tbuckley/cabot-search huggingface dataset:
Post-prostatectomy PSA slope (ProsVue) in Gleason score ≥7 disease
Authors: Judd W. Moul, Hans Lilja, Oliver John Semmes, Robert Vessella, Jonathan E. McDermed, Mark J. Sarno, Robert E. Klem
Journal: Journal of Clinical Oncology (2012)

e15113 Background: A case-cohort designed multicenter clinical study addressed the prognostic value of the linear slope of PSA in 304 men after radical prostatectomy (RP) – 64 with clinical recurrence and 240 with stable disease. PSA was measured with Nucleic Acid Detection Immunoassay (NADiA) technology having a limit of quantification of 0.00065 ng (0.65 pg) per mL. Least-squares linear PSA slope (ProsVue) was calculated using 3 serum samples drawn 1.5-20 months (mo) post-RP. Multivariate Cox proportional hazards regression analysis showed that a ProsVue cutpoint of ≤2.0 pg/mL/mo was an independent prognostic factor for identifying men at reduced risk for recurrence along with clinical evaluation (HR=9.824). Of traditional risk factors – pre-RP PSA, Gleason score (GS) and pathologic stage, only GS was an independent prognostic factor (HR=5.3). This study tested the prognostic performance of ProsVue in a 164-man subset with pathologic GS ≥7. Methods: Recurrence was documented by positive imaging, positive biopsy or prostate cancer death. The same ProsVue cutpoint dichotomized men “at reduced” or “not at reduced” recurrence risk compared to clinically recurrent or stable disease status. Uni- and multivariate Cox proportional hazards regression were employed. Results: Median age, pre-RP PSA and percent tumor volume in the subset were 62.6, 7.2 ng/mL, and 20%. Distributions of GS 7, 8, 9 were 76.8%, 14.6% and 8.5%, respectively. Pathologic stages were T0-T2, T3a, T3b and T4 in 41%, 57%, 29% and 7% of men, respectively. Median follow-up in stable and recurrent groups was 10.8 and 4.8 yr. The table compares results in the full cohort and the GS ≥7 subgroup. Conclusions: ProsVue prognostic performance is maintained with GS ≥7. Performance parameters, especially the multivariate hazard ratio (HR) are minimally attenuated vs. the full case-cohort. [Table: see text]
Primary care quality and breast cancer care engagement during treatment: Results from the iCanCare Study.
Authors: Lauren P. Wallner, Paul Abrahamse, Christopher Ryan Friese, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2015)

e20637 Background: Collaborative care between cancer specialists and primary care providers ensures high quality cancer care from treatment into survivorship. Yet, little is known about patient’s perspectives about the level of PCP engagement in breast cancer (BC) care during treatment. Methods: A weighted random sample of newly diagnosed breast cancer patients in the Georgia and Los Angeles SEER registries were surveyed approximately 6 months after diagnosis (expected final N=2700, 68% current response rate). A primary care provider (PCP) quality scale was created by averaging patient responses (5 categories, never to always) to 5 questions: ease of access to PCP (3 questions) and PCP’s awareness of patient values (2 questions) and then categorized (avg. score 4 or more (high), vs. 3 (moderate), vs. <3 (low)). PCP BC engagement was defined by asking women how informed their PCP was about their ongoing cancer care. Patient factors associated with perceived PCP quality and BC engagement and the association between perceived PCP quality and PCP BC engagement were evaluated using logistic regression. Results: In a preliminary sample (N=1,787), 63% reported high PCP quality and 65% reported high PCP BC engagement. Women with higher PCP quality reported higher PCP BC engagement (table), which persisted after controlling for age, race, insurance, chemotherapy and comorbidity (p<.0001). Women who reported less PCP BC engagement were more likely to be younger than 65 (OR: 1.9, 95%CI: 1.5, 2.3), have received chemotherapy (OR: 1.3, 95%CI: 1.1, 1.6), and have no comorbidities (OR: 2.1, 95%CI: 1.5, 2.9). Conclusions: PCP engagement in breast cancer care during treatment is high for most women. However, there remains opportunity for improvement in PCP engagement, as many women report less engagement despite high quality primary care. Targeting these patients and their clinicians may be particularly effective in interventions to improve collaborative care in cancer. Funding: NCI P01CA163233. PCP engagement about oncology care N (%). Less engaged Highly engaged Total Primary care quality Low (<=2.9) 112 (82) 24 (18) 136 (100) Moderate (3) 254 (49) 269 (51) 523 (100) High (>=4) 252 (22) 876 (87) 1128 (100)
Validation of diagnosis codes to identify side of colon in an electronic health record registry.
Authors: Patricia Luhn, Deborah Kuk, Gillis Carrigan, Nathan Nussbaum, Rachael Sorg, Rebecca Rohrer, Melisa Tucker, Brandon Arnieri, Michael Taylor, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2017)

568 Background: The anatomical side of the colon from which a tumor arises is prognostic. Real-world evidence (RWE) studies in colon cancer should include this information. Can International Classification of Diseases (ICD) codes be reliably used to determine side of tumor, and, if so, when? Should electronic health records (EHR) be reviewed to supplement? Methods: Flatiron Health maintains an EHR-derived registry for metastatic colon cancer patients (current N = 9403). A random sample of 100 patients was included in this study. Data about tumor site was compared using ICD codes versus data abstracted from unstructured documents in the EHR (e.g., surgical notes). Concordance was determined via observed agreement and Cohen’s kappa coefficient (𝜿). Accuracy of ICD codes was determined by calculating the sensitivity, specificity, and positive predictive values, and corresponding 95% confidence intervals (CI), using abstracted data as the gold standard. Results: Sampled patients had similar side of colon distribution compared with the full registry: left colon (32% vs. 30%, respectively), right (17% vs. 25%), transverse (7% vs. 5%), unspecified side (39% vs. 37%), and rectum (5% vs. 2%). ICD codes can be general, or specific to the side of tumor. The observed agreement between the ICD codes and abstracted data for tumor site for all sampled patients was 0.57 (𝜿 = 0.42). When restricting to the 56% of patients with a side-specific ICD code, the observed agreement was 0.91 (𝜿 = 0.85). See table for all accuracy estimates. Conclusions: RWE offers growing opportunities for oncology research. Before meaningful RWE analyses can take place, data must be carefully characterized. Here, we describe tumor side EHR data in colon cancer and find that ICD codes specifying tumor side are available over half of the time. When these ICD codes are available, the accuracy of tumor side information in ICD codes is high. When not available, the dataset can be supplemented by chart abstraction. [Table: see text]
The effect of chemotherapy delivered until progression versus complete stop on the overall survival of patients with metastatic colorectal cancer: A meta-analysis of randomized trials.
Authors: Allan Andresson Lima Pereira, Juliana Florinda De Mendonga Rego, Paulo Marcelo Hoff, Andre Deeke Sasse, Rachel Pimenta Riechelmann
Journal: Journal of Clinical Oncology (2014)

3542 Background: The impact of the duration of chemotherapy on the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) is controversial. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) that compared chemotherapy continuously administered until progression versus complete treatment interruption after first line therapy for patients with mCRC Methods: We searched medical literature databases and oncology conferences proceedings for RCTs that compared the OS of mCRC patients who received first line chemotherapy until progression with those who were offered complete treatment stop after a fixed number of cycles. RCT that evaluated the role of any kind of maintenance therapy were excluded. A meta-analysis of reported Hazard Ratios for OS, with respective 95% confidence intervals, was performed using the fixed-effect models. Results: Our search retrieved 106 trials, of which sox were eligible (N=2373). The meta-analysis (N=2,334) showed a statistically significant OS benefit in favor of chemotherapy delivered until progression (HR= 0.89, 95%CI= 0.82 to 0.98; p= 0.01; I2 0%). The range of chemotherapy-free interval in the complete-stop group across trials was 3.7 – 4.3 months. Only three trials reported quality of life (QoL) data. Chemotherapy administered until progression was associated with more adverse effects and impaired QoL. Conclusions: Chemotherapy administered continuously until progression for mCRC patients is associated with a modest but significant improvement in OS. However mCRC is a heterogeneous disease and identification of molecular biomarkers could help clinicians to predict which patients would benefit from continuous or intermittent cancer-directed therapies.
Rapid Detection of Urinary Tract Infections via Bacterial Nuclease Activity
Authors: Katie S. Flenker, Elliot L. Burghardt, Nirmal Dutta, William J. Burns, Julia M. Grover, Elizabeth J. Kenkel, Tyler M. Weaver, James Mills, Hyeon Kim, Lingyan Huang, Richard Owczarzy, Catherine A. Musselman, Mark A. Behlke, Bradley Ford, James O. McNamara
Journal: Molecular Therapy (2017)

Rapid and accurate bacterial detection methods are needed for clinical diagnostic, water, and food testing applications. The wide diversity of bacterial nucleases provides a rich source of enzymes that could be exploited as signal amplifying biomarkers to enable rapid, selective detection of bacterial species. With the exception of the use of micrococcal nuclease activity to detect Staphylococcus aureus, rapid methods that detect bacterial pathogens via their nuclease activities have not been developed. Here, we identify endonuclease I as a robust biomarker for E. coli and develop a rapid ultrasensitive assay that detects its activity. Comparison of nuclease activities of wild-type and nuclease-knockout E. coli clones revealed that endonuclease I is the predominant DNase in E. coli lysates. Endonuclease I is detectable by immunoblot and activity assays in uropathogenic E. coli strains. A rapid assay that detects endonuclease I activity in patient urine with an oligonucleotide probe exhibited substantially higher sensitivity for urinary tract infections than that reported for rapid urinalysis methods. The 3 hr turnaround time is much shorter than that of culture-based methods, thereby providing a means for expedited administration of appropriate antimicrobial therapy. We suggest this approach could address various unmet needs for rapid detection of E. coli. Rapid and accurate bacterial detection methods are needed for clinical diagnostic, water, and food testing applications. The wide diversity of bacterial nucleases provides a rich source of enzymes that could be exploited as signal amplifying biomarkers to enable rapid, selective detection of bacterial species. With the exception of the use of micrococcal nuclease activity to detect Staphylococcus aureus, rapid methods that detect bacterial pathogens via their nuclease activities have not been developed. Here, we identify endonuclease I as a robust biomarker for E. coli and develop a rapid ultrasensitive assay that detects its activity. Comparison of nuclease activities of wild-type and nuclease-knockout E. coli clones revealed that endonuclease I is the predominant DNase in E. coli lysates. Endonuclease I is detectable by immunoblot and activity assays in uropathogenic E. coli strains. A rapid assay that detects endonuclease I activity in patient urine with an oligonucleotide probe exhibited substantially higher sensitivity for urinary tract infections than that reported for rapid urinalysis methods. The 3 hr turnaround time is much shorter than that of culture-based methods, thereby providing a means for expedited administration of appropriate antimicrobial therapy. We suggest this approach could address various unmet needs for rapid detection of E. coli.
New aspects regarding the cosmetic outcome after neoadjuvant radiochemotherapy in breast cancer patients.
Authors: Christiane Matuschek, Edwin Boelke, Werner Audretsch, Vanessa Speer, Sylvia Wollandt, Wilfried Budach, Carolin Nestle Kraemling
Journal: Journal of Clinical Oncology (2015)

e11505 Background: Neoadjuvant radiochemotherapy (NRT-CHX) is an innovative technique for the treatment of patients with locally advanced non inflammatory breast cancer (LABC). The aim of this study was to analyze the long term cosmetic outcome in breast conserving and mastectomy patients after NRT-CHX. Methods: In a time period from 1991 to 1998 a total of 315 LABC patients (cT1-cT4/cN0-N1) were treated with NRT-CHX. 160 patients received a breast conserving surgery (BCS) and 154 patients were treated with mastectomy (ME). One patient had no surgery.Preoperative radiotherapy (RT) consisted of external beam radiation therapy (EBRT) of 50 Gy (5 × 2 Gy/week) to the breast and the supra-/infraclavicular lymph nodes (255 patients) combined with a consecutive electron boost in 214 cases or - a 10-Gy interstitial boost with (192)Ir afterloading before EBRT in 101 of the patients' cases. Chemotherapy with CMF and AC/EC was administered prior to RT in 192 patients, and Mitoxantrone concomitantly in n=113 patients; 10 patients received no chemotherapy. The cosmetic outcome was assessed by patient questionnaire, a panel evaluation of 5 independent investigators graduated in 4 grades (excellent, good, moderate and bad), and breast retraction assessment (BRA). Quality-of-life was assessed by EORTC QLQ-C30 and BR23 and late radiation side effects by LENT/SOMA scale. Results: In 64 patients after breast conserving surgery and 43 patients after mastectomy a long term follow up of the cosmetic outcome was possible. Most patients rated their overall cosmetics as
HMGA2 Orchestrates the Tumorgenesis of Myeloproliferative Neoplasms (MPN) in Corporation with JAK2V617F
Authors: Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kazuei Ogawa, Yuko Hashimoto, Kayo Harada-Shirado, Hiroshi Ohkawara, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Motohiko Oshima, Atsushi Iwama, Yasuchika Takeishi
Journal: Blood (2016)
Oxidative modification of proteins of blood plasma in the development of ovarian cancer relapse.
Authors: Ekaterina Igorevna Surikova, Galina Nerodo, Irina Aleksandrovna Goroshinskaya, Polina Sergeevna Kachesova
Journal: Journal of Clinical Oncology (2013)

e22002 Background: Comparative analysis of oxidative modification of proteins of blood plasma level in patients with ovarian cancer in a state of remission and during the formation of tumor relapse with various intensity of bloodstream in it. Methods: The research includes 61 patients with ovarian cancer, from whom 11 women were in a state of remission, and 50 had local relapse in the cavity of the lesser pelvis. With the help of ultra-sonic scanner we evaluated the intensity of vascularization and the speed of bloodstream in relapsing tumors. We also studied the level of blood plasma spontaneous metal catalyzed oxidative modification of proteins (OMP), spectrophotometrically registering 2, 4-dinitrophenylhydrazines. Results: In remission there was noted the increase of OMP products level by 74.4% under 530 nm (p&lt;0.05) in blood plasma as compared with the its level in healthy women. During the progress of avascular relapse there was noted the increase of OMP products level by 63.3% under 370 nm (p&lt;0.001) and decrease of OMP products level by 32.2% under 530 nm as compared with the level in remission. In the group with hyper intensive bloodstream in relapse tumor the level of OMP products increased by 37.4% under 370nm (p&lt;0.05) and the level of products decreased by 24% under 530 nm as compared with the group with avascular relapse. In case with metal catalyzed OMP the low level of OMP products under 370 nm (by 18-28% lower than the level of OMP of healthy women, p&lt;0.01), the high level of OMP products under 530 nm (by 24-47% higher than the level of OMP of healthy women, p&lt;0.01) remained, and the level of OMP under 430 nm was increasing as compared with healthy women. Conclusions: The increase of OMP products of neutral character registered under 370 nm, and the decrease of the products of the basic character registered under 530 nm take place during the progress of cancerous process and intensification of the bloodstream in a tumor. The dynamics metal catalyzed OMP products shows the heightened formation of the products of the basic character (430 and 530 nm), being the markers of proteins fragmentation.
Efficacy of risk-reducing mastectomy (RRM) on overall survival (OS) in BRCA1/2-associated breast cancer (BC) patients.
Authors: Bernadette Anna Maria Heemskerk-Gerritsen, Maartje Hooning, Christi J van Asperen, Margreet GEM Ausems, Margriet Collée, Liesbeth Jansen, Marleen Kets, Kristien Keymeulen, Hanne EJ Meijers-Heijboer, Theo AM van Os, Hans FA Vasen, Linetta Koppert, Matti A. Rookus, Caroline Seynaeve
Journal: Journal of Clinical Oncology (2013)

1502 Background: RRM in BRCA1/2 mutation carriers with a history of unilateral BC significantly reduces the risk of developing contralateral BC (CBC). However, the outcome regarding OS is insufficiently known. Methods: The efficacy of RRM on CBC incidence and OS was studied in a Dutch multicenter cohort consisting of 515 BRCA-associated BC patients (399 BRCA1, 116 BRCA2) of whom 177 BRCA1 and 48 BRCA2 carriers underwent RRM. Data on patient, tumor and treatment characteristics were collected up to June 30, 2012. Women contributed person-years of observation (PYO) to the Non-RRM group from the date of primary BC (PBC) diagnosis or DNA diagnosis (whichever came last) to the date of death, RRM, or last contact. Contribution of PYO to the RRM group started at the date of RRM until similar endpoints as described for the Non-RRM group. Results: Regarding PBC, no significant differences in size, nodal status, differentiation grade, hormone and Her2Neu receptor, and endocrine therapy were observed between the Non-RRM and RRM group. Median age of PBC diagnosis was 42 years for Non-RRM and 38 for RRM women (p&lt;0.001). Median time period between PBC and RRM was 2.3 years (range 0.02-20.1). PBC treatment included radiotherapy for 68% of Non-RRM versus 50% of RRM women (p&lt; 0.001). Compared to Non-RRM, chemotherapy was more often given to RRM women (66% versus 49%; p&lt;0.001), and more RRM women underwent risk-reducing salpingo-oophorectomy (81% versus 67%; p&lt;0.001), while ovarian cancer incidence was not different. With a median FU of 11.7 years after PBC diagnosis, 58 CBC cases were observed in Non-RRM women, while 4 CBC cases occurred after RRM, yielding incidence rates (per 1000 PYO) of 30.6 and 2.5, respectively (adjusted HR 0.09, 95% CI 0.03-0.24). In the Non-RRM group 45 women died during 2408 PYO versus 17 women in the RRM group during 1756 PYO, yielding mortality rates (per 1000 PYO) of 18.9 and 9.7, respectively (adjusted HR 0.56, 95% CI 0.32-0.99). 10 year OS was 80% for the Non-RRM and 90% for the RRM group (p=0.008). Conclusions: RRM in BRCA mutation carriers with unilateral BC reduces CBC incidence and is associated with improved OS. Further research is needed to identify potential prognostic factors for this survival benefit.
Lung Adenocarcinoma and Squamous Cell Carcinoma Gene Expression Subtypes Demonstrate Significant Differences in Tumor Immune Landscape
Authors: Hawazin Faruki, Gregory M. Mayhew, Jonathan S. Serody, D. Neil Hayes, Charles M. Perou, Myla Lai-Goldman
Journal: Journal of Thoracic Oncology (2017)

IntroductionMolecular subtyping of lung adenocarcinoma (AD) and lung squamous cell carcinoma (SCC) reveal biologically diverse tumors that vary in their genomic and clinical attributes.MethodsPublished immune cell signatures and several lung AD and SCC gene expression data sets, including The Cancer Genome Atlas, were used to examine immune response in relation to AD and SCC expression subtypes. Expression of immune cell populations and other immune related genes, including CD274 molecule gene (CD274) (programmed death ligand 1), was investigated in the tumor microenvironment relative to the expression subtypes of the AD (terminal respiratory unit, proximal proliferative, and proximal inflammatory) and SCC (primitive, classical, secretory, and basal) subtypes.ResultsLung AD and SCC expression subtypes demonstrated significant differences in tumor immune landscape. The proximal proliferative subtype of AD demonstrated low immune cell expression among ADs whereas the secretory subtype showed elevated immune cell expression among SCCs. Tumor expression subtype was a better predictor of immune cell expression than CD274 (programmed death ligand 1) in SCC tumors but was a comparable predictor in AD tumors. Nonsilent mutation burden was not correlated with immune cell expression across subtypes; however, major histocompatibility complex class II gene expression was highly correlated with immune cell expression. Increased immune and major histocompatibility complex II gene expression was associated with improved survival in the terminal respiratory unit and proximal inflammatory subtypes of AD and in the primitive subtype of SCC.ConclusionsMolecular expression subtypes of lung AD and SCC demonstrate key and reproducible differences in immune host response. Evaluation of tumor expression subtypes as potential biomarkers for immunotherapy should be investigated.
ESTUDIO MULTICÉNTRICO, LONGITUDINAL Y PROSPECTIVO PARA EVALUAR LAS COMPLICACIONES DERIVADAS DE LA POLIPECTOMÍA GÁSTRICA Y DUODENAL
Authors: H Córdova, C Loras, L Argüello, A Naranjo, F Riu, J Gornals, D Nicolás, L Hernández, S Santolaria, E Pérez-Cuadrado Robles, C Leal, C Pons, O García, M Papo, L Ulla José, N Rojas, G Fernández Esparrach
Journal: Endoscopy (2015)

Introducción: La polipectomía gástrica y duodenal es una técnica común, aunque existe poca información sobre sus potenciales complicaciones.