tbuckley/cabot-search huggingface dataset:
Mutational analysis of KRAS, BRAF, and p53 genes in borderline and malignant epithelial ovarian tumors.
Authors: A. Mosconi, V. Ludovini, L. Pistola, F. R. Tofanetti, M. G. Mameli, P. Anastasi, S. Porrozzi, A. Cavaliere, M. G. Cantelmi, L. Crino
Journal: Journal of Clinical Oncology (2010)

e21069 Background: Recently, a two-pathway model of ovarian carcinogenesis has been proposed. In this model, all epithelial tumors are divided into 2 groups. Type I tumors include low-grade serous carcinoma, mucinous, endometrioid and clear cell carcinomas which develop slowly in a stepwise fashion. They evolve from adenofibromas or borderline tumors, have frequent mutations of the KRAS and BRAF, but lack TP53 mutations. Type II tumors are rapidly growing neoplasms, including high-grade serous carcinoma, carcinosarcomas, and undifferentiated carcinoma. Most are characterized by TP53 mutations and lack mutations of KRAS and BRAF. Methods: A total of 32 malignant epithelial ovarian carcinomas were evaluated for mutational analysis of KRAS, BRAF, and p53 genes. The histologic cell type was serous in 17 cases (15 grade 2-3, 2 Grade 1), endometrioid in 3 cases, clear cell in 2 cases, undifferentiated in 1 cases, and borderline in 9 cases (7 serous, 2 mucinous). Genomic DNA was isolated from paraffin-embedded tumor specimens using QIAmp DNA extraction kit and automatically purified by Biorobot EZ1 instrument (Qiagen). KRAS (exons 2 and 3), BRAF (exons 11 and 15) and p53 (exons 5-8) genes were amplified by nested PCR and sequenced in both sense and antisense direction using 3500 Genetic Analyzer (Applied Biosystems, Foster City, CA). Results: Five of 9 (56 %) borderline tumors (BT) had either a KRAS or BRAF mutation: 3/7 serous BT contained mutant BRAF, whereas the 2 mucinous BT contained KRAS mutation. KRAS mutations were also identified in 2 /3 endometriod carcinomas. The frequency of KRAS or BRAF mutations in type 1 tumors (BT, serous G1, endometriod, or clear cell) was higher than in type II tumors (serous G2-3, undifferentiated): 44% (7/16) vs 6% (1/16), respectively. No p53 mutations were detected in type I tumors. In contrast, p53 gene mutations were identified in 6/16 (37%) type II. Conclusions: Our results support that the majority of type I and type II ovarian carcinomas develop independently and are characterised by different molecular genetic changes. In the future, the combined analysis of morphological parameters and molecular genetic features could identify possible new therapeutic targets for ovarian carcinomas. No significant financial relationships to disclose.
Evaluation of hematologist/oncologist attributes by physicians and patients: A survey study.
Authors: Kaitlin McIntyre, Cory Patrick, Rakesh Singal, Damien Mikael Hansra
Journal: Journal of Clinical Oncology (2016)

124 Background: We aim to compare what attributes are important to hematology/oncology (hem/onc) physicians (MD) and patients (pts). Methods: IRB approval obtained. Pts and MDs at an academic tertiary care medical center were enrolled to complete a survey. Demographics include: age, gender, race, and ethnicity. Clinical info collected: cancer subtype and treating MD. Survey consisted of 5 questions assessing opinions on physician attributes. Patients were asked: “It is important that my doctor” is friendly, is empathetic, is knowledgeable, well dressed, and engaged in research. MDs were asked: “It is important to be” friendly, empathetic, knowledgeable, well dressed, and engaged in research. Answers recorded on a 5 point scale (1 = highly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) &amp; converted into 2 categories (1,2,3 = neutral/disagree vs. 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance between MD &amp; pts responses. Results: 1008 pts and 55 MDs enrolled from June 2013 to October 2015. Pt mean age 55, range 18-88 with 45% male &amp; 55% female. 62% of pts were Hispanic vs. 38% not Hispanic. 16% white, 14% black/African American, 2% Asian/Pacific Islander, &amp; 6% other. 21% of pts had hematologic disorders (92% malignant 8% benign) vs. 79% of pts had solid malignancies. Significant difference was seen for research where 93% of pts agree that having a doctor who is engaged in research is important vs. 63% of MDs, p &lt; 0.0001. A majority of pts and MDs agree that friendliness (92% vs. 91% resp., p = 0.6032), empathy (91% vs. 93% resp., p = 1.000), fund of knowledge (95% vs. 94% resp., p = 0.7442), being well dressed (79% vs. 69% resp., p = 0.0901), is important but no significant differences seen. Conclusions: Hem/onc pts and MD agree that friendliness, empathy, fund of knowledge, being well dressed are important attributes in a hem/onc MD. A significantly increased percentage of patients find it important that their hem/onc MD is engaged in research. It is expected that increased hem/onc MD research will not only contribute to society but also it could improve patient satisfaction.
Time to publication of the results of clinical trials conducted by Japan Clinical Oncology Group (JCOG).
Authors: H. Katayama, K. Nakamura, J. Mizusawa, A. Takashima, F. Kunieda, K. Kanato, S. Matsubara, A. Kimura, T. Shibata, I. Saito, H. Fukuda
Journal: Journal of Clinical Oncology (2011)

e16640 Background: It was previously reported that the median times from abstract presentation to publication in ECOG were 35, 26, 33 months for phase I, II, III trials (ASCO 2010). JCOG has the same issue that the process from trial development to publication is slow. The aim of this study is to evaluate the duration from primary analysis to publication in JCOG. Methods: The study inclusion criteria was i) clinical trials conducted by JCOG between 1991 and 2010, and ii) primary analysis was finished. All data was collected from the JCOG database. The primary endpoint is time from primary analysis to publication, which means from the date when the report of primary or final analysis was submitted to the investigators to the date when the manuscript was accepted to journal. Unpublished trials were censored at January 2011. Time from protocol approval to trial activation, time from trial activation to accrual termination, and time from accrual termination to primary analysis were also calculated. In addition, we investigated whether the time from primary analysis to publication is shorter in positive trials. We defined “positive trial” when the trial had met the primary endpoint. Results: Among 76 clinical trials included in the analysis, 61.8% (47/76) has already been published. Eight trials (10.5%) were closed early without a definitive answer because of poor accrual. Median time from primary analysis to publication in all trials was 32.2 months (range 7.7-106.9). The median time of each period is shown in the table. Thirty-one trials (40.8%) were positive. Median time from primary analysis to publication was 23.6 months for the positive trials, and 31.3 months for the others. Conclusions: In JCOG, time from primary analysis to publication took more than 2 years, which was similarly slow as ECOG. We are trying to improve the process for rapid publication. Approval to activation Activation to accrual termination Accrual termination to analysis Analysis to publication Phase I (n=3) 1.1m 13.3m 10.5m 33.7m Phase II (n=41) 1.2m 32.1m 27.6m 23.6m Phase III (n=29) 1.8m 54.8m 22.5m 30.4m Others (n=3) 1.3m 16.2m 24.4m 32.2m
Array-based comparative genomic hybridization analysis to identify prognostic markers for resected pancreatic cancer.
Authors: J. Lee, I. Petrini, J. Hwang, E. Giovannetti, J. Voortman, Y. Wang, S. M. Steinberg, N. Funel, P. S. Meltzer, Y. Wang, G. Giaccone
Journal: Journal of Clinical Oncology (2011)

4097 Background: The clinical relevance of genomic imbalances in pancreatic cancer is uncertain. The aim of this study was to evaluate whether alterations in specific genes influenced clinical outcome in resected pancreatic cancer patients. Methods: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens from a Korean cohort, including 24 patients who received adjuvant chemotherapy regimens with gemcitabine or 5-fluorouracil. Statistical analysis enabled us to assess the interaction of copy number alterations with clinicopathological variables and overall survival (OS). Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent Italian cohort of 61 resected pT3N1Mx stage pancreatic cancers treated with gemcitabine adjuvant therapy. Results: Recurrent copy number gains were observed in chromosome 1q, 11q, 18q11.1-11.2, and 20q13.13; and losses in chromosome 2p, 9p, 10q, 14q, 15q, 18q12.2-23, 19q, 20q11.1, 21p, and 22q. Loss of cytoband 18q22.3 (in 8 patients) was significantly more frequent in patients surviving shorter than the median OS (p=0.021, Fisher-Exact test). This cytoband encodes 5 genes, including CNDP2, whose copy number was associated with OS (p=0.019, log-rank test). The copy number of this gene was subsequently assessed in the Italian cohort, where patients with deletion (N=41) had shorter OS (p=0.003, log-rank test). Multivariate analysis of the two cohorts showed that loss/deletion of 18q22.3/CNDP2 was an independent poor prognostic factor for OS (hazard ratio 2.72, p=0.0007) after adjusting for other factors influencing clinical outcome. Conclusions: Through aCGH analysis, we identified loss/deletion of 18q22.3/CNDP2 as a potentialindependent poor prognostic factor in resected pancreatic cancer. Given the heterogeneity of the two cohorts, further confirmation on a large number of patients is warranted. However, the combined Cox model suggests that this genetic alteration may have a meaningful impact on OS of pancreatic cancer patients, and its biological implications are being investigated.
Valproic Acid Induces Apoptosis in Chronic Lymphocytic Leukemia Cells by Targeting Several Pro- and Anti-Apoptotic Genes.
Authors: Basile Stamatopoulos, Nathalie Meuleman, Alain Kentos, Philippe Hermans, Philippe Martiat, Dominique Bron, Laurence Lagneaux
Journal: Blood (2007)
Alteration of microbiota in esophagitis and Barrett's esophagus and further modification by PPI treatment.
Authors: Elizabeth E. Half, Itay Amir, Uri Gophna, Fred M. Konikoff
Journal: Journal of Clinical Oncology (2013)

16 Background: Gastroesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the esophagus. The incidence of esophageal adenocarcinoma (EAC) has increased almost six fold in the past 30 yrs despite the increased use of Proton Pump Inhibitors (PPIs) to treat reflux. Recently, erosive esophagitis has been shown to increase the risk of EAC relative to patients with normal esophagus (NE). The reason for this remains unknown. Aim: To determine whether the microbiota of gastric refluxate and esophageal biopsies differs between patients with heartburn and NE vs. patients with abnormal esophageal mucosa [esophagitis or Barrett's esophagus (BE)] and to elucidate the effect of PPIs on bacterial communities. Methods: Gastric fluid and esophageal biopsies were collected during endoscopy from 13 BE/esophagitis patients and from 7 with NE. To reveal how PPIs alter the microbiota, samples were obtained from 8 of the patients (2 NE, 4 esophagitis and 2 with BE), before and after 8 weeks of PPI therapy. DNA was extracted and 16S rRNA gene pyrosequencing of microbial communities was performed. Results: Significant differences in the composition of gastric fluid bacteria, but not the esophagus-associated microbiota, were found between patients with heartburn and NE vs. patients with esophagitis and/or BE. Notably, Enterobacteriaceae (specifically Escherichia and Enterobacter) were significantly enriched in gastric fluid of patients with BE/esophagitis (P=0.01) compared to NE. PPIs had a remarkable effect on microbial communities both in the stomach and the esophagus. In gastric fluid, Moraxellaceae were decreased (P=0.016), whereas Erysipelotrichaceae were increased (P=0.031) following PPI treatment. Esophageal biopsies revealed genera belonging to the Microccocaceae, known to be opportunistic human pathogens, which increased following PPIs (P =0.031). Conclusions: Gastric fluid microbiota is modified in heartburn patients with esophagitis and/or Barrett's esophagus compared to patients with normal esophagus. PPI treatment markedly alters gastric and esophageal microbial populations. These modified bacterial communities may predispose to inflammation, dysplasia and cancer.
Comparative outcomes of oncologic therapy in gastric extranodal marginal zone (MALT) lymphoma: Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare database.
Authors: Adam J. Olszewski
Journal: Journal of Clinical Oncology (2013)

75 Background: Therapy for H. pylori (HPy)-negative or recurrent gastric MALT lymphoma is largely based on single-arm trials. The aim of this observational study was to compare outcomes after surgery, radiation (XRT) or chemotherapy (CT) in the SEER-Medicare dataset. Methods: Gastric MALT lymphoma cases diagnosed between 1997 and 2007 were selected, excluding patients without adequate Medicare coverage at diagnosis or follow up. Outcomes of XRT and CT were compared in stage IE group balanced by a propensity score. Flexible parametric models were used to study overall (OS) and lymphoma-specific survival (LSS). Treatments were evaluated with competing risk models, reporting hazard ratios (HR) and 95% confidence intervals (95%CI). Results: Among 1134 patients (median age: 77 years, median follow-up data: 4.3 years), 50% had no recorded oncologic treatment, 5% underwent surgery, 21% XRT and 24% CT as initial therapy, at a median of 3.4 months from diagnosis. HPyinfection was recorded in 19%. Oncologic therapy was more frequent in patients who were younger, diagnosed after 2000, with stage &gt;IE and no poor performance status (PS) indicator. Worse LSS was associated with increasing age, male sex, poor PS, gastrointestinal hemorrhage/perforation, stage &gt;IE, B-symptoms, being widowed or prior malignancy. In the 347 stage IE patients who received XRT or CT within 2 years of diagnosis, XRT alone as initial therapy was associated with better CSS than CT (HR 0.27, 95%CI 0.13-0.55, P&lt;0.001). OS did not differ. Among the 321 patients treated with CT, 45% received rituximab (R) alone, 43% cyclophosphamide-based and 10% fludarabine-based regimens. The median OS after CT was 5.8 years without significant difference between these groups. Compared with patients receiving R alone, LSS was worse for those treated with CT alone (HR=2.31, 95%CI 1.2-4.26, P=.007), but did not significantly differ for those treated with R+CT (HR=1.63, 95%CI 0.84-31.17, P=0.15). Conclusions: XRT may be a preferable choice in elderly patients with stage IE gastric MALT lymphoma. In those requiring CT, addition of CT to rituximab alone is not associated with improved LSS.
Association of care transitions with treatment delay for patients with muscle-invasive bladder cancer.
Authors: Jeffrey J. Tomaszewski, Elizabeth Handorf, Anthony Corcoran, Reza Mehrazin, Daniel Canter, Justin E. Bekelman, Alexander Kutikov, David Y. T. Chen, Robert G. Uzzo, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2014)

346 Background: Population-based data suggest an association between timely treatment (&lt;3 months) and improved survival in patients undergoing radical cystectomy (RC). Hypothesizing that care transitions at the time of hospital referral may delay timely treatment in patients with muscle invasive bladder cancer (MIBC), our objective was to identify the association between care transitions and treatment delay ≥3 months using a large national tumor registry. Methods: Using the National Cancer Database, all patients with stage ≥II urothelial carcinoma treated with RC from 2003-2010 were identified. A care transition was defined as a change in hospital from diagnosis to first course of treatment. A logistic regression model was used to test the association between care transition and treatment delay (from diagnosis to RC or initiation of neoadjuvant chemotherapy), adjusting for year, demographic, clinicopathologic, and hospital characteristics. Results: Of 22,251 patients identified, 14.2% of patients experienced a treatment delay of ≥3 months. Further, this proportion increased over the study period (13.5% [2003-2006] versus 14.8% [2007-2010], p=0.01). 19.4% of patients undergoing a care transition experienced a delay to definitive treatment compared to 10.7% of patients diagnosed and treated at the same hospital (p&lt;0.001). The proportion of patients experiencing a care transition increased over the study period (37.4% [2003-2006] versus 42.3% [2007-2010], p&lt;0.001). Following adjustment, patients were more likely to experience a treatment delay when undergoing a care transition (OR 2.0 [CI 1.8-2.2]). Additional covariates associated with treatment delay included African American race (OR 1.5 [CI 1.3-1.7]), Hispanic ethnicity (OR 1.6 [CI 1.3-1.9]), insurance status (Medicaid OR 1.4 [CI 1.1-1.7], Medicare OR 1.2 [CI 1.08-1.34], no insurance OR 1.3 [CI 1.07-1.54]), and Charlson comorbidity count ≥2 (OR 1.3 [CI 1.08-1.45]). Conclusions: Patients with MIBC who experienced a care transition between diagnosis and treatment hospitals were more likely to experience a treatment delay of ≥3 months. Strategies to expedite care transitions at the time of hospital referral may be a means to improve quality of care.
Evaluation of triptolide pro-drug (Minnelide) as an anti-stromal and anti-tumoral therapeutic option for pancreatic cancer.
Authors: Sulagna Banerjee, Shrey Modi, Xianda Zhao, Vikas Dudeja, Ashok Saluja
Journal: Journal of Clinical Oncology (2016)

262 Background: In pancreatic cancer, the stromal microenvironment is considered to be the major reason behind the failure of conventional and targeted therapy. The desmoplastic stroma is responsible for compression of vasculature in the tumor resulting in impaired drug delivery. Pancreatic stellate cells contribute extensively to this desmoplastic reaction. Our group has recently evaluated a water-soluble pro-drug of triptolide (Minnelide) in pre-clinical studies for pancreatic cancer with very promising results. The current study evaluates the ability of Minnelide to deplete the stromal architecture and the stellate cell population in pancreatic cancer resulting in increased drug delivery. Methods: Patient tumor xenografts in SCID mice (PDX) and KRAS G12D TP53-PDX-Cre spontaneous pancreatic tumor mice (KPC) were treated with 0.42mg/kg Minnelide. Vascular patency was studied by terminal perfusion of mice with 4% PFA following injection with tomato lectin. Drug delivery was determined by quantitating accumulated doxorubicin in the tumor tissue. Cell viability was studied by MTT assay and the invasion of cells in vitro was studied using Boyden Chamber assay. Results: Minnelide treatment decreased Hyaluronic acid (HA) in PDX (48% of control) as well as in KPC model (52% of control). Expression of HA synthase (HAS) genes were decreased in both tumor models in response to Minnelide (22% of control in PDX and 35% of control in KPC tumors). HAS Enzyme activity also consistently decreased in both the models after treatment with Minnelide (28% of control in PDX and 31% of control in KPC). In vitro, triptolide decreased the invasion of the tumor cells towards the stellate cells indicating an inhibition of crosstalk. Treatment with Minnelide resulted in “open” and functional vessels in the treated animals resulting in increased drug delivery. Median survival of animals increased by 38 days after treatment with Minnelide. Conclusions: Our study showed that Minnelide depleted the stromal architecture leading to increased functional vasculature and enhanced drug delivery in the tumor. This is an extremely promising observation for Minnelide that is currently under clinical trial.
Recombinant Porcine Factor VIII Corrects Thrombin Generation and Improves Clot Structure In Vitro in Plasma Containing Anti-Factor VIII Inhibitory Antibodies
Authors: Claude Negrier, Shannon L. Meeks, Johannes Oldenburg, Uri Martinowitz, Jean-Claude Bordet, Bernd Poetzsch, Raed Al Dieri, Yesim Dargaud, Coen Hemker, Carel Eckmann, Ed Gomperts, Martin Lee
Journal: Blood (2011)
The risk of subsequent malignancies in cervical cancer survivors as compared with breast and colorectal cancer survivors: United States 1992-2007.
Authors: J. M. Underwood, S. H. Rim, E. Tai, T. Fairley
Journal: Journal of Clinical Oncology (2011)

9043 Background: According to the U.S. Surgeon General, cervical cancer is causally linked to smoking tobacco. Persistent smoking among cervical cancer survivors may increase their risk for subsequent malignancies, including tobacco-related cancers. Despite these risks, nearly 40% of the approximately 247,000 women diagnosed with cervical cancer in the U.S. continue to smoke after diagnosis. This study describes the relative risk of developing subsequent malignancies among cervical cancer survivors. Methods: We examined data from 13 Surveillance, Epidemiology and End Results (SEER) registries from 1992-2007. We calculated the relative risk [observed/expected incidence ratios (O/E)] and 95% confidence intervals (CI) for all subsequent and tobacco-related malignancies among cervical cancer survivors. Tobacco-related cancers (lung, pharynx, larynx, esophagus, stomach, pancreas, kidney, bladder, cervix and leukemia) were defined according to the 2004 Surgeon General’s Report on “The Health Consequences of Smoking.” Relative risks for subsequent malignancies were also calculated for female survivors of breast and colorectal cancer for comparison. Results: Overall, the relative risk for diagnosis with a subsequent cancer (excluding non-melanoma skin cancers) was higher among cervical cancer survivors (O/E: 1.4; 95%CI: 1.4-1.5) compared to breast (O/E: 1.2; 95%CI: 1.2-1.2) and colorectal cancer survivors (O/E: 1.2; 95%CI: 1.1-1.2). The relative risk of developing subsequent tobacco-related cancers was also higher among cervical cancer survivors (O/E: 2.3; 95%CI: 2.1-2.5) compared to breast (O/E: 1.0; 95%CI: 1.0-1.1) and colorectal cancer survivors (O/E: 1.1; 95%CI: 1.1-1.2). Conclusions: Women with cervical cancer are at increased risk for subsequent cancers, including tobacco-related cancers, when compared to breast and colorectal cancer survivors. Cervical cancer survivors should be targeted for intervention with evidence-based cancer preventive measures, including increased guidance about smoking-cessation and the availability of cessation treatments.
FOXP3 Expression in Diverse T-Cell Lymphomas.
Authors: Brady E. Beltrán-Gárate, Pilar Quiñones, Domingo Morales, Julia Huamani-Zavala, Osbert Mejía, Miriam Vidurrizaga, Jose Malaga, Jorge Castillo-Aguirre, Luis Riva, Fernando Hurtado de Mendoza, Antonio A. Carrasco-Yalan
Journal: Blood (2006)