of a Processed Hematopoietic Stem Cell Product (FCRx) in Unmatched Related and Unrelated Donor — Recipient Pairs Is Associated with High Levels of Donor Chimerism and Donor-Specific Tolerance to Kidney Allografts
Authors: Joseph R. Leventhal, John P. Galvin, James Mathew, Lorenzo Gallon, Kadiyala Ravindra, Mitchell E. Horwitz, Michael Abecassis, Suzanne T Ildstad
Journal: Blood (2018)
Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Intermediate or High Risk Relapsed/Refractory Myelofibrosis
Authors: Naveen Pemmaraju, Vikas Gupta, Gary J. Schiller, Sangmin Lee, Abdulraheem Yacoub, Haris Ali, Moshe Talpaz, Megan Sardone, Halyna Wysowskyj, Shay Shemesh, Janice Chen, Arturo Olguin, Christopher Brooks, Vanessa Dunn, Animesh Pardanani, Ayalew Tefferi, Srdan Verstovsek, Joseph David Khoury, Mrinal M. Patnaik
Journal: Blood (2018)
Self-Endorsed Cognitive Problems Vs. Objectively-Assessed Cognitive Impairment in Blood or Marrow Transplantation (BMT) Recipients — a Longitudinal Study
Authors: Donna Murdaugh, Alysia Bosworth, Sunita Patel, Noha Sharafeldin, Yanjun Chen, Liton F. Francisco, Stephen J Forman, F. Lennie Wong, Smita Bhatia
Journal: Blood (2018)
Monitoring <i>EGFR</i> T790M with plasma DNA in lung cancer patients treated with EGFR tyrosine kinase inhibitor in prospective observational study.
Authors: Naoko Sueoka-Aragane, Nobuyuki Katakami, Miyako Satouchi, Soichiro Yokota, Keisuke Aoe, Kentaro Iwanaga, Kojiro Otsuka, Shinya Kimura, Shunichi Negoro
Journal: Journal of Clinical Oncology (2014)

11014 Background: Use of plasma DNA to detect mutations has spread widely as a form of liquid biopsy. The gatekeeper T790M mutation of EGFR has been observed in half of lung cancer patients who acquired resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI). We recently developed a novel sensitive, fully-automated monitoring system, MBP-QP (mutation-biased PCR and quenching probe), to detect T790M using plasma DNA. To determine the usefulness of the MBP-QP method for monitoring T790M during treatment with EGFR-TKI, a prospective clinical study was performed. Methods: This was a prospective, multicenter, observational study involving lung adenocarcinoma patients carrying EGFR activating mutations, such as L858R and exon 19 deletions, who were treated with EGFR-TKI. The primary objective was to determine whether T790M could be detected using plasma DNA at the time of progressive disease (PD). The secondary objective was to assess correspondence between T790M measured using plasma and that using cancer specimens. The association between detection of T790M and effect of EGFR-TKI was also investigated as an exploratory objective. Results: Ninety non-small cell lung cancer patients treated with EGFR-TKI were enrolled from seven hospitals in Japan: 92.1% had adenocarcinoma, 62% at stage IV, and 29% had postoperative recurrent disease. According to the investigators’ evaluations, T790M was detected in 26% (15/58) of the patients who acquired resistance to EGFR-TKI. A central review showed that the frequency of T790M positives among the patients with PD was 22% (12/55). When EGFR-TKI was discontinued because of PD, T790M was detected in 33% (17/52), whereas any patients who were discontinued for other reasons such as adverse effects did not show T790M positivity. Eight re-biopsy specimens were obtained at the time of occurrence of PD, and the concordance rate was 63%. Conclusions: T790M was detected in plasma DNA at the time of PD occurrence. Compared to the frequency using re-biopsy reported by other papers, liquid biopsy covered approximately half of the total patients with PD. The relationship between T790M positivity and detailed characteristics of progression was analyzed. Clinical trial information: UMIN000005131.
The cost of treatment of childhood cancer in Africa: Affordable and cost effective.
Authors: Daniela Cristina Stefan
Journal: Journal of Clinical Oncology (2014)

e17546 Background: Infections and nutrition are the most important causes of mortality in African children, while childhood cancer is not listed amongst the top 20 causes of death. Annually more than 50,000 African children will suffer from cancer. Survival rates remain low mainly due to lack of affordability and high rates of abandonment. Lack of information on the costs of care makes it impossible for policy makers to adopt affordable interventions. The aim of this study is to estimate the health systems costs of cancer care in Africa and to propose a more effective approach to investigations and treatment for the most common cancers. Methods: The costs of cancer were estimated using administrative data for the different period of time (2000-2010) in different African units. We derived direct and indirect financial and economic costs from a health systems perspective. Costs included drugs, personnel and annuitized capital costs. The diseases analysed included nephroblastoma, retinoblastoma, Burkitt lymphoma and HIV associated malignancies (Kaposi sarcoma and NHL). Results: The cost of treating nephroblastoma varied between $877 for stage 1 and 5 times more for stage 4 ($4,488.70). Treating one patient with nephroblastoma averted more than 32 DALYs. The cost of treating BL was $1,034 for group B and $2,997 for group C. The first line treatment of KS cost $1,080 and the paclitaxel salvage regimen $1,663. Conclusions: Treating childhood cancers in Africa is cost effective. Key policy points from our research are the need for (1) recognition of childhood cancer as a health problem by African governments (2) improving awareness and early diagnosis (3) adapted protocols for local resource limited conditions (4) affordability of treatment.
The risk of second malignancies after treatment for localized prostate cancer.
Authors: Elizabeth J. Davis, Cecilia Yee, Jennifer Beebe-Dimmer, Kathleen A. Cooney
Journal: Journal of Clinical Oncology (2014)

5034 Background: Prostate cancer has an excellent prognosis with a 10-year relative survival of 99.7%. The long survival for this common cancer raises questions about the risk of second primary malignancies after initial therapy for localized disease. Methods: A population-based cohort of 441,504 men diagnosed with prostate cancer between 1992 and 2010 was identified from Surveillance, Epidemiology and End Results Program data (SEER13). Standardized incidence ratios (SIR) were calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population according to whether or not men received radiation therapy (external beam radiation therapy or EBRT) as their initial treatment for prostate cancer. Only new primary cancers that arose 10 years or more after prostate cancer treatment were considered. Results: Compared to men who were not treated with radiation, men treated with EBRT were significantly more likely than the general population to be diagnosed with rectal (SIRradiation=1.70 versus SIRnoradiation=0.74, p <0.0001) and bladder cancer (SIRradiation=1.42 versus SIRnoradiation=0.76; p<0.0001). Both groups were at reduced risk of second primary malignancy and second solid tumors overall, but the magnitude of the reduction was less among men who received radiation (e.g., for solid tumors SIR=0.72; 95% CI=0.69,0.76 for those treated with EBRT compared to SIR=0.51; 95% CI=0.49,0.52 for those not exposed to radiation). Conclusions: Men who receive ERBT for localized prostate cancer have a significantly increased risk of later diagnoses of bladder and rectal cancer. Although the absolute risk of developing these cancers is small, physicians should discuss this information with patients before decisions are made on primary treatment for localized prostate cancer.
Expression of folate pathway genes and risk of recurrent disease in stage III colorectal cancer.
Authors: Yvonne Wettergren, Elisabeth Odin, Arvid SondÃƒÂ©n, Bengt Gustavsson, Göran Carlsson
Journal: Journal of Clinical Oncology (2014)

e14567 Background: Colorectal cancer is commonly treated with 5-fluorouracil in combination with 5--formyltetrahydrofolate (leucovorin). Metabolic action of leucovorin requires several enzymatic steps that are likely dependent on the expression level of corresponding coding genes, thus influencing response to leucovorin. The purpose of the retrospective study was to identify folate pathway genes with possible impact on leucovorin metabolism. Methods: Relative expression of 22 genes putatively involved in leucovorin transport/metabolism was determined in tumor and mucosa samples from 193 patients with stage III colorectal cancer using quantitative real-time polymerase chain reaction. After surgery, patients received adjuvant 5-fluorouracil-based chemotherapy, including leucovorin, and were followed for 3-5 years. Results: Low expression of the following genes in tumor tissue correlated significantly with increased risk of recurrent disease, measured as disease-free survival: SLC46A1/PCFT (p<0.001), ABCC3 (p<0.01), FPGS (p<0.01), SLC19A1/RFC-1 (p<0.01), ATIC (p<0.05), GGH (p<0.05), MTFMT (p<0.05), MTHFD1 (p<0.05) and MTHFD1L (p<0.05). Expression of 50% of analysed genes differed significantly between mucosa and tumor tissue. Conclusions: Low response to 5-fluorouracil plus leucovorin therapy in some patients may be linked to low expression of identified folate-associated genes. Indeed, such patients may warrant a different, more intensified, therapeutic approach than those with high gene expression. One approach would be to use the directly active folate [6R]5,10-methylenetetrahydrofolate, which does not require metabolic activation - its effects are therefore likely to be independent of these folate-associated genes. Future prospective studies are needed to confirm this.
Serogroup C Neisseria meningitidis disease epidemiology, seroprevalence, vaccine effectiveness and waning immunity, England, 1998/99 to 2015/16
Authors: Helen Findlow, Helen Campbell, Jay Lucidarme, Nick Andrews, Ezra Linley, Shamez Ladhani, Ray Borrow
Journal: Eurosurveillance (2019)

BackgroundIn 1999, the United Kingdom (UK) was the first country to introduce meningococcal group C (MenC) conjugate vaccination. This vaccination programme has evolved with further understanding, new vaccines and changing disease epidemiology.AimTo characterise MenC disease and population protection against MenC disease in England.MethodsBetween 1998/99-2015/16, surveillance data from England for laboratory-confirmed MenC cases were collated; using the screening method, we updated vaccine effectiveness (VE) estimates. Typing data and genomes were obtained from the Meningitis Research Foundation Meningococcus Genome Library and PubMLST Neisseria database. Phylogenetic network analysis of MenC cc11 isolates was undertaken. We compared bactericidal antibody assay results using anonymised sera from 2014 to similar data from 1996-1999, 2000-2004 and 2009.ResultsMenC cases fell from 883 in 1998/99 (1.81/100,000 population) to 42 cases (0.08/100,000 population) in 2015/16. Lower VE over time since vaccination was observed after infant immunisation (p = 0.009) and a single dose at 1-4 years (p = 0.03). After vaccination at 5-18 years, high VE was sustained for ≥ 8 years; 95.0% (95% CI: 76.0- 99.5%). Only 25% (75/299) children aged 1-14 years were seroprotected against MenC disease in 2014. Recent case isolates mostly represented two cc11 strains.ConclusionHigh quality surveillance has furthered understanding of MenC vaccines and improved schedules, maximising population benefit. The UK programme provides high direct and indirect protection despite low levels of seroprotection in some age groups. High-resolution characterisation supports ongoing surveillance of distinct MenC cc11 lineages.
Tissue Repair in the Mouse Liver Following Acute Carbon Tetrachloride Depends on Injury‐Induced Wnt/β‐Catenin Signaling
Authors: Ludan Zhao, Yinhua Jin, Katie Donahue, Margaret Tsui, Matt Fish, Catriona Y. Logan, Bruce Wang, Roel Nusse
Journal: Hepatology (2019)

In the liver, Wnt/β-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We examined Wnt gene expression and signaling after injury, and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4 ) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene axis inhibition protein 2 (Axin2). Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single-cell RNA sequencing, we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of β-catenin in peri-injury hepatocytes results in delayed repair and ultimately injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury. Conclusion: Our findings highlight the importance of the Wnt/β-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establish a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.
HMGB1 Causes Anemia of Inflammation By Modulating Erythropoietin Signal Transduction
Authors: Brian M Dulmovits, Julien Papoin, Jian Hua Li, Huan Yang, Ronak H Shah, Ryo Kurita, Yukio Nakamura, Yousef Al-Abed, Lily Huang, Betty Diamond, Jeffrey M Lipton, Mohandas Narla, Ulf Andersson, Kevin Tracey, Lionel Blanc
Journal: Blood (2018)
Abstract 20503: Prevalence and Significance of Atrial Fibrillation in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Andrea Mazzanti, Kevin Ng, Riccardo Maragna, Gaetano Vacanti, Maira Marino, Nicola Monteforte, Massimo Morini, Raffaella Bloise, Carlo Napolitano, Silvia G Priori
Journal: Circulation (2017)

Background: Preliminary data suggest that Atrial Fibrillation (AFib) is common in patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) and present at a younger age than in controls....