tbuckley/cabot-search huggingface dataset:
Impact of a genomic classifier of metastatic risk on treatment recommendations post-radical prostatectomy: Report from the DECIDE study group.
Authors: Ketan K. Badani, Darby J. S. Thompson, Christine Buerki, Elai Davicioni, Jill Garrison, Mercedeh Ghadessi, Anirban Pradip Mitra, Penelope J. Wood, John C. Hornberger
Journal: Journal of Clinical Oncology (2013)

e16044 Background: Only a minority of prostate cancer patients with adverse pathology and biochemical recurrence (BCR) post radical prostatectomy (RP) experience metastasis and die from prostate cancer. Improved risk prediction models using genomic information may enable clinicians to better weigh the risk of metastasis and the morbidity and costs of treatment in a clinically heterogeneous population. We present a clinical utility study that evaluates the influence on urologist treatment recommendations for patients at risk of metastasis using a genomic-based prediction model (Decipher). Methods: A prospective, pre-post design was used to assess urologist treatment recommendations following RP in both the adjuvant (without any evidence of PSA rise) and salvage (BCR) settings. Urologists were presented de-identified pathology reports and genomic classifier (GC) test results for 24 patients from a previously conducted GC validation study in high-risk post RP men. Participants were fellowship trained, high-volume urologic oncologists (n=21) from 18 US institutions. Treatment recommendations for secondary therapy were made based solely on clinical information (pre-GC) and then with genomic biomarker information (post-GC). This study was approved by an independent IRB. Results: Treatment recommendations changed from pre-GC to post- GC in 43% of adjuvant, and in 53% of salvage setting case evaluations. In the adjuvant setting, urologists changed their treatment recommendations from treatment (i.e. radiation and/or hormones) to close observation post-GC in 27% of cases. However, for cases with low GC risk (&lt;3% risk of metastasis), 79% of these men were recommended for observation post-GC. Consistent trends were observed in the salvage setting including 24% patients with low GC risk recommended for observation even after BCR. Conclusions: These results indicate that urologists across a range of practice settings are likely to change many treatment decisions when presented with genomic biomarker information following RP. Implementation of the GC test into routine clinical practice may better direct treatment decision-making post-RP.
Phase II monotherapy study of YM155, a novel survivin suppressant, administered by 168-hour continuous infusion in previously treated hormone refractory prostate cancer (HRPC)
Authors: V. Karavasilis, A. Mita, G. Hudes, D. Quinn, A. Ferrari, I. Kocak, A. Keating, P. Bartes, D. Charleston, J. de Bono
Journal: Journal of Clinical Oncology (2007)

5135 Background: In a PC-3 tumor cell model YM155 inhibited survivin mRNA transcription and survivin protein expression and showed potent (nM) anti-proliferation activity with strong signs of tumor regression. In a phase I study, two highly refractory HRPC patients exhibited a &gt; 50% reduction of PSA from baseline. Methods: Patients with metastatic HRPC who received prior taxane chemotherapy were eligible. The primary endpoint is PSA response rate (decline by ≥ 50%). Other endpoints include objective tumor response by RECIST and evaluation of toxicity. A two stage Simon study design required one response in stage I (N=13) and 3 responses in stage II (N=14). If 4 responses are achieved then an additional 33 pts (N=60) will be enrolled to further characterize the efficacy and safety. Patients are considered evaluable if they complete 2 cycles. YM155 is given as a 168 hour continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m 2 /day. Results: First two stages are enrolled with treatment ongoing. Data on 32 pts is provided. Median age is 67 y/o (range 53 - 81) with ECOG PS of 0 - 2. All but one patient received at least one prior taxane containing regimen. Two patients are PSA responders to date. One achieved response at cycle 2 (currently at cycle 3) and one at cycle 6 (currently at cycle 10). The median number of cycles is 3 (range 1 - 10). Two patients discontinued due to adverse events; in only one patient was the event (fever) considered related to study drug. Five/32 patients reported grade 3, 4, or 5 AE considered related to drug (coagulopathy secondary to coumadin therapy followed by intracranial hemorrhage, fatigue, URI, decreased Hgb, thrombocytopenia). Seven/32 patients remain on drug including the two responders. Conclusions: The preliminary data of YM155 in HRPC demonstrates activity and has an acceptable toxicity profile. No significant financial relationships to disclose.
Phase I study of enzastaurin (ENZ) and bevacizumab (BV) in patients with advanced cancer: Safety, pharmacokinetics (PK), and response assessment
Authors: M. A. Carducci, D. K. Armstrong, C. Collins, T. Wang, S. Schaefer, S. Ermisch, L. C. Musib, S. Nicol, D. E. Thornton, Z. Zhang
Journal: Journal of Clinical Oncology (2009)

3517 Background: ENZ, an oral kinase inhibitor, suppresses tumor growth through PKC and PI-3 kinase/AKT. BV binds VEGF and inhibits angiogenesis. Since ENZ and BV are complementary in inhibiting angiogenesis, we conducted a Phase I study of ENZ / BV. Methods: Eligible patients (pts) had advanced cancer, adequate organ function and no co-morbidities for increased risk of drug-related toxicities. Six pts were enrolled per cohort; if ≤1 DLT the next cohort opened. A loading dose of ENZ 1125 mg was given on Day 1, C1. After 1 cohort combining ENZ 500 mg/QD and BV at 5mg/kg IV q 2 wks, subsequent cohorts alternated pts between BV 10 mg/kg IV q 2 wks and BV 15 mg/kg IV q 3wks with escalating doses of ENZ (500 mg/QD, 250 mg/BID, and 375 mg/BID) for a total of 7 cohorts. DLT was defined as C1: Grade (G)4 neutropenia ≥7 days, febrile neutropenia, G3 thrombocytopenia with bleeding or G4 thrombocytopenia; G3/G4 non-hematological toxicities, and toxicities associated with BV. ENZ PK was performed at steady-state on Day 1, C2. Results: 43 pts (21 with ovarian cancer) are evaluable for toxicity. Two DLTs (G3 elevated aminotransferase and intraparenchymal hemorrhage) occurred at different dose levels. No apparent increase in ENZ or BV toxicity was seen. Two SAEs (DVT and myocardial ischemia) in two pts occurred at DL 3 after 3 cycles and 13 cycles, respectively. Common toxicities included fatigue, chromaturia, dry/sore mouth, nausea and diarrhea. Nine of 43 pts (21%) had a response (CR, PR), 6 responses were in the ovarian subset (29%). Median time to progression was 3.9 mos (range 0–19.2 mos) and 7.7 mos for ovarian pts (range 0.3–19.2 mos). Overall, 43% remained on study without disease progression for &gt;6 mos (51% of ovarian pts remained on study for &gt;6 mos). Mean steady-state ENZ concentrations (%CV) at 500 mg/QD, 250mg/BID and 375mg/BID were 1080 nmol/L (82.8 %), 516 nmol/L (102%) and 1120 nmol/L (93.3%), respectively. Conclusions: The addition of ENZ to BV in any of the currently approved BV dosing schedules is well tolerated and clinically active in advanced cancer pts. ENZ exposures are highly variable and comparable across the three dose groups. The combination of ENZ / BV demonstrates encouraging activity, specifically in our population of ovarian cancer pts. [Table: see text]
A Text-Book of Elementary Analytical Chemistry, Qualitative and Volumetric.
Journal: JAMA (1907)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Search for Optimal Stereotactic Body Radiotherapy Dose in Inoperable, Centrally Located Non–Small-Cell Lung Cancer Continues
Authors: Terence T. Sio, Pranshu Mohindra, Nathan Y. Yu, Jonathan B. Ashman, Thomas B. Daniels, Kenneth W. Merrell, Steven E. Schild
Journal: Journal of Clinical Oncology (2019)
Impact of first-line platinum therapy on survival in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine.
Authors: Ronan Fougeray, Toni K. Choueiri, Francesc Pons, Fabio Augusto Barros Schutz, Yacine Salhi, Jonathan E. Rosenberg, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2012)

e15007 Background: Standard first-line therapy of advanced TCCU is based on cisplatin-based combinations. In patients deemed unfit to receive CISPLATIN, carboplatin-based or non-platinum combinations are considered. A phase III trial comparing vinflunine (VFL) and best supportive care (BSC) with BSC alone for second-line treatment of advanced TCCU patients demonstrated a survival advantage for VFL+BSC. We studied the impact of the first-line platinum therapy on overall survival in second line setting. Methods: Eligible 357 patients of the phase III study were split in the two following subsets: CISPLATIN (Patients with prior CISPLATIN administration) and NO CISPLATIN (patients without prior CISPLATIN administration). Survival was measured from the date of random assignment. Overall Survival (OS) was calculated using Kaplan-Meier method, with log-rank comparisons. Multivariate Analysis of OS was analyzed with the Cox proportional hazards model, including prognostic factors for second-line setting previously identified (Bellmunt, 2010). Updated survival data in 11/2008 cut-off date was used. Results: CISPLATIN group represented 70.3% (n=251) and NO CISPLATIN 29,7% (n= 106). CISPLATIN group had less Liver involvement (25% vs 43%, p=0.0007) and better WHO-PS (&gt;1: 66% vs 76%; p=0.0478). OS was higher in CISPLATIN group for all eligible patients (HR: 0.77; CI 95% 0.61-0.97; p=0.0294), for VFL+BSC arm (HR: 0.78; CI 95% 0.59-1.02; p=0.0693) and for BSC arm (HR: 0.68; CI 95% 0.42-1.08; p=0.0978). Multivariate analysis including prognostic factors (liver involvement, hemoglobin, PS) and prior platinum administration, did not show effect of CDDP on OS. VFL reduced the risk of death by 24% in CDDP-group (HR: 0.76; CI 95% 0.58-0.99; p=0.043) and by 35% in NO CDDP –group (HR: 0.65; CI 95% 0.41-1.04; p=0.0724). Conclusions: Differences in prognostic factors between CISPLATIN and NO CISPLATIN groups may explain the differences in OS in patients who undergo 2nd line therapy. The choice of Cisplatin or no Cisplatin chemotherapy in the first line did not impact subsequent benefit of vinflunine over best supportive care.
Lectures on Appendicitis and Notes on Other Subjects.
Journal: JAMA (1897)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Fecal DNA Testing for Colorectal Cancer Screening
Authors: John M. Carethers
Journal: Annual Review of Medicine (2019)

Fecal (or stool) DNA examination is a noninvasive strategy recommended by several medical professional societies for colorectal cancer (CRC) screening in average-risk individuals. Fecal DNA tests assay stool for human DNA shed principally from the colon. Colonic lesions such as adenomatous and serrated polyps and cancers exfoliate cells containing neoplastically altered DNA that may be detected by sensitive assays that target specific genetic and epigenetic biomarkers to discriminate neoplastic lesions from non-neoplastic tissue. Cross-sectional validation studies confirmed initial case-control studies’ assessment of performance of an optimized multitarget stool DNA (mt-sDNA) test, leading to approval by the US Food and Drug Administration in 2014. Compared to colonoscopy, mt-sDNA showed sensitivity of 92% for detection of CRC, much higher than the 74% sensitivity of another recommended noninvasive strategy, fecal immunochemical testing (FIT). Detections of advanced adenomas and sessile serrated polyps were higher with mt-sDNA than FIT (42% versus 24% and 42% versus 5%, respectively), but overall specificity for all lesions was lower (87% versus 95%). The mt-sDNA test increases patient life-years gained in CRC screening simulations, but its cost relative to other screening strategies needs to be reduced by 80–90% or its sensitivity for polyp detection enhanced to be cost effective. Noninvasive CRC screening strategies such as fecal DNA, however, have the potential to significantly increase national screening rates due to their noninvasive nature and convenience for patients.
Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels
Authors: Qiaoli Ma, Yann Decker, Andreas Müller, Benjamin V. Ineichen, Steven T. Proulx
Journal: The Journal of Experimental Medicine (2019)

The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.
Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration
Authors: Joshua W.D. Tobin, Colm Keane, Jay Gunawardana, Peter Mollee, Simone Birch, Thanh Hoang, Justina Lee, Li Li, Li Huang, Valentine Murigneux, J. Lynn Fink, Nicholas Matigian, Frank Vari, Santiyagu Francis, Robert Kridel, Oliver Weigert, Sarah Haebe, Vindi Jurinovic, Wolfram Klapper, Christian Steidl, Laurie H. Sehn, Soi-Cheng Law, Michelle N. Wykes, Maher K. Gandhi
Journal: Journal of Clinical Oncology (2019)

Understanding the immunobiology of the 15% to 30% of patients with follicular lymphoma (FL) who experience progression of disease within 24 months (POD24) remains a priority. Solid tumors with low levels of intratumoral immune infiltration have inferior outcomes. It is unknown whether a similar relationship exists between POD24 in FL.Digital gene expression using a custom code set-five immune effector, six immune checkpoint, one macrophage molecules-was applied to a discovery cohort of patients with early- and advanced-stage FL (n = 132). T-cell receptor repertoire analysis, flow cytometry, multispectral immunofluorescence, and next-generation sequencing were performed. The immune infiltration profile was validated in two independent cohorts of patients with advanced-stage FL requiring systemic treatment (n = 138, rituximab plus cyclophosphamide, vincristine, prednisone; n = 45, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), with the latter selected to permit comparison of patients experiencing a POD24 event with those having no progression at 5 years or more.Immune molecules showed distinct clustering, characterized by either high or low expression regardless of categorization as an immune effector, immune checkpoint, or macrophage molecule. Low programmed death-ligand 2 (PD-L2) was the most sensitive/specific marker to segregate patients with adverse outcomes; therefore, PD-L2 expression was chosen to distinguish immune infiltrationHI (ie, high PD-L2) FL biopsies from immune infiltrationLO (ie, low PD-L2) tumors. Immune infiltrationHI tissues were highly infiltrated with macrophages and expanded populations of T-cell clones. Of note, the immune infiltrationLO subset of patients with FL was enriched for POD24 events (odds ratio [OR], 4.32; c-statistic, 0.81; P = .001), validated in the independent cohorts (rituximab plus cyclophosphamide, vincristine, prednisone: OR, 2.95; c-statistic, 0.75; P = .011; and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: OR, 7.09; c-statistic, 0.88; P = .011). Mutations were equally proportioned across tissues, which indicated that degree of immune infiltration is capturing aspects of FL biology distinct from its mutational profile.Assessment of immune-infiltration by PD-L2 expression is a promising tool with which to help identify patients who are at risk for POD24.
Safety and anticancer activity of low dose regimen of NGRhTNF, a new vascular targeting agent, in solid advanced malignancies (NGR002 phase I trial)
Authors: C. Gallo-Stampino, G. Rizzardi, S. Toma, A. Corti, P. Scifo, G. Citterio, V. Gregorc, A. Del Maschio, F. Caligaris-Capio, C. Bordignon
Journal: Journal of Clinical Oncology (2007)

3540 Background: NGRhTNF is a vascular targeting agent (VTA) exploiting a tumour homing peptide (CNGRCG) selectively binding angiogenic vessels in solid tumours where NGRhTNF specific binding relies on dynamic interactions with TNF-receptors and aminopeptidase N (CD13). NGRhTNF combines activity on tumour vascular permeability and direct anticancer activity. Consistently, mouse preclinical data indicate significant synergy between low dose NGRhTNF and cytotoxic agents. Methods: 4 dose levels of NGRhTNF (0.2 up to 1.6 mcg/sqm) have been administered q 3 w in 16 patients. Main end-points included safety, anticancer activity and pharmacokinetic.Measurement of circulating tumor and endothelial cells (CTC and CEC), sTNFRI and s TNFRII, along with plasma cyto-chemokine profile have been performed. Results: 16 patients were enrolled (6F/10M);median age 60,range 43–73). Toxicity was limited to constitutional symptoms, and chills were the most frequent event (40%). Over a median follow-up of 15 weeks, stable disease was achieved in 44% of patients, with long lasting disease control in 2 cases (27 and 75 weeks, with establishment of indication to radical surgery after 75 weeks, presently tumor free after removal of the residual tumor mass). In these 2 patients, VEGF, MMP-9, CA125, significantly decreased over time. DCE-MRI indicates that NGRhTNF increases vascular permeability after first drug exposure, particularly at the dose of 0.4 mcg/sqm, while following multiple infusions it exerts an antivascular effect, as demonstrated by the decrease of K trans values. Moreover NGRhTNF is able to elicit inflammatory and immune responses over time, as indicated by the modulation of expression of multiple cyto-chemokines. Finally, changes in CTC levels over time consistently matched the clinical outcome. Conclusions: Low dose NGRhTNF has an optimal safety profile along with anticancer activity acting on tumour vasculature and inducing relevant biological effects, thus rendering the agent suitable for a development both as monotherapy and in combination with chemotherapeutics. The phase II program is due to start in early 2007. [Table: see text]
Opioids and a failure to declare competing interests
Authors: Juliet Dobson
Journal: BMJ (2019)

The BMJ will have noticed that we published no print issue this week.Many of you will have on holiday and, if you're lucky, switched off from medical reading for a week or two.So we are using this opportunity to highlight some recent online articles that you may have missed.On 26 August, a judge in Oklahoma ordered the drug company Johnson and Johnson to pay the state $572m (£467m; €516m) for its role in the state's opioid crisis (doi:10.1136/
Insight Medicine Lacks — The Continuing Relevance of Henrietta Lacks
Authors: Shakkaura Kemet
Journal: New England Journal of Medicine (2019)

remain a central tenet of public health programs.Public health leaders can ensure that global guidance considers all risks related to DTG, including those associated with receiving inferior regimens, and that women receive all the information they need to make their own, informed choices about treatment.The views expressed in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the Department of Health and Human Services, or the U.S. government.Disclosure forms provided by the
Improving the Understanding of Genetic Variants in Rare Disease With Large-scale Reference Populations
Authors: Nicola Whiffin, James S. Ware, Anne O’Donnell-Luria
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The First Experience of Treatment of Patients with Primary Mediastinal Lymphoma Using the R-m-NHL-BFM-90/R-EPOCH Protocol
Authors: Nelly Gabeeva, Daria Koroleva, Anastasya Belyaeva, Anna Smolyaninova, Natalia G. Chernova, Valery Lapin, Alla M. Kovrigina, Eugene E. Zvonkov, Valery G. Savchenko
Journal: Blood (2018)