tbuckley/cabot-search huggingface dataset:
Evaluation of an oral direct anti-Xa anticoagulant, apixaban, for the prevention of venous thromboembolism in patients with myeloma treated with IMiD* compounds: A pilot study (MYELAXAT).
Authors: Brigitte Pegourie, Gilles Pernod, Lionel Karlin, Lofti Benboubker, Frederique Orsini, Mourad Tiab, Sophie Auger-Quittet, Philippe Rodon, Bruno Royer, Xavier Leleu, Benoit Bareau, Manuel Cliquennois, Jean-Gabriel Fuzibet, Eric Voog, Karim Belhadj, Olivier Decaux, Philippe Rey, Borhane Slama
Journal: Journal of Clinical Oncology (2017)

8019 Background: The risk of venous thromboembolism (VTE) is higher in myeloma patients recieving IMiD* compounds (IMiD*: registered). A VTE prophylaxis using low-molecular-weight heparin or aspirin is proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficiency and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with IMiD* compounds, using apixaban in a preventive scheme. Methods: Myeloma patients requiring Melphalan-Prednisone-Thalidomide in first line, or Lenalidomide-Dexamethasone in relapse, asymptomatic regarding VTE at inclusion, were enrolled between 2014 - 2016. All patients recieved apixaban, 2.5 mg x 2/day for 6 months, and were monthly monitored. Venous (pulmonary embolism – PE, or symptomatic proximal or distal deep vein thrombosis - DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. Based on meta-analysis of Carrier regarding VTE recurrence, and results from the ADOPT study in medical conditions regarding hemorrhages, &lt; 13 symptomatic VTE events, &lt; 3 severe and &lt; 14 clinically relevant non major (CRNM) bleeding were expected on the treatment period. Results: 104 patients were enrolled (mean age 69.8 +/- 7.8yrs), 11 in first line, 93 in relapse. No PE or arterial cardiovascular events were reported. Two venous thrombotic events were registered, i.e an asymptomatic proximal DVT (patient in relapse) and a symptomatic distal DVT, although apixaban was stopped 14 days before, due to Lenalidomide-induced thrombopenia. Only one major and 11 CRNM hemorrhages were reported. Conclusions: Referring to the incidence of thromboembolic events in Carrier’s meta-analysis, and to hemorrhagic events in medical patients recieving apixaban in primary VTE prophylaxis, apixaban used in a preventive scheme seems to be efficient and safe in preventing VTE in myeloma patients treated with IMiD* compounds. Clinical trial information: NCT02066454.
Impact of value of research analyses on SWOG’s clinical trial capsule scoring.
Authors: Josh John Carlson, David Kim, Gregory F. Guzauskas, Caroline Savage Bennette, Dawn L. Hershman, Laurence H. Baker, Nathaniel Hendrix, Anirban Basu, David Leroy Veenstra, Scott Ramsey
Journal: Journal of Clinical Oncology (2017)

e18311 Background: The Institute of Medicine has called for approaches to help maximize the return on research investments in cancer clinical trials. Value of Research (VOR) analysis is a health economics technique that estimates the clinical and economic returns for research investments and can inform research prioritization. Our objective was to evaluate the impact of VOR estimates on SWOG executive committee’s (EC) clinical trial proposal review scores. Methods: We used a previously developed minimal modeling approach to calculate per-patient and population-level (based on US cancer incidence) VOR estimates for 9 phase II and III SWOG research proposals between February 2015 and December 2016. VOR estimates were presented to EC members who determine which studies to submit to the National Cancer Institute (NCI) for funding approval. EC members scored proposals on scientific merit and potential impact before and after receiving VOR estimates. Scores ranged from 1 (best) to 5. We used the Wilcoxon signed rank test to evaluate the change in pre-post scores. Results: Study characteristics, VOR estimates, and pre-post scores are below. EC scores changed after receiving VOR estimates for 8 of 9 proposals. There was no association between VOR estimates and the magnitude of the change in proposal scores (all p &gt; 0.2). Proposals with larger planned annual enrollment had larger changes in scores (0.3 more points [95% CI: 0.2, 0.56] per 100 patient increase; p = 0.04). Conclusions: Presenting VOR estimates influenced EC scores for SWOG trial proposals. VOR may add important data to inform reviews of trial proposals within NCI Cooperative Clinical Trials group settings. [Table: see text]
Lean and fat-mass changes following upfront docetaxel compared to androgen deprivation monotherapy in metastatic castration-naïve prostate cancer.
Authors: Romy Jose Thekkekara, Surabhi Pathak, Udit Yadav, Ahmed T Ahmed, Michael Russell Mullane, Kumar Kunnal Batra, Thomas E. Lad, Caroline Kato, Sarah P Psutka
Journal: Journal of Clinical Oncology (2018)

e17020 Background: Sarcopenia refers to the functional decline associated with severe deficiency of skeletal muscle mass (lumbar skeletal muscle index (SMI) < 55cm2/m2 for males). The objective of the study is to evaluate body composition changes following systemic treatment in metastatic castration sensitive prostate cancer (mCSPC) in an ethnically diverse inner city population. Methods: Retrospectively, clinical data for 59 mCSPC patients treated at Cook County Hospital (2010-17) were reviewed. Body composition was analyzed using axial computed tomography (CT) images at the level of the third lumbar vertebrae before and after treatment. Data was analyzed with descriptive statistics, Wilcoxon signed rank tests and Cox Proportional Hazards analysis. Results: The median age of the patients studied was 59 (IQR 55-64) years and included 38 (64.4%), 11(18.6%), and 9(15.3%) African Americans, Caucasians and Hispanics respectively. Twenty five patients received upfront docetaxel (UD) in addition to androgen deprivation therapy (ADT). Median time between CTs was 38 (IQR: 26-68) weeks. There was no significant difference in body mass index (BMI) pre- and post-therapy (26 vs.27 kg/m2, p = 0.86). Median SMI declined from 52 to 48 cm2/m2 (p < 0.001) as did the Fat-free mass index (FFMI) from 18 to 17 kg/m2 (p < 0.001). The prevalence of sarcopenia increased from 57.6% pre-treatment to 76.3% post-treatment (p = 0.003). There was a significant increase in median fat mass index (FMI) following treatment from 7.3 to 7.7 kg/m2 (p = 0.03). There were no significant changes in BMI, SMI, FFMI, or FMI between men treated with ADT monotherapy vs. ADT + UD (p > 0.05 for all). Median progression-free survival (PFS) was 96 weeks in nonsarcopenic men vs. 46 weeks in sarcopenic men at diagnosis (HR: 1.89 CI 1.012 to 3.528; p = 0.046). Conclusions: Systemic therapy for mCSPC is associated with significant loss of muscle mass and increase in adipose burden without changes in BMI. Sarcopenia was associated with significantly shorter time to progression. The use of UD was not associated with accelerated lean muscle loss compared to ADT monotherapy.
Risks of upper respiratory tract infection and pneumonia in patients with multiple myeloma receiving Daratumumab: A systematic review and meta-analysis of randomized controlled trials.
Authors: Katy Ticona, Aung Tun, Elizabeth Guevara
Journal: Journal of Clinical Oncology (2018)

e20005 Background: The addition of human anti CD38 IgGκ monoclonal antibody Daratumumab (DARA) to standard multiple myeloma (MM) regimen significantly improves response rates, progression-free survival and the risk of death with notable safety concerns. We performed a systematic review & meta-analysis of RCTs to determine the risk of upper respiratory tract infection (URI) and pneumonia in MM patients receiving DARA Methods: We conducted a literature search using MEDLINE, EMBASE and SCOPUS databases using the terms “multiple myeloma AND daratumumab”, “MM AND daratumumab”, “plasma cell disorder AND daratumumab” through January 2018. The primary meta-analytic approach was a fixed effects model using the Mantel-Haenszel method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Pooled rates of URI & pneumonia were estimated by multiplying the median follow-up duration by the sample size. Results: 1744 patients were eligible. Study arm used bortezomib (V), mephalan (M), prednisone (P) plus DARA; V, dexamethasone (D) plus DARA; and lenalidomide (R), D plus DARA. The control arm used VMP, VD, and RD. The pooled risk ratio for URI was 1.59 (95% CI: 1.33 – 1.91, P = 0.00001) and the absolute RD was 0.1 (95% CI: 0.06 – 0.14, P = 0.00001) with grade 3 or 4 RR of 1.4 (95% CI: 0.63 – 3.15, P = 0.41) and the absolute RD of 0 (95% CI: -0.01 – 0.02, P = 0.41). Pooled RR for pneumonia was 1.48 (95% CI: 1.14 - 1.93, P = 0.002) & absolute RD was 0.05 (95% CI: 0.02 - 0.08, P = 0.004) while the pooled RR for grade 3 or 4 pneumonia was 1.35 (95% CI: 0.98 – 1.86, P = 0.07) and the absolute RD was 0.02 (95% CI: -0.00 – 0.05, P = 0.07). Over median follow up of 24 months, the RR for URI was 1.46 (95% CI: 1.33 – 1.61, P < 0.00001) and RD was 0.18 (95% CI: 0.14 – 0.23, P < 0.00001) while the RR for pneumonia was 1.35 (95% CI: 1.15 – 1.58, P < 0.0003) and RD was 0.07 (95% CI: 0.03 – 0.11, P < 0.0002). Conclusions: Addition of DARA to standard MM regimen contributes a significantly higher risks of URI and pneumonia, without remarkable increase in the risks of grade 3 or 4 events.
Prognostic impact of microsatellite instability status and BRAF V600E mutation in sporadic colorectal cancer.
Authors: Eiji Oki, Yu Nakaji, Ryota Nakanishi, Koji Ando, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ogaki, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2016)

e15105 Background: Several studies have reported intrinsic subtypes in colorectal cancer CRC), showing that microsatellite instability (MSI) and B-type Raf kinase (BRAF) status are important factors of prognosis. Using a BRAF V600E-specific antibody that has recently become commercially available, we investigated BRAF V600E mutation by immunohistochemistry (IHC) and MSI status. Methods: Tissue samples from 472 patients with CRC were analyzed by IHC using BRAF V600E-mutation specific antibody. We performed a direct sequence with 254 samples from patients to examine concordance with the real gene mutation. MSI status was assessed using fluorescent-labeled primers and an automated DNA sequencer. MSI-H was defined as replication error in ≥ 2 markers. Results: The frequency of MSI-H was 9.3% (44/472) and BRAF V600E mutation detected by IHC in 8.7% patients (41/472). Using direct sequence results as reference, sensitivity and specificity for detection of mutation by IHC were 100% (17/17) and 98.7% (234/237), respectively. BRAF V600E mutations were significantly correlated with the anatomical site of tumor (P = 0.0035), histologic type (P < 0.0001), and MSI status (P < 0.0001). Consistent with other published series, patients with BRAF V600E mutation exhibited a significantly shorter overall survival (hazard ratio = 1.500, P = 0.0432) after surgery. Particularly, microsatellite stable/BRAF mutation group had a worse prognosis than MSI-H/BRAF wild-type group (hazard ratio = 2.621, P = 0.0004). Conclusions: In this study, we showed that immunohistochemistry using BRAF V600E-specific antibody is useful for diagnosis and is concurs with direct sequence. CRC cases can be stratified by combined BRAF V600E mutation and MSI status as a prognostic biomarker after curative surgery.
Rapid/warm autopsy to reveal APOBEC-mutagenesis as driver of heterogeneity of metastatic thoracic tumors.
Authors: Nitin Roper, Tapan K Maity, Shaojian Gao, Abhilash Karavattu Venugopalan, Xu Zhang, Romi Biswas, Susan Perry, Constance Cultraro, Chul Kim, Raffit Hassan, Anish Thomas, Arun Rajan, David E Kleiner, Stephen M. Hewitt, Javed Khan, Udayan Guha
Journal: Journal of Clinical Oncology (2017)

9023 Background: Intratumor heterogeneity has been characterized among multiple cancer types. In lung adenocarcinoma, APOBEC-mutagenesis has been shown to be a source of heterogeneity. However, these data are largely limited to early stage primary tumors. There is limited information about the role of APOBEC-mutagenesis and somatic variants, copy number changes, transcript and protein expression in influencing tumor heterogeneity in metastatic lung adenocarcinoma and other thoracic tumors. Methods: We applied whole exome sequencing, RNA-seq, OncoScan CNV and mass spectrometry-based proteomic analyses on 46 tumor regions from metastatic sites including lung, liver and kidney, obtained by rapid/warm autopsy from 4 patients (pts) with stage IV lung adenocarcinoma, 1 pt each with pleural mesothelioma and thymic carcinoma. The autopsy procedure was initiated between 2-4 hours of death. Results: All tumors displayed organ-specific, branched evolution that was consistent across exome, transcriptome and proteomic analyses. The degree of heterogeneity at the genomic and proteomic level was patient-specific. There was extensive heterogeneity within the tumors of one of four patients with lung adenocarcinoma and in the thymic carcinoma patient (both non-smokers) with multiple driver mutations and copy number changes occurring in only some of the tumors suggesting ongoing late tumor evolution. Further examination of the heterogenous thymic and lung adenocarcinoma tumors showed strong enrichment with the APOBEC-mutagenesis pattern and high associated levels of APOBEC3B mRNA. Conclusions: Metastatic lung adenocarcinoma, thymic carcinoma and mesothelioma evolve through a branched, organ-specific process with marked differences in the acquisition of significant driver mutations and copy number changes. APOBEC3B is a potential driver of heterogeneity in pts with advanced, heterogeneous metastatic lung adenocarcinoma and thymic carcinoma and needs to be evaluated further.
Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment
Authors: Xu Wu, Wei Hu, Lan Lu, Yueshui Zhao, Yejiang Zhou, Zhangang Xiao, Lin Zhang, Hanyu Zhang, Xiaobing Li, Wanping Li, Shengpeng Wang, Chi Hin Cho, Jing Shen, Mingxing Li
Journal: Acta Pharmaceutica Sinica B (2018)

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, we summarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.
Internal decompression of the acutely contused spinal cord: Differential effects of irrigation only versus biodegradable scaffold implantation
Authors: James D. Guest, Simon W. Moore, Alex A. Aimetti, Artem B. Kutikov, Andrea J. Santamaria, Christoph P. Hofstetter, Alexander E. Ropper, Nicholas Theodore, Thomas R. Ulich, Richard T. Layer
Journal: Biomaterials (2018)
TCT-287 Efficacy of Intravascular Ultrasound for Patients with Peripheral Artery Diseases Presenting Aorto-Iliac Artery Disease
Authors: Takuya Tsujimura, Osamu Iida, Mitsutoshi Asai, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takashi Kanda, Shota Okuno, Yasuhiro Matsuda, Toshiaki Mano
Journal: Journal of the American College of Cardiology (2018)
Clinical practice evaluation of opioids induced constipation management in oncologic patients: The EIO-50 project.
Authors: Vicente Guillem, Salvador Bofill, Margarita Feyjoo, Antonio Anton, Enrique Aranda, Carlos Camps, Alfredo Carrato, Manuel Constenla, Juan J. Cruz-Hernández, Eduardo Diaz Rubio, Jesus Garcia-Foncillas, Pedro Gascon, Rafael Lopez, Begoña Soler, Yolanda Escobar
Journal: Journal of Clinical Oncology (2018)

e22175 Background: Opioid-induced constipation (OIC) is a common distressing symptom associated with cancer pain treatment. Consensus guidelines for management of OIC are limited and little is known about the decision tree health care professional (HCP) use to manage OIC. The aim of this study was to learn about the diagnostic and treatment criteria of OIC in clinical practice. This study was promoted by ECO Foundation (Excellence and Quality in Oncology), a platform of experts representing the major Spanish hospitals involved in the treatment of cancer patients. Methods: An on-line survey was completed by 135 investigators: 122 medical oncologists (90.4%) and 13 palliative care specialists (9.6%). The questionnaire included 50 items about the management of OIC. Results: OIC was considered a relevant side effect by 97% of the specialists, with a relevance score of 7.8 out of a 10 points scale. OIC was directly managed without referring the patient to another specialist by 86%. HCP reported that most patients with cancer pain (71.2%) maintained the opioid treatment over six months, and 54.4% developed OIC. Only 14.8% HCP used algorithms for the diagnosis of OIC and 14.1% for OIC treatment. Healthy life-style was considered first-line treatment for OIC by 85.5%, although 53% of patients did not respond. Laxatives were prescribed on 99.3% of cases, but only 38.3% recommended them throughout the opioid treatment period, and 33% did not achieve a response to laxatives. Peripherally Active µ-Opioid Receptor Antagonist (PAMORA) were considered by 80% of the HCP a good alternative for the specific treatment of OIC in cancer patients. Indeed, PAMORA were considered the most effective measure with a score of 8 out of a 10 points scale. Conclusions: OIC is considered a frequent and relevant opioid side effect among cancer patients in Spain. Although most of the HCP are aware of OIC existence from the beginning of opioid treatment, there is a limited consensus on the OIC diagnostic and treatment criteria. The narrow effectiveness of traditional therapies and the emerging of more effective pharmacological approaches, suggest the need of standardized and updated guidelines for OIC diagnosis and management in cancer patients.
Single agent HuMab-5B1 (MVT-5873), a monoclonal antibody targeting sLea, in patients with pancreatic cancer and other CA19-9 positive malignancies.
Authors: Eileen Mary O'Reilly, Judy Sing-Zan Wang, Kenneth H. Yu, Maeve Aine Lowery, Anna M. Varghese, Johanna C. Bendell, Erkut Hasan Borazanci, Hayley Estrella, Kimberly Fowler, Mariella Hoskin, H. Toni Jun, Teresa J. Melink, Paul Maffuid, Pamela Klein, John Gutheil, Todd Michael Bauer
Journal: Journal of Clinical Oncology (2017)

4110 Background: MVT-5873, a fully human IgG1 monoclonal antibody (mAb), targets sialyl Lewis A (sLe a ), an epitope on CA19-9. CA19-9 is expressed in pancreatic (PDAC) and other GI cancers, plays a role in tumor adhesion and metastasis, and is a marker of an aggressive tumor phenotype. MVT-5873 is active as a single agent and with chemotherapy in murine xenografts. Methods: MVT-5873 was given IV every other week (Group 1) or weekly (Group 2). Eligible patients had progressive, locally-advanced or metastatic PDAC or other CA19-9+ malignancy and ECOG PS ≤1. Dose escalation followed a 3+3 design with a 10 patient expansion at MTD. Endpoints include safety, MTD, pharmacokinetics (PK) and efficacy. Exploratory endpoints include changes in serum CA19-9 levels. Results: As of 2-Feb 2017, data are available from N = 25 in Groups 1 (N = 9) and 2 (N = 16) at doses ranging from 1 to 3 mg/kg. Dose limiting toxicities of transient grade 3 elevations in AST, ALT, and total bilirubin were encountered at 3 mg/kg in both groups. Liver function laboratory abnormalities typically emerged and resolved within a week of dosing without significant clinical sequelae. Of toxicities deemed possibly related, most were low grade and included GI toxicity (abdominal pain/cramps/diarrhea/nausea) and infusion reactions. Infusion reactions were mitigated by using pre-medications and decreasing the infusion rate. Initial PK data demonstrate initial (20 hours) and terminal (211 hours) half-lives, comparable to other mAbs. Stable disease of &gt; 4 months was observed in 24% of patients. CA19-9 levels were measured pre- and post-dose with each treatment. Immediate reductions showed dose-dependent reductions of up to 97% from baseline at 3 mg/kg. Downward trends of CA19-9 with successive doses were seen, with 48% and 22% of patients exhibiting ≥50% and ≥90% reductions in CA19-9 levels, respectively. Conclusions: Single agent MVT-5873 appears safe and tolerable at biologically active doses. DLTs included reversible serologic liver toxicity. The safety profile, efficacy, and reductions in serum CA19-9 levels over time support further development of MVT-5873 in this indication both as a single agent and in combination. Clinical trial information: NCT02672917.
Paradoxical survival of Hispanics with colorectal cancer: SEER-based cohort.
Authors: Mahmoud Chaker, Anas M Saad, Muneer J Al-Husseini, Mohamed M Gad, Ahmad Rachid, Asfar S. Azmi
Journal: Journal of Clinical Oncology (2018)

e15652 Background: Hispanic populations in the United States are historically underserved with less access to health care as well as lower quality of the provided medical care. With the Colorectal Cancer (CRC) being the third most common cancer in both men and women in the United States, studies were lacking at comparing the survival of Hispanics to non-Hispanics. We aim to study the survival of Hispanic patients with CRC. Methods: We got 547,108 with CRC, of which 42,712 were Hispanics diagnosed between 1973 and 2014 from the SEER database. We calculated the overall and colorectal cancer-specific survival of Hispanics, and non-Hispanics, using unadjusted Kaplan-Meier test and multivariable covariate-adjusted Cox models. Results: The median overall survival of Hispanics was 81 months (95% CI, 78.602- 83.398) and was significantly higher (p < .001) than the overall survival of non-Hispanics; 59 months (95%CI, 58.548- 59.452). Colorectal cancer-specific survival followed a similar trend and Hispanics had better survival outcomes. When we adjusted for age, sex, marital status, stage, grade, and surgery, non-Hispanics were associated with worse survival outcomes (HR = 1.119, 95%CI [1.097-1.140], p < .001). Adjusted cancer-specific survival followed the same trend, and non-Hispanics had worse outcomes (HR = 1.080, 95%CI [1.052-1.108], p < .001). Conclusions: Hispanics with CRC have better overall survival as well as colorectal cancer-specific survival than non-Hispanics. Further studies are required to evaluate the underlying socioeconomic, nutritional, and/or genetic differences contributing to the disparities in survival and the superior survival in Hispanic patients.