tbuckley/cabot-search huggingface dataset:
Adjuvant chemotherapy in American and Italian patients with BRCA1/2-associated breast cancer.
Authors: A. Cappetta, R. Nanda, C. Liao, D. Huo, L. F. Chen, G. Artioli, V. Zagonel, O. I. Olopade
Journal: Journal of Clinical Oncology (2011)

1084 Background: BRCA1-associated breast cancers have pathologic features and biologic behavior that are distinct from sporadic breast tumors while BRCA2 tumors are indistinguishable. Comparative survival studies have reported conflicting results and recent studies suggest relative resistance to taxane-based chemotherapy in patients with BRCA1 mutations. To determine if there are differences in long-term outcomes for BRCA1, BRCA2 and high-risk non-carriers with stage I, II, and III breast cancer based on adjuvant therapy received, we conducted a retrospective analysis in US and Italian patients. Methods: Patients diagnosed with breast cancer between January 1, 1990 and December 31, 2008 were identified at the University of Chicago Cancer Risk Clinic and the Veneto Institute of Oncology in Padua. There were 80 BRCA1carriers, 78 BRCA2 carriers and 177 high-risk non-carriers ascertained within the same time period. End points were recurrence-free survival (RFS) and overall survival (OS) by type of adjuvant chemotherapy received. Hazard Ratios (HR) and 95% Confidence Intervals (95% CI) were calculated from Cox proportional hazard models. A multivariate analysis was used to adjust for year at diagnosis, stage, grade and Estrogen Receptor (ER) status. Results: The median follow up was 4.98 (0.03-18.9). The RFS-adjusted hazard ratios were not significantly different among mutation carriers and non-carriers (HR among BRCA1 carriers, 0.52; 95% CI, 0.21 to 1.31; HR among BRCA2 carriers, 0.68; 95% CI, 0.31 to 1.48; P=0.326). The OS-adjusted hazard ratios were not significantly different (HR among BRCA1 carriers, 1.24; 95% CI, 0.45 to 3.45; HR among BRCA2 carriers, 0.89; 95% CI, 0.33 to 2.38; P=0.837). Ten year survival was 78% for BRCA1, 83% for BRCA2 and 92% for non-carriers, respectively. The risk of recurrence and death was also not statistically significant among patients treated with different chemotherapy regimens. Conclusions: RFS and OS survival are similar for carriers of a BRCA mutation and non-carriers.
Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Onartuzumab Plus Bevacizumab Versus Placebo Plus Bevacizumab in Patients With Recurrent Glioblastoma: Efficacy, Safety, and Hepatocyte Growth Factor and O<sup>6</sup>-Methylguanine–DNA Methyltransferase Biomarker Analyses
Authors: Timothy Cloughesy, Gaetano Finocchiaro, Cristóbal Belda-Iniesta, Lawrence Recht, Alba A. Brandes, Estela Pineda, Tom Mikkelsen, Olivier L. Chinot, Carmen Balana, David R. Macdonald, Manfred Westphal, Kirsten Hopkins, Michael Weller, Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, David S. Shames
Journal: Journal of Clinical Oncology (2017)

Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression. The primary end point was progression-free survival by response assessment in neuro-oncology criteria. Secondary end points were overall survival, objective response rate, duration of response, and safety. Exploratory biomarker analyses correlated efficacy with expression levels of MET ligand hepatocyte growth factor, O
Low Dose Unfractionated Heparin (UFH) Prophylaxis Is a Safe Strategy for the Prevention of Hepatic Sinusoidal Obstruction Syndrome (SOS) in Adult Allogeneic Stem Cell Transplant (HSCT) Recipients
Authors: Valkal Bhatt, Meighan Palazzo, Kathleen Kilroy, Patrick Hilden, Molly Maloy, Juliet N. Barker, Hugo R. Castro-Malaspina, David J Chung, Parastoo B Dahi, Katharine C. Hsu, Alan M Hanash, Ann A. Jakubowski, Robert R. Jenq, Guenther Koehne, Heather Landau, Esperanza B Papadopoulos, Miguel-Angel Perales, Craig S. Sauter, Roni Tamari, Marcel van den Brink, James W. Young, Sergio A. Giralt, Doris M Ponce
Journal: Blood (2015)
The Zinc Finger Protein Gfi1 Controls TLR4-Mediated Inflammatory Response by Directly Antagonizing NF-κB Transcription Factor
Authors: Ehssan Sharif-Askari, Hui Zeng, Lothar Vassen, Christian Kosan, Cyrus Khandanpour, Florian Heyd, Tarik Moroy
Journal: Blood (2008)
Value of preoperative biopsy and radiological assessment for the diagnosis of mixed hepatocellular cholangiocarcinoma (HCC-CC).
Authors: Mohamed Bouattour, Johanna Wassermann, Nathalie Guedj, Valerie Paradis, Chantal Dreyer, Laurent Castera, Valérie Vilgrain, Sandrine J. Faivre, Eric Raymond
Journal: Journal of Clinical Oncology (2012)

176 Background: Mixed tumors with hepatocellular and cholangiocarcinoma component (HCC-CC) are rare variants of primary liver tumors. In this study, we aimed to describe clinical, radiological and histopathological features of patients with resected HCC-CC. Methods: From 2000 to 2010, patients (pts) with diagnosis of mixed HCC-CC based on surgical specimen were identified from our database. Demographic, clinical, radiological and pathological data were analyzed retrospectively, along with outcome after resection. Results: Among 18 pts, 6 men (33%) and 12 women (67%) were identified. The median age was 64 years (range 38- 75). Nine pts (50%) had at least one risk factor for chronic liver disease including alcohol consumption (6), NASH (3) and HBV infection (2). Twelve (67%) and 6 pts (33%) underwent major and minor hepatic resections respectively. The positive predictive value of radiological and pathological diagnosis was reviewed. Imaging by CT scan and/or MRI suggested characteristics of HCC and CC in 5 and 6 pts respectively. In 3 pts imaging showed combined features of HCC and CC while it was atypical in 4 cases. Preoperative biopsy was performed in 10 pts and analyzed using only morphological features. Biopsy sample was non contributive in 2 cases and concluded to CC, HCC and mixed HCC-CC in 5, 2 and 1 cases respectively. This contrasted with examination of resection specimen showing evidence of HCC combined with CC phenotype. Immunostaining on resection specimens showed the presence of differentiation markers for both hepatocytes and biliairy cancer cells (CK7 +, CK19 +, anti-hepatocyte +, and glypican +). Non tumor liver analysis showed normal underlying liver, non extensive fibrosis ≤ F2, extensive fibrosis &gt; F2 without cirrhosis and cirrhosis in 2, 3, 7 and 6 specimens respectively. With more than 6 months follow-up (range 6 -59 months) the recurrence rate was higher than 50%. Conclusions: Mixed HCC-CC are not accurately identified by preoperative biopsy using only morphological features and CT scan/MRI assessment. Following resection, mixed HCC-CC behave more like CC than HCC.
Prospective randomized controlled trial of robotic versus open radical cystectomy for bladder cancer: Median 3-year follow-up.
Authors: Angela Smith, Jeffrey W. Nix, Matthew Edward Nielsen, Eric Wallen, Raj Pruthi
Journal: Journal of Clinical Oncology (2012)

284 Background: We reported our results on a prospective, randomized trial of open vs. robotic cystectomy in 2008. Three years later, we report our findings with regard to overall (OS) and disease-specific survival (DS), recurrence rates and long-term complications. Methods: A prospective, randomized study comparing open vs. robotic cystectomy for bladder cancer was initiated at our institution with IRB approval in 2008. A target accrual of 40 patients was established to evaluate for non-inferiority based upon nodal yield. Peri-operative and pathologic results were reported in 2008. We now report our median 36-month follow-up for this patient cohort. Results: Of the 41 patients, 21 were randomized to robotic and 20 to open. On surgical pathology, in the robotic group 14 patients had &lt;= pT2, 3 pT3/T4, and 4 N+ disease. In the open group, 9 had &lt;= pT2, 5 pT3/T4, and 7 N+ disease. No positive margins were noted. With median follow-up of 35 and 36 months in the robotic and open arms, OS was 65% (13/20) and 81% (17/21) respectively (p=0.3058). DSS was 68% in the open group (13/19) and 85% in the robotic group (17/20) (p=0.2733). There were 7 recurrences (35%) in the open cohort compared to 3 patients (14%) undergoing the robotic procedure (p=0.1589). Examining overall complications, there were no differences between the open and robotic groups when evaluating 30-day complications and &gt;=90 day complications (p=0.8651). The open and robotic cohorts demonstrated 2 strictures in each cohort. Two parastomal hernias were noted in the open group compared to none in the robotic group. On multivariate analysis, controlling for age, BMI and pathologic stage, cystectomy type did not predict OS or DSS, recurrences, or complications. Conclusions: Median 3-year follow-up evaluating open versus robotic cystectomy demonstrates no differences with regard to OS, DSS, cancer recurrence or long-term complications. Although this study was not powered to assess survival differences, this is the first randomized study to report such data in a non-selected population with 3-year median follow-up.
Factors associated with cystosarcoma phyllodes of the breast after core needle biopsy identify cellular fibroepithelial lesion.
Authors: D. Gould, J. Salmans, B. Lassinger, A. Contreras, C. Gutierrez, E. Bonefas, K. Liscum, E. J. Silberfein
Journal: Journal of Clinical Oncology (2011)

e11518 Background: Cystosarcoma phyllodes (CP) represents less than 1% of all breast neoplasms and can mimic fibroadenoma on core needle biopsy (CNB). When CNB specimens suggest CP, excision is recommended. However, the treatment of fibroepithelial lesions with cellular stroma on CNB is controversial as a large percentage may prove to be fibroadenoma. We sought to identify clinicopathologic factors that were associated with CP after CNB suggested cellular fibroepithelial lesion. Methods: A retrospective database identified 65 patients over a 10 year period that underwent surgical resection of the breast after CNB identified cellular fibroepithelial lesion. An additional 21 patients with CNB findings of fibroadenoma eventually underwent resection of a CP and were included in the analysis. Patients were grouped by pathologic diagnosis at surgical resection as either fibroepithelial lesion or CP. Clinical and pathologic data were analyzed to look at differences between groups. Results: Forty-three patients were diagnosed with a fibroepithelial lesion on both CNB and surgical resection and 43 patients were diagnosed with either fibroepithelial lesion or fibroadenoma on CNB and CP on surgical resection. There was no significant difference in age between the groups (39 vs. 35.3 years, NS), however, the mean radiographic size was larger in the CP group (2.5 vs. 4 cm, p<.05). Compared with African-American, Caucasian and Asian race, Hispanic race was associated with CP on final pathology (p<.05). Conclusions: If cellular fibroepithelial lesion is identified on CNB of the breast in a woman in the fourth decade of life, larger size and Hispanic race are associated with the presence of CP. These results may help guide clinicians in treatment planning for this subgroup of patients.
Retrospective analysis of surgery in metastatic GIST patients sensitive to imatinib: A Spanish Group for Research on Sarcoma (GEIS) study.
Authors: J. Rubió, J. Martinez-Trufero, A. Lopez-Pousa, X. Garcia del Muro, J. Fra, A. Redondo, N. Lainez, A. Poveda, A. Casado, C. M. Valverde, A. De Juan, I. Sevilla, R. Andres, J. Cruz, M. J. Safont, J. Martin Broto, X. Garcia-Albeniz, J. Maurel
Journal: Journal of Clinical Oncology (2011)

10055 Background: The role of surgery of metastasis in GIST patients sensitive to imatinib is controversial. We performed a retrospective analysis of such patients to estimate its potential benefit and to assess whether a phase III trial may be justified. Methods: 192 metastatic or locally advanced GIST patients undergoing imatinib treatment from 17 Spanish institutions were retrospectively reviewed. 162 patients considered imatinib-sensitive (PFS>6 months) were included in the analysis. The patients were divided in two groups: the first group treated with surgery of metastasis or primary tumor (29 patients) after achieving partial response or stable disease (PR/SD) and the second group without surgery or undergoing surgery at progressive disease (133 patients). Progression free survival (PFS) was defined as the time from starting treatment with imatinib to progression or death. Cox proportional hazards model was used to adjust the multivariate model of PFS. Results: Baseline characteristics did not differ significantly between groups. There was a trend to receive surgery for women and younger patients. Adjusting by age, sex, ECOG, neutrophil count, primary site and the presence of liver metastasis, surgery did not improve the PFS (HR 1.16, 95% CI 0.6-2.24). The multivariate analysis identified female sex (HR 0.52, 95% CI 0.31-0.85). ECOG performance status 0 vs 1-3 (HR 1.78, 95% CI 1.06-2.98) and small bowel site of primary tumor (HR 0.53, 95% CI 0.32-0.88) as factors predicting PFS. Conclusions: In this retrospective study, surgery of metastasis in patients with advanced GIST achieving partial response or stabilization with imatinib did not impact on PFS. News trials evaluating surgery in Imatinib-sensitive patients should consider this results.
Third of partners have vacant GP posts for 12 months or more, survey finds
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Almost a third (31%) of partners in general practices in England said that they had vacancies for GPs that they were unable to fill for more than 12 months, a survey by the BMA has found.

The responses from 3567 GP partners were part of a survey sent to all GP members of the BMA. It …
Experience with sorafenib treatment of hepatocellular carcinoma (HCC) in patients in a Brazilian center.
Authors: Daniele Evaristo Alves, Rogério Alves, Paula Poletti, Otavio Gampel
Journal: Journal of Clinical Oncology (2012)

350 Background: HCC is the most important cause of death in patients with liver cirrhosis. Sorafenib is established as treatment for patients with compensated liver disease, but there are few studies for patients with more advanced cirrhosis. Methods: From May 2008, 75 patients intermediate - advanced (according to BCLC) HCC patient initiated sorafenib at 800 mg daily doses, 71 were treated or had been treated for more than 1 month and were recruited to data analysis on August 2011, regarding sex, age, association with diabetes, etiology of cirrhosis, treatment intervals, dose reductions, adverse events, response rates, Child-Pugh’s classification, global survival and survival according Child-Pugh status Results: The median age of study population of 75 patients (60 men and 15 women) was 63,78 years. The cirrhosis etiology was 46% VHC, 13% N.AS.H, 10,71% cryptogenic cirrhosis and 6.15% with VHB. 40% of the patients were Child A, 41.5% B and 10.8% C . 34% were diabetic, the median treatment interval of sorafenib was 223 days (7-1080 days); Overall response rate was 66%: 37.5 % had stable disease and 25% had partial response with tumor shrinkage by Recist criteria. Adverse events were related in 53.84 % of the patients and 60 % of them needed to have dose modifications. The common adverse events were diarrhea: 48.5%, nausea and vomiting: 31.4 %, abdominal pain: 45.7%, hand-foot syndrome 25.7%, arterial hypertension 8.5% and 8.5 % bleeding. The incidence of adverse events didn’t differ considering each Child-Pugh’s subgroup. The median survival time was 12.1 months. The one and two year survival preliminary rate were 75 % and 68% in Child-Pugh A patients and 40 and 10 % in Child-Pugh B patients (p=0.002) respectively. Conclusions: Our results contributed to emphasize treatment safety of sorafenibe within Hcc patients with more advanced liver disease. In this study population, 52.7% of the patients had liver disease Child B/C and sorafenib was well tolerated (53 % had adverse events) in all subgroups with acceptable response and treatment intervals despite of advanced liver disease, but the survival rates trends to be statistically higher in patients with Child A than Child B.
Acute variceal bleeding in patients on primary prophylaxis with nonselective beta‐blockers: A poor prognosis factor?
Authors: Javier Martínez, Luis Téllez, Agustin Albillos
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the article by Ribeiro de Souza et al. addressing the impact of nonselective beta‐blockers (NSBBs) on short‐term prognosis in patients with cirrhosis admitted for their first episode of acute variceal bleeding (AVB).1 The authors adjusted their series of 49 patients on primary prophylaxis with NSBBs and 93 not on NSBBs for propensity and Model for End‐Stage Liver Disease score. No influence of NSBBs used for primary prophylaxis on short‐term prognosis (i.e., 5‐day rebleeding and 6‐week mortality) was detected in patients with AVB. The message of Ribeiro de Souza et al.'s study is timely as recent publications have raised concern about the use of NSBBs for primary and secondary prophylaxis in specific clinical situations (i.e., refractory ascites).2 Our prospective data (January 2010‐December 2015) are in line with the results of Ribeiro de Souza et al. We analyzed 106 patients with a first episode of AVB, 30 on primary prophylaxis with NSBBs (28.3%, study group) and 76 not taking NSBBs (71.7%, control group). Participants were well matched (for age, sex, etiology, previous ascites or hepatic encephalopathy, hepatocellular carcinoma, Child, and Model for End‐Stage Liver Disease on admission), except for a lower heart rate in the study group (77 versus 98 bpm, P < 0.001). Rebleeding occurred in 17 of the 106 patients (16%), 2 in the study group (6.6%) and 15 in the control group (19.7%) (P = 0.1). The odds ratio of NSBBs for bleeding was 0.3 (95% confidence interval 0.2‐2.5, P = 0.5). Fourteen of the 106 (13%) patients died during admission, 3 in the study group (10%) and 11 in the control group (14.5%) (P = 0.5). Finally, 3 patients in the NSBB group (10%) and 15 in the control group (19.7%) died before 6 weeks (P = 0.2). Adjusted odds ratios for in‐hospital and 6‐week mortality were not significantly different between the two groups: 0.5 (95% confidence interval 0.2‐2.5) and 1.44 (95% confidence interval 0.1‐1.7), respectively. These results reinforce the concept that variceal bleeding prophylaxis with NSBBs does not negatively affect the short‐term prognosis of an AVB episode. NSBBs are the cornerstone of primary and secondary prophylaxis of variceal bleeding,4 and treatment with NSBBs should not be a concern if AVB arises.
Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial
Authors: Olivier Devuyst, Arlene B. Chapman, Ron T. Gansevoort, Eiji Higashihara, Ronald D. Perrone, Vicente E. Torres, Jaime D. Blais, Wen Zhou, John Ouyang, Frank S. Czerwiec
Journal: Journal of the American Society of Nephrology (2016)

The vasopressin–cAMP–osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points. At baseline, lower Uosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200–300 mOsm/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renal benefit occurred in subjects achieving greater suppression of Uosm, that is, those with better eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.
SGX70393 Inhibits Bcr-AblT315I In Vitro and In Vivo and Completely Suppresses Resistance When Combined with Nilotinib or Dasatinib.
Authors: Thomas O’Hare, Christopher A. Eide, Jeffrey W. Tyner, Amie S. Corbin, Matthew J. Wong, Sean Buchanan, Kevin Holme, Katayoun A. Jessen, Crystal Tang, Hal A. Lewis, Richard D. Romero, Stephen K. Burley, Michael W. Deininger
Journal: Blood (2007)
NY-ESO-1 Specific T-Cells Are Spontaneously Present in High-Risk Myeloma and Kill Primary Myeloma Cells.
Authors: Frits van Rhee, Susann M. Szmania, Amberly Moreno, Ramesh Batchu, Mindy Pomtree, Nancy Rosen, Michele Cottler-Fox, Bart Barlogie, Guido J. Trico
Journal: Blood (2004)