tbuckley/cabot-search huggingface dataset:
Rapid detection of cancer-related cfc-DNA biomarkers directly from whole blood.
Authors: Michael James Heller, Avery Sonnenberg
Journal: Journal of Clinical Oncology (2012)

14 Background: We have developed a “Sample to Answer” dielectrophoretic (DEP) technology for detecting cancer and other disease-related cfc-DNA biomarkers directly from whole blood. Using AC/DC electric field microarray devices specifically designed for the isolation of cfc-DNA, exosomes and cellular nanoparticulates from blood samples, experiments were carried out by adding about 20ul of the patient blood sample to the DEP microarray device. Methods: The DEP field was applied at 10 kHz and 20 Vp-p for 15 minutes to nine microelectrodes. The microarray was then washed three times with 0.5x PBS with the DEP field on, and finally examined by epifluorescent microscopy. Results: For Chronic Lymphocytic Leukemia (CLL) cancer patient blood samples, results clearly show greenish white fluorescent circles around the nine DEP microelectrodes on the array. This is the SYBR Green fluorescent stained cfc-DNA from the CLL cancer patient blood sample now concentrated in the DEP high field regions. Normal blood samples show little or no fluorescence around the DEP high field microelectrodes. More than fifty CLL samples have been analyzed to date. Conclusions: DEP devices are now being used to collect cfc-DNA from other cancer patient whole blood, plasma and serum samples. Blood sample to PCR is now achieved in less than twenty minutes. Newer work has demonstrated that PCR can be carried out in-situ (in the same device). Thus, the new DEP technology and devices set the stage for “seamless sample to answer” diagnostic systems which will allow a variety of important cancer and other disease biomarkers to be rapidly isolated and analyzed directly from whole blood and other clinical samples.
Predictive role of fluorodeoxyglucose positron emission tomography (<sup>18 f</sup>F-FDG CT-PET) in early assessment of response to bevacizumab and FOLFOX-6 combined neoadjuvant therapy for liver metastasis (LM) from colorectal cancer (CRC)
Authors: N. Malavasi, B. Bagni, F. Bertolini, C. Dealis, R. Depenni, M. Cucca, A. Casolo, G. Ponti, G. Luppi, P. F. Conte
Journal: Journal of Clinical Oncology (2008)

15094 Background: Dynamic functional imaging, in particular 18F-FDG CT-PET is currently the most powerful tool for molecular imaging potentially predictive of early response to anti-angiogenetic drugs. Methods: Patients (pts) with histologically confirmed initially unresectable LM, without evidence of extra-hepatic disease, received neoadjuvant Bevacizumab 5 mg/Kg and Folfox-6 every 2 weeks for 6 courses. Primary objective was to estimate the percentage of pts amenable to complete resection after the neadjuvant therapy. We tried to identify a possible contribution of CT-PET as marker for early assessment of response comparing CT-PET performed at baseline and within the 7th day from the beginning of therapy (CT-PET G.E. Discovery STE was used). Images were semiquantitatively analyzed by measuring the mean standardized uptake value (SUV). The region of interest was placed on the transaxial plane of the emission image with an 18F-FDG uptake area 1cm diameter. SUV was calculated as (activity in the region interest [MBq/mL])/(injected dose [MBq]/weight [Kg]); we assumed maximal value of each detection. Results: From September 2005 up to now, 11 pts are evaluable for CT-PET response. Median baseline SUVmax value was 8. Pts with SUVmax ≥ 8 at baseline were 8; we observed 2(25%) clinical complete responses (CR), 5(62%) partial responses (PR), and 1(13%) stable disease. Pts with SUVmax <8 at baseline were 3; we observed 3 stable disease (100%). Radical surgery was possible in 7/8 pts (87%) with basal median SUVmax ≥8 (2 CR underwent biopsy to confirm pathological complete response and 5 PR underwent liver resection) and no pts with basal median SUVmax <8 underwent surgery of LM (p=0.0072). Moreover we observed after the first cycle of therapy median SUVmax was 4; in the responder group median SUVmax decreased >50% if compared to baseline. Conclusions: CT-PET as imaging marker seems to be early predicitive of response to Bevacizumab and FOLFOX-6 neoadjuvant therapy in pts with LM from CRC. The use of CT-PET for therapy monitoring appears clinically feasible since simplified methods (SUV) are sufficiently reliable. No significant financial relationships to disclose.
Outcomes and efficiency of National Cancer Screening Program for gastric cancer in Korea.
Authors: B. Kim, W. Cheon, J. Kim, J. Park, S. Kim
Journal: Journal of Clinical Oncology (2011)

13 Background: Gastric Cancer is a major cause of death and a substantial socioeconomic burden in Korea. The National Cancer Screening Program for Medicaid recipients was initiated in 1999 and has contributed to reduction of cancer-related mortality in Korea. Endoscopy may be cost-effective screening tool in Korea, where the cost of endoscopy and UGIS are similar and the gastric cancer incidence is high. Most of Japanese studies on the efficiency of mass screening for gastric cancer have dealt with photoflurography as a screening tool. Although biennial gastric cancer screening by endoscopy has been increasing in Korea as part of the National Cancer Screening Program, few studies have evaluated its efficiency. Therefore, we analyzed the outcomes and efficiency of the National Cancer Screening Program for gastric cancer using endoscopy in Korea. Methods: We reviewed results from the National Cancer Screening Program for gastric cancer at Chung-Ang University Yongsan Hospital in Korea from March 2003 to March 2008. The study population was comprised of Medicaid recipients ≥ 40 years of age who were taken from the National Health Insurance Corporation. Results: A total of 7,278 asymptomatic subjects underwent endoscopy for gastric cancer screening. The mean age of the screened subjects was 51.3 years for men and 48.9 years for women. The male to female ratio of the screened subjects was 1.2:1. Gastric cancer was diagnosed in 32 (0.44%) of 7,278 subjects (22 men and 10 women). Their mean age was 54.4 years. Of these, 21 subjects (0.29%) were diagnosed as early gastric cancer and 11 subjects (0.15%) were advanced gastric cancer. The proportion of EGCs among total gastric cancers was 65.6%. The compliance with this program was low (59% for men and 49% for women). Conclusions: Despite accomplishments of the National Cancer Screening Program for gastric cancer in Korea, its effectiveness remains an issue. Efficiency and cost-effectiveness analysis will be needed for successful progression. No significant financial relationships to disclose.
Genomic characterization of primary and metastatic prostate cancer (PC) using a targeted next-generation sequencing assay.
Authors: Wassim Abida, Ryan Brennan, Joshua Armenia, Kristen Rebecca Curtis, Anuradha Gopalan, Maria E. Arcila, Daniel Costin Danila, Dana E. Rathkopf, Michael J. Morris, Susan F. Slovin, David B. Solit, David Michael Hyman, Jeremy C. Durack, Stephen Barnett Solomon, Victor E. Reuter, Barry S. Taylor, Michael F. Berger, Nikolaus Schultz, Howard I. Scher
Journal: Journal of Clinical Oncology (2016)

254 Background: Genomic alterations in PC have been described across the disease continuum, creating opportunities for selective clinical trial enrollment of patients (pts) with high-risk or metastatic disease based on their tumor profile. MSK-IMPACT is an exon capture-based sequencing assay performed in a CLIA-certified laboratory that targets 410 cancer-associated genes, many of which are potential drug targets. We assessed mutations and copy number alterations (CNAs) in primary and metastatic samples from untreated, hormone-treated and castration resistant pts. Methods: PC pts were enrolled on an IRB-approved protocol for tumor genomic profiling. Fixed tumor and matched germline samples were subjected to DNA sequencing analysis using MSK-IMPACT for the identification of somatic mutations and CNAs. Results: 315 samples from 271 pts were successfully sequenced (Table). Overall success rate was 80% (67% for bone). 14 tumors were pathologically classified as neuroendocrine or had neuroendocrine features. 23% of patients had tumor somatic alterations in DNA repair genes (BRCA2, BRCA1, ATM, FANCA and CDK12). Additional alterations were observed in PI3K, MAPK and Wnt-βCatenin pathway genes. Common alterations in the metastatic tumors include TP53 deletion/mutation (42%), AR amplification/mutation (38%), PTEN deletion/mutation (27%), RB1 deletion/mutation (20%), BRCA2 deletion/mutation (11%), FOXA1 mutation (11%) and SPOP mutation (4%). Among metastatic samples, tumors from pts with castration-resistant disease had higher CNA burden when compared to tumors from non-castration-resistant pts (0.31 vs. 0.19 fraction genome altered, p &lt; 0.05, unpaired t-test), as well as higher rates of AR amplification/mutation (49% vs. 3%, p &lt; 0.01, Fisher’s exact test). Conclusions: Genomic profiling of primary and metastatic prostate tumors is feasible with the clinical MSK-IMPACT sequencing assay and has identified actionable alterations in &gt; 40% of patients. This is allowing for selective trial enrollment and further investigation of PC genomics. [Table: see text]
Gastric cancer prevention and early detection program for an at-risk population: A prospective study of the Korean American community.
Authors: Yanghee Woo, Garrick Trapp, Jae Geun Hyun, Chul Soo Hyun, Lu Zen Katherine, Tamas Gonda, Paul Eliezer Oberstein, John A. Chabot, Timothy C. Wang
Journal: Journal of Clinical Oncology (2015)

42 Background: Gastric cancer development is multifactorial with varying incidence rates. People of Korean heritage have the highest rate of gastric cancer in the world and among Americans. While this gastric cancer disparity is well known, an evaluation of the population-specific risk factors and the effectiveness of selective screening in the Korean American communities have not been studied. Methods: Korean Americans living in Northern New Jersey over 40 years of age without a known history of gastric cancer were eligible to participate in this prospective study. Each participant received a 30-minute one-to-one consultation with a gastric cancer surgeon, given a 44-item questionnaire, and underwent an upper endoscopy with biopsies. The consultation included assessment for the presence of relevant history, symptoms, and signs. The questionnaire addressed patient-specific demographic, epidemiologic, and cultural information. Two gastroenterologists blinded to the consultation and questionnaire results performed the upper endoscopies. Results: Between September 2013 and September 2014, one hundred participants enrolled in our study. All participants denied the presence of alarm symptoms, such as acute weight loss, melena or persistent vomiting. Risk factors, including prior H. pylori infection (25%), family history of gastric cancer (15%), cigarette smoking (16%), and daily intake of salty and pickled foods (87%) were present. On upper endoscopy, 18% of the participants were found to have “moderate to severe H. pylori associated chronic active gastritis." Other endoscopic findings were mild gastritis (61%), severe erosive gastritis (4%), polyps (4%), and metaplasia (21%). Only 4 patients had normal mucosal pathology. Gastric dysplasia or cancer has not yet been identified. Conclusions: Korean Americans have high rates of modifiable risk factors for developing gastric cancer. Novel population-specific gastric cancer prevention and early detection strategies should be designed to eliminate gastric cancer from the Korean American Community.
Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Call to Action
Authors: Fernando Bril, Kenneth Cusi
Journal: Diabetes Care (2017)

Traditionally a disease of hepatologists, nonalcoholic fatty liver disease (NAFLD) has recently become a major concern for a broad spectrum of health care providers. Endocrinologists and those caring for patients with type 2 diabetes mellitus (T2DM) are at center stage, as T2DM appears to worsen the course of NAFLD and the liver disease makes diabetes management more challenging. However, the nature of this relationship remains incompletely understood. Although the increasing prevalence of NAFLD is frequently attributed to the epidemic of obesity and is often oversimplified as the “hepatic manifestation of the metabolic syndrome,” it is a much more complex disease process that may also be observed in nonobese individuals and in patients without clinical manifestations of the metabolic syndrome. It carries both metabolic and liver-specific complications that make its approach unique among medical conditions. Diabetes appears to promote the development of nonalcoholic steatohepatitis (NASH), the more severe form of the disease, and increases the risk of cirrhosis and hepatocellular carcinoma. Patients and physicians face many uncertainties, including fragmented information on the natural history of the disease, challenges in the diagnosis of NASH, and few pharmacological agents with proven efficacy. However, recent advances in diagnosis and treatment, combined with the risk of serious consequences from inaction, call for health care providers to be more proactive in the management of patients with T2DM and NASH.
Radiologic response (RR) by MRI in patients (pts) with muscle-invasive urothelial cancer (MIUC) undergoing neoadjuvant chemotherapy.
Authors: Angela Q. Qu, Toni K. Choueiri, Susanna J. Jacobus, Jonathan E. Rosenberg, Nikhil H. Ramaiya, Katherine Maragaret Krajewski
Journal: Journal of Clinical Oncology (2013)

283 Background: Standard response criteria do not always provide a meaningful assessment of treatment benefit in pts with MIUC. We examined the utility of contrast-enhanced imaging in predicting disease free survival (DFS) in MIUC pts, and its correlation with pathological downstaging on radical cystectomy (RC) specimen. Methods: Baseline and post chemotherapy imaging, primarily gadolinium-enhanced pelvic MRI, from pts enrolled on a phase II prospective study of neoadjuvant cisplatin-based chemotherapy were reviewed by 2 oncoradiologists (NR, KK). DFS was defined as time from RC to evidence of disease progression or death. Qualitative (QL) RR was defined by at least moderate decrease in the primary tumor and lymph nodes after chemotherapy, with visually decreased primary tumor bulk by at least half, normalization of node size, and delayed enhancement of residual tumor and nodes. Quantitative (QN) RR was assessed according to anatomic TNM downstaging per AJCC staging criteria 7.0. Fisher’s exact test was used to compare RR with pathological dowstaging. DFS distributions within RR subgroups were estimated with the Kaplan-Meier method and compared using the logrank test. Results: All 39 pts from the original study were included in this analysis. At baseline, 42% of pts had cT2 disease, 42% had cT3, 16% had cT4, and 45% had N1 disease. 91% of pts had bladder primary, and 84% of pts were assessed by MRI. Results showed QL RR in 64% (90% CI 50-77) of pts, QN RR in 61% (90% CI 47-75), and ≤pT1N0M0 in 49% (90% CI 35-63). While there was no association between pathological downstaging and QN RR, there was a modest association with QL RR (p=0.096). 60% of pts with QL RR achieved ≤pT1N0M0 and 71% of pts without QL RR were &gt;pT2. QL RR was also a strong predictor of DFS with an 18-month DFS advantage of 83% (95% CI 56-94) among responders vs. 32% (95% CI 6-63) in non-responders (p=0.036). Conclusions: QL RR post neoadjuvant therapy is modestly associated with pathological downstaging in pts with MIUC and strongly predictive of DFS. Results suggest post-chemotherapy, pre-operative imaging may be a valuable prognostic tool. Confirmation in other UC populations and treatment settings should be explored.
Does focal high-intensity focused ultrasound have a role in treating localized prostate cancer in the elderly?
Authors: Stephanie Guillaumier, Neil McCartan, Louise Dickinson, Yomi Fatola, Alex Freeman, Richard Hindley, Mark Emberton, Hashim Uddin Ahmed
Journal: Journal of Clinical Oncology (2015)

133 Background: There is an increase in the ageing population leading a significant proportion of men diagnosed with prostate cancer being over 75 years of age. Misconceptions regarding treating the elderly are still rife. The body of evidence that has recently emerged shows that this cohort of patients should be offered the same curative therapies as their counterparts. This study looks at the feasibility of focal HIFU in treating localised prostate cancer in those aged over 75 years of age. Methods: Our independent academic HIFU registry incorporates a total of 60 patients who were diagnosed with low, intermediate and high risk localized adenocarcinoma of the prostate, stage T2a-T3aN0M0 and treated with focal HIFU using Sonablate500, between 2004 and 2014. We divided the patient cohort into those that were treated within the remit of a trial protocol, and those that were not. Results: As biochemical failure is difficult to define, we looked at the medium-term transition rates to redo HIFU, local salvage and systemic therapy. 12% required re-treatment with HIFU. 8% transitioned into local salvage or systemic therapy of which 1 patient had radiotherapy and 4 were subsequently treated with androgen deprivation therapy). The table below outlines the complication rates associated with focal HIFU. Conclusions: Focal HIFU has been shown to be both feasible and effective in the elderly population. It is a safe modality of treatment to use in this patient cohort with a low complication profile. Long-term studies are however necessary. [Table: see text]
Do bisphosphonates increase esophageal cancer risk? A meta-analysis.
Authors: I. C. Ditah, S. Janarthanan, N. Tageja
Journal: Journal of Clinical Oncology (2011)

31 Background: Oral bisphosphonates are known to cause severe esophagitis in some users. This has lead to some authors speculating that they may also increase the risk of esophageal cancer. However, studies investigating the association have yielded inconsistent results. The aim of this work is to summarize available data on the magnitude and direction of the association in a meta-analysis. Methods: A standardized search was independently conducted by two investigators from January 1990 through September 2010 on Medline and PubMed. Identified articles that met the exposure and outcome definition were manually reviewed for any additional references. Only full articles that provided risk estimates for the association were eligible for inclusion. The most adjusted risk estimates were abstracted independently by the two authors and synthesized using the random-effects model. A stratified analysis by study design has also been done. All studies were evaluated for publication bias before analysis. Results: Five studies, three case-controls and two cohort studies were eligible for analysis. The combined risk estimate for esophageal cancer was 0.86 (95% CI: 0.62, 1.09). This result remained consistently nonsignificant among the case control studies with a risk estimate of 1.26 (95% CI: 0.94, 1.57). However, there was a significant decrease in the risk of esophageal cancer among the cohort studies with a risk ratio of 0.35 (95% CI: 0.00, 0.71). There was no heterogeneity among the studies by study design. No evidence of publication bias was found, even by study design. Conclusions: This meta-analysis shows that the evidence in support of an association between bisphosphonates and esophageal cancer is lacking. Large studies with appropriate comparison groups, adequate follow-up, robust characterization of the exposure and information on potential confounders are warranted to determine whether bisphosphonates increase esophageal cancer risk. No significant financial relationships to disclose.
Referral patterns and characteristics of uninsured versus insured patients referred to the outpatient supportive care center (SCC) at a comprehensive cancer center.
Authors: Ahsan Azhar, Sriram Yennu, Aashraya Ramu, Haibo Zhang, Ali Haider, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

116 Background: Multiple barriers exist in providing quality palliative care to low-income patients with cancer. Such disparities may negatively influence effective management of symptoms including pain. Our objective was to compare referral patterns and characteristics (level of symptom distress) of uninsured vs insured patients. Methods: We reviewed randomly selected charts of 100 Indigent (IND) and 100 Medicaid (MC) patients and compared them with a random sample of 300 patients with insurance (INS) referred during the same time period (1/2010 to 12/2014) to our SCC. Data was collected for date of registration at the cancer center, diagnosis of Advanced Cancer (ACD), first visit to the SCC (PC1), symptom assessment (Edmonton Symptom Assessment Scale-ESAS) at PC1. We excluded self-pay patients. Results: Results for IND, MC and INS (n = 481) respectively are as follows: Mean (SD) Age in yrs. was 50 (12), 48 (11) and 63 (13); p &lt; 0.001. Percentage of non-white was 44%, 51% and 19.5%; p &lt; 0.001. Percentage of unmarried patients was 64%, 68% and 33%; p &lt; 0.001. Mean (SD) ESAS score at PC1 for pain was 5.6 (3.2), 6.7 (2.5), 4.9 (3.2); p &lt; 0.001. Percentage of patients on opioids upon referral was 86%, 62%, and 54%; p &lt; 0.001. Mean (SD) for referral time in months from ACD to PC1 was 8.7 (SD 10.4), 12.3 (SD 18.1) and 12 (SD 19.9) p = 0.31; for no. of encounters with SC per month were 0.46 (0.45), 0.41 (0.46) and 0.3 (0.55); p = 0.01; for survival in months (PC1 to last contact) was 6.4 (5.8), 5.6 (6.4) &amp; 6 (7.22) p = 0.77. Conclusions: Uninsured patients had significantly higher levels of pain, were more frequently on opioids, younger, non-white and not married. They also required a larger number of SCC encounters. Insurance status did not impact timing of SCC referral or SCC follow ups at our cancer center.