tbuckley/cabot-search huggingface dataset:
Use of stem cell transplantation (SCT) as initial therapy in multiple myeloma (MM) and impact of sociodemographic factors in the era of novel agents: Analysis of 137,409 patients using the National Cancer Data Base (NCDB).
Authors: Mohammed Al-Hamadani, Ronald S. Go
Journal: Journal of Clinical Oncology (2013)

8580 Background: Novel agents for MM became available in the past decade. Our study aim was to determine whether the rate of SCT utilization as part of initial therapy in patients with MM had changed in the US after the introduction of novel agents. We also determined the impact of various sociodemographic factors. Methods: De-identified patient level data were obtained from the NCDB bParticipant User File. NCDB is a nationwide oncology outcomes database, which comprises approximately 70% of all newly diagnosed cancer cases in the United States. Results: A total of 137,409 MM patients were included in the study. The median age was 68 years (range, 18-90+). The population was predominantly male (54%), white (79%), non-Hispanic (87%), and living in a metro (78%), low- or middle-income (annual income &lt; $46,000; 63%), and low- or moderate-education (&gt; 14% without high school diploma; 66%) areas. Most patients had minimal or no co-morbidities (Charlson-Deyo score of 0-1; 93%) and treated in the community setting (62%). The rate of SCT use as initial therapy consistently increased annually from 5% in 1998 to 12% in 2010. This was true for all socio-demographic subgroups except for those who were age &gt; 75 years, treated in the Northeast, and the medically uninsured. Multivariate logistic regression showed that the following characteristics were significant main predictors of lower likelihood of SCT use (odds ratio): age &gt; 65 years (0.18), non-white race (0.57), Hispanic ethnicity (0.68), lack of high education (0.89), annual income &lt; $30,000 (0.76), diagnosed before the era of novel agents (1998-2003) (0.70), covered by a non-managed care insurance (0.57), treatment in a non-academic facility (0.28), residence at a non-metro area (0.88), and treatment facility located outside of the Midwest or West (0.62). In contrast, sex was not significant. Conclusions: Even after the introduction of novel agents, the rate of SCT as initial therapy in MM continues to increase annually in the US. Significant disparity exists in the rate of SCT use by demographic, social, and geographic factors as well as the type of treatment facility.
Obstructive sleep apnoea in acute coronary syndrome: the invisible threat?
Authors: Michael Arzt, Andrea Hetzenecker, Patrick Lévy
Journal: European Respiratory Journal (2017)

Worldwide, coronary artery disease (CAD) is the single most common cause of death [1]. Over seven million people every year die from CAD, accounting for 13.2% of all deaths [1, 2]. The presentation of acute coronary syndrome (ACS) can be unstable angina, non-ST elevation myocardial infarction (NSTEMI) or ST elevation myocardial infarction (STEMI) [1, 3]. In patients with acute coronary syndrome polygraphy monitoring is required to detect sleep-disordered breathing <http://ow.ly/JjZi309czta>
FIRST study: Updated overall survival (OS) in stem cell transplant (SCT)-ineligible newly diagnosed multiple myeloma (NDMM) patients (pts) treated with continuous lenalidomide plus low-dose dexamethasone (Rd) vs melphalan, prednisone, and thalidomide (MPT).
Authors: Thierry Facon, Cyrille Hulin, Meletios A. Dimopoulos, Andrew Belch, Donna Ellen Reece, John V. Catalano, Antonio Pinto, Heinz Ludwig, Nizar J. Bahlis, Michele Cavo, Philippe Moreau, Lugui Qiu, Richard LeBlanc, Rik Schots, S. Vincent Rajkumar, Jennifer Marek, Guang Chen, Annette L. Ervin-Haynes
Journal: Journal of Clinical Oncology (2015)

8524 Background: MPT is considered a standard treatment (Tx) option in many countries for SCT-ineligible pts with NDMM. The FIRST trial showed that continuous Rd improved progression-free survival (PFS) and was associated with an OS advantage vs MPT (Benboubker, NEJM2014). This abstract presents an updated OS and safety analysis, not initially planned, but requested by regulatory authorities. Methods: SCT-ineligible NDMM pts were randomized 1:1:1 to Tx with continuous Rd (28-day cycles), Rd for 18 cycles (Rd18), or MPT for 12 cycles (42-day cycles). The primary endpoint was comparison of PFS (Rd vs MPT) based on IRAC review. Secondary endpoints included OS, overall response rate, and safety. Time from randomization to second progression or death (PFS2) was an additional analysis. Results: 1623 pts were randomized; 535 pts received continuous Rd, 541 received Rd18, and 547 received MPT. As of March 3, 2014, 91 pts remained on Tx with Rd. 697 pts (42.9%) have died (38.9% Tx with Rd, 42.1% with Rd18, and 47.7% with MPT). With a median follow-up of 45.5 mos, median OS was 58.9 vs 56.7 vs 48.5 mos for pts treated with continuous Rd, Rd18, and MPT, respectively (for continuous Rd vs MPT, HR = 0.75 [95% CI, 0.62-0.90]). The majority of 2nd-line Tx were bortezomib-based (55.7% of pts who began 2nd line Tx). 58% of pts had a PFS2 event; median PFS2 was extended with continuous Rd vs Rd18, and MPT (42.9, 40.0, and 35 mos, respectively; HR for continuous Rd vs MPT = 0.74 [95% CI, 0.63-0.86]). Average Tx duration for continuous Rd, Rd18, and MPT was 97.8, 54.8 and 51.9 wks, respectively. Discontinuation of lenalidomide vs thalidomide due to AEs was 22.6 vs 27.0%. Conclusions: In this updated analysis from the FIRST trial, OS benefit was maintained with continuous Rd and it was better tolerated vs MPT in SCT-ineligible NDMM pts. PFS2 improvements suggest benefit of continuous Rd is retained through 2nd-line therapy and does not induce resistance. Safety profile remained consistent with the interim analysis. These findings reinforce continuous Rd as a new standard of care for the studied population. Clinical trial information: NCT00689936.
Rituximab and yttrium-90 ibritumomab tiuxetan radioimmunotherapy as treatment options in patients with indolent lymphoma of the orbit
Authors: B. Esmaeli, B. Pro, M. Saville, P. Mc Laughlin
Journal: Journal of Clinical Oncology (2006)

15532 Objective: To report a cohort of patients with lymphoid tumors of the orbit whose disease responded to immunotherapy with rituximab alone or rituximab followed by Zevalin (yttrium-90 ibritumomab tiuxetan). Methods: Between October 2002 and June 2005, 9 patients with indolent non-Hodgkin’s lymphoma and 1 with orbital benign lymphoid hyperplasia were treated with monoclonal antibodies against CD20. 6 patients with orbital lymphoma (3 follicular B-cell, 2 MALT, and 1 mantle cell lymphoma) received rituximab followed by Zevalin. 2 patients with indolent orbital lymphoma (one with follicular B cell and the other with small lymphocytic lymphoma) and 1 patient with benign lymphoid hyperplasia received rituximab alone. 3 out of the 6 patients who received Zevalin were part of a prospective trial evaluating the efficacy of Zevalin for indolent B-cell lymphoma of the orbit; the rest were treated in other trials at M. D. Anderson. Clinical records and imaging studies were reviewed to document response. Results: 4 men and 5 women were between23 and 83 years old (median age, 63 years). Of the 8 patients with orbital lymphoma, 4 had stage IE, 4 had stage IV, and 6 had previously untreated disease. All 9 patients experienced resolution of the orbital tumor in response to monoclonal antibodies against CD20. Follow-up time ranged from 6 to 32 months (mean, 12 months) after completion of immunotherapy. There were no serious systemic or ocular side effects during the study period. The most common side effect was mild fatigue. All 6 patients treated with Zevalin had transient pancytopenia which normalized within 3 months. Conclusions: Rituximab and Zevalin may be considered as alternative treatment modalities to radiotherapy for indolent B-cell lymphoma or MALT of the orbit. Systemic targeted immunotherapy may potentially have the advantage of lower rate of distant (out-of-field) relapse and less ocular toxicity compared with radiotherapy; these potential advantages would have to be verified in long-term studies and in larger number of patients. [Table: see text]
Efficacy and safety of imatinib in CML over 10 years.
Authors: Rüdiger Hehlmann, Lida Kalmanti, Christian Dietz, Michael Lauseker, Lisa Heinrich, Ulrike Proetel, Andreas Hochhaus, Martin C. Müller, Alice Fabarius, Stefan W. Krause, Jolanta Dengler, Christiane Falge, Gabriela M. Baerlocher, Lothar Kanz, Frank Stegelmann, Michael Pfreundschuh, Karsten Spiekermann, Markus Pfirrmann, Susanne Saussele, Joerg Hasford
Journal: Journal of Clinical Oncology (2014)

7021 Background: Tyrosine kinase inhibitors (TKI) have changed the natural course of CML. With the advent of 2nd generation TKI and the now available choice of drugs, safety issues have gained interest. Methods: We have used 1,551 patients of the randomized CML-Study IV for a long-term safety and efficacy evaluation of imatinib. Adverse drug reactions (ADR) were reported at each follow-up visit, coded and graded according to the NCI CTC AE list. Molecular analysis for residual BCR-ABL transcripts was adjusted by the international scale. Results: 1,501 patients have received imatinib and were evaluable. Median age at diagnosis was 53 years, 88 % were EUTOS low risk. At the last evaluation (04/11/2013) 1,003 patients still received imatinib, 164 have died, 275 have been switched to a 2nd generation TKI, 106 have been transplanted (numbers in part overlapping). The longest observation time was 11.5 years, the median observation time 6.5 years. Efficacy: 10-year progression-free and overall survival probabilities were 81% and 84%, respectively. 10-year cumulative response rates reached 89% for MMR, 81% for MR4, 74% for MR4.5 and 63% for MR5. Safety: In 1,018 out of 1,375 patients (74%) non-hematologic ADR were reported during imatinib treatment, in 193 grade 3/4 ADR (14%); 8-year probabilities (all grades) were: fluid overload or edema 41 (36–46)%, gastrointestinal 38 (34–43)%, myalgia or arthralgia 25 (21–29)%, rash 20 (17–24)%, musculoskeletal 17 (13–22)%, fatigue 17 (13–20)%, neurological 11 (8–13)%, and flu-like 10 (8–13)%. Probability profiles over time have been generated for each ADR. In 5 patients peripheral arterial occlusive disease grade 2 or 3 was reported, but none could be clearly assigned to imatinib. A definite association between any ADR and death was not found. Most patients had their first ADR during the first three years with decreasing frequency later on. Conclusions: Given that no imatinib-related death was recorded and that grade 3/4 ADR could typically be symptomatically improved and tolerated we consider imatinib a safe, comparably well tolerated TKI even after prolonged treatment. After 10 years imatinib continues to be an excellent choice for the treatment of CML in most patients. Clinical trial information: NCT00055874.
Building a crowd-sourced challenge using clinical trial data.
Authors: Fang Liz Zhou, Justin Guinney, Kald Abdallah, Thea C Norman, Brian Bot, James Costello, Liji Shen, Tao Wang, Yang Xie, Gustavo A. Stolovitzky
Journal: Journal of Clinical Oncology (2015)

e16047 Background: Community-based competitions have proven effective at drawing large cross-disciplinary teams to solve complex problems in medicine; however, few competitions have been conducted using cancer clinical trial data due to privacy, legal concerns, and restricted availability of data. Project Data Sphere, LLC (PDS) and Sage Bionetworks/DREAM are launching “Prostate Cancer DREAM Challenge” (Challenge) using historical comparator arm clinical trial data from PDS, an independent initiative of the non-profit CEO Roundtable on Cancer. The goal is to improve understanding of disease progression and treatment toxicity in order to improve clinical management and patient outcomes. Methods: The control arms of four phase 3 clinical trial data sets in metastatic castrate-resistant prostate cancer (mCRPC) - over 2,000 patients - were curated to create training and validation data sets. A team of prostate cancer clinicians and scientists selected 2 Challenge questions: prediction of OS, and prediction of treatment discontinuation. Curation was followed by a “Dry Run”, a mini-simulation of the competition to assess data quality and evaluate baseline predictive models. Challenge organizers set up the legal and data governance framework to facilitate data hosting on Synapse, Sage Bionetworks’ data platform; and promoted the Challenge to a broad and diverse audience. Results: A framework for conducting a crowd-sourced competition using clinical trial data has been established, with an expected launch by Q1 2015. The “Dry Run” implemented the recently published Halabi mCRPC OS model (Halabi, et al., JCO, 2014) and demonstrated robust predictive performance in the data (tAUC = 0.70; P = 6e-07 log rank test). Exploratory (de novo) modeling revealed potential improvements to the model, supporting the concept of an open community Challenge to improve existing state-of-the-art clinical models. Conclusions: The Challenge serves as a proof of concept for a new research paradigm in which historical clinical trial data may be used to crowd-source solutions to clinical questions. By sharing insights from the Challenge we encourage innovative approaches to using such data.
A randomized phase II study of elotuzumab with lenalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.
Authors: Philippe Moreau, Paul Gerard Guy Richardson, Andrzej J. Jakubowiak, Sundar Jagannath, Marc Raab, Thierry Facon, Ravi Vij, Donna Ellen Reece, Darrell White, Lotfi Benboubker, Jeffrey A. Zonder, Jean-Francois Rossi, Claire Tsao, Teresa Parli, Glenn Scott Kroog, Anil Singhal, Sagar Lonial
Journal: Journal of Clinical Oncology (2012)

8020 Background: Elotuzumab (Elo) is a humanized monoclonal IgG1 antibody targeting CS1, a cell surface glycoprotein. CS1 is highly expressed on &gt;95% of multiple myeloma (MM) cells, with lower expression on natural killer cells and little to no expression on normal tissues. A phase 1 trial of Elo plus lenalidomide and low-dose dexamethasone (Elo/Len/Dex) demonstrated an 82% objective response rate (ORR) in patients (pts) with relapsed/refractory (RR) MM (Lonial et al. J Clin Oncol, in press). Methods: In this phase 2 study, previously treated pts with MM were randomized to Elo 10 or 20 mg/kg IV (days 1, 8, 15, and 22 every 28-days in first 2 cycles and days 1 and 15 of subsequent cycles), Len 25 mg PO (days 1-21) and Dex 40 mg PO weekly. Prophylaxis for infusion-related reactions (IRs) was administered prior to each Elo infusion. Treatment continued until disease progression or unacceptable toxicity. The primary objective was to assess efficacy (ORR ≥partial response [PR]) according to IMWG criteria. Results: Among73 pts (median age 63 years; range, 39-82), 55% had received ≥2 prior therapies, 60% had received prior bortezomib, and 62% prior thalidomide. ORR was 82% for all pts including 48% ≥ very good PR (VGPR). The ORRs were 92% in the 10 mg/kg group (n=36) and 73% in the 20 mg/kg group (n=37). Median time to best response was 2.2 months (range, 0.7-17.5). After a median follow-up of 14.1 months, median progression-free survival (PFS) has not been reached, with PFS rates of 75% (10 mg/kg) and 65% (20 mg/kg). Elo/Len/Dex also showed encouraging activity in pts with high-risk cytogenetics (ORR 80%) and/or Stage 2-3 MM (ORR 81%). The most common grade 3/4 toxicities were neutropenia (16%), lymphopenia (16%), and thrombocytopenia (16%). Investigator-designated IRs were reported in 12% of pts (all grades); 1 pt (1.4%) had grade 3 IR (rash). Conclusions: Elo/Len/Dex was generally well tolerated and resulted in a high ORR, and PFS not reached after 14.1 months of median follow-up in pts with RR MM. Updated results will be presented at the meeting. Two phase 3 trials of 10 mg/kg Elo/Len/Dex are ongoing in newly diagnosed MM (ELOQUENT1; CA204-006; NCT01335399) and RR MM (ELOQUENT2; CA204-004; NCT01239797).
Blood oxygen level dependent (BOLD) contrast MRI and breast cancer chemotherapy response
Authors: D. Tripathy, L. Jiang, N. Rao, R. McColl, X. Xie, P. Weatherall, M. Story, L. Ding, R. Mason
Journal: Journal of Clinical Oncology (2006)

10514 Background: Tumor microcirculation and oxygenation play critical roles in tumor growth and response to cytotoxic treatment. Assessing these parameters in vivo may provide a useful tool for evaluating therapy in real time. Deoxyhemoglobin (dHbO 2 ) can serve as an endogenous contrast agent causing signal loss in echo planar MR images. Tumor characteristics or interventions affecting tumor oxygenation, which convert dHbO 2 to HbO 2 produce a BOLD signal gain, may complement conventional MRI. Material and Methods: Ten patients with locally advanced breast cancer received doxorubicin and cyclophosphamide (AC) for four cycles every 2 or 3 weeks followed by paclitaxel for 4 cycles. Prior to chemotherapy and after 1 and 4 cycles of AC, MRI was performed on a 1.5 T scanner. For the BOLD study, patients breathed room air (RA) for 45 sec, then oxygen for 6 min and finally RA again. The BOLD imaging an Echo Planar technique with TR/TE (500/41.4 ms) 256 matrix and 20cm field of view. This was followed by dynamic contrast enhanced (DCE) MRI study. Pre and 1 to 4 day post-treatment tumor biopsies for hypoxia response proteins by immunohistochemistry and global RNA by gene array expression analysis (Illumina platform) were obtained. Results: MRI showed mild BOLD contrast enhancing regions in all evaluable patients with a typical signal enhancement of ∼2%. All 3 patients with an initial high BOLD-effect (&gt;7%) achieved a pathological response after chemotherapy compared to 4 who did not (p &lt; 0.03). The MRI-DCE tumor response signal decreased with chemotherapy, but no correlation with pathological response was seen. No clear difference in hypoxia-induced proteins (eg. HIF1-alpha, VEGF, CA IX ) was seen according to pathological response or BOLD. Distinct gene expression patterns at baseline and after therapy emerged depending on BOLD response involving development, apoptosis and cell cycle pathways. Discussion: BOLD MRI can provide a non-invasive, easily repeatable in vivo approach to assess breast tumor physiology and its sensitivity to hypoxia (vascular oxygenation) may add value by measuring hypoxia and predicting response to therapy. BOLD MRI appears promising to select ideal candidates for hypoxia targeting with anti-angiogenic agents combined with chemotherapy and such studies are under way. No significant financial relationships to disclose.
Prognostic impact of preoperative albumin to globulin ratio in curative colon cancer patients.
Authors: Yuji Toiyama, Hiroyuki Fujikawa, Yasuhiro Inoue, Hiroki Imaoka, Masato Okigami, Hiromi Yasuda, Junichiro Hiro, Shigeyuki Yoshiyama, Susumu Saigusa, Minako Kobayashi, Masaki Ohi, Toshimitsu Araki, Yasuhiko Mohri, Masato Kusunoki
Journal: Journal of Clinical Oncology (2017)

647 Background: Albumin to globulin ratio (AGR) has been reported to predict long term mortality in patients with several cancers. However, prognostic impact of preoperative AGR in colon cancer patients with curative intent has not yet been fully addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in stage I-III colon cancer patients. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA] and AGR) from 251 curative colon cancer patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.32 in current study. Results: Several clinicopathological categories related with tumor progression such as lymph node metastasis, T4 tumor, large tumor size, undifferentiated tumor, venous and lymphatic invasion, and high CEA were significantly associated with low AGR level. The patients with low AGR were significantly poorer OS (P = 0.001) and DFS (P = 0.003) than those with high AGR, respectively. In addition, multivariate analyses demonstrated that low AGR was independently associated with early recurrence (HR = 2.87, P = 0.007) and poor prognosis (HR = 2.56, P = 0.008), respectively. On the other hand, sub analysis of survival curves revealed that stage III colon cancer patients with low AGR were significantly poorer OS (P = 0.007) and DFS (P = 0.02) than those with high AGR, respectively. Furthermore, significantly poorer OS and DFS were also shown in stage I-II colon cancer patients with low AGR, respectively (OS: P = 0.02, DFS: P = 0.01). Conclusions: Preoperative AGR was an independent predictor of early recurrence and poor prognosis in curative colon cancer patients. AGR may represent a simple, potentially useful predictive biomarker for selecting stage I-II colon cancer patients who might need adjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage III colon cancer patients.
An exploratory study to investigate the immunomodulatory activity of BMS-936558 in patients with metastatic clear-cell renal cell carcinoma.
Authors: Charles G. Drake, Mayer N. Fishman, Brendan D. Curti, Jenny J. Kim, Walter Michael Stadler, Douglas G. McNeel, Toni K. Choueiri, Bruce Redman, Gary R. Hudes, Maria Jure-Kunkel, Dan McDonald, Ashok Kumar Gupta, Ashutosh Kumar Pathak, Jon Wigginton, Mario Sznol
Journal: Journal of Clinical Oncology (2012)

TPS2613 Background: With the enhanced understanding of the immune response to a tumor, new immunotherapeutic agents may expand treatment options for metastatic renal cell carcinoma (mRCC). The programmed death-1 (PD-1) receptor is upregulated by activated lymphocytes, and upon binding to its ligands, inhibits lymphocyte function. In a phase 1 study of the anti-PD-1 monoclonal antibody BMS-936558, encouraging antitumor activity has been observed in patients with previously treated mRCC. Responses occurred in extensive mRCC and were durable in many patients. Here we describe an exploratory study to investigate the immune-regulatory activity of various doses of BMS-936558 in patients with metastatic clear-cell RCC. Methods: Eighty patients with metastatic clear-cell RCC will be enrolled in this open-label, parallel group, randomized study. Patients who have received prior treatment with ≥3 therapies, including ≥1 anti-angiogenic therapy, will be enrolled in Arms 1-3 (~20 patients per arm); 20 treatment-naïve patients will be enrolled in Arm 4. BMS-936558 will be administered every 3 weeks until disease progression or unacceptable toxicity at 0.3 mg/kg (Arm 1), 2 mg/kg (Arm 2), and 10 mg/kg (Arms 3 and 4). Patients in the 0.3-mg/kg group may escalate to 2 mg/kg if not responding. Tumor assessments will occur every 6 weeks for the first 12 months then every 12 weeks for the remainder of the study. The primary objective is to evaluate the effects of BMS-936558 on the frequency of circulating immune cell subsets, levels of soluble factors associated with immune responses, and tumor infiltrating lymphocyte populations (based on pre-treatment and week 5 paired biopsies). Secondary objectives are to assess the safety, tolerability, antitumor activity, and immunogenicity of BMS-936558. Exploratory objectives include the association of clinical activity and safety with selected biomarkers in peripheral blood and tumor microenvironment and the characterization of the pharmacokinetics of BMS-936558. As of February 1, 2012, 30 patients were enrolled.