tbuckley/cabot-search huggingface dataset:
Does supplemental interphase FISH analysis to standard chromosom analysis improve the detection of myelodysplastic syndrome?
Authors: Benjamin Joseph Lang, Carol Minyon, Neelam Dhiman, Saurabh Gupta, Stella Wenceslao, Milena Vuica-Ross, Robin Dobson
Journal: Journal of Clinical Oncology (2017)

7060 Background: Our objective was to evaluate whether the addition of interphase FISH analysis to standard chromosome analysis (CA) improves the detection of chromosomal abnormalities in patients with work up for myelodysplastic syndromes (MDS), acute myeloid leukemia, and myelodysplastic/myeloproliferative disorders and thereby increases diagnostic and prognostic information. We performed a retrospective data review of all MDS orders between January and September 2015 at our institution and evaluated concurrent tests for discrepancies between CA and FISH results. Our aim was to evaluate best practices with regard to diagnostic test utilization, specifically to assess the diagnostic and prognostic value of FISH in addition to CA for patients with potential and known MDS. Methods: Retrospective data review of concurrent test orders of CA and myelodysplastic FISH panel were reviewed. The myelodysplastic FISH panel consists of screening for monosomy 5/deletion 5q, monosomy 7/deletion 7q, CEP7, trisomy 8, and D20S108 (20q12). The results of CA and FISH results were analyzed using a chi-square test to evaluate statistical significance. Results: A total of 1121 samples were queried, of which 55 were excluded due to inability to perform CA and limited diagnostic value of accompanying standalone FISH data on the 4 markers tested in this study. Analysis of the eligible 1066 samples showed that the standalone CA had significantly higher sensitivity (p &lt; 0.0001) in detecting abnormal cases (N = 247, 23.17%) as compared to standalone FISH analysis (N = 180, 16.89%). Overall, 173 (16.23%) cases were determined to be abnormal by both methods. CA correctly interpreted 1059 of 1066 cases (99.34%).Only 7 samples were interpreted as normal by CA but were found to be abnormal by FISH. This results in overall 0.66% (2.76% of the abnormal cases) of abnormalities that would have been missed by CA only. Conclusions: These findings suggest that FISH studies with 4 markers used in this study provide limited additional utility in cases with a complete CA.
Chronic heart failure in adults: summary of updated NICE guidance
Authors: Jacqui Real, Emma Cowles, Anthony S Wierzbicki
Journal: BMJ (2018)

### What you need to know

### What’s new in this guidance

The prevalence of heart failure is increasing because of an ageing population and improved survival of chronic diseases that contribute to heart failure. Heart failure includes reduced ejection fraction ( 50%) disease. The National Institute for Health and Care Excellence (NICE) guideline on chronic heart failure was last updated in 2010. Since then, further evidence on novel and existing therapies, for example mineralocorticoid receptor antagonists (MRAs), has emerged. New research has also been published on diagnosing heart failure and approaches to heart failure care, including monitoring, rehabilitation, and the composition of the multidisciplinary team.

This article summarises …
TCT-565 A Comparison of Clopidogrel Versus Newer P2Y12 Antagonists for Percutaneous Coronary Intervention in Patients with Out-of-Hospital Cardiac Arrest Managed with Therapeutic Hypothermia: A Meta-analysis
Authors: Ayman Elbadawi, Islam Elgendy, Ahmed Mohamed, Kirolos Barssoum, Gbolahan Ogunbayo, khaled Ziada
Journal: Journal of the American College of Cardiology (2018)
Disparities in AIDS-related Kaposi sarcoma incidence and survival.
Authors: Firas El Chaer, E. Susan Amirian, Christine Hartman, Elizabeth Chiao
Journal: Journal of Clinical Oncology (2016)

e18072 Background: With advances in combined antiretroviral therapy (ART), Kaposi’s sarcoma (KS) incidence has decreased over the past decade. Geographical and racial disparities may contribute to variation in the incidence and outcomes of multiple cancers in the U.S., including KS. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed KS incidence and survival by race and geographical region in the ART era. Methods: Incident cases of KS in males from 2000 to 2012 were obtained from 17 SEER population-based cancer registries. Only KS cases < age 55 at the time of diagnosis were included in order to exclude cases of classic KS. Both overall and age-standardized KS incidence rates were calculated and stratified by race (White, Black and other), and geographic region (West, South, Northeast and Midwest). Joinpoint analyses were conducted to evaluate incidence trends and multivariable Cox proportional hazards regression models were used to calculate adjusted hazard ratios (aHR) for overall and cause-specific mortality. Results: There were 4,455 KS patients identified; 64% were White and the median age at diagnosis was 40. Among White men, the annual percent change (APC) for KS incidence significantly declined from 2000-2012 with a joinpoint in 2008 demonstrating a larger decline (2000-2008 APC: -3.3, p < 0.05, 2008-20012 APC -7.6, p < 0.05). The APC for Black men significantly declined until a joinpoint in 2009 demonstrating a non-significant increase (2000-2009 APC -3.9, p < 0.05, 2000-2012 APC +8.63, p > 0.05). Among Black men in the South the APC significantly increased throughout the entire period from 2000-2012 (+3.5, p < 0.05). Black men had higher aHRs of overall (aHR 1.46, 95% CI: 1.30-1.64) and cancer-specific (aHR 1.51, 95% CI: 1.32-1.72) mortality compared to other races. Conclusions: Although the incidence of KS significantly decreased among White men in the U.S., it has recently increased among Black men. In particular, among Black men in the South, the incidence significantly increased throughout the study period. Black men also had an increased risk of cancer-specific and overall mortality compared to all other races. Further research is required to identify the factors contributing to these disparities.
Results of a phase II randomized study evaluating the potential benefit of a postoperative intraperitoneal immunotherapy after resection of peritoneal metastases from gastric carcinoma metastases (IIPOP- NCT01784900).
Authors: Diane Goere, Olivier Glehen, Christophe Mariette, Anne Auperin, Dominique Elias
Journal: Journal of Clinical Oncology (2017)

4064 Background: Prognosis of patients with peritoneal extension from gastric carcinoma remains poor. The aim of this multicentre, open-label, phase 2 randomized study was to analyze the potential survival benefit of an immediate postoperative intraperitoneal immunotherapy using a bi-specific (anti-EpCAM, anti-CD3), trifonctional agent named catumaxomab. Methods: Patients with limited synchronous carcinomatosis from gastric carcinoma (Peritoneal cancer index (PCI) ≤ 12), were treated after complete resection (gastrectomy plus all peritoneal deposits), by an intraperitoneal infusion of catumaxomab during 5 days. Patients were randomized between 2 arms according to the total doses administered of catumaxomab (100µg vs 140µg). The first end-point was the 2-year overall survival (OS). Forty randomized patients were required (20 in each arm), considering that a 2-year OS rate ≤ 30% would be considered as unacceptable, and ≥ 55%, a promising survival rate. The study was stopped prematurely due to the manufacturing stop of the catumaxomab. Results: Between March 2013 and September 2014, 26 patients were included in the study; among them, 11 were randomized, with a median PCI of 9 [1-12]. Seven patients received the whole planned treatment of catumaxomab; in the remaining 4 patients, interruptions were related to postoperative complications. One patient died postoperatively of multiorgan failure and grade 3-5 complications occurred in all the patients, without difference between the 2 groups. At the end of the follow-up, 3 were alive (25, 30, 36 months). The median OS was 19 months, and the 1 and 2- year OS rates were 63.6% and 36.4% respectively. Conclusions: This study has to be stopped prematurely; however, encouraging results regarding overall survival were observed. Intraperitoneal immunotherapy represents an innovative and promising treatment in patients with peritoneal metastases, considering the poor response to systemic chemotherapy and the “immunocompetence” of the peritoneum. The evaluation of a potential benefit of a local immunotherapy has to be pursued. Clinical trial information: NCT01784900.
External validation of a prognostic score in patients (pts) with high-grade gastrointestinal neuroendocrine carcinomas (GI-NECs).
Authors: Angela Lamarca, Thomas Walter, Marianne E. Pavel, Ivan Borbath, Patricia Freis, Barbara Nuñez, Alexa Childs, Mairead G McNamara, Richard Hubner, Rocio Garcia-Carbonero, Tim Meyer, Jorge Barriuso, Juan W. Valle
Journal: Journal of Clinical Oncology (2016)

4089 Background: Prognostic markers for risk-stratification of pts with GI-NECs are lacking. We aimed to externally validate our previously-designed prognostic score (Training Cohort [TC]) derived from 109 pts (Lamarca et al, ASCO 2015). The score included five variables (presence of liver metastases, alkaline phosphatase (ALK), lactate dehydrogenase (LDH), ECOG performance status (PS) and Ki67) and was able to prognosticate overall survival (OS). Methods: Pts diagnosed with GI-NECs were identified retrospectively from 5 European centres (April’00 – Dec’15); pts with data for all 5 variables identified from the TC were eligible for the Validation Cohort (VC). To externally validate the score (power: 80% and two-tailed α-error: 0.05), a minimum of 82 pts was required. The primary end-point was OS; Cox regression and Kaplan-Meier estimates were applied; and univariate/multivariable analyses performed. Results: Of 209 pts identified; 178 were eligible. The median follow-up time was 11.8 months (range 0.2-167.4); 121 pts (68%) had died at time of the analysis. Median age: 58.7 yrs (range 22.2-85.5); 62% were male, 81% metastatic, 18% foregut, 3% midgut, 41% pancreas, 17% hindgut and 21% unknown primary. The median Ki67 was 55% (21-100), ECOG PS 0: 35%, 1: 46%; 66% received chemotherapy. The baseline median ALK and LDH were 133 IU/l (30-2363) and 347 IU/l (107-3786), respectively; there were significant differences (p < 0.05) in Ki67 and LDH between TC and VC. The estimated median OS was 16.1 months (95%CI 14.6-19.4). Both score (p < 0.001) and stage (p = 0.002) were significant in the univariate analysis. On multivariable analysis (adjusted for stage), the score was prognostic for OS (HR 1.4, 95%CI 1.1-1.6; p = 0.001) validating previous TC results. The score classified pts into different groups with incremental risk of death: groups A/B (0-2 points; 117 pts (66%); median OS 20.7 months [95%CI 17.2-28.1]) and C/D (3-6 points; 61 pts (34%); median OS 8.1 months [95%CI 4.8-9.4]). Conclusions: This international external series validates the capability of our prognostic score to predict OS in pts with GI-NECs; these results may inform clinical decision-making and trial design.
Impact of provider volume on outcomes of patients with Hodgkin lymphoma.
Authors: Catherine Gorman Ireland, Muhammad Mudassir Mirza, Alexandria Tran, Jason Claud Chandler, Monika Metzger, Michael Gary Martin
Journal: Journal of Clinical Oncology (2016)

e18203 Background: We previously reported that low volume centers have higher inpatient mortality (OR 3.26) than high-volume centers ( > 3 inpatient chemotherapy (CT)/month (m)) when delivering CT for patients (pts) with AML (Giri Blood 2015). We hypothesized that an outcome-volume relationship would also exist for high volume (HVP) versus low volume providers (LVP) caring for pts with Hodgkin lymphoma (HL). Methods: After obtaining IRB approval we performed a retrospective chart review of all pts treated with ABVD for HL at the West Cancer Center from Jan 2010 to June 2015. Pts were divided into HVP (provider prescribing > 3 CT per m) and LVP ( < 3 CT per m). EFS was defined as death from any cause or treatment failure, OS as death from any cause. All analyses were performed using Microsoft Excel and GraphPad Prism. Results: 93 pts received at least one dose of CT. 21 pts were cared for by a HVP and 72 by LVP (range 1-9 pts) delivering a mean of 3.3 and 0.8 doses of CT per month, respectively. While there were more females in the HVP versus LVP (56% vs. 29%) there were no statistical differences in age, IPS (which includes gender) or stage distribution between the HVP and LVP groups. Unfavorable risk ( ≥ 2B) pts (HVP 62% vs. LVP 57%, p = 0.803) were also well balanced. HVP were less likely to cause total dose delays (OR 0.32, CI 0.1584-0.6511, p = 0.0007) and to hold doses for afebrile neutropenia (ANP) (OR 0.05, CI 0.0032-0.8509, p = 0.0006). The toxic death rate was not statistically lower in the HVP group (OR 0.18, CI 0.010-3.189, p = 0.1913). HVP delivered significantly fewer prophylactic growth factors (0% of doses vs. 42%, OR 0.00, CI < 0.000-0.060, p < 0.0001). Both EFS (HR 6.68, CI 1.103-7.626, p = 0.0321) and OS (HR 3.68, CI 1.110-12.22, p = 0.032) were significantly inferior in the LVP group. Conclusions: Pts with HL treated by LVP may have worse outcomes compared to patients treated by HVP similar to what we demonstrated for pts with AML in LV centers. This may be explained in part by lack of familiarity with the NCCN guidelines that lead to treatment delays for ANP and consequently lower dose-intensity.
Toxicity and efficacy of concomitant chemoradiotherapy (CCRT) in elderly patients with oropharyngeal carcinoma (OPC) in the intensity modulated radiotherapy (IMRT) era.
Authors: Zachary Stephan Zumsteg, Benjamin H. Lok, Allen S. Ho, Nadeem Riaz, Stephen L. Shiao, Sean Matthew McBride, C. Jillian Tsai, Shrujal S. Baxi, Eric Jeffrey Sherman, Nancy Y. Lee
Journal: Journal of Clinical Oncology (2016)

10050 Background: CCRT has been shown to improve survival in OPC compared to radiation alone, but has demonstrated no survival benefit in patients > 70 years old, possibly due to toxicity. However, the development of IMRT and the increased prevalence of HPV-associated OPC have radically altered the treatment and epidemiology of OPC. We aimed to study the tolerability of concomitant CCRT for elderly OPC patients in the modern era. Methods: Records from 74 consecutive patients with stage III-IVB OPC ≥ 70 undergoing definitive CCRT from 2002 to 2013 at a single institution were reviewed. Patients were stratified according to systemic therapy received, including cisplatin (CDDP), carboplatin with either 5-FU or paclitaxel (CARB), or cetuximab. Results: Median follow-up was 44 months. The median age was 74.5 years, with significantly older patients receiving cetuximab (P = 0.004). There was no difference in KPS (P = 0.11) or Charlson comorbidity index (P = 0.79). In total, 28, 20, and 26 patients received CCRT with CDDP, CARB, and cetuximab, respectively, and radiation was completed 100%, 95%, and 96% of these patients (P = 0.52). Radiation interruptions longer than 1 day were needed in 4% (CDDP), 20% (CARB), and 15% (cetuximab, P = 0.19). Unplanned hospitalizations during CCRT occurred in 29%, 55%, and 58% of patients receiving CDDP, CARB, and cetuximab, respectively (P = 0.03). There were two treatment-related deaths, both in patients treated with cetuximab. At 5 years, locoregional control was achieved in 100%, 88%, and 60% (P < 0.001) and overall survival was 97%, 69%, and 47% (P = 0.04) with CDDP, CARB, and cetuximab, respectively. p16 staining was performed in 28 patients, and 21 of these were positive, including 11 of 13 tested CDDP patients. Conclusions: Toxicity from CCRT remains a significant challenge for elderly patients with OPC. We found no evidence this was mitigated by cetuximab. Nevertheless, a subset of elderly patients, predominantly with p16-positive tumors, appear to tolerate CDDP-based treatment with acceptable toxicity and excellent outcomes. Further identification of this subgroup is crucial to personalize therapy for elderly OPC patients.
Variety of hormones produced by rare neuroendocrine tumors (NETs): Examination of epidemiology and prognostic factors for NETs in Italy.
Authors: Silvia Fanello, Lucia Mangone, Claudio Sacchettini, Massimo Vicentini, Carmine Pinto
Journal: Journal of Clinical Oncology (2016)

e15656 Background: Neuroendocrine tumors (NETs) are considered rare tumors and can produce a variety of hormones. In this study, we examined the epidemiology and prognostic factors for NETs, in Italy. Methods: The Italian Association of Cancer Registries (AIRTUM) were researched to identify NETs: 38/39 cancer registries participated for the period 1976-2010. Malignant infiltrating tumors were included with the following morphology codes: 8150-8157, 8240-8246 and 8249. Results: We identified 9,707 patients with NETs: 55% males; 61% in the age 50-74 years, 17.5% under 50 years and 21.5 % in the 75+. We observed a significant increase in the reported annual age-adjusted incidence from 1976 (0.7/100,000) to 2010 (5.3/100,000). The highest rate was recorded in northern Italy (Milan 5.8/100,000), the lowest in southern Italy (Ragusa 0,81/100,000). The distribution of the tumor site was: lung 32.8%, small intestine 14.4%, colon 10.7%, stomach 8.8%, rectum 4.7%, breast 1.4%, other sites 20.3% and in 6.9% the primary site was unknown. Overall we found 2033 second tumors: 29 NETs and 2004 other sites: these were divided into before (1,360, 68%), and after (644, 22%) diagnosis of NETs. Among after diagnosis, we separate the synchronous within two months of diagnosis (78 cases, mainly lung 19% and colon 14%) by metachronous if diagnosed after two months of diagnosis (566 cases, mainly skin 18%, prostate12,5%, colon 8,5%, lung and bladder). Conclusions: We observed a increased reported incidence of NETs over time, suggesting that NETs are more prevalent than previously reported. Clinicians need to be become familiar with the natural history and patterns of disease progression, which are characteristics of these tumors. The association with second cancers should better direct the follow- up of patients with NETs .
CABOPRE: Phase II study of cabozantinib prior to cytoreductive nephrectomy (CN) in locally advanced and/or metastatic renal cell carcinoma (mRCC).
Authors: Guillermo de Velasco, Borja GonzÃ¡lez, Teresa Alonso, Alvaro Pinto, Juan Francisco Rodriguez-Moreno, Juan Manuel Sepúlveda, Jose Carlos Villa, Natalia Miranda, Félix Guerrero, Daniel E. Castellano
Journal: Journal of Clinical Oncology (2018)

TPS4603 Background: Cabozantinib is a small molecule tyrosine kinase inhibitor (TKI) of VEGFR2, MET and AXL that has shown a statistically significant improvement for mRCC patients in all three endpoints of clinical efficacy (objective response rate [ORR], progression free survival [PFS], and overall survival [OS]) in a phase III randomized trial compared to everolimus, as well as a significant clinical benefit in PFS and ORR over sunitinib as first-line therapy in patients with IMDC intermediate- or poor-risk. Although no robust evidence is available, CN remains as the standard of care in patients who will be treated with VEGF TKI. CABOPRE is a multicenter, non-randomized, uncontrolled phase II trial that evaluates the efficacy and safety of cabozantinib as perioperative therapy in patients with advanced RCC who are candidates for CN. Methods: Eligible patients are aged ≥ 18 years, mRCC with a component of clear cell, suitable for CN with acceptable risk for surgery, PS 0-1, no prior systemic therapy. Cabozantinib 60mg PO QD is administered for 12 weeks before CN (cabozantinib is stopped at least 72 hours before CN). A 14-day treatment break is required after surgery and then cabozantinib is continued until progression disease or toxicity. The primary endpoint is ORR by RECIST 1.1 at 12 weeks after initiation of therapy. Secondary endpoints include PFS at 12 months and OS. Based on Simon two-stage minimax design (p0 = 0.25, p1 = 0.45, alpha = 0.05, power = 90%) up to 50 patients will be recruited consecutively. Tumor biopsies and peripheral blood will be collected to assess changes in tumor microenvironment at 3 different time points: 1) at baseline, prior to initiation of cabozantinib, 2) before cytoreductive nephrectomy 3) at disease progression. Biomarkers study will include, but not limited to the expression of c-MET and AXL in exosomes derived from tumor cells.
Vasodilators in VSDs.
Authors: R Macri, S Redaelli
Journal: Circulation (1977)

Dr. Hollander and his associates undoubtedly demonstrated that intravenous hydralazine produces beneficial hemodynamic effects in hypertensive patients with evidence of congestive heart failure and I apologize for our oversight.The purpose of our study, however, was to evaluate the hemodynamic effects of long-term use of oral hydralazine in normotensive patients with chronic refractory heart failurea different subset of patients than these studies by Dr.
The impact of kidney function on the efficacy and safety of pazopanib in metastatic renal cell carcinoma (mRCC) patients: CORE-URO-01 study.
Authors: Maria Giuseppa Vitale, Cristina Masini, Giuseppe Procopio, Ugo De Giorgi, Sebastiano Buti, Sabrina Rossetti, Roberto Iacovelli, Claudia Mucciarini, Laura Cosmai, Francesca Vignani, Giuseppe Prati, Sarah Scagliarini, Annalisa Berselli, Carmine Pinto
Journal: Journal of Clinical Oncology (2017)

e16063 Background: Pazopanibhas been approved for treatment of patients (pts) with mRCC based on the prospective randomized trial that enrolled only pts with adequate renal parameters. There are no data on the toxicity profile and efficacy of pazopanib in pts with renal insufficiency (RI).The aim of this study is to investigate the effect of renal function on treatment outcomes in pts treated with pazopanib for mRCC. Methods: We retrospectively analyzed the data of the mRCC pts treated with pazopanib with respect to renal function in eleven Italian institutions from January 2010 to June 2016. Baseline glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula at the time of therapy initiation. Pts with MDRD &lt; 60 mL/min/1.73 m 2 (group 1) were compared with pts with MDRD ≥60 mL/min/1.73 m 2 (group 2) in terms of response rates, progression free survival (PFS), overall survival (OS) and side effects. Results: One hundred and twenty-ninepts with mRCC were included in this study: 70 pts in group 1 and 59 pts in group 2. 67% of pts were male, median age was 66 years (34-83) and median CrCl was 49 ml/min (6.3-59.5) in group 1. In group 2, 64% of pts were male, median age was 65 years (38-80), and median CrCl was 64 ml/min (58.1-137.1) Pts with MDRD &lt; 60 were more likely to have had a previous nephrectomy (84.3% vs 79.7%). No difference between the 2 groups was observed in terms of outcomes: PFS was 9.6 months (0.6–56.9) and 9.0 months (0.4–60.1), OS was 16.1 months (1.3–56.9) and 17.0 months (1.2–60.1), for MDRD &lt; 60 group and MDRD ≥60 respectively. The disease control rate was 85.8% in group 1, and 72.9% in group 2. About grade 1-2 toxicity, no difference between the 2 groups was reported (67.1% vs 67.8%) while a higher incidence of grade 3-4 toxicity was evident in the group 1 (25.7% vs 18.6%). Conclusions: RI was commonly observed in pts with mRCC. Renal function at therapy initiation does not adversely affect the efficacy and safety of pazopanib. More frequent monitoring of side-effects in patients with RI is recommended.