tbuckley/cabot-search huggingface dataset:
Prevalence and Safety of Off-Label Use of Chemotherapeutic Agents in Older Patients With Breast Cancer: Estimates From SEER-Medicare Data
Authors: Anne A. Eaton, Camelia S. Sima, Katherine S. Panageas
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Prescribing drugs outside of the label indication is legal and may reflect standard practice; however, some off-label use may be inappropriate. This study measured the prevalence and safety of off-label use both in accordance with practice guidelines and inconsistent with practice guidelines in older patients with breast cancer. Patients and Methods: The SEER-Medicare data set was used to identify women diagnosed with breast cancer. Intravenous chemotherapy was identified using Medicare claims and classified as either on-label, off-label but included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer ("off-label/supported"), or off-label and not included in the NCCN Guidelines ("off-label/unsupported"). Hospitalization/emergency department (ED) admission rates were compared. Results: A total of 13,347 women were treated with 16,127 regimens (12% of women switched regimen); 64% of regimens were off-label/supported, 25% were on-label, and 11% were off-label/unsupported, and hospitalization/ED admission occurred in 27%, 25%, and 32% of regimens, respectively (P<.0001). Drugs never included in the NCCN Guidelines for Breast Cancer accounted for 19% of off-label/unsupported use (1% of total use). Conclusions: Off-label use without scientific support was not common, whereas 64% of use was off-label/supported, reflecting the fact that widely accepted indications are often not tested in registration trials. Off-label/supported use will likely increase as more drugs are expected to have activity across cancer sites, and therefore understanding the implications of such use is critical.
Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on inhibition of homeoprotein Six1
Authors: Tak Pan Ng, Kwan Man, Qiao Cheng, Bai Shun Sun, Terence Kw Lee, Ronnie Tp Poon, Chung Mau Lo, Sheung Tat Fan
Journal: Cancer Research (2007)

2184   We previously demonstrated that overexpression of homeoprotein Six1 in hepatocellular carcinoma (HCC) patients is associated with venous infiltration, later pathologic tumor metastasis (pTNM) stage and poor overall survival rate (Ng  et al ., 2006). In this study, short hairpin RNA (shRNA) interference approach was used to suppress the expression of Six1 in a HCC cell line MHCC97L which is capable of local and distant metastases. Stable transfectant MHCC97L-shSix1carrying Six1 specific shRNA plasmid exhibited suppression of Six1 expression to about 40% of the control cell line MHCC97L.  In vitro  functional assays demonstrated that the growth rate and proliferation ability of MHCC97L-shSix1 were markedly suppressed comparing with the control cells. Furthermore, noticeable decrease in cell motility and invasiveness were observed in MHCC97L-shSix1. Data from  in vivo  xenograft tumorigenesis model demonstrated that the growth rate of subcutaneous xenograft in MHCC97L-shSix1 group was significantly reduced (P in vitro  and  in vivo  metastatic ability of MHCC97L implied its potential therapeutic application on treatment of HCC metastasis.
VEGF, PDGF alpha, PDGF beta, and C-Kit expression are not independent survival predictors in stage D<sub>2</sub> prostate cancer (PC)
Authors: B. Kasimis, V. T. Chang, D. Hoover, M. Sikder, S. Gounder, C. Finch Cruz, M. L. Gonzalez, J. Cogswell, S. Srinivas, M. Blumenfrucht
Journal: Journal of Clinical Oncology (2007)

15623 Background: In PC, overexpression of VEGF, PDGF alpha, PDGF beta, and C-Kit has been reported in over 50% of biopsy samples and may be important predictors of survival. Methods: In an ongoing project, we reviewed the records of 26 patients (pts) with stage D 2 PC and stained their archival tissue specimens for VEGF, PDGF alpha, PDGF beta, and C-Kit expression. Immunohistochemistry was performed at US LABS (Irvine CA). All immunostains were evaluated by two pathologists. Immunoreactivity was scored using a semiquantitative system for intensity of staining (0–3+) and % of tumor cells (0–3+). The total score was obtained by averaging the scores between the two readers. All pts had androgen deprivation and were followed at 3 months intervals with physical examination, CBC, chemistry profile and PSA levels. A stepwise Cox model was used with variables: Gleason score, Hemoglobin (Hgb), Alkaline Phosphatase (Alk Phos), PSA, LDH levels, and C-Kit positive or negative staining. Results: Median values were as follows: age 69 years (56–91), Alk Phos 139 U/L(60–1298), PSA 178 ng/ml (1.8–5677), LDH 169 IU/L (100–350), Hgb 12.8 gm/dl (6.8–16.3), Gleason score 8 (5–10), Survival 26 mos (8.3–144.1). The median value for C-Kit staining was 3 on a scale of 0–6. 18 pts were grouped into low staining group (0–4) and 8 pts in a high staining group (4.5–5). The Kappa Coefficient for C-Kit was 0.83, and ranged from 0.78–0.91 for the other 3 stains. In univariate survival analyses, C-Kit staining was a predictor for survival (p=0.037) but not PDGF alfa, PDGF beta, or VEGF. In the stepwise Cox model, independent survival predictors in order of significance were the Gleason score, Hgb, and PSA levels. Conclusions: In this sample, VEGF, PDGF alpha, PDGF beta, and C-Kit overexpression by immunohistochemistry in archival tissue are not independent predictors of survival. The C-Kit, however, has a small association with survival but may have collinearity with known predictors of survival. No significant financial relationships to disclose.
The nuclear factor kB (NFkB) and Notch signaling pathways and BRCA1 mRNA expression in stage IV non-small cell lung cancer (NSCLC) patients (p).
Authors: M. Santarpia, M. Sanchez-Ronco, I. Magri, S. Viteri, C. Costa, A. Gasco, M. Gonzalez Cao, N. Mederos, F. Salazar, J. Bertran-Alamillo, A. Gimenez Capitan, G. Altavilla, S. Benlloch, Z. Yeste, E. Aldeguer, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2011)

7586 Background: Little is known about the potential effect of genetic alterations in the NFkB and Notch pathways on NSCLC p. Musashi 2 activates HES-1 in the Notch pathway, and HES-1 can abrogate CYLD. A20, AEG-1, EZH2 and TRAF6 are also involved in NFkB activation. BRCA1 and RAP80 are modulators of cisplatin-based chemotherapy. Mutations in NFKBIA and DUSP22, which prevent NFkB activation, were described in the sequencing exome of a single NSCLC p, together with K-ras mutations. Methods: mRNA expression of Musashi 2, CYLD, HES-1, A20, EZH2, AEG-1, TRAF6, NFKBIA, RelA, BRCA1 and RAP80 was analyzed by quantitative RT-PCR in tumor samples from 60 advanced NSCLC p. Expression levels by terciles were correlated with clinical characteristics and outcome to chemotherapy. Mutations in NFKBIA and DUSP22 were sequenced in 28 and 21 patients, respectively, and in 12 cancer cell lines. Results: p characteristics: 36 male; 39 adenocarcinomas; 22 smokers; 23 bone metastases; 9 EGFR mutations; 10 K-ras mutations. No NFKBIA or DUSP22 mutations were observed in any of the p or cell lines. PFS was 12.3 months (m) for p in the lowest tercile of AEG-1 expression vs 9.3 m for p in the intermediate tercile and 4.8 for p in the highest tercile (P=0.002). The multivariate analysis showed that only AEG-1 expression was associated with shorter PFS (HR, 1.43; P=0.006). Expression levels of the other genes did not correlate with outcome. However, we had previously generated a two-gene risk model based on AEG-1 and BRCA1 expression: p with high levels of both genes are considered high-risk, p with low levels of both genes are low-risk, and p with high levels of one and low levels of the other gene are intermediate-risk. In the present study, PFS was 13 m in the low-risk group, while it was 7.6 m for the intermediate-risk group and 5.3 m for the high-risk group (P=0.02). Conclusions: NSCLCs have variegated gene expression. AEG-1 and BRCA1 mRNA expression is a genetic signature that can be used as a prognostic model for the management of NSCLC p.
Clinical tools to enhance survivorship cancer.
Authors: Katherine Ramsey Gilmore, Guadalupe R. Palos, Paula A. Lewis-Patterson, Patricia Chapman, Delrose Jones, Weiqi Bi, Maria Alma Rodriguez
Journal: Journal of Clinical Oncology (2015)

245 Background: Clear patient-centered recommendations for follow-up and health maintenance is a primary goal of ASCO’s model for survivorship and palliative care. The Commission on Cancer also sought to improve the quality of survivorship care by requiring accredited programs to implement survivorship care plans (SCPs) and treatment summaries by 2015. Our aim is to describe the SCP's components and metrics collected in 12 survivorship clinics of an academic cancer center. Methods: A multidisciplinary team was convened to develop clinical practice tools to guide providers on transitioning patients to a survivorship clinic. These tools were based on 4 IOM's domains: surveillance, risk reduction, late effects management, and emotional function.Algorithms are supported with a Passport Plan for Health (Passport) specifically designed for each disease. These clinical tools allowed clinicians to provide recommendations for each survivor. Tools were electronically available to survivors and their primary care providers. Descriptive statistics were used to summarize metrics in this analysis. Results: To date, 44 cancer-site specific algorithms and 19 Passports have been launched and used by clinicians in 12 survivorship clinics.Metrics collected are: a) number of Passports completed, b) providers’ completion of SCPs, and c) dates with counseling recommendations outlined in the treatment pathways. Since FY08, 25,912 Passports were distributed to 13,105 survivors. In FY14, 6,160 Passports were issued (80.7% provider completion rate). Passport completion varied by provider (7%-97%). Survivors were counseled for recommendations related to colonoscopy (97% of the time), skin screening (98%), mammogram (97%), gynecological screening (95%), and prostate screening (74%). Conclusions: Algorithms and SCPs serve as clinical tools to help providers and survivors manage physical and emotional issues. These tools increase standardization in the delivery of survivorship care, safety, quality, and promote communication among survivors and providers across clinical settings.
Effects of multiple courses of oral gefitinib, topotecan, and cyclophosphamide in poor risk neuroblastoma
Authors: A. Donfrancesco, M. De Ioris, A. Jenkner, I. Ilari, L. De Sio, A. Castellano, P. Fidani, A. Serra, R. Cozza, C. De Laurentis, C. Dominici
Journal: Journal of Clinical Oncology (2007)

20009 Background: Gefitinib (G) has shown potent inhibitory activity on neuroblastoma (NB) cell proliferation in in vitro models. Experimental data have also reported that the addition of G to cytotoxic drugs can increase in vitro and in vivo antitumor activity in several tumor models, but if this will translate in significant clinical benefits, with respect to survival, is still unclear. We evaluated the feasibility of administering an oral regimen including G combined with topotecan (TPT) and cyclophosphamide (CPA) in heavily pretreated pts with relapsed/resistant metastatic NB. Methods: Patients received oral CPA (50 mg/m 2 /day) followed by TPT (0.8 mg/m 2 /day) plus G (at the fixed dose of 250 mg/day) for 14 consecutive days in an outpatient setting. Courses were repeated every 28 days until progression, and response was evaluated every second course. Expression of EGFR mRNA in primary tumors was assessed by real-time RT-PCR. Results: Six pts (1M/5F), median age 5.4 years (range 4.1–8.2), were enrolled between October 2004 and October 2006. All pts were relapsed after high-dose chemotherapy and hemopoietic rescue with PBSCs. At the time of inclusion, 3 pts were in PR after 8 courses of second-line therapy, whilst 2 pts had achieved SD after 1 and 8 courses of second-line therapy, resp; 1 pt had PD right after PBSC rescue. Significant levels of EGFR mRNA were detected in 4/6 tumors. A median of 7.5 courses (range 1–24) per pt were administered. In 4 pts, the dose of TPT and CPA was reduced by 25% after the first course. After a median follow-up of 12 months (range 1–26), 1 pt is DOD at 15 months since the inclusion and 5 pts are alive, 1 in VGPR (26+ months) and 5 with SD (26+, 1+, 4+, 9+ and 18+ months). Median PFS is 7.5 months (range 1–26). Neutropenia grade 4 was observed in 4/6 pts; rash grade 2 in 2 pts, and hepatic (LFT increase) grade 3 toxicity in 1. Conclusions: The regimen was feasible and well tolerated in this series of heavily pretreated pts. PFS is encouraging, but deserves further evaluation and longer follow-up. Additional molecular studies are ongoing aimed at identifying the subset of NB pts most likely to benefit from the synergy between G and cytotoxic drugs observed in preclinical models. No significant financial relationships to disclose.
Abstract 13614: Increasing Time Between First Diagnosis of Atrial Fibrillation and Catheter Ablation Adversely Affects Long-Term Outcomes
Authors: Thomas J Bunch, Heidi T May, Tami L Bair, David L Johnson, J. P Weiss, Brian G Crandall, Jeffrey S Osborn, Jeffrey L Anderson, Joseph B Muhlestein, Donald L Lappe, John D Day
Journal: Circulation (2012)

Background: Many patients who develop atrial fibrillation (AF) will experience a worsening of their arrhythmia over time. Catheter ablation is an effective rhythm control strategy with favorable lo...
Abstract 17393: Functional Molecular Imaging Characteristics of Ischemic and Non-Ischemic Scar Substrate and successful VT Ablation Sites using 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography
Authors: Mohammed S Abdulghani, Ramazan Asoglu, Mark Smith, Wengen Chen, Rama Vunnam, Tommas Klein, Anastasios Saliaris, Vincent See, Stephen Shorofsky, Vasken Dilsizian, Timm Dickfeld
Journal: Circulation (2014)

Background: Molecular imaging techniques such as 18 FDG PET enables a functional assessment of the anatomic scar substrate and may provide complementary insights in the complex scar substrate of ischemic and non-ischemic patients presenting for ablation of drug-refractory ventricular tachycardia. Method: Out of 68 patients with drug refractory VT undergoing VT ablation 10 patients with ischemic cardiomyopathy with pre-procedural FDG PET/perfusion imaging and well-defined successful VT ablation sites were identified. Metabolic FDG-PET maps were normalized to perfusion maps and reconstructed as 757 segment polar plot and compared to co-registered high-resolution voltage map for each patient. Result: A total of 4194 mapping points were analyzed for metabolic activity. Voltage defined scar (<0.5mV; n=1546 mapping points) demonstrated a metabolic activity of 57±42%, which significantly increased to 72±47% in the border zone (0.5-1.5mV; n=1296 mapping points; p1.5mV; n=1352 mapping points) with 88±43% (p<0.001)...
Non-Hodgkin's Lymphoma Involving the Heart
Authors: Curt Beckwith, James Butera, Ara Sadaniantz, Thomas C. King, James Fingleton, Alan G. Rosmarin
Journal: Journal of Clinical Oncology (2000)

Article Tools Non-Hodkin's Lymphoma Involving the Heart Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.9.1996 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10784641 Non-Hodgkin's Lymphoma Involving the Heart Curt BeckwithxCurt BeckwithSearch for articles by this author , James ButeraxJames ButeraSearch for articles by this author , Ara SadaniantzxAra SadaniantzSearch for articles by this author , Thomas C. KingxThomas C. KingSearch for articles by this author , James FingletonxJames FingletonSearch for articles by this author , Alan G. RosmarinxAlan G. RosmarinSearch for articles by this author Show More The Miriam Hospital, Brown University School of Medicine, Providence, RI https://doi.org/10.1200/JCO.2000.18.9.1996 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Abstract 15884: Cardiosphere-Derived Cells Confer Acute Cardioprotection Following Ischemia-Reperfusion Injury in Rats: Role of Macrophage Polarization
Authors: Geoffrey de Couto, Hideaki Kanazawa, Eleni Tseliou, Linda Marbán, Eduardo Marbán
Journal: Circulation (2014)

Introduction: Cardiosphere-derived cells (CDCs) confer both cardioprotection and regeneration in acute myocardial infarction (MI). However, only long-term (&gt;3 wks) post-MI endpoints have been studied, making it impossible to investigate the cardioprotective effects in isolation. Macrophages (MF) concentrate within the heart following ischemic injury as part of the inflammatory response to injury. Here we test the hypothesis that CDCs are cardioprotective by modifying MF within the myocardium post-MI. Methods &amp; Results: Wistar-Kyoto rats (aged 8-12 wks) underwent 45 min of ischemia followed by 20 min of reperfusion, then intracoronary (i.c.) infusion of either saline or CDCs (5x10 5 ). The use of a 48 hr endpoint enabled the selective study of cardioprotection. CDC-treated animals had preserved ejection fraction (59.2% vs. 47.4%; p&lt;0.001) and reduced infarct size (TTC; 6.3% vs. 13.6%; p&lt;0.01). The finding that CDC-treated hearts contained fewer CD68 + MF (p&lt;0.05) suggested a mechanistic role for MF, a conjecture which we tested in detail. MF isolated from CDC-treated hearts secreted lower amounts of proinflammatory cytokines ( Nos2, Tnf, Il1b ; p&lt;0.05). Systemic depletion of MF with clodronate liposomes attenuated the benefits of CDC therapy post-MI (p&lt;0.05). In vitro , MF conditioned by transwell exposure to CDCs (M CDC ) exhibited distinct gene profiles relative to proinflammatory M 1 or “healing” M 2 polarization states (M CDC : Il10 ; M 1 : Nos2 ; M 2 : Arg1, Pparg ). Adoptive transfer of selective MF populations into the heart (i.c.; 20 min post-reflow) revealed that M CDC , but not M 1 or M 2 MF, could recapitulate the reduction in infarct size (M CDC : 4.5%; M 1 : 14.0%; M 2 : 10.8%; p&lt;0.05). In vitro co-culture shows that M CDC selectively reduce cardiomyocyte apoptosis following oxidant stress (M CDC : 9.9%; M 1 : 39.4%; M 2 : 37.4%; p&lt;0.001). Conclusions: CDCs are cardioprotective when administered 20 min after reflow; the timing distinguishes this form of cardioprotection from preconditioning or ischemic postconditioning. Various lines of evidence indicate that CDCs work by polarizing MF toward a cardioprotective phenotype. The findings motivate further translational development of the adjunctive use of CDCs post-MI to limit infarct size.
Routine short course pre-op radiotherapy or selective post-op chemoradiotherapy for resectable rectal cancer? Preliminary results of the MRC CR07 randomised trial
Authors: D. Sebag-Montefiore, R. Steele, P. Quirke, R. Grieve, S. Khanna, J. Monson, A. Holliday, L. Thompson, G. Griffiths, R. Stephens
Journal: Journal of Clinical Oncology (2006)

3511 Background: Radiotherapy reduces local recurrence (LR) when combined with surgery in resectable rectal cancer. The Medical Research Council CR07 trial was designed to compare two different radiotherapy policies when combined with mesorectal excision. Methods: Patients with operable non-metastatic adenocarcinoma of the rectum were randomised to either routine pre-op short course radiotherapy [25Gy/5F] (PRE) or selective post-op chemoradiotherapy (POST) for patients with involvement of the circumferential resection margin (CRM) - [45Gy/25F + 5fluorouracil]. Results: A total of 1350 patients were randomised from 52 centres in the UK, Canada, New Zealand and South Africa between March 1998 and August 2005. Median follow-up is 3 years. Patients (73% male, median age 65 years, 79% PS0) were well balanced between the 2 arms. 595 of 674 (88%) of the pre-op group received their allocated treatment. Of the 676 patients allocated to the selective post-op chemoradiotherapy arm, 73 (11%) were CRM +ve and 51 of these (70%) received chemoradiotherapy. Post operative chemotherapy was received by 85% of patients with stage III disease. At the time of analysis 23 PRE and 61 POST patients had confirmed LR, 96 and 106 patients respectively distant metastases, and 115 and 146 respectively had died. The 3 year rates for LR (primary end point) were 4.7% and 11.1% for PRE and POST groups respectively (HR 2.47, 95% CI 1.61–3.79), for disease free survival 79.5% and 74.9% (HR 1.31, 95% CI 1.02–1.67) and for overall survival 80.8% and 78.7% (HR 1.25, 95% CI 0.98–1.59. The LR benefit in favour of PRE was consistent for tumours 0–5,5–10 and &gt;10cm from the anal verge (HR 2.00, 2.14 and 4.97 respectively). Further subset analysis based on TNM stage and operation performed will be presented. Conclusions: These preliminary results indicate that routine short course pre-operative radiotherapy results in a signifcant reduction in local recurrence and improved disease free survival at 3 years when compared with a highly selective post operative approach. No significant financial relationships to disclose.
A New Pair of Lungs
Authors: Jack Coulehan
Journal: Annals of Internal Medicine (2016)

On Being a Doctor5 January 2016A New Pair of LungsJack Coulehan, MDJack Coulehan, MDFrom Center for Medical Humanities, Compassionate Care, and Bioethics, Stony Brook University, Stony Brook, New York.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1639 Audio Reading - “A New Pair of Lungs” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A New Pair of Lungs," by J. Coulehan. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The first time Max walked into my office, I felt like electricity had energized the room. She couldn't have been more than 4 feet, 10 inches and was bony thin, but her persona was dazzling. She thrust out her hand and said, “Hi, doc. I'm Max.”Max's previous internist had recently retired, so she decided to try the medical center for primary care. Max suffered from bronchiectasis caused by a mysterious condition called sick cilia syndrome. Because her cilia couldn't clear secretions, repeated pulmonary infections had destroyed much of her lung tissue. As a social worker and recovering alcoholic, Max ... Author, Article, and Disclosure InformationAffiliations: From Center for Medical Humanities, Compassionate Care, and Bioethics, Stony Brook University, Stony Brook, New York.Corresponding Author: Jack Coulehan, MD, 51 Pineview Lane, Coram, NY 11727; e-mail, john.[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “A New Pair of Lungs” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "A New Pair of Lungs," by J. Coulehan. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 5 January 2016Volume 164, Issue 1Page: 66-67KeywordsDyspneaHearingLiver transplantationLung transplantationLungsPhysiotherapyPneumoniaSteroidsThoraxTransplantation ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...