tbuckley/cabot-search huggingface dataset:
A randomized, double-blind phase II trial of docetaxel plus prednisone (DP) combined with either AT-101 or placebo for the first-line therapy of metastatic castration-resistant prostate cancer (CRPC)
Authors: G. Sonpavde, V. B. Matveev, J. M. Burke, J. R. Caton, M. T. Fleming, P. A. Karlov, J. Holmlund, B. A. Wood, M. Brookes, L. H. Leopold
Journal: Journal of Clinical Oncology (2011)

4528 Background: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 protein family has broad preclinical activity including synergy with docetaxel (D). AT-101 has demonstrated activity alone and in combination with D in D-refractory patients with metastatic CRPC. Methods: A randomized, double-blind, placebo-controlled phase II trial was conducted to compare the combination of DP with either A or placebo in chemo-naive men with progressive metastatic CRPC. A key requirement was progression (bone scan, RECIST or rising PSA ≥ 2 ng/mL) despite androgen deprivation. Stratification factors were pain and performance status. Patients received DP (75mg/m2 day 1; 5mg PO b.i.d.) Q 21 days (1 cycle) with either A (40 mg b.i.d.) or placebo PO on days 1-3. Radiological assessments were performed every 3 cycles. Primary endpoint was overall survival (OS) and 221 patients were planned for 110 events (80% power, HR 0.67, 1-sided alpha 0.1). Results: 221 patients were randomized and baseline factors were balanced in the 2 groups. Median OS for patients on ADP was 17.8 months vs. 17.5 months for Placebo-DP (HR 1.06, 95% CI 0.72-1.55). The median PFS was 11.0 months and 10.3 months for ADP and Placebo-DP arms respectively (HR 0.88, 95% CI 0.63, 1.22). PSA reductions of ≥50% or ≥30% were seen in 54% and 66% of ADP treated patients compared to 46% and 54% of controls, respectively. Measurable disease control rates for ADP and placebo-DP were 93% and 80%, respectively. Grade 3/4 AEs that occurred with higher incidence in the AT-101 arm of the trial compared to placebo included cardiac AEs (5% v 2%), lymphopenia (23% v 16%), neutropenia (47% v 40%), ileus (2% v 0%) and pulmonary embolism (6% v 2%). The incidence of grade 1/2 peripheral neuropathy was 24% vs. 13%. In a subgroup of patients with poor-risk CRPC (n=34), efficacy endpoints favored ADP (median OS 19 vs.14 months). Conclusions: The combination of AT-101 with DP in men with chemonaive metastatic CRPC was well tolerated but did not extend OS compared to placebo-DP. There was a potential benefit in a subset of high-risk patients.
Feasibility and Toxicity of Nonmyeloablative Hematopoietic Cell Transplantation (HCT) with or without Imatinib for Philadelphia Chromosome (Ph+) Acute Lymphoblastic Leukemia (ALL).
Authors: L. Norasetthada, M. B. Maris, B. M. Sandmaier, D. G. Maloney, G. Georges, B. Druker, J. Radich, R. Storb
Journal: Blood (2004)
Androgen pathway constitutional polymorphism predictors of progression-free and overall survivals in advanced castrate-resistant prostate cancer (CRPC) patients treated with ketoconazole (KC).
Authors: T. L. Davis, J. Jung, K. A. Carr, S. Philips, Y. Mohammadi, M. T. Campbell, L. Li, C. Sweeney, T. C. Skaar, N. M. Hahn
Journal: Journal of Clinical Oncology (2011)

54 Background: Recent trials have highlighted the clinical utility of second-line hormonal therapies for CRPC. KC, an oral inhibitor of CYP3A4 and CYP17, is commonly used in this setting. Germline SNPs in genes critical to hormone synthesis, transport, metabolism, binding sites, and degradation may contribute to variability in outcomes observed in KC treated CRPC pts. Methods: Between 1/07 and 10/08, all PCa pts seen in the Indiana University Simon Cancer Center oncology clinics were approached for recruitment to the Prostate Cancer Genetic Risk Evaluation of SNPs Study (PROGRESS). Participants completed a demographic and clinical questionnaire and provided a peripheral blood sample. Only pts with initiated on KC were included in this analysis. Germline DNA was analyzed for SNP genotyping on a 128-SNP chip using a TaqMan OpenArray GT Kit. The chip included genes critical to hormone signaling, transport, and elimination pathways with minor allele frequencies &gt; 5%. Pts were followed for progression-free survival (PFS) and overall survival (OS) endpoints. Univariable analyses were performed to identify significant associations between SNP genotype, clinical parameters, and PFS and OS outcomes. Results: Between January 2007 and October 2008, 39 pts with CRPC initiated on KC therapy enrolled. Demographics included: age (median) – 70 yrs, prostate specific antigen (PSA) (median) – 13.0 ng/ml, PSA doubling time (median) – 2.9 months, metastatic –85%, ECOG PS 0– 74%. Age &lt; 70 was associated with shorter PFS (p=0.010) and age &gt; 70 was associated with shorter OS (p=0.030). SNPs significantly associated with PFS and OS are summarized in the table. Conclusions: Interpatient differences in hormonal pathway germline SNPs may contribute to variability in clinical outcomes in pts treated with KC. [Table: see text] No significant financial relationships to disclose.
Association of <i>BRCA1</i> promoter methylation in triple-negative breast cancer (TNBC) with resistance to standard anthracyline-based adjuvant chemotherapy.
Authors: P. Sharma, B. F. Kimler, Y. A. Park, S. R. Stecklein, Q. J. Khan, B. K. Petroff, O. W. Tawfik, R. A. Jensen
Journal: Journal of Clinical Oncology (2011)

1123 Background: Methylation of the BRCA1 promoter is one of the mechanisms contributing to loss of BRCA1 expression in sporadic TNBC. Relative to other classes of chemotherapeutic agents, BRCA1-deficient cancers appear to be intrinsically sensitive to DNA damaging agents. However, it is not known if presence of BRCA1 promoter methylation (PM) in sporadic TNBC impacts response to chemotherapy. Aim: To investigate the prognostic significance of BRCA1 PM with respect to RFS and OS in patients receiving chemotherapy for stage I-III TNBC. Methods: TNBC patients undergoing chemotherapy b/w 1996-2008 were identified and their formalin-fixed paraffin-embedded (FFPE) breast tumor specimens were retrieved. Genomic DNA was isolated, bisulfite converted and then subjected to BRCA1 promoter methylation-specific PCR. RFS and OS were calculated by Kaplan-Meier method. Cox proportional hazards models were fit to determine the association of BRCA1 PM with the risk of death. Results: DNA was isolated from primary tumor specimens of 39 subjects. BRCA1 PM specific PCR was successful in 95% (37/39) of specimens and was detected in 30% (11/37) of subjects. The median age was 52 yrs (33-80), median tumor size: 2 cm, LN+: 51%, Stage III: 32%. All patients received neo/adjuvant chemotherapy (anthracycline: 90%, taxane: 73%). At a median follow up of 6 yrs, there have been 18 (48%) recurrences and 14 (37%) deaths. Node positivity, higher tumor stage and presence of BRCA1 PM were significantly associated with worse RFS and OS. 5-year RFS was 27% and 61% respectively for patients with and without BRCA1 PM (p =0.034). Similarly, 5-year OS was 36% and 81% respectively for patients with and without BRCA1 PM (p =0.004). After adjustment for stage and N status presence of BRCA1 PM was significantly associated with poor OS (p=0.002). Conclusions: BRCA1 PM methylation was detected in approximately 30% of TNBC patients and was associated with significantly poor outcomes using standard anthracycline chemotherapy. Alternative therapeutic modalities (platinum/PARP inhibitors) which are more likely to be effective against BRCA1-deficient tumors should be explored for patients with sporadic TNBC and BRCA1 PM.
Risk Factors For Chronic Eye and Mouth GVHD In Unrelated Hematopoietic Cell Transplantation: T Cell Depletion Is The Only Risk Factor Identified and Appears To Be Favorable
Authors: Mohamed Shanavas, Nada Hamad, Fotios V. Michelis, Jieun Uhm, Vikas Gupta, John Kuruvilla, Hans A. Messner, Jeffrey H. Lipton, Dennis Dong Hwan Kim
Journal: Blood (2013)
Erratum. Psychosocial Care for People With Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care 2016;39:2126–2140
Authors: Deborah Young-Hyman, Mary de Groot, Felicia Hill-Briggs, Jeffrey S. Gonzalez, Korey Hood, Mark Peyrot
Journal: Diabetes Care (2017)

In the print version of the article listed above, the sentence on page 2131: “Further, providers should consider asking whether there …
Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations
Authors: Akihiro Hoshino, Satoshi Okada, Kenichi Yoshida, Naonori Nishida, Yusuke Okuno, Hiroo Ueno, Motoi Yamashita, Tsubasa Okano, Miyuki Tsumura, Shiho Nishimura, Sonoko Sakata, Masao Kobayashi, Haruna Nakamura, Junji Kamizono, Kanako Mitsui-Sekinaka, Takuya Ichimura, Shouichi Ohga, Yozo Nakazawa, Masatoshi Takagi, Kohsuke Imai, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Shigeaki Nonoyama, Tomohiro Morio, Hirokazu Kanegane
Journal: Journal of Allergy and Clinical Immunology (2016)
Frequent Gains of Chromosome Arm 1q21 in Plasma Cell Dyscrasia Detected by Fluorescence In Situ Hybridization: Incidence Increases from MGUS to Relapsed Myeloma and Is Related to Disease Progression and Prognosis.
Authors: Ichiro Hanamura, Peter Stewart, Frederica Cavallo, Bart Burington, Erik Rasmussen, John Crowley, Fenghuang Zhan, Yongsheng Huang, Bart Barlogie, John Shaughnessy
Journal: Blood (2005)
Peripheral T Cell Apoptosis Is Associated with Homeostatic T Cell Proliferation and Plays a Significant Role in Post-Transplant Immune Deficiency.
Authors: Onder Alpdogan, Neel Patel, David Suh, Jeremy Grubin, Suzanne McGoldrick, Odette M. Smith, Sydney Lu, Christopher King, Adam Kochman, Vanessa Hubbard, Marcel R.M. van den Brink
Journal: Blood (2006)
Hospital doctors warn of massive job losses if Obamacare is repealed
Authors: Michael McCarthy
Journal: BMJ (2016)

If Congress repeals the Affordable Care Act (ACA) without replacement, US hospitals will lose hundreds of billions of dollars, which would be devastating and lead to massive job losses, US hospital groups have said in letters sent to President-elect Donald Trump and congressional leaders on 6 December.

The letters, which were signed by Rick Pollack, president and CEO of the American Hospital Association, and Chip Kahn, president and CEO of the Federation of American Hospitals, were accompanied by a report1 that analyzed the potential impact of a repeal bill that was passed earlier this year by congressional Republicans. The bill would have become law if it had not …
Capture and analysis of prostate cancer circulating tumor cells (CTCS) using geometrically enhanced differential immunocapture (GEDI).
Authors: M. Jodari, M. Loftus, J. Gleghorn, G. Gakhar, E. Pratt, S. T. Tagawa, N. H. Bander, P. Giannakakou, B. Kirby, D. M. Nanus
Journal: Journal of Clinical Oncology (2011)

53 Background: EpCAM-based immunocapture of prostate cancer (PC) CTCs yields relatively low purity and specificity. We developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that incorporates flow dynamics and utilizes a mAb to prostate-specific membrane antigen (PSMA) to optimize isolation and analysis of CTCs from PC patients. Methods: GEDI microfluidic silicon chips, fabricated using standard photolithography techniques, were functionalized by chemical cross-linking ending with a neutravidin terminated surface to which anti-PSMA biotinylated-mAb J591 was bound. C4-2 (PSMA+) and PC-3 (PSMA-) cells were used for chip optimization. 1 mL of peripheral blood from PC patients was flowed (1mL/hour) over functionalized chips. Captured cells were washed with PBS × 30 min, fixed with 3.7% formaldehyde, immunofluorescently stained for DAPI, androgen receptor (AR), tubulin and EpCAM and analyzed by high resolution point-scanning confocal microscopy. PSMA+, DAPI+, and CD45- cells were manually scored. RNA was extracted from unfixed captured CTCs using lysis buffer flowed thru the chip. Results: ∼80% capture efficiency was achieved from 26 PSMA positive C4-2 cells spiked into 1 mL blood flowed through the GEDI chip. RNA extracted from 50 C4-2 cells in 1 mL blood flowed thru the chip detected a known AR point mutation by RT-PCR and Sanger sequencing. Immunofluorescence staining of PSMA+ cells captured on the chip detected changes in AR subcellular localization and microtubule structure following treatment with DHT or paclitaxel, respectively. 10 patients with metastatic PC were analyzed by CellSearch (range 0-201 cells/7.5 mL) and GEDI chip (range 35-&gt;1200 cells/mL) yielding a 7-&gt;350 fold enrichment using GEDI. Captured PC cells isolated from PC patient incubated in 50 nm paclitaxel (ex vivo) overnight demonstrated microtubule bundling, indicative of drug-target engagement. Conclusions: PSMA based GEDI microfluidic CTC capture is highly specific and sensitive in capturing PSMA positive PC CTCs; and allows detailed CTC analysis including protein expression and subcellular localization, mutational analysis and drug sensitivity assessment. [Table: see text]
Prognostic factors and survial of advanced renal cell carcinoma with predominant sarcomatoid histology.
Authors: I. Park, J. Lee, J. Ahn, D. Lee, C. Song, J. Hong, C. Kim, H. Ahn
Journal: Journal of Clinical Oncology (2011)

400 Background: Sarcomatoid renal cell carcinoma (SRCC) is known to have aggressive clinical course and poor response to treatment. Very limited data of clinical feature, prognostic factor, and survival are available for advanced disease with predominant sarcomatoid histology. We evaluated clinical features, response to treatment, and prognostic factors for survival. Methods: Between 2001 and 2010, 30 patients with metastatic or recurrent RCC with predominant sarcomatoid histology (sarcomatoid component 30% or more for resected kidney or exclusive sarcomatoid carcinoma on needle biopsy) were treated at our institution. We reviewed these patients' records to identify clinical and pathologic features which could affect survival. The role of nephrectomy and systemic therapy on patient outcome was also investigated. Results: There were 20 male and 10 female patients with a median age of 58 years (range, 43–83). Twenty patients had initially metastatic disease and 16 patients (53%) had ECOG performance status (PS) of 0–1. The most frequent metastatic site was lung (57%) followed by bone (43%) and distant lymph nodes (23%). Fourteen (70%) out of 20 patients with initially metastatic disease underwent primary nephrectomy and six patients also underwent metastasectomy. The median % of sarcomatoid component was 80% (range, 30–100%). All patients (N=10) who received immunotherapy had progressive disease as their best response and only one out of 5 patients treated with sunitinib or everolimus had a partial response. With a median follow-up duration of 22 months, the median survival was 3.6 months (95% CI, 0∼7.5) with 6-month survival rate of 43%. Only ECOG PS had impact on survival (P&lt;0.001: ECOG=0, 14.1 months; ECOG=1, 7.4 months; ECOG=2, 3.2 months, and ECOG=3, 1.64 months). Survivals for initially metastatic disease were not significantly different whether patients underwent nephrectomy or not (2.0 months vs. 3.4 months, HR=0.62, 95% CI, 0.16–2.44 after correcting for potential prognostic factors). Conclusions: Patients with SRCC have a fulminant clinical course and the majority of patients had disease progression irrespective of any treatment. Only performance status dose have impact on overall survival. No significant financial relationships to disclose.
Predictors and prevalence of germ-line BRCA mutations in high-risk patients among different ethnicities.
Authors: S. S. Riaz, S. Ahsan, R. E. Bloom
Journal: Journal of Clinical Oncology (2011)

190 Background: Germ-line mutations in tumor suppressor genes, BRCA1 and BRCA2, confer high risks of breast and ovarian cancer in affected individuals. Genetic testing for these pathogenic mutations has potentially important health implications for judicious counseling and screening of high risk individuals. Methods: A retrospective analysis was conducted of all the patients seen at our oncology/genetics clinic from 2000 to 2010. A population of over 500 patients was identified, out of whom 310 subjects underwent risk factor assessment. BRCA testing was performed on 231 of these subjects whereas 79 subjects were not tested secondary to lack of insurance/follow up, or patient/physician preference. Various ethnic groups were identified which included 138 Caucasian, 41 African American, 28 Ashkenazi Jewish, 4 Middle Eastern, 2 Asian and 2 Hispanic subjects. The ethnicity of 16 subjects was unknown secondary to lack of documentation. Results: BRCA mutation testing was completed on 231 subjects out of whom 34 were identified as carriers, comprising 31 female and 3 male individuals. 25 subjects carried BRCA1 and 11 subjects carried BRCA2 mutations, whereas 2 subjects carried both mutations simultaneously. In terms of racial prevalence, the population screened was divided into 4 main groups. Using the Maximum Likelihood Ratio Chi-Square Test, a p-value of 0.96 (p=0.9633) was obtained which indicated that the proportion of mutation did not differ for the races among the population screened. Conclusions: The estimated ethnicity prevalence of BRCA mutations was found to be the highest in African American followed by Caucasian and Ashkenazi Jewish subjects in the population screened at our facility. Overall, BRCA mutations are more common in the Jewish population on which most of the research has been focused. Our study is one of the few to indicate the possibility of high prevalence of mutations in the under-studied and less reported high risk kindred, that is, the African Americans. [Table: see text]
Undertreatment of Patients (Pts) with Myelodysplastic Syndromes (MDS): Analysis of a Large Electronic Medical Records (EMR) Database Cohort of US Pts with MDS
Authors: David P. Steensma, Bart L Scott, Xiaomei Ma, Albert Fliss, Pavel Kiselev, Arlene S. Swern, Mary M. Sugrue
Journal: Blood (2016)
Haplotransplants Versus Other Alternative Donors for Allogeneic Stem Cell Transplantation in Non Hodgkin Lymphoma (NHL): A Retrospective Analysis of the EBMT Lymphoma Working Party
Authors: Sascha Dietrich, Herve Finel, Carmen Martinez, Johanna Tischer, Didier Blaise, Patrice Chevallier, Luca Castagna, Noel Milpied, Andrea Bacigalupo, Paolo Corradini, Mohamad Mohty, Miguel A. Sanz, Andrea Velardi, Andreas Hausmann, Silvia Montoto, Olivier Hermine, Norbert Schmitz, Harry C Schouten, Anna Sureda, Alina Tanase, Stephen Robinson, Peter Dreger
Journal: Blood (2014)
Capecitabine (Cap) combined with bevacizumab (Bev) with or without vinorelbine (Vin) in first-line metastatic breast cancer (MBC): First safety results from the randomized CARIN trial.
Authors: S. Hegewisch-Becker, C. A. Lerchenmuller, A. Welt, T. Decker, M. Just, C. Steffens, A. Hipper, N. Marschner
Journal: Journal of Clinical Oncology (2011)

1044 Background: In RIBBON-1, the combination of Bev with Cap as 1st-line therapy for MBC significantly improved progression-free survival (PFS) compared with Cap alone, with limited impact on tolerability. Vin and Cap are active agents with few overlapping toxicities. The CARIN trial aims to further improve efficacy by adding Vin to Cap/Bev, giving a non-taxane alopecia-sparing regimen. Methods: Patients (pts) are randomized (1:1) to receive Cap 1000 mg/m2 BID days 1–14 + Bev 15 mg/kg q3w (Arm A) or the same Cap/Bev regimen combined with iv Vin 25 mg/m2 days 1+8 (Arm B). Treatment is continued until progression or unacceptable toxicity. Key eligibility criteria include measurable or non-measurable HER2-negative MBC or locally recurrent disease, no prior chemotherapy for MBC, ECOG ≤2, and no brain metastases. Endpoints include PFS (primary), objective response rate, overall survival, and safety. As of Jan 2010, all 400 pts had been enrolled. The protocol-specified interim safety analysis includes the first 50 pts from each study arm after at least 4 cycles of study therapy. Results: Median age of all pts was 61 years. A total of 364 cycles were analyzed. 13 pts in Arm A and 11 in Arm B discontinued before completing 4 cycles due to progression or other reasons. Adverse events (AEs) led to discontinuation in 3 vs 4 pts, respectively. Average Cap dose intensity was 93.3% in Arm A and 84.6% in Arm B. Vin average dose intensity was 92.5%. Dose delays were less common in Arm A (19 cycles vs 58 in Arm B). AEs were less frequent in Arm A (467 events vs 684 in Arm B); grade 3/4 AEs were in a similar range (56 vs 81, respectively). The most common grade 3/4 AE was neutropenia (2 cases in Arm A, 30 in Arm B; 2 vs 18 pts, respectively). Typical Bev-associated grade 3/4 AEs were rare (hypertension and thromboembolic event each in 1 patient in each arm). Conclusions: The Vin/Cap/Bev regimen is tolerable. Additional AEs in Arm B were consistent with the known safety profile of Vin. Importantly, although the dose intensities were reasonably high in both arms, the slightly increased incidence of AEs in Arm B did not lead to a higher discontinuation rate. Updated results will be presented.
Alemtuzumab Consolidation Does Not Improve Outcome for CLL Patients with High Risk Genomic Features on Successive CALGB Trials.
Authors: Jeffrey A. Jones, Amy Stark, Weiqiang Zhao, Thomas S. Lin, Kanti R Rai, Guido Marcucci, Bercedis Peterson, Richard A. Larson, Nyla A. Heerema, John C. Byrd
Journal: Blood (2011)
Maintenance Treatment with Lenalidomide After Transplantation for MYELOMA: Final Analysis of the IFM 2005-02.
Authors: Michel Attal, Valerie cances Lauwers, Gerald Marit, Denis Caillot, Thierry Facon, Cyrille Hulin, Philippe Moreau, Claire Mathiot, Murielle Roussel, Catherine Payen, H. Avet-Loiseau, jean Luc Harousseau
Journal: Blood (2010)