tbuckley/cabot-search huggingface dataset:
Burden of illness estimates of metastatic breast cancer (MBC) in the United States.
Authors: S. Sorenson, A. Benedict, D. A. Yardley, M. Martin, K. B. Knopf, F. Pan, J. Goh, C. Giorgetti, C. Chen
Journal: Journal of Clinical Oncology (2010)

6009 Background: Understanding the cost burden of treating patients (pts) with MBC is challenging but critical to informing cancer policy. Cost estimates vary due to differences in study methodology, the existence of dated information on treatment (tx) patterns and limited availability of cost data related to targeted therapies. This model quantified the magnitude and drivers of overall direct costs of MBC representative of current medical practice in the United States. Methods: A recent incidence- based burden of illness model followed pts with MBC for 5 yrs, from diagnosis, through active tx (if applicable), to palliative care and death. The incidence of MBC, tx costs (including dosage, administration frequency, line of tx, current market share, tx-related grade 3/4 toxicities, and medical follow-up), and care costs were taken from published data and physician input to estimate pt numbers and average tx costs. Modeling using prevalence data from SEER was conducted to estimate the number of pts progressing from early breast cancer (EBC) to MBC. Overall survival based on SEER data was assessed and costs were assigned to living pts monthly, according to their disease stage. Results: Considering pts diagnosed with de novo MBC and those who progressed following EBC, the incidence of MBC in the US is 48,550 pts/yr. The annual cost per pt is $36,677 (∼f$1.7 billion for all pts). Cost drivers are shown below (Table). Taxanes, anti-HER2 txs, and other targeted txs account for 32%, 22%, and 26% of tx costs, respectively. Conclusions: Targeted txs are often added to chemotherapy to improve outcomes in pts with MBC. A significant number of pts are diagnosed with de novo MBC or progress following EBC. While active treatments are the greatest cost drivers, both supportive and palliative care impact the total cost of treating MBC in the United States. Per pt costs in this model are ≂̃f$37,000 dollars, which are ∼f$6,000 higher than those estimated in studies utilizing data from the 1990s. Cost ($)/pt Cost (all pts; $) % of total Diagnosis 493 23,929,201 1.3 Tx (drug and administration) 14,780 717,590,448 40.3 Toxicity 3,806 184,793,577 10.4 Medical follow-up 5,004 242,948,640 13.6 Palliative/supportive care 10,404 505,118,013 28.4 Terminal care 2,189 106,286,936 6.0 Total 36,677 1,780,666,815 100.0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer United Biosource Corporation Pfizer Pfizer
Medullary renal cell carcinoma (RCC): Genomics and treatment outcomes.
Authors: Maria Isabel Carlo, Yingbei Chen, Joshua Chaim, Devyn Taylor Coskey, Kaitlin Woo, James Hsieh, Martin Henner Voss, Darren R. Feldman, Robert J. Motzer, Chung-Han Lee
Journal: Journal of Clinical Oncology (2016)

4556 Background: Medullary RCC is a rare and aggressive type of kidney cancer that primarily affects young adults with sickle cell trait. Recent reports have identified loss of expression of SMARCB1, a chromatin remodeling gene, as a molecular hallmark of this cancer. There is no defined standard treatment for this entity, although most patients receive platinum-based therapy based on small retrospective series (JCO 29; 2011: Abstract 386). Methods: We performed a retrospective analysis on 36 patients given a pathologic diagnosis of medullary RCC at MSKCC from 1995 to 2015. The goal was to characterize the genomics and report on clinical outcomes with systemic therapy. Results: Median age was 28 years (range 12-72), most patients were male (75%), African American (70%; n = 20/29 with race reported) and presented with metastatic disease (83%); 100% (n = 27/27 tested) had sickle cell trait. All patients with available tissue (n = 23) lacked SMARCB1 expression by IHC. Analysis with in-situ hybridization for SMARCB1 (n = 8) revealed loss of heterozygosity with concurrent translocation in 6, and biallelic loss in 2 (Table). Next-generation targeted sequencing (NGS) showed no VHL mutations. Overall survival (OS) in 32 evaluable patients was 5.8 months (95% CI 4.1-10.9). 11 patients received platinum-based therapy; 4 had a partial response, 2 had stable disease, 4 had progressive disease, 1 was non-evaluable; their median PFS was 2.9 months (95% CI 2.0-Not Reached). 3 patients received VEGF or mTOR inhibitors; none had a response. Conclusions: Outcome was mostly poor in this cohort of patients with medullary RCC. We confirmed uniform loss of SMARCB1 as the key molecular feature in this tumor; novel agents targeting chromatin remodeling, such as EZH2 inhibitors, should be explored in this disease. Patient SMARCB1 Expression (IHC) SMARCB1 FISH Analysis Targeted NGS 1 No Hemizygous loss /translocation N/A 2 No Hemizygous loss / translocation N/A 3 No Homozygous loss N/A 4 No Hemizygous loss / translocation AKT3; CDKN2B; ERBB2; GPS2; MLL; MTOR; POLE; SPEN; TET1 5 No Homozygous loss MTOR; FH; STK40; MLL; POLE; IDH; SETD2; RASA1; AR; ATRX 6 No Hemizygous loss / translocation NF1; NSD1 7 No Hemizygous loss / translocation PDGFRB 8 No Hemizygous loss / translocation ERG
Abstract B19: Vascular normalization suppresses tumor progression and potentiates docetaxel chemotherapy in prostate cancer
Authors: You Hyun Kang, Hyun A Jin, Jun Hyeok Heo, Ki Hong Kim, Kyung Seok Han, Sung Joon Hong
Journal: Cancer Research (2016)

Abstract Background: Tumor requires excessive oxygen and nutrients due to their rapid growth. Tumor is generally vascular but the vasculature is not physiologic but leaky, dilated, and tortuous. The inefficiency of tumor vessels induces hypoxic stress that makes the tumor more aggressive. Here, we investigated the role of normalizing tumor vasculature on tumor progression and treatment efficacy of conventional chemotherapy in prostate cancer. Methods: Human vascular endothelial cell (HUVEC) was used to evaluate the effects of SAC-1004 on endothelial cells. Immunofluorescent confocal imaging with immunocytochemistry was performed for E-cadherin expression in HUVECs. MTS assay was performed to assess cell proliferation of HUVECs and PC-3 cells after SAC-1004 treatment. Immunohistochemical staining with anti-CD31 and anti-SMA antibodies was performed to assess vasculature in vivo. PC-3 subcutaneous xenografts were developed to evaluate the effects of SAC-1004 on tumor vasculature and tumor growth in prostate cancer. Magnetic resonance images were taken to assess vascular perfusion in xenografts. SAC-1004 was administrated via tail vein once a day for 7 days. Docetaxel was administrated intravenously once a week. Results: SAC-1004 restored junction protein E-cadherin in vitro in endothelial cells and significantly reduced VEGF-induced retinal vascular leakage. SAC-1004 promoted proliferation of HUVECs in vitro in a dose-dependent manner. However, proliferation of cancer cells was not significantly affected by SAC-1004 treatment. Reduced vascular leakiness and improved hypoxia were found in PC-3 xenografts treated with SAC-1004 treatment and magnetic resonance imaging after SAC-1004 treatment for 7 days confirmed improved perfusion in the PC-3 xenografts treated with SAC-1004 compared with control. Interestingly, SAC-1004 treatment suppressed tumor growth in PC-3 xenografts but SAC-1004 followed by intravenous docetaxel treatment showed the most potent tumor suppression compared with control in PC-3 xenografts. Conclusions: SAC-1004 improves hypoxic tumor microenvironment and restores abnormal leak vasculature of tumor by restoring endothelial cell junction in prostate cancer. Vascular normalization induced tumor regression and docetaxel combination following vascular normalization sensitized prostate cancer to docetaxel treatment. Citation Format: You Hyun Kang, Hyun A Jin, Jun Hyeok Heo, Ki Hong Kim, Kyung Seok Han, Sung Joon Hong. Vascular normalization suppresses tumor progression and potentiates docetaxel chemotherapy in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B19.
20-year epidemiology and treatment experience with lung cancer in Manitoba, Canada
Authors: M. W. Pitz, G. Musto, E. Kliewer, S. Navaratnam
Journal: Journal of Clinical Oncology (2007)

17041 Background: Surgical techniques, radiotherapeutic technology, and systemic therapies have evolved to improve the care of lung cancer patients. We sought to determine the impact of these improvements on the outcome and pattern of care for patients diagnosed with lung cancer in Manitoba. Methods: Patients diagnosed with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) from January 1, 1986 to December 31, 2005 were identified from the Manitoba Cancer Registry (MCR). Demographic, diagnostic, treatment, and outcome data were extracted and analyzed to determine changes over time. Joinpoint Regression Program 3.0 was used for linear regression analysis. Results: 10 679 diagnoses of NSCLC (84.3%) and 1983 diagnoses of SCLC (15.7%) were identified from the MCR. The mean age at diagnosis for NSCLC was 68.7 years, with an increasing linear trend over time (slope (m) = .19, p &lt; .001). There was a trend away from primary surgical treatment (m = -.30, p = .005) and chemotherapy and/or radiotherapy (CRT) (m = - .29, p=.015) and towards no active treatment (m = .59, p &lt; .001). A positive linear trend in survival was seen for patients with NSCLC whose primary treatment was surgical (m = .70, p&lt;.001). For patients treated with CRT, there was an inflection point at 1994 with no trend prior (m= .03, p = .92) and a significant positive trend after (m = .58, p = .029). Overall survival of all NSCLC patients did not follow a trend from 1986 until 1998 (m = -.01, p = 0.97), but has shown a significant linear trend after the 1998 inflection point (m = .96, p = .036). The mean age at diagnosis for SCLC was 66.7 years, with no significant change over time (m = .075, p=.088). There was no significant improvement in survival over time with CRT (m = .13, p=.25) or in the proportion treated with CRT (m = 0.20, p=.51). Conclusions: Oncologic treatment has been administered more selectively to patients with NSCLC over time. There has been improved survival of NSCLC patients treated surgically and non-surgically that has translated into an improvement in the overall survival of NSCLC patients in Manitoba. There has been little change in the treatment pattern and outcome of patients with SCLC over time. No significant financial relationships to disclose.
Genetic and Epigenetic Defects in DNA Repair Lead to Synthetic Lethality of Poly (ADP-Ribose) Polymerase (PARP) Inhibitors in Aggressive Myeloproliferative Disorders
Authors: Michael A McDevitt, Brian D Koh, Anand Patel, Alison R. Moliterno, Weijie Poh, James G. Herman, Robert L Dilley, B. Douglas Smith, Judith E. Karp, Jaroslaw P Maciejewski, Scott H. Kaufmann, Keith W. Pratz
Journal: Blood (2011)
In Multiple Myeloma, Minimal Residual Disease (MRD) Is an Early Predictor of Progression and Is Modulated By Maintenance Therapy with Lenalidomide
Authors: Manuela Gambella, Paola Omedè, Stefania Oliva, Milena Gilestro, Vittorio Emanuele Muccio, Daniela Drandi, Simone Ferrero, Francesca Gay, Francesca Patriarca, Carmela Palladino, Maria Teresa Petrucci, Norbert Pescosta, Anna Marina Liberati, Tommaso Caravita, Francesco Di Raimondo, Alberto Rocci, Pellegrino Musto, Mario Boccadoro, Antonio Palumbo
Journal: Blood (2014)
GW26-e4554 The Clinical Study of Under the Guidance of The New Three - Dimensional Mapping for Radiofrequency Ablation of Arrhythmias
Authors: Dongming Xie, Guolao Zhang, Yihong Yang, Zhanglin Yan, Xiangzhong Liao, Xufeng Zhou, Jiayuan Ling, Jinhai Zhu, Bei Wang, Ping Lai, Kun Xiao
Journal: Journal of the American College of Cardiology (2015)
Approving a Problematic Muscular Dystrophy Drug
Authors: Aaron S. Kesselheim, Jerry Avorn
Journal: JAMA (2016)

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Survival Benefit of Asymptomatic Cytomegalovirus Reactivation and Early Lymphocyte Recovery after HLA-Identical Allogeneic Peripheral Blood Stem Cell Transplantation.
Authors: Dong Hwan Kim, Sang Kyun Sohn, Jin Ho Baek, Jong Gwang Kim, Kyu Bo Lee, Jae-Hoo Park
Journal: Blood (2005)
A phase II study of sorafenib in malignant mesothelioma with pharmacodynamic imaging using <sup>18</sup>fdg-PET.
Authors: S. Irshad, S. Popat, R. N. Shah, S. Burbridge, R. Lal, L. Lang-Lazdunski, Z. Viney, P. Marsden, S. Barrington, J. F. Spicer
Journal: Journal of Clinical Oncology (2010)

7038 Background: Sorafenib inhibits tyrosine kinases including receptors for VEGF, which are present at particularly high circulating levels in mesothelioma patients. Antibodies to VEGF, VEGFR1 and VEGFR2 inhibit mesothelioma growth. RECIST is of questionable value in mesothelioma as clinical benefit may occur in the absence of tumour shrinkage. Changes in FDG-PET avidity may provide an earlier and more accurate response assessment method. This study used radiological response to measure progression-free survival (PFS) and changes in PET parameters to explore efficacy of sorafenib in mesothelioma. Methods: The efficacy of continuous daily oral sorafenib 400 mg BD was evaluated in a single arm phase II trial. The primary endpoint was PFS at 24 weeks assessed by CT using modified RECIST every 8 weeks. Reference values for PFS in mesothelioma have been published previously and are applicable to the second line setting (28% of patients are reported as progression-free at 24 weeks). Eligible patients had received prior platinum combination chemotherapy. Results: 19 patients have been treated (13 male:6 female) (median age 64 [56-78]) (ECOG PS: 0 [2], 1 [16] and 2 [1]). Sixteen patients were evaluable for response. The median duration of treatment was 16 weeks (136 days). One partial response was observed and 13 patients demonstrated stable disease as best response, of which 5 (31%) remained progression-free at 24 weeks. Eleven patients required a dose reduction for toxicity. The most frequent adverse events were fatigue, hand-foot syndrome, diarrhoea and hypertension. All patients had two 18FDG-PET scans before and on treatment at 8 weeks. Conclusions: Sorafenib is associated with manageable toxicity in mesothelioma. Prolonged stable disease according to radiological response was seen in some patients on this trial. Evidence for sorafenib efficacy in mesothelioma will be further explored by analysis of metabolic response using FDG-PET. No significant financial relationships to disclose.
Phase 2 study of programmed death-1 antibody (anti-PD-1, MK-3475) in patients with microsatellite unstable (MSI) tumors.
Authors: Dung T. Le, Nilofer Saba Azad, Dan Laheru, Ilene S. Browner, Hao Wang, Jennifer N. Uram, Holly Kemberling, Lei Zheng, Robert Iannone, Evan Friedman, Amy Meister, Ross C. Donehower, Ana De Jesus-Acosta, Luis A. Diaz
Journal: Journal of Clinical Oncology (2014)

TPS3128 Background: We hypothesize that a correlation may exist between the number of somatic mutations in individual tumors and the response to immune checkpoint inhibitors since each protein-coding mutation has the potential to serve as a novel antigen for an immune response. This may explain why lung cancers and melanomas, which harbor hundreds of somatic tumors, respond so well to these agents. Microsatellite unstable (MSI) tumors are deficient in DNA mismatch repair which leads to hundreds to thousands of spontaneous mutations. Furthermore, similar to melanoma, MSI positive colon cancers, there is often prominent lymphocyte infiltration. PD-1 is upregulated on activated T cells and provides inhibitory signals to T cells undergoing activation. MK-3475 is a humanized monoclonal IgG4 antibody against PD-1 and is showing activity in multiple tumor types. This study aims to establish the treatment benefit and evaluate MSI as a predictive marker of response to anti-PD-1 blockade. Methods: This is an open-label, 2-stage, phase 2 study to evaluate the clinical activity of MK-3475 in 3 cohorts of patients: MSI positive colorectal cancer (CRC); MSI negative CRC; and MSI positive solid tumors but not CRC. MK-3475 will be administered at 10 mg/kg every 14 days. The co-primary endpoints for CRC cohorts are immune-related progression-free survival (irPFS) rate at 20 weeks and objective response rate assessed using immune related response criteria. The primary endpoint for the cohort with other solid tumors is irPFS at 20 weeks. Secondary endpoints include disease control rate, progression-free survival, overall survival and safety. Each MSI positive and MSI negative CRC cohort will evaluate up to 25 patients, and the cohort with MSI positive solid tumors but not CRC will enroll up to 21 patients. Results from exome sequencing and PD-L1 expression using IHC on tumor tissue will be correlated with response. Clinical trial information: NCT01876511.
Short-Term Preoperative High-Intensity Interval Training in Patients Awaiting Lung Cancer Surgery: A Randomized Controlled Trial
Authors: Marc Licker, Wolfram Karenovics, John Diaper, Isabelle Frésard, Frédéric Triponez, Christoph Ellenberger, Raoul Schorer, Bengt Kayser, Pierre-Olivier Bridevaux
Journal: Journal of Thoracic Oncology (2016)
Frequency of First-line Antibiotic Selection Among US Ambulatory Care Visits for Otitis Media, Sinusitis, and Pharyngitis
Authors: Adam L. Hersh, Katherine E. Fleming-Dutra, Daniel J. Shapiro, David Y. Hyun, Lauri A. Hicks
Journal: JAMA Internal Medicine (2016)

of the population report penicillin allergy 3 and 10% of visits for sinusitis 4 and OM result from failed first-line therapy, 5 suggesting that approximately 80% of visits for these diagnoses should be treated with first-line therapy.This study has limitations.It was not possible to confirm the presence of allergy or previous treatment history, factors that influence appropriate antibiotic selection.These data are from 2010 to 2011 but are the most recent complete data available from NAMCS/NHAMCS, and we do not have reason to believe practice patterns have substantially changed.This study provides evidence of substantial overuse of non-first-line antibiotics for 3 of the most common conditions in ambulatory care that collectively account for more than 40 million antibiotic prescriptions annually. 2 These findings indicate that the problem of inappropriate antibiotic prescribing includes not only prescriptions that are unnecessary altogether, but also selection of inappropriate agents. 2 As a result, stewardship interventions should address both antibiotic overuse and inappropriate antibiotic selection to improve patient safety and health care quality.Implementation of stewardship strategies is a key component to meeting the National Action Plan goal of reducing inappropriate antibiotic use by 50% in outpatient settings.
Clinicopathologic characteristics of microsatellite instability (MSI) tumors in resected gastric cancer patients.
Authors: H. J. Cho, J. Kim, S. Im, M. Kim, S. Han, D. Oh, T. Kim, H. Yang, W. Kim, Y. Bang
Journal: Journal of Clinical Oncology (2010)

4040 Background: The DNA mismatch repair (MMR) pathway plays a prominent role in the correction of errors made during DNA replication and genetic recombination and in the repair of small deletions and loops in DNA. Defects in MMR can precipitate microsatellite instability (MSI). DNA MMR also plays a role in the toxicity and the efficacy of DNA-damaging agents including cisplatin. Several PARP inhibitors were developed and showed potentiating the effects of DNA damaging agents. We investigated the frequency of MSI tumors in gastric cancer patients for future clinical trial and explored whether these tumors are associated with specific clinicopathologic characteristics. Methods: Between Feb 2005 and Jan 2006, 732 consecutive gastric cancer patients who received curative resection with D2 dissection in Seoul National University Hospital were recruited for MSI analysis. MSI status was determined using all five of the NCI recommended panel of markers (BAT26, BAT25, D2S123, D5S346 and D17S250). Results: MSI-H (2 or more markers of instability) and MSI-L (only 1 marker of instability) phenotype was observed in 72 (9.8%) and 48 patients (6.6%), respectively. MSI-H was associated with older age (p < 0.0001), well or moderate differentiation (p < 0.0001), intestinal type (p < 0.0001), antral location (p < 0.0001) and presence of lymphatic invasion (p < 0.0001). After 44.2 months of median follow up, 101 patients (13.8%) experienced disease recurrence and MSI-H was associated with longer disease-free survival (DFS), although statistical significance was not reached yet (p = 0.148). Conclusions: Gastric cancer with MSI-H phenotype had specific clinicopathologic features and showed a tendency of longer DFS compared with MSI-L/MSS phenotype. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AZ-KCSG Fellowship
Use of Post-Transplant Cyclophosphamide (PTCy) with Mycophenolate Mofetil and Tacrolimus in HLA Matched Allogeneic Hematopoietic Cell Transplant Is Safe and Associated with Acceptable Transplant Outcomes
Authors: Brian T Hess, Feng Gao, John F. DiPersio, Peter Westervelt, Ravi Vij, Geoffrey L. Uy, Keith Stockerl-Goldstein, Camille N. Abboud, Mark A. Schroeder, Iskra Pusic, Armin Ghobadi, Amanda F. Cashen, Todd A Fehniger, Meagan A. Jacoby, Rizwan Romee
Journal: Blood (2015)
Mesodermal Development From Reprogrammed Fanconi Anemia Cells Is Affected by ALDH2 Enzymatic Activity
Authors: Naoya Suzuki, Asuka Hira, Akira Niwa, Megumu Saito, Keitaro Matsuo, Tatsutoshi Nakahata, Minoru Takata, Miharu Yabe
Journal: Blood (2012)
The Clinical Utility of the 1-Deamino-8-D-Arginine Vasopressin (DDAVP) Trial in the Management of Patients with Von Willebrand Disease: A Retrospective Study.
Authors: Stephen S. Opat, Jake Shortt, Malgorzata B. Gorniak, Heather A. Aumann, Margaret F. Collecutt, Alison M. Street
Journal: Blood (2006)