tbuckley/cabot-search huggingface dataset:
Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab (R-InO) versus chemotherapy for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL).
Authors: Nam H. Dang, Michinori Ogura, Sylvie Castaigne, Luis Fayad, Mats Jerkeman, John A. Radford, Antonio Pezzutto, Igor Bondarenko, Douglas Allan Stewart, Michael Shnaidman, Sharon Sullivan, Erik Vandendries, Kensei Tobinai, Rod Ramchandren, Paul A. Hamlin, Eva Giné, Kiyoshi Ando
Journal: Journal of Clinical Oncology (2014)

8529 Background: InO is an anti-CD22 antibody conjugated to calicheamicin; R-InO has shown activity in pts with relapsed/refractory aggressive B-NHL in a phase 1/2 study (Fayad, J Clin Oncol 2013; 31, 573-583: ORR, 74% and 20% for relapsed and refractory pts, respectively). Methods: This randomized, phase 3 trial (NCT01232556) compared efficacy and safety of R-InO (R 375 mg/m2 IV–day [d] 1; InO 1.8 mg/m2 IV–d 2 [each cycle]; 28 d cycles) vs investigator's choice (IC: R-bendamustine [R-B: R 375 mg/m2 IV–d 1, B 120 mg/m2–d 1 and d 2 each cycle] or R-gemcitabine [R-G: R 375 mg/m2 IV–d 1, 8, 15, 22 cycle 1, d 1 all other cycles; G 1000 mg/m2–d 1, 8, 15 each cycle]) in adults with relapsed/refractory CD22+ aggressive B-NHL; not candidates for high-dose chemotherapy. Endpoints were OS (primary), PFS, ORR (CR + PR); safety. A planned interim analysis based on 108 events (~40% of planned OS events) was conducted in May, 2013 when enrollment was stopped for futility. We present preliminary results for all enrolled pts. Results: 338 pts were enrolled (age ≥65 y, 68%; DLBCL, 91%; sIPI [≥4], 24%; best prior response of progressive disease [PD], 28%; previous time-to-progression ≥12 mo, 32%). See Table for efficacy results. Most common AEs (R-InO vs IC): thrombocytopenia (59% vs 37%), neutropenia (32% vs 47%), nausea (29% vs 33%), fatigue (33% vs 25%), and leukopenia (21% vs 31%). 2 R-InO pts had venoocclusive disease (VOD) on study treatment (1 additional pt had VOD after an allotransplant and ~13 mo after 1 R-InO dose). Treatment-related death occurred in 6 pts (4 R-InO, 2 IC). Among R-InO vs IC pts, 28% vs 15% discontinued due to AEs; 53% vs 57% due to PD. Conclusions: Although R-InO activity was observed, there was no statistical difference in ORR, PFS, or OS between R-InO vs IC treated pts. R-InO was not superior to IC among subgroups analyzed to date (to be presented). Poorer outcomes in this phase 3 study vs the phase 1/2 study may reflect more refractory pts in this study. Clinical trial information: NCT01232556.Efficacy (95% CI). R-InO (n=166) IC (n=172) ORR, % 41 (33.4–48.9) 44 (36.6–51.9) CR 15 19 PR 26 26 Median, mo DOR 11.6 (7.8–NR) 6.9 (4.6–10.8) PFS 3.9 (2.9–5.0) 3.6 (2.8–4.9) OS 8.6 (6.7–11.8) 9.3 (7.5–13.9) HR = 1.13; p = 0.80
Mucositis in cancer patients: Prototypic semi-mechanistic kinetic model
Authors: D. E. Peterson, R. V. Lalla, R. Srivastava, L. M. Loew
Journal: Journal of Clinical Oncology (2007)

19617 Background: Recent research advances have helped (i) define pathobiology of alimentary tract mucosal injury secondary to cancer therapy and (ii) link molecular mechanisms with clinically important outcomes. Recently-developed computational biology modeling may further enhance these advances. Semi-mechanistic (SM) modeling allows one to approach quantitative analysis of a biochemical system that is incompletely determined. In this study, data from sequential oral mucosal biopsies in 3 patients developing oral mucositis secondary to hematopoietic stem cell transplantation (HSCT) conditioning were utilized to establish a prototypic computational model for this toxicity. Methods: Plasma and oral mucosal biopsy specimens were obtained from 3 autologous HSCT patients before and after administration of conditioning chemotherapy: Day -10, +10, +28 and +100; Day 0 was day of transplant. Full-thickness tissue samples were measured by RT- PCR for COX-1, COX-2, IL-1β and TNF-a. Plasma samples were measured by ELISA for PGE2 and PGI2, markers of COX-2 activity. The SM model was implemented as a system of 6 ordinary differential equations with 15 parameters. Parameter estimation and simulations were conducted based on experimental results, using a combination of Mathematica, Berkeley Madonna and Virtual Cell software packages. Results: The SM model captured the behavior of COX-1, IL-1β and PGE2 dynamics, predicting an exponential decay for each of these species. Half-lives relative to average steady-state values were found to be 9.7 days, 8.7 days and 9.3 days for COX-1, IL-1β and PGE2 respectively. Correlation ratios for each of these species were calculated to be 0.62, 0.61 and 0.90 respectively. Conclusions: This prototypic model provides a basis for development of a detailed mathematical model for quantifying relevant components of the mucositis pathway. This combination of modeling and experiment could also identify gaps in the pathway that would be important targets for new hypotheses, including possible feedback mechanisms relative to inflammatory cytokines. No significant financial relationships to disclose.
OUTCOMES OF ASIAN PATIENTS WITH ATRIAL FIBRILLATION COMPARED TO NON-ASIANS IN THE ENGAGE AF-TIMI 48 TRIAL
Authors: Tze-Fan Chao, Shih-Ann Chen, Christian Ruff, Rose Hamershock, Elliott Antman, Eugene Braunwald, Robert Giugliano
Journal: Journal of the American College of Cardiology (2017)
EFFICACY AND SAFETY OF BIVALIRUDIN IN PATIENTS UNDERGOING PHARMACOINVASIVE STRATEGY FOLLOWING FIBRINOLYSIS FOR ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
Authors: Mohammed Rashid, Jordan Bernick, George Wells, Melissa Blondeau, Aun-Yeong Chong, Alexander Dick, Michael Froeschl, Chris Glover, Benjamin Hibbert, Marino Labinaz, Christina Osborne, Juan Russo, Derek So, Michel Le May
Journal: Journal of the American College of Cardiology (2017)
Clinical response, progression-free survival (PFS), and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) vs IPI monotherapy in CheckMate 069 study.
Authors: F. Stephen Hodi, Michael Andrew Postow, Jason Alan Chesney, Anna C. Pavlick, Caroline Robert, Kenneth F. Grossmann, David F. McDermott, Gerald P. Linette, Nicolas Meyer, Jeffrey K. Giguere, Sanjiv S. Agarwala, Montaser F. Shaheen, Marc S. Ernstoff, David R. Minor, April Salama, Matthew Hiram Taylor, Patrick Alexander Ott, Christine E. Horak, Paul Gagnier, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2015)

9004 Background: Combined blockade of T-cell checkpoints by NIVO and IPI demonstrated a high objective response rate (ORR), promising overall survival (OS), and a manageable safety profile in pts with advanced MEL in a phase I study, based on which an appropriate dose was selected for registrational trials. We report efficacy and safety of the NIVO + IPI combination vs IPI alone in treatment-naïve pts with advanced MEL, including pts with poor prognostic factors, in a phase II study. Methods: Pts (N = 142) with metastatic or unresectable MEL were randomized 2:1 to receive IPI 3 mg/kg combined with either NIVO 1 mg/kg or placebo Q3W × 4, followed by NIVO 3 mg/kg or placebo Q2W until disease progression or unacceptable toxicity. The primary endpoint was ORR in BRAF wild-type (WT) pts. Secondary and exploratory objectives included PFS in BRAF WT pts, ORR and PFS in BRAF V600 mutation-positive (MT) pts, and safety. Results: In BRAF WT pts (n = 109), ORR was 60% (43/72) for NIVO + IPI; 11% (4/37) for IPI alone (P < 0.0001); complete responses were reported in 12 (17%) and 0 pts, respectively. Median PFS was 8.9 months for the combination vs 4.7 months for IPI alone (P = 0.0012). Higher ORR was observed for NIVO + IPI vs IPI in predefined pt subgroups with poor prognostic factors, such as elevated baseline LDH (53% vs 0%) and M1c stage disease (62% vs 25%). Similar ORR and PFS results were observed in 33 BRAF MT pts. Grade 3–4 drug-related adverse events (AEs) were reported in 51% of pts receiving NIVO + IPI vs 20% for IPI alone. The safety profile of NIVO + IPI was similar across pt subgroups, including age. Select AEs related to the combination regimen were consistent with phase I reports and most resolved with immunosuppressive medication ( > 83% across organ categories) with the exception of endocrinopathies. Updated results from a planned data analysis in March 2015 will be presented. Conclusions: NIVO + IPI significantly improved ORR and PFS compared with IPI alone and had a manageable safety profile. The efficacy and safety of the combination was similar across pt subgroups and provided a favorable risk-benefit ratio in treatment-naïve pts with advanced MEL. Clinical trial information: NCT01927419.
Adverse events (AEs) and the return of myelofibrosis (MF)-related symptoms after interruption or discontinuation of ruxolitinib (RUX) therapy.
Authors: Srdan Verstovsek, Ruben A. Mesa, Jason R. Gotlib, Vikas Gupta, John F. DiPersio, John V. Catalano, Michael W.N. Deininger, Carole Brennan Miller, Richard T. Silver, Moshe Talpaz, Elliott F. Winton, Jimmie Huling Harvey, Murat O. Arcasoy, Elizabeth O. Hexner, Roger M. Lyons, Ronald Paquette, Azra Raza, William Sun, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2012)

6624 Background: RUX is a JAK1/JAK2 inhibitor that demonstrated significant clinical benefit in patients (pts) with MF in COMFORT-I (NCT00952289), a phase 3, randomized (1:1), double-blind, placebo (PBO)-controlled study (N=309). Methods: Pts assessed MF-related symptoms daily using the modified Myelofibrosis Symptom Assessment Form v2.0; Total Symptom Score (TSS) was calculated from individual scores for abdominal discomfort, pain under left ribs, early satiety, night sweats, itching, and bone/muscle pain. Therapy was interrupted if platelet or absolute neutrophil count fell below 50,000/µL or 500/µL, respectively. AEs were evaluated during treatment interruption or discontinuation. The protocol suggested an optional tapering strategy and possible addition of steroids if RUX therapy was discontinued for reasons other than thrombocytopenia. Results: In RUX-treated patients with treatment interruption, TSS gradually returned to baseline levels over approximately 1 week. The most common AE leading to treatment interruption or discontinuation in each group was thrombocytopenia (n=11, RUX) and abdominal pain (n=4, PBO). Of these, only 1 RUX pt discontinued for thrombocytopenia. A summary of new onset/worsening AE data after treatment interruption or discontinuation is presented (Table). Of 58 pts who discontinued study treatment, 23 (n=10, RUX; n=13, PBO) experienced a total of 43 SAEs (19, RUX; 24, PBO) that showed no specific pattern or difference between treatment groups. Four of 21 RUX-treated pts had dose tapering following study drug discontinuation. Conclusions: Apart from the expected return of MF-related symptoms, there was no pattern of AEs to suggest that RUX interruption or discontinuation is associated with a specific withdrawal syndrome. [Table: see text]
LOWER ON-TREATMENT LOW-DENSITY LIPOPROTEIN CHOLESTEROL IS ASSOCIATED WITH LOWER CARDIOVASCULAR RISK IN VERY HIGH RISK PATIENTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: ANALYSES FROM THE ODYSSEY TRIALS
Authors: Kausik Kumar Ray, Antonio Vallejo-Vaz, Henry Ginsberg, Michael Davidson, Robert H. Eckel, Veronica Lee, Laurence Bessac, Robert Pordy, Alexia Letierce, Christopher Cannon
Journal: Journal of the American College of Cardiology (2017)
Implications of Low Zinc and Copper Levels As Well As Altered Iron Trafficking Proteins on Oxidant Stress in Patients with Transfusion Dependant Thalassemia
Authors: Patrick B Walter, Michael Minkley, Caitlin Curtis, Hodge Maeve, Razavi Morty, Sarah Ewing, Ashutosh Lal, Anne Higa, David Killilea, Terry Pearson, Ellen B. Fung
Journal: Blood (2016)
Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients
Authors: Thomas A. Mavrakanas, Caroline F. Samer, Sharon J. Nessim, Gershon Frisch, Mark L. Lipman
Journal: Journal of the American Society of Nephrology (2017)

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml (P<0.001). Trough levels increased from 45 to 132 ng/ml (P<0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml (P=0.03), and trough levels increased to 218 ng/ml (P=0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided.
Significant Activity of the JAK2 Inhibitor, INCB018424 in Patients with Secondary, Post-Myeloproliferative Disorder (MPD) Acute Myeloid Leukemia (sAML): Results of An Exploratory Phase II Study.
Authors: Farhad Ravandi, Srdan Verstovsek, Zeev Estrov, Jan A. Burger, Solly George, Carol Bivins, Jorge Cortes-Franco, William M Garrett, Robert C Newton, Hagop Kantarjian
Journal: Blood (2009)
GLOBAL LONGITUDINAL STRAIN CORRECTED BY RR-INTERVAL IS A SUPERIOR PREDICTOR OF ALL-CAUSE MORTALITY IN PATIENTS WITH SYSTOLIC HEART FAILURE AND ATRIAL FIBRILLATION
Authors: Daniel Modin, Morten Sengeløv, Peter Jørgensen, Niels Eske Bruun, Flemming Javier Olsen, Maria Dons, Thomas Fritz-Hansen, Jan Jensen, Tor Biering-Sorensen
Journal: Journal of the American College of Cardiology (2017)
SINUS NODE DYSFUNCTION IN BATTEN DISEASE: A RARE MANIFESTATION OF A RARE DISEASE
Authors: Amole Ojo, Prakash Harikrishnan, Odunayo Olorunfemi, Sei Iwai, Anoshia Raza, Tanya Dutta, Tonusri Nag, Jason Jacobson, Tasleem Katchi, Martin Cohen, Sohaib Tariq
Journal: Journal of the American College of Cardiology (2017)
A feasibility study of an electronic interface between Internet-based survivorship care plans and electronic medical records (EMR)/tumor registries.
Authors: Christine Hill-Kayser, Linda A. Jacobs, Steven C Palmer, Margaret K. Hampshire, Carolyn Vachani, Stephen B. Edge, Erica J. McNamara, James M. Metz
Journal: Journal of Clinical Oncology (2015)

9589 Background: SCP are recommended for all cancer survivors by the Institute of Medicine and Commission on Cancer (CoC). Barriers to implementation include time/ resource limitations, survivor access, and concerns about accurate treatment summary information. This study was performed to evaluate the feasibility of interface development between an SCP and an EMR and cancer registry. Methods: An information technology (IT) application was developed to extract data from the EMR in use at Penn Medicine (EPIC), as well as from the registry at Baptist Memorial Hospital in Memphis, a community hospital utilizing the CoC Rapid Quality Reporting System (RQRS). Data were transferred via XML tunnel to auto-populate an Internet-based tool for creation of SCP (LIVESTRONG Care Plan) that had been previously used for creation of more than 35,000 plans and available at www.oncolink.org / www.livestrongcareplan.org. Results: Design phase involved IT staff at Penn Medicine, RQRS, and OncoLink. Data (demographics, surgeries, chemotherapy drugs, radiation site) were extracted from EMR/RQRS, de-identified, and tunneled to the OncoLink platform, without transfer of PHI. Care plans were created and linked to EMR/registry via global unique identifiers; after auto-population and creation, SCP were tunneled back to the EMR to become part of the medical record, with the entire process occupying less than one minute. During clinical testing at the EMR site, SCP were created by nurse practitioners during scheduled clinic visits. Overall, 147 survivors were screened, 146 eligible, and 89 received SCP. Of these, 60 received breast cancer SCP, 27 colorectal SCP, and 2 both. Survivors were 85% women, 58% Caucasian, median age 56y (24-81y). Conclusions: This is a feasible and rapid solution for the auto-population of SCP with EMR and/or registries, taking less than 1 minute to complete. It represents a future methodology through which widespread implementation of SCP may be undertaken. Future directions include further clinical testing, as well as assessment of provider perceived usefulness, ease of use, and integration into routine clinical care.
Molecular cytology for prostate cancer detection: Multiplex fluorescent staining of urine sediment in the era of new prostate-specific biomarkers
Authors: Kazutoshi Fujita, Jessica Beckman-Hicks, Yuko Konishi, Charles Ewing, Angelo De Marzo, George Netto, William Isaacs, Christian Pavlovich, Alan Meeker
Journal: Cancer Research (2008)

3644  Purpose: Prostate cancer (PCa) molecular markers are detectable in urine after prostatic manipulation, suggesting that whole prostate cells might also be detectable and useful for diagnosis. However, identification of PCa cells by traditional cytology has been hampered by low numbers of PCa cells present, and by high false negative rates. Identification of new molecular markers of prostate cancer, plus significant advances in antibody and in situ nucleic acid detection methods, led us to re-visit the cell-based approach to prostate cancer detection in urine samples. The aims of this study were to develop a highly sensitive and non-invasive method to detect small numbers of PCa cells via fluorescent staining for multiple molecular markers in urinary sediments.  Procedures: We optimized methods for sample collection, cell preservation and staining using antibodies plus FISH for identification of prostate cancer cells in urine specimens. Elevated staining by anti-alpha-methylacyl CoA racemase (AMACR) antibody and decreased telomere FISH staining were used as markers of PCa cells, anti-Nkx3.1 to confirm prostatic origin, anti-nucleolin as a marker of nucleoli and DAPI as a marker of nuclei. For the optimization studies, LNCaP (prostate cancer) and TR4 (bladder cancer) cells were spiked into human urine, isolated, cytospun onto glass slides and stained. For clinical specimens, urine samples were obtained after DRE from 35 patients in the urology clinic and from 15 normal or NED men without DRE, for a total of 50 specimens (positive controls; N=27, negative controls; N=23).  Results: PCa cells were successfully visualized in urine cytospins by combined staining for AMACR, Nkx3.1, Nucleolin, and telomeres in addition to abnormal nuclear morphology revealed by DAPI. In normal cells from urine, the nucleoli were small and scant, and either or both of the AMACR and Nkx3.1 stains were negative. Of the 27 samples from men with biopsy-proven prostate cancer, 8 were noted to have prostate cancer cells or cells highly suspicious for prostate cancer by morphologic and staining criteria. All of the negative controls were read as negative. Sensitivity was 29.6% (8/27), and specificity was 100% (8/8).  Conclusion: Staining voided urine sediment with multiple molecular markers has the potential to diagnose prostate cancer. Our data show that prostate cancer cells can be isolated intact from urine and specifically identified by a multi-staining cytology protocol, even when very few cancer cells are present. Specificity was 100%, however sensitivity was only 29.6%, thus we are currently evaluating other markers and techniques in order to improve this assay for potential diagnostic use.
Age-stratified phase I trial of a combination of bortezomib, gemcitabine, and liposomal doxorubicin in patients with advanced malignancies
Authors: G. S. Falchook, N. Dhillon, S. Moulder, M. Duvic, C. Ng, D. Hong, L. Camacho, J. Lim, M. Wang, L. Fayad, R. Kurzrock
Journal: Journal of Clinical Oncology (2007)

14087 Background: Bortezomib, a potent proteasome and NF-kB inhibitor, potentiates the activity of chemotherapy in a variety of tumors in vitro and in mouse models, and preclinical data suggest that the combination of bortezomib, gemcitabine, and liposomal doxorubicin is synergistic. Because tolerance to combination therapy may be attenuated in elderly patients, we performed a phase I age- stratified trial to determine the maximum tolerated dose (MTD), toxicity, and antitumor activity of this combination. Methods: Starting doses were bortezomib 0.7 mg/m 2 (days 1 and 8), gemcitabine 500 mg/m 2 (days 1 and 8), and liposomal doxorubicin 20 mg/m 2 (day 1). Two parallel age-stratified arms (&lt; 65 and = 65 years old) were accrued, with at least three patients per dose level per arm. Each treatment cycle was 21 days. Results: 47 patients have enrolled, and the MTD has not yet been reached. For patients &lt; 65 years old, accrual continues at the ninth dose level with bortezomib 1.3 mg/m 2 (days 1, 4, 8, 11), gemcitabine 800 mg/m 2 (days 1 and 8), and liposomal doxorubicin 40 mg/m 2 (day 1). For patients = 65 years old, accrual continues at the fourth dose level with bortezomib 1.0 mg/m 2 (days 1, 4, 8, 11), gemcitabine 800 mg/m 2 (days 1 and 8) and liposomal doxorubicin 20 mg/m 2 (day 1). The most common side effects have been thrombocytopenia and neutropenia, with thrombocytopenia necessitating dose delays and withholding of doses. In the arm with patients = 65 years old, a dose-limiting toxicity of grade 3 fatigue was observed at dose level 4, and that cohort is currently undergoing dose expansion. Seven patients have achieved a partial response, including one patient with small cell lung carcinoma (6 months; 3 prior therapies) and all of six evaluable patients with cutaneous T cell lymphoma (1, 3, 4, 6, 7, and 8 months; median 4 prior therapies). Stable disease = 6 months was observed in 5 patients with various solid tumors (7, 7, 8, 9, and 9 months; median 4 prior therapies). Conclusions: This combination regimen is well tolerated. Dose-limiting toxicity has developed earlier in the elderly cohort, as predicted. Antitumor activity in heavily pretreated patients with advanced malignancies has been observed. No significant financial relationships to disclose.