tbuckley/cabot-search huggingface dataset:
Association of higher health care costs with contralateral prophylactic mastectomy (CPM) within two years of initial surgery attributable to breast reconstruction.
Authors: Mary Chen Schroeder, Yu-Yu Tien, Ingrid Lizarraga, Lillian M. Erdahl, Ronald Weigel, Alexandra Thomas, Sonia L Sugg
Journal: Journal of Clinical Oncology (2016)

1057 Background: Prior estimates of costs associated with CPM have been limited to single institution studies or simulation-based decision models and have failed to take into account costs associated with breast reconstruction (BR), also correlated with CPM. Our study uses actual charges incurred in a population-based dataset to estimate costs for the initial procedures as well as surgical complications and additional (addl) breast procedures for CPM and UM. Methods: Women receiving immediate CPM or UM in 2008-2010 were identified from SPARCS, the state of New York’s all payer data reporting system for inpatient stays and outpatient encounters. Claims submitted within two years of the primary breast surgery were collected. Surgical complications and addl breast procedures were also identified. Summed charges were transformed to costs following published cost-to-charge ratios. Log-linear models were fitted to estimate costs of CPM and UM, controlling for age, race, year, insurance status, BR, and the interaction between extent of mastectomy and BR. Results: In our final cohort of 13,110 women, 11% received CPM. Median total costs were 46% ($7,521.72) higher for CPM than UM (p < .01). Those with CPM were more likely than UM to experience complications (30% v 21%, p < .01) and have addl breast procedures (80% v 45%, p < .01), and thus higher follow up costs. However, BR was not uniformly distributed by extent of surgery, as 93% of CPM and 46% of UM patients received BR (p < .01). When stratified by BR, rates of complications did not differ by CPM or UM, but were much higher for those who underwent BR than those who did not (31% and 12% respectively, p < .01). Controlling for BR and patient characteristics, costs were similar between CPM and UM in terms of complications (p = .27), addl breast procedures (p = .19), and overall follow up (p = .98). Conclusions: Despite lack of survival benefit, a growing number of average-risk women elect CPM, often with BR. In our cohort, the complications, addl breast procedures, and higher follow up costs associated with CPM were driven by BR. These additional costs associated with BR should be considered when evaluating the benefit-cost ratio of CPM.
Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis – A pooled analysis
Authors: Fred Poordad, David R. Nelson, Jordan J. Feld, Michael W. Fried, Heiner Wedemeyer, Lois Larsen, Daniel E. Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R. Foster
Journal: Journal of Hepatology (2017)

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients.
Estimation of Eligibility for Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Associated Costs Based on the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk)
Authors: Salim S. Virani, Julia M. Akeroyd, Vijay Nambi, Paul A. Heidenreich, Pamela B. Morris, Khurram Nasir, Erin D. Michos, Vera A. Bittner, Laura A. Petersen, Christie M. Ballantyne
Journal: Circulation (2017)
Performance of genomic data strategies for cancer precision medicine across distinct contexts and ethnicities.
Authors: Andrea Garofalo, Lynette M. Sholl, Brendan Reardon, Ali Amin-Mansour, Diana Miao, David Liu, Nelly Oliver, Arezou A Ghazani, Stacy W. Gray, Pasi A. Janne, Judy Ellen Garber, Steven Joffe, Neal Ian Lindeman, Levi A. Garraway, Nikhil Wagle, Eliezer Mendel Van Allen
Journal: Journal of Clinical Oncology (2016)

1500 Background: The expanding appeal of clinical tumor profiling has led to many sequencing strategies, ranging from small gene panels to exomes, with or without patient-matched germline data. This diversity of approaches may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling, and emerging immunotherapies that leverage genome-wide data. Methods: We modeled common tumor profiling modalities - large (n = 300 genes) and small (n= 15 or 48 genes) panels - onto clinical whole exomes (WES) from 157 patients with lung or colon adenocarcinoma. We created a tumor-only analysis algorithm to assess germline false positives (variants erroneously called as somatic), impact of patient ethnicity on results, and neoantigen detection. Results: The germline false positive rate with tumor-only large panel sequencing was 14% (144/1012 variants). For patients whose results underwent molecular pathologist review, 50/54 (93%) false positives were correctly interpreted as likely germline events. Using dbSNP, increased germline false positives were observed in tumor-only sequencing of ethnic minorities compared to white patients (p < 0.001; Fisher’s Exact). ExAC (60,706 germline exomes) usage mitigated this disparity (p= 0.53). Large panel mutational load correlated with WES mutational load (r2 = 0.93; p < 0.001), with average nonsynonymous mutation rates of 5.5/Mb and 8.8/Mb in WES and panels, respectively. Neoantigen load correlated (r2 = 0.80; p < 0.001), though WES identified a broader spectrum of neoantigens (ñWES = 38 ± 300; ñpanel = 1 ± 4). Small panels did not predict mutational or neoantigen load. Conclusions: Large tumor-only targeted panels were sufficient for most alteration identification and mutational load prediction if paired with expanded germline analysis strategies and molecular pathologist review. Matched sequencing reduced overall false positive mutation calls, and WES provided the largest number of neoantigens. In the absence of patient-matched germline data, large germline databases are required in analysis workflows to minimize false positive mutation calling and mitigate ethnic disparities.
Sociodemographic factors associated with developing head and neck and esophageal cancers following breast cancer.
Authors: Albina Tyker, Krista Dollar, Matthew Simpson, Eric Adjei Boakye, Mark A Varvares, Nosayaba Osazuwa-Peters
Journal: Journal of Clinical Oncology (2017)

e13063 Background: Breast cancer survivors may develop other primary malignancies due to several factors. However, sociodemographic factors associated with the development of head and neck (HN) and esophageal second primary malignancies (SPMs) following management of primary breast cancer (BC) have not been well studied. This study examined the association between BC patients’ sociodemographic characteristics and the development of an esophageal or HN SPM. Methods: Patients ( n= 505,641) diagnosed with breast cancer between 1973 and 2013 in the Surveillance, Epidemiology, and End Results (SEER) 9 program were used for this analysis. HN SPMs included oral cavity, pharynx, larynx, and sinuses. Cox proportional hazards regression was used to evaluate estimators of survival based on age at diagnosis, race, marital status, treatment type, and year of diagnosis. Results: A total of 284 BC patients developed an esophageal SPM, and 969 developed HN SPM. In the adjusted model, increased age at BC diagnosis was a significant predictor for developing both HN and esophageal SPMs. For every 1-year increase in age at diagnosis, the hazard of developing an esophageal SPM increased (HR: 1.05; 95% CI: 1.04-1.06) and HN SPM increased (HR: 1.02; 95% CI: 1.02 -1.03). Hispanic women had a decreased hazard (HR: 0.63; 95% CI: 0.47-0.85) of developing HN SPM compared to non-Hispanic White women, however there was no significant difference for esophageal SPM. Women that were married had a decreased hazard (HR: 0.70; 95% CI: 0.55-0.90) of developing esophageal SPM compared to unmarried women. Conclusions: Sociodemographic factors may be important in the development of SPMs after treatment for breast cancer. While older women with BC were more likely to develop SPMs of the HN and esophagus, Hispanic breast cancer survivors and married women were less likely to develop SPMs of the HN and esophagus. To optimize survival benefits in the breast cancer population, there is need to further explore these sociodemographic factors associated with developing SPMs.
helicobacter pylori cagA, cagE and BabA2 genotypes in patients with intestinal metaplasia and gastritis
Authors: A Nami, M O'Sullivan, H O'Connor, C O'Morain
Journal: Endoscopy (2006)

Helicobacter pylori (H.pylori) is involved in the multistep process that finally leads to gastric malignancies. The link of genotypes of H.pylori with clinical diseases remains controversial. The aim of the study was to investigate the H.pylori cytotoxin-associated gene (cagA), cagE and blood group antigen-binding adhesin (babA2) in patients with Intestinal Metaplasia (IM) and Gastritis (G) as a control group. A total of 36 gastric biopsy specimens (antrum & corpus) were obtained from patients with IM and G based on histopathology findings. DNA extraction and PCR were used to detect the presence or absence of bacterial virulence genes (cagA, cagE and babA2).
Evolution of RAS testing in colorectal cancer in France, Germany, Italy, Spain and UK (EU5).
Authors: Alec Bruce, Caroline Anger, Chetna Gajperia
Journal: Journal of Clinical Oncology (2015)

e14679 Background: EGFR monoclonal antibodies, cetuximab (cetux) and panitumumab (pani) are treatment choices for colorectal cancer (CRC) patients with KRAS wild type (WT) disease. Despite this, a number of KRAS WT patients fail to respond to these therapies. There has been discussion to expand CRC testing to include NRAS. This study evaluates the trends in RAS testing across the EU5, as identifying the right patients for treatment is paramount in ensuring optimal treatment outcomes. Methods: IMS Oncology Analyzer, an anonymised patient database ( > 57,000 patients annually) collected through a quarterly physician panel survey, from 2009 to 2014, provides data on patterns of cancer care in the European Union across a range of different cancers. Inclusion criteria were metastatic patients diagnosed with CRC who are currently receiving chemotherapy. RAS testing uptake was analyzed from time 0 (Q1 2009 for KRAS and Q4 2013 for NRAS) until 2014. Results: In Q2 2009, 43% (278/646) of patients were tested for KRAS status in EU5. While France, Germany, Italy and Spain had established testing rates between 48-58%, the UK testing rate was 5% (6/116). Over the following years KRAS testing continued to increase at a rate of 3%, these rates differed slightly by market – FR 1.5%, DE 3.0%, IT, 2.2%, ES 2.0%, UK 11.5%. Current testing rates across the EU5 are at 84%. In Q3 2014, 47% (183/386) of KRAS tested patients in EU5 were KRAS mutant (MT). Following the regulatory requirement for NRAS testing for cetuximab, total RAS testing increased from 14% (268/1980) to 44% (228/513) in Q3 2014 at a rate of 37%. As with KRAS, the slowest uptake for total RAS testing was observed in the UK (25% in Q3 2014). In Q3 2014 K/NRAS dual testing identified 11% of KRAS WT patients as NRAS MT. Conclusions: Testing for KRAS mutations is now commonplace across EU5, with over 80% of patients being tested. NRAS testing however is a fairly recent requirement set out by the EMA in Nov 2013. A clear uptake of NRAS testing is observed following this time period and can be expected to become more routine within clinical practice as physicians strive to better personalize cancer treatment management.
The relation between Body Mass Index, molecular subtypes, and histopathological features in breast cancer.
Authors: Suleyman Sahin, Gokmen umut Erdem, Fatih Karatas, Aydin Aytekin, Ali Riza Sever, Kadri Altundag
Journal: Journal of Clinical Oncology (2016)

e13100 Background: Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer (BC). However, there are controversial results regarding the various effects of BMI on BC. This paper aims to investigate the association between BMI at presentation and the histopathological features and molecular subtypes of the tumor in patients with BC. Methods: A total of 3767 BC patients were enrolled in this study. All patients’ BMI at the time of initial diagnosis and tumor demographics were recorded. BMI was stratified into 3 groups as normal-weighted (BMI < 25 kg/ m2), over-weighted (BMI = 25-29.9 kg/ m2) and obese (BMI ≥ 30 kg/ m2). Molecular subtypes were categorized into 4 groups as luminal, HER2/luminal, HER2 over-expressive and triple negative breast cancer (TNBC), according to the ER/PR and HER2 status. Distribution of molecular subtypes, tumor characteristics and overall survival (OS) analysis according to the BMI groups were evaluated Results: Obesity was significantly associated with older ages at presentation when compared to normal and overweight BMI in both premenopausal (P < 0.001) and postmenopausal period (P < 0.001). TNBC was significantly more frequent in premenopausal patients with BMI ≥ 30 kg/ m2 compared to BMI < 30 kg / m2 (P = 0.005). Additionally, premenopausal patients with BMI ≥ 30 kg/ m2 had less common luminal subtype (P = 0.029) and more frequently presented with higher tumor stage (P = 0.012) and tumor grade (P = 0.004) in comparison to patients with BMI < 25 kg / m2. On the other hand, premenopausal patients with BMI < 25 kg / m2 had significantly more ER positive tumors (P < 0.001) compared to their counterparts with BMI ≥ 25 kg/ m2. Premenopausal obese patients with TNBC (P = 0.001) and luminal subtype (P = 0.002) had significantly shorter OS duration compared to overweight counterparts. Conclusions: Our data indicated that BMI at presentation was associated with a decreased incidence for luminal and an increased incidence for TNBC subtype among premenopausal patients. However, this significance was not present in postmenopausal patients. Accordingly, a plausible etiological heterogeneity in BC might play a role among molecular subtypes in every life stages of women.
Risk of uterine cancer in BRCA1 and BRCA2 mutation carriers.
Authors: Yeh Chen Lee, Roger L Milne, Charmaine Smith, Sandra Picken, Stephanie Camm, Sue-Anne McLachlan, Michael Friedlander, John L. Hopper, Kelly-Anne Phillips
Journal: Journal of Clinical Oncology (2016)

1529 Background: The risk of uterine cancer (UC) in BRCA1 or BRCA2 mutation carriers is unclear. Previous studies have generally suggested about a 2-fold increase in risk, with one recent study suggesting a much higher relative risk when analysis was limited to serous UC. We sought to assess whether Australian mutation carriers are at increased risk of developing UC compared to the general population. Methods: Prospective cohort study of Australian BRCA1 and BRCA2 mutation carriers in the kConFab familial breast cancer cohort. Eligible mutation carriers had a uterus present and no previous history of UC at cohort entry. Information on cancer events, epidemiological and lifestyle factors was collected by interview at cohort entry and then every 3 years using a mailed questionnaire. Self-reported cancer events were verified with pathology reports obtained from the treating institutions, and date of surgery and histologic subtype abstracted. Censoring occurred at UC diagnosis, last follow-up or death. Expected UC incidence was determined using population-based data from the Australian Institute of Health and Welfare. The risk of UC in mutation carriers relative to the general population was evaluated by calculating standardized incidence ratios (SIR). Results: 1111 mutation carriers were identified in kConFab, of which 283 were excluded due to hysterectomy (for non-malignant reasons) prior to cohort entry (278), prior history of UC (2) or being a non-resident of Australia (3). The remaining 828 were prospectively followed for a median of 9.0 years. 5 incident cases of UC were reported, compared to 2.04 expected (SIR = 2.45, 95%CI 0.80-5.72, p = 0.11). In 438 BRCA1 mutation carriers, and 390 BRCA2 mutation carriers, 3 and 2 incident cases of UC were reported, respectively compared to 1.04 expected (SIR = 2.87, 95%CI 0.59-8.43, p = 0.18) and 0.99 expected, (SIR = 2.01, 95%CI 0.24-7.30, p = 0.52), respectively. All cases were endometroid subtype. Conclusions: In this study no incident cases of serous UC were reported. Our findings of SIRs of approximately 2 are consistent with those from other reports and do not support routine prophylactic hysterectomy for BRCA1 and BRCA2 mutation carriers. Large collaborative studies are required to definitively address this question.
Effect of interferon-based and -free therapy on early occurrence and recurrence of hepatocellular carcinoma in chronic hepatitis C
Authors: Hiroko Nagata, Mina Nakagawa, Yasuhiro Asahina, Ayako Sato, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Shun Kaneko, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Toshihiko Nouchi, Hideki Sakai, Makoto Tomita, Mamoru Watanabe
Journal: Journal of Hepatology (2017)
The impact of sex, race, and socioeconomic status (SES) on outcomes in 6,870 patients with esophageal cancer.
Authors: Phu N. Tran, Thomas H. Taylor, Samuel Jacob Klempner, Jason A. Zell
Journal: Journal of Clinical Oncology (2016)

1562 Background: Esophageal cancer (EC) claims 15,000 lives annually in the U.S. African-American (AA) race and low SES have been suggested as poor prognostic factors. However, it is not clear to what degree the inferior survival in AAs is due to SES, treatment disparities, tumor biology or other causes. In this population based study, we analyzed the independent effects of race, gender, treatments and SES on overall survival (OS). Methods: Data regarding all EC cases from 2004 to 2010 were obtained from the California Cancer Registry with follow-up through 2012. We conducted descriptive analyses of clinical variables and survival analyses by Kaplan-Meier method and Cox proportional hazards regression. Results: Of the 6870 EC cases examined, 71% (4951) were Caucasians (Cs), 6% (388) African Americans, 14% (959) Hispanics (Hs), and 8% (572) Asians (As). Adenocarcinoma predominated overall (58%) and among Cs (66%) and Hs (56%). SCC predominated among AAs (79%) and As (75%). Compared to Cs, AAs were more likely to be in the lowest SES strata (40.6% vs 11.3%) and were less likely to receive surgery in Stage I-III diseases (23.7% vs 45.1%). AAs presented at similar stage (p 0.79) and were as likely to receive chemotherapy (47 % vs 53% p 0.14) and radiotherapy (49 % vs 48% p 0.77). By univariate analyses, AAs had lower OS vs Cs and this disparity was due to higher mortality risk in AA males vs C males (HR 1.24). After adjustments for stage, grade, multimodal therapies and SES, the mortality risk in AA males did not differ from C males (HR 1.03), with SES and surgery accounting for the largest impact on OS. Conclusions: We observed that AAs had lower OS compared to Cs and the survival differences were mainly accounted by gender differences, SES, and surgery. These data underscore the importance of further health disparity research in EC. Race Cs AAs Hs As Both F M Both F M Both F M Both F M Med OS (95% CI) mons 9 (9-10) 9 (8-10) 10 (9-10) 8 (6-10) 9 (7-12) 7 (6-9) 9 (8-10) 6 (5-9) 9 (8-10) 9 (8-11) 10 (6-12) 9 (8-11) 1 yr OS % 42 41 43 38 42 35 39 32 40 41 42 40 3 yr OS % 19 19 19 18 19 17 18 15 18 22 24 21 5 yr OS % 14 13 14 12 13 11 13 13 13 15 19 14
Salicylates Inhibit Adhesion and Transmigration of T Lymphocytes by Preventing Integrin Activation Induced by Contact With Endothelial Cells
Authors: Roberto Gerli, Cristina Paolucci, Paolo Gresele, Onelia Bistoni, Stefano Fiorucci, Christopher Muscat, Silvia Belia, Alberto Bertotto, Vincenzo Costantini
Journal: Blood (1998)
Reversan, a novel inhibitor of MRP1, increases the therapeutic index of conventional chemotherapeutic agents
Authors: Catherine Burkhart, Jayne Murray, Nadezhda Isachenko, Marina Pajic, Fujiko Watt, Claudia Flemming, Janice Smith, Katerina Gurova, Glenn Marshall, Murray Norris, Andrei Gudkov, Michelle Haber
Journal: Cancer Research (2008)

3242  One of the major causes of treatment failure in human malignancies is intrinsic or acquired multidrug resistance that can be mediated by ABC transporters, such as P-glycoprotein or the multidrug resistance-associated protein (MRP1). MRP1 has been closely linked to poor treatment response in several cancers, most notably neuroblastoma. Using a cell-based readout system, we previously identified the pyrazolopyrimidine, Reversan, as a potent modulator of MRP1-mediated drug resistance both in vitro and in vivo. We have found that not only was Reversan effective in vitro against neuroblastoma, it increased the sensitivity of other drug refractory tumor cells (e.g. colon and renal cell carcinoma) to conventional chemotherapeutic agents that were themselves substrates for MRP1 (e.g. doxorubicin, vincristine and etoposide). Analysis of transporter specificity revealed that Reversan was effective against both MRP1 and P-glycoprotein but not against MRP2-5. In an effort to structurally optimize Reversan for the identification of more potent compounds with superior pharmacological properties, we tested 26 structural analogs of Reversan for their ability to reverse the resistance of MRP1-overexpressing cells to cytotoxic drugs. Twenty of the twenty-six analogs increased the sensitivity of MDCKII-MRP1 cells to vincristine to at least the level observed in the parental cells, which do not overexpress MRP1. However, Reversan remained the most potent pyrazolopyrimidine evaluated. To date, we have determined that Reversan can increase the in vivo efficacy of chemotherapeutic agents (e.g. etoposide) when administered either intraperitoneally or orally in the absence of increased toxicity. In addition, this molecule did not contribute to thrombocytopenia but rather appeared to protect against neutropenia in mice treated with etoposide. Therefore, Reversan represents a new class of non-toxic MRP1 inhibitor that may be clinically useful for the treatment of neuroblastoma and other MRP1-positive tumors by increasing the sensitivity of these drug refractory tumors to conventional chemotherapeutic agents.