tbuckley/cabot-search huggingface dataset:
Efficacy and safety of gemcitabine, oxaliplatin and paclitaxel (GOP) in cisplatin-refractory germ cell tumors in routine care: Registry data from an outcomes research project.
Authors: Christoph Alexander Seidel, Anja Lorch, Annette Dieing, Marcus Hentrich, Mareike Hornig, Viktor Grünwald, Richard Cathomas, Johannes Meiler, Maike De Wit, Carsten Bokemeyer, Karin Oechsle
Journal: Journal of Clinical Oncology (2015)

e15570 Background: Chemotherapy (CTX) with gemcitabine, oxaliplatin and paclitaxel (GOP) has demonstrated efficacy in multiply relapsed and/or cisplatin-refractory germ cell tumor (TGCT) patients (pts) within a phase II-study setting [Bokemeyer et al. 2008]. We have analysed the efficacy and safety of GOP in routine clinical practice. Methods: Overall, 63 refractory TGCT pts treated with GOP between 01/04 - 01/15 outside clinical trials were included in this database. Pts characteristics, prior treatment, response rate, toxicity, progression free (PFS) and overall survival (OS) were analysed. Results: GOP was applied as 2nd - 8th treatment line (median 4th) after cisplatin-based CTX. 70% of pts had undergone high-dose CTX. 73% of pts had an impaired ECOG performance status. Complete remissions (CR) were achieved in 7/63 pts (11%; 4 pts CTX plus residual tumor resections and 3 pts CTX alone). Partial remissions (PR) were detected in 18 pts (29%) and stable disease in 11 pts (17%). 20 pts (32%) had progressive disease at first treatment evaluation. Median (mean) PFS for the total cohort was 3.7 (10.6) months (95%CI 2.53-4.76) and OS 13.3 (23.6) months (95%CI 8.6-18.0), respectively. Overall, 7/63 pts (11%) remained disease-free > 2 years. Dose reductions due to toxicities from prior therapies or during GOP treatment were performed in 56%; treatment had to be stopped due to toxicity in 6%. Most common toxicities: Thrombocytopenia 47%, leukopenia 40%, anemia 32%, polyneuropathy 15%, infection 9% and nausea 8%. Univariate analysis revealed objective tumor remission (PR+CR) (p = < 0.001) and the ECOG (p = 0.026) as prognostic indicators for OS. Conclusions: These results confirm the previous study data demonstrating that GOP+/- secondary surgery is effective and safe in heavily pretreated refractory GCT pts. A distinct activity with ORR of 40%, a median OS of 13.3 months and long term survival in 11% was achieved in routine care. These data support the recommendation to use GOP in multiply refractory TGCT pts after failure of high-dose CTX. Complete secondary tumor resection should be considered whenever possible to achieve long-term disease control.
Plasma cell-free DNA-based prognosis in metastatic hormone sensitive prostate cancer.
Authors: Manish Kohli, Siddhartha Yadav, Winston Tan, Irbaz Bin Riaz, Tiantian Zheng, Amy Wang, Carlos Montesinos, Calvin Wong, Peter Du, Shidong Jia, Jianjun Yu
Journal: Journal of Clinical Oncology (2019)

242 Background: We evaluated plasma cell free based genomic aberrations for prognosticating survival of newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patients (pts). Methods: Plasma was collected from mHSPC pts enrolled between 2009-2014. Platelet poor plasma (PPP) fractions were processed uniformly and cell free DNA (cfDNA) extracted using Qiagen kits. Pts were followed after initiating hormonal therapy until death. Next Gen Sequencing (NGS) of cfDNA was performed using Illumina HiSeq X for a preselected panel of 128 genes (PredicineDDR-77 cancer driver genes; 29 genes in BRCA-FA homologous recombination deficiency (HRD) pathway; 22 DNA damage repair pathway genes). Statistical analyses of plasma genome based aberrations with overall survival (OS) were performed in R 3.5.1. Cox proportional-hazard models were used for survival analysis. Results: An average of 2.5 ml PPP from 99 pts yielded a median of 10.5 ng (range: 2.8-702) cfDNA per sample. 15/99 pt samples with a yield &lt; 5 ng were excluded from sequencing; 9/99 samples failed NGS. Median follow-up time was 80.2 months (mths) (Range: 74.7, 87]); median OS was 69.1 mths (range: 54,NR). 29 pts with full NGS data had high volume metastatic disease. cfDNA yield correlated with metastatic volume (P = 0.01). Univariate analysis revealed both variables prognostic for OS (Metastatic volume: log-rank P=0.01, HR=2.1, 95% CI: 1.1-3.8; cfDNA yield: P =0.04, HR = 1.3, 95% CI: 1.03-1.7). Multivariate regression showed prognostic value of cfDNA yield remained independent of metastatic volume (P = 0.03, HR = 1.34, 95% CI: 1.02-1.76). 54/67 samples with NGS data had at least one mutation/copy number variation detected. Top mutated genes included TP53 (N=18), ATM (N=9), CHEK2 (N=7), FANCM (N=6), RB1 (N=6), BRCA2 (N=5), PIK3CA (N=4) and 37/67 pts harbored 1≥ variant in HDR pathways. These pts had a shorter survival (median: 58.6 mths) (P=0.04, HR= 2.28, 95% CI: 1.01-5.18) and pts with ATM mutations did significantly worse (median survival: 47.4 mths) (HR=4.03, P=0.0005, 95% CI: 1.73-9.37). Conclusions: Plasma cfDNA yield is prognostic for survival in newly diagnosed mHSPC state and presence of HRD pathway genomic aberrations in plasma cfDNA are associated with poor survival.
Utility of PET-CT vs CT alone to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer.
Authors: Mostafa Atri, Zheng Zhang, Farrokh Dehdashti, Susanna Lee, Shamshad Ali, Wui-Jin Koh, Kathleen N. Moore, Lisa Michelle Landrum, Jae-Weon Kim, Paul DiSilvestro, Eric Lawernce Eisenhauer, Frederick M. Schnell, Michael Gold
Journal: Journal of Clinical Oncology (2015)

5585 Background: To assess if PET-CT improves accuracy of CT to detect lymph node (LN) metastasis in advanced cervical cancer. Methods: This was a prospective ACRIN/GOG multicenter trial. Patients underwent contrast enhanced PET-CT followed by extra-peritoneal or laparoscopic pelvic and abdominal lymphadenectomy. Seven independent blinded readers reviewed PET-CT and CT only images at least one month apart. Region correlation was performed between pathology and central review results for abdomen (right and left para-aortic, right and left common iliac) and pelvis (right and left external iliac and right and left obturator) regions. Abdomen and pelvic regions were combined, respecting laterality, to calculate accuracy values for these regions at participant level. Reference standard was pathology of resected LNs. Reader average sensitivities/specificities of PET-CT vs CT were compared with generalized linear mixed models. Reader average AUCs were compared with Obuchowski’s method. Fleiss’ kappa was used to assess reader agreement. Results: A total of 153 patients had PET/CT and pathology proof in the abdomen from 169 patients who were enrolled between September 2007 and December 2012. Forty-three of 153 patients had metastasis to abdominal LNs. Forty abdominal positive and 40 randomly selected abdominal negative patients were used for review based on sample size calculation. Reader study cases ranged from 24 to 74 years old (mean;48.9±10.6). Cancer stages were: IB = 25, II = 44, III = 11; sixty-nine squamous cell carcinomas, 6 adenocarcinoma and 5 others. Mean sensitivities of PET-CT/CT alone in abdomen were 0.50 (CI:0.44,0.56)/0.42 (CI:0.36,0.48) (p = 0.052) and in pelvis 0.83 (CI:0.78,0.87)/0.79 (CI:0.73,0.83) (p = 0.15). Corresponding specificities were 0.85 (CI:0.80,0.89)/0.89 (CI:0.84,0.92) (p = 0.21) and 0.63 (CI:0.54,0.70)/0.62 (CI:0.53,0.69) (p = 0.83). Mean AUCs were 0.70 (CI:0.61,0.79)/0.68 (CI:0.59,0.77) (p = 0.43) and 0.80 (CI:0.71,0.88)/0.76 (CI:0.67,0.85) (p = 0.21). Kappa for PET/CT was 0.65 in pelvis and 0.77 in abdomen. Conclusions: Addition of PET to diagnostic CT resulted in statistically borderline increase in sensitivity to detect LN metastasis in abdomen. Clinical trial information: ACRIN6671GOG0233.
Lanreotide depot/autogel (LAN) vs. placebo (PBO) for carcinoid syndrome (CS) in patients with neuroendocrine tumors (NETs): Subgroup analysis of the ELECT study.
Authors: Aaron Vinik, Edward M. Wolin, Helene Audry, Edda Gomez-Panzani, George A. Fisher
Journal: Journal of Clinical Oncology (2015)

4103 Background: ELECT, a large phase 3 study of the long-acting somatostatin analog (SSA) LAN for symptomatic control of CS in NET patients showed significant improvement over PBO in % days with short-acting octreotide use as rescue medication. Here, we investigate reduction in use of rescue medication for LAN vs PBO in subgroups defined by baseline characteristics. Methods: Patients with histologically confirmed NETs and history of CS received double-blind LAN 120 mg (n=59) or PBO (n=56) every 4 wks for 16 wks, with access to short-acting octreotide for breakthrough symptoms (NCT00774930). Least-squares mean differences in % of days rescue octreotide use for LAN vs PBO were calculated by ANCOVA within subgroups. Results: The significant reduction for LAN vs PBO in rescue medication use in the overall population (Table; approximately one-third lower for LAN group relative to PBO group) was generally consistent with reductions favoring LAN over PBO across subgroups, except small subgroups in which CIs were wide (e.g. BMI ≥30). Conclusions: Beneficial effects of LAN for CS symptom control in NET patients are consistent regardless of baseline characteristics. Clinical trial information: NCT00774930. Subgroup Short-acting octreotide use, % days* Treatment difference (LAN – PBO) [95% CI]* LAN PBO Overall population (n=115) 33.7 48.5 -14.8 [-26.8, -2.8] Age <65 y (n=78) 35.8 53.2 -17.4 [-34.1, -0.6] ≥65 y (n=37) 25.8 45.5 -19.7 [-35.5, -3.9] Gender Male (n=48) 36.7 60.8 -24.1 [-45.7, -2.5] Female (n=67) 33.7 39.1 -5.4 [-21.5, 10.7] BMI <25 (n=41) 29.9 48.5 -18.6 [-39.6, 2.3] >25 to <30 (n=50) 30.9 52.7 -21.8 [-39.6, -4.1] ≥30 (n=21) 37.4 31.6 5.8 [-32.4, 44.0] Race/ethnicity Caucasian (n=96) 34.2 48.7 -14.5 [-27.6, -1.4] Other (n=19) 21.9 46.6 -24.8 [-70.4, 21.0] Region US (n=40) 19.6 30.2 -10.7 [-32.5, 11.2] Ex-US (n=75) 39.5 55.8 -16.3 [-31.6, -1.0] Prior SSA No (n=51) 25.3 44.3 -18.9 [-37.0, -0.9] Yes (n=64) 33.9 44.2 -10.3 [-26.5, 5.9] Time since diagnosis <1 y (n=41) 39.1 53.3 -14.2 [-36.3, 7.9] ≥1 y (n=74) 28.8 38.3 -9.5 [-24.4, 5.4] *LS mean, from subgroup ANCOVAs containing treatment, stratification factor(s) and baseline parameters (octreotide, diarrhea and flushing events), intent-to-treat population.
Carfilzomib, Cyclophosphamide and Dexamethasone (KCD) Versus Bortezomib, Cyclophosphamide and Dexamethasone (VCD) for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): First Final Analysis of the Phase 2 Muk <i>Five</i> Study
Authors: Kwee Yong, Samantha Hinsley, Holger W. Auner, Debbie Sherratt, Ruth Mary De Tute, Sarah Brown, Louise Flanagan, Cathy Williams, Jamie Cavenagh, Martin F Kaiser, Neil Rabin, Karthik Ramasamy, Mamta Garg, Stephen F. Hawkins, Ceri Bygrave, Gareth J. Morgan, Faith E. Davies, Roger G Owen
Journal: Blood (2017)
Updated Preliminary Results of a Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination with Idelalisib in Patients with B-Cell Lymphoma
Authors: Franck Morschhauser, John Radford, Loic Ysebaert, Stephen E Spurgeon, Ebenezer A Kio, Gilles Salles, Xi Huang, Siddhartha Mitra, Simon Rule, Martin J.S. Dyer
Journal: Blood (2018)
Abstract P208: Demographic and Socioeconomic Determinants of Acute Myocardial Infarction Hospitalization Risks in Florida
Authors: Evah W Odoi, Nicholas Nagle, Russel Zaretzki, Melissa M Jordan, Kristina W Kintziger
Journal: Circulation (2019)

Introduction: A better understanding of the dynamics of the spatial relationships between myocardial infarction (MI) hospitalization risks and socioeconomic determinants of health (SDoH) is crucial more optimal targeting of efforts geared towards reducing cardiovascular health disparities and improving population health. The objectives of this study were to identify county-level SDoH of MI hospitalization risks, and to explore whether the associations between MI hospitalizations risks and its predictors varied with geographic location to determine if certain predictors are more important in specific geographic areas in Florida. Methodology: A multivariable global Negative Binomial Regression model (NBR) was used to identify county-level SDoH predictors of inpatient MI hospitalizations occurring in Florida between 2005 and 2014. A local Geographically Weighted Negative Binomial Regression model was then used to explore whether the associations between MI hospitalization risks and SDoH predictors identified in the global NBR model varied depending on geographic location in the state. The spatial distribution of MI hospitalization risks, significant SDoH predictors and non-stationary local regression coefficients were mapped using ArcGIS. Results: The risks of MI hospitalizations were significantly higher in counties with high proportions of residents with less than high school education (P &lt; 0.0001) and divorced residents (P = 0.03). However, they were significantly lower in counties with high proportions of rural residents (P&lt; 0.0001) and African Americans (P = 0.022), and marginally lower in counties with low rates of health insurance coverage (P = 0.056). The strength of associations between MI hospitalization risks and the proportion of population with less than high school education attainment and health uninsurance rate varied based on geographic location in Florida. Conclusion: Race, marital status, educational attainment, rurality and health insurance coverage were significant determinants of MI hospitalization risks in Florida. The strength of associations between MI hospitalization risks and education attainment and health insurance coverage were not constant across the state. These findings indicate that a one-size-fits-all approach is not appropriate for reducing the burden of MI and addressing geographic disparities in utilization of MI care in Florida. Rather, policies and interventions prioritizing identified SDoH factors should be tailored to location-specific community contexts to improve cardiovascular health in Florida.
Екатеринославские медики — члены общества «Просвита» К 150-летию Всеукраинского общества «Просвита» (1868–2018)
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2019)

В статье освещаются жизненный путь, профессиональная и общественная деятельность екатеринославских медиков — членов общества «Просвита». Собрана информация о 28 знаменитых и известных деятелях. Они внесли значительный вклад в развитие медицины, национальной культуры, литературы и просветительского движения на Екатеринославщине.
Abstract 11422: Bola3 Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension
Authors: Qiujun Yu, Yi-Yin Tai, Ying Tang, Jingsi Zhao, Thomas Bertero, Vinny Negi, Miranda K Culley, Rajeev Saggar, Rajan Saggar, W. Dean Wallace, David J Ross, Aaron B Waxman, Stacy G Wendell, Steven J Mullett, Omar F Khan, James Dahlman, GorcsanJohn, Sara O Vargas, Kathleen J Haley, Rahul Kumar, Brian B Graham, Robert Langer, Daniel G Anderson, Bing Wang, Sruti Shiva, Stephen Y Chan
Journal: Circulation (2018)

Background and Hypothesis: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a dea...
Abstract 20653: Evaluation of the Pooled Cohort Risk Equations for Cardiovascular Risk Prediction in a Multiethnic Cohort of Women: The Women’s Health Initiative
Authors: Samia Mora, Nanette K Wenger, Nancy R Cook, Jingmin Liu, Barbara Howard, Marian Limacher, Simin Liu, Karen Margolis, Lisa Martin, Nina Paynter, Paul Ridker, Jennifer Robinson, Jacques Rossouw, Monika Safford, JoAnn E Manson
Journal: Circulation (2017)

Introduction: We evaluated the predictive accuracy of the 2013 Pooled Cohorts Equations (PCE) in the Women’s Health Initiative (WHI), a multiethnic cohort of contemporary U.S. postmenopausal women....
The efficacy of enzalutamide for castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P).
Authors: Hideji Kawanishi, Masashi Kato, Akiyuki Yamamoto, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2019)

209 Background: Enzalutamide (ENZ) was approved to prolong survival for castration-resistant prostate cancer (CRPC) patients before and after chemotherapy. No factor was identified to predict the effectiveness of ENZ so far. .Intraductal carcinoma of the prostate (IDC-P) was newly recognized on 2017 EAU guideline and considering as a poor prognostic factor、although there has been no reports to predict the therapeutic effects of ENZ according to the presence of IDC-P. In this study, we evaluated the efficacy of ENZ for CRPC patients with or without IDC-P. Methods: We retrospectively identified 199 CRPC patients treated with ENZ from 2014 to 2018 in author-affiliated hospitals. All needle biopsy slides were reviewed by a single genitourinary pathologist and IDC-P was defined according to the criteria of McNeal at initial biopsy. Endpoint is overall survival (OS) from the time of CRPC diagnosis and time to treatment failure of ENZ. PSA response is defined as over 50% PSA decline from baseline. Results: The median patient age was 71 (range, 49–90) years. The median initial PSA was 154 ng/ml (range, 3.9–24736 ng/ml). The patients who received docetaxel were 42/199 (21%). IDC-P was detected in 98 patients (49%) at initial prostate biopsy. PSA response was 70.5% in patients without IDC-P and 53.9% in patients with IDC-P. The median OS from the time of CRPC was 37.9 and 71.5 months with and without IDC-P, respectively (P=0.013). There was no significant difference on OS in CRPC patients with IDC-P between before and after docetaxel (P=0.941). Same result was observed in CRPC patients without IDC-P (P=0.86). In time to treatment failure by ENZ, patients with IDC-P showed worse prognosis than patients without IDC-P after docetaxel (P=0.068). On the other hand, the difference disappeared before docetaxel regardless the presence of IDC-P (P=0.94). Conclusions: IDC-P is a poor prognostic factor for CRPC patients treated with ENZ. ENZ may be most effective for CRPC patients with IDC-P before chemotherapy.
Age independent survival benefit for patients with hepatocellular carcinoma (HCC) without metastases at diagnosis: a population-based study
Authors: Enrico N De Toni, Anne Schlesinger-Raab, Martin Fuchs, Wolfgang Schepp, Ursula Ehmer, Fabian Geisler, Jens Ricke, Philipp Paprottka, Helmut Friess, Jens Werner, Alexander L Gerbes, Julia Mayerle, Jutta Engel
Journal: Gut (2019)

Objective Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients. Design 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Tumour characteristics and outcome were analysed by time period and according to age and presence of metastases at diagnosis. Overall survival (OS) was analysed using Kaplan-Meier method and relative survival (RS) was computed for cancer-specific survival. Cox proportional hazard models were conducted to control for prognostic variables. Results While incidence of HCC remained substantially stable, tumours were diagnosed at increasingly earlier stages, although the median age at diagnosis increased. The 3 years RS in HCC improved from 19.8% in 1998–2002, 22.4% in 2003–2007, 30.6% in 2008–2012 up to 31.0% in 2013–2016. Median OS increased from 6 months in 1998–2002 to 12 months in 2008–2016. However, analysis according to the metastatic status showed that survival improved only in patients without metastases at diagnosis whereas the prognosis of patients with metastatic disease remained unchanged. Conclusion These real-world data show that, in contrast to the current assumptions, the incidence of HCC did not increase in a representative German region. Earlier diagnosis, likely related to the implementation of screening programmes, translated into an increasing employment of effective therapeutic options and a clear survival benefit in patients without metastases at diagnosis, irrespective of age.
Scientists call for moratorium on editing heritable genes
Authors: Owen Dyer
Journal: BMJ (2019)

A group of scientists and ethicists, writing in Nature , have called for a global moratorium on all clinical uses of human germline editing to make genetically modified children.1

Among those calling for the moratorium are two leading pioneers of the CRISPR gene editing technology which holds the promise of breakthroughs in tackling inherited diseases but also opens the door to rogue human experimentation, designer babies, and potentially to permanent changes in the human genome.

Emmanuelle Charpentier of the Max Planck Institute and Feng Zhang of MIT and Harvard’s Broad Institute joined 16 other specialists from seven countries in calling for the formation of an international regulatory organisation to monitor the use of gene editing.

Francis Collins, director of the US National Institutes of Health, gave …
Rectal adenocarcinoma: Results of adjuvant chemotherapy in a retrospective cohort.
Authors: Pablo Reguera Puertas, Vanessa Pachón Olmos, Reyes Ferreiro Monteagudo, Federico Longo, Carmen Guillén Ponce, María Ángeles Vaz Salgado, Mercedes Rodríguez Garrote, Maria Gion Cortés, Ainhoa Madariaga Urrutia, Alfonso Cortés Salgado, Silvia Patricia Cortez Castedo, Jacobo Muñoz del Toro, Julie Earl, Asuncion Hervás Morón, Eva Fernández Lizarbe, Cayetano Sempere Ortega, Javier Díe Trill, Antonio Rey Ibarra, Alfredo Carrato
Journal: Journal of Clinical Oncology (2015)

e14539 Background: The role of adjuvant chemotherapy (AC) after chemo-Rt and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides, guidelines from different expert groups are conflicting. Methods: 171 patients diagnosed from January 2003 to December 2011 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or MRI were collected retrospectively from the Pathology Department data base. Results: Of the 171 patients 62% were male, with a median of age at diagnosis of 69.3 years (range 31.3-85.3 years). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 13% of patients achieved a pathological complete response. 72.5% of the cohort received adjuvant chemotherapy. The main reasons for not receiving chemotherapy were ECOG ≥ 2, surgery complications and a patient decision. 51.6% of patients received an oxaliplatin based regimen and the median time of chemotherapy duration was four months. Local relapse was diagnosed in 6.4% of patients while a systemic relapse was found in 21.1%. Patients without AC had a mean OS of 98.8 months versus 113.1 in the AC cohort (p 0.023) without reaching the median after 61.6 months of median follow-up. AC and postsurgical stage were the only significant, independent predictive factors for OS according to multivariate Cox regression. Conclusions: AC after chemo-Rt and surgery in stage II and III rectal cancer as a standard does not exist. In our cohort, AC showed a significant improvement in OS, but the limitations of a retrospective study should be considered, as well as the impact of surgery on metastasis and salvage chemotherapies. Randomized studies are clearly needed.