tbuckley/cabot-search huggingface dataset:
Prothrombotic profile in multiple myeloma: Response to treatment and associated thrombotic complications: A prospective observational study.
Authors: Dipanjan Panda, Atul Sharma, Vinod Raina, Lalit Kumar, Renu Saxena, Sanjay Thulkar
Journal: Journal of Clinical Oncology (2013)

e19531 Background: Venous thromboembolism (VTE) is a major complication of Multiple myeloma. The exact cause of thrombosis, role of anti myeloma drugs especially immunomodulators and steroids and the relation of thrombosis with alteration of thrombotic profile is not clear. While some available data is suggestive of low incidence of VTE in Asian population, true incidence and risk factors of VTE in Indian population is not known.So the present study was undertaken to have an evaluation of prothrombotic factors in Indian population. Methods: A prospective observational study was conducted from July 2008 to November 2009 at All India Institute of Medical Sciences (AIIMS), New Delhi, India. Thirty patients of newly diagnosed myeloma were recruited and were treated with thalidomide and dexamethasone for 4 months. Prothrombotic profile including protein Cand S, activated protein C resistance, plasma fibrinogen, factor VII and von Willebrand factor level was measured and Doppler study was done at baseline and after 4 months. Statistical analysis was done using SPSS 15 software. Frequency distribution, mean, median, range, standard deviation, Inter Quartile Range were calculated. To find out difference between pre and post treatment, Macnemar chi-square test (for proportion) and paired t test (mean) were done. Results: At the base line 4 patients (13%) had low protein C, 3 (10 %) had low protein S and 2 patients (6%) had high factor VIII. Post induction therapy 7 patients showed low protein C, 1 had low protein S and 1 had high factor VIII value. Rest of the factors was within normal limit both at baseline and post treatment in other patients. During the study period 2 subjects developed DVT. While one had low protein S, other patient had low protein C and low anti thrombin III which was done to find out the cause of DVT. Conclusions: Incidence of DVT in our patients seems to be less than western published data. Although thrombotic factors abnormalities are present in myeloma patients but the relation of coagulation factor abnormalities and development of DVT require further study. A larger prospective trial may be required to get a clear picture.
Current alignment between the practice patterns of gastrointestinal (GI) cancer clinical investigators (CI) and general medical oncologists (MO) in the treatment of metastatic GI cancers.
Authors: Neil Love, Gloria Kelly, Kirsten Miller, Douglas Paley, Jonathan Moss, Kathryn Ziel
Journal: Journal of Clinical Oncology (2017)

724 Background: CI with an interest in specific cancers amass a unique body of knowledge and relevant experiences that may make their practice patterns different from those of MO. This initiative sought to document and compare the stated management approaches of CI and MO. Methods: InMay 2016, as part of a continuing medical education (CME) project, 31 CI elected to complete a 78-item survey assessing their usual treatments for various metastatic colorectal, gastric and pancreatic cancer clinical scenarios. A stipend was provided for participation. On June 4, 2016, 13 clinical questions from the CI survey were posed to 140 MO, 103 US-based and 37 non-US-based, prior to a CME symposium on GI cancers. Responses of the groups were compared. Results: For 10 out of 13 questions, there was relative concordance between CI and MO responses. However,for 3 there was considerable variation (see Table). Conclusions: Although CI and MO approach the care of many patients with GI cancers in a similar manner, important and noteworthy variations exist. These findings indicate that the documentation and comparison of treatment recommendations could be a novel strategy to elucidate misalignment between CI and MO and impel either or both to rethink current approaches. Additional work is needed to validate these findings and understand potential implications and applications. [Table: see text]
Analysis of the Sub-Clonal Origins of Compound Mutations in Patients with Refractory Ph+ Malignancies Treated with Ponatinib
Authors: Justin R. Pritchard, Michael W. Schmitt, J. Graeme Hodgson, Stephanie Lustgarten, Shijie Tang, Lawrence A. Loeb, Jerald P. Radich, Victor M. Rivera
Journal: Blood (2016)
Phase I clinical and pharmacologic study of the focal adhesion kinase (FAK) inhibitor GSK2256098 in pts with advanced solid tumors.
Authors: Jean-Charles Soria, Hui Kong Gan, Hendrik-Tobias Arkenau, Sarah Patricia Blagden, Ruth Plummer, Malcolm Ranson, T.R. Jeffry Evans, Gerard Zalcman, Rastislav Bahleda, Antoine Hollebecque, Charlotte Lemech, Jennifer Brown, Vijay Gopal Reddy Peddareddigari, Diana Gibson, Sharon Cornell Murray, Noelia Nebot, Jolly Mazumdar, Ronald Alan Fleming, Michael Millward
Journal: Journal of Clinical Oncology (2012)

3000 Background: FAK has an important role in cancer invasion and metastasis. FAK and phospho-FAK (pFAK) are increased in advanced cancer and are correlated with poor prognosis. GSK2256098 is a potent and specific small molecule inhibitor of FAK. Methods: This is a first-time in cancer pts, dose escalation study (NCT01138033) to identify the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity. Part 1 used a modified accelerated titration procedure switching to standard 3+3 design based on toxicity during the first 21 days of treatment. Pts were treated with GSK2256098 orally twice daily (BID) with food. Safety was established in cohorts of 1-6 pts. After MTD determination, Parts 2 and 3 were opened to further evaluate safety, PK and PD. Serial PK samples were obtained over 24 h on Days 1 and 15. Pre- and post-dose skin, hair and tumor tissue biopsies were analyzed for pFAK. Results: 57 pts with advanced solid tumors have been treated at escalating doses ranging from 80 mg to 1500 mg BID: median age=58.8 (range 21-84). The most common tumor types include: mesothelioma (23), ovary (7), colon (3), kidney (3), and pancreas (3). MTD was determined to be 1000 mg BID. DLTs were Gr 2 proteinuria (1000 mg), Gr 2 nausea, vomiting, fatigue (1250 mg) and Gr 3 asthenia (1500 mg). Most frequent toxicities were nausea (32 pts, 56%), diarrhea (31 pts, 54%), vomiting (25 pts, 44%), decreased appetite (18 pts 32%) and asthenia (11 pts, 19%). The majority of toxicities were Gr 1-2; Gr 3 drug-related events included hypertriglyceridemia (n=2), hyperlipasemia (2), asthenia (1), increased amylase (1), and loss of consciousness (1). Few dose reductions and interruptions have occurred. Minor responses/stable disease (SD) were observed in pts with mesothelioma (-12%, 27 wks), melanoma (-26%, 54 wks), and naso/pharyngeal cancer (-31% target lesion, 30 wks) and SD in renal cell (48+ wks). In preliminary analysis of single-dose PK, exposure generally increased in a dose-proportional manner, and the geometric mean t½ was 4.2 h. Accumulation was not observed with repeat dosing. Conclusions: GSK2256098 is well tolerated with evidence of clinical activity. PK supports BID dosing.
Biomarker for benefit from ipilimumab: Correlation of breadth of humoral tumor-antigen-specific immunity with outcome.
Authors: Sarah Gabrielle Ellis, Matthew Wheater, Katherine Tier, Angelica Cazaly, James Smart, Jeffrey Theaker, Henry Hepburne-Scott, Phoebe Bonner-Ferraby, Christian H.H Ottensmeier
Journal: Journal of Clinical Oncology (2012)

8566 Background: Checkpoint blockade through CTLA4 with ipilimumab has for the first time improved survival in patients with advanced melanoma. Immune-mediated toxicity and increase in humoral and T-cell anti-NY-ESO-1 immune responses after treatment are both linked with benefit. However there is currently no broadly relevant, immunological biomarker for predicting outcome prior to initiation of therapy. Methods: Using a novel immunological assay developed by Serametrix Corporation we analysed the presence of antibodies to a proprietary panel of tumour associated antigens (TAAs) in 34 patients with advanced melanoma, given ipilimumab at 3mg/kg as second or subsequent line of treatment. Results: 34 patients were consented and analysed, 22 females, 13 males. With a median age of 63 years median overall survival was 24 weeks; 6/34 patients had an objective response to ipilimumab (17.6%, median survival not reached). Antibody (AB) responses were tested against the panel of 26 TAAs. This panel includes BRAF, Cancer/Testis and other described or novel TAAs. We observed a wide range in the incidence and levels of antibody response. 12 patients had no detectable immunity, 6 an AB response to a single antigen, 5 AB response to 2, and 11 patients to 3 or more TAA. Five patients had either pre-existing anti-BRAF antibodies or developed these after CTLA4-blockade. Survival was significantly longer in those patients with pre-existing antibodies to 2 or more TAA, compared to those with 0 or 1 specificities (median survival 39.4 vs 16.4 weeks p=0.02). Conclusions: Patients with advanced melanoma had variable levels of humoral immunity to a large number of TAA, including to BRAF. The presence of antibody response to 2 or more TAA correlated with longer survival following treatment with ipilimumab and appears to provide a biomarker for identifying those patients that are most likely to respond to checkpoint blockade with ipilimumab.
Phase I/II Study of Monotherapy with Subcutaneous Injections of Low-Dose Anti-CD20 Veltuzumab in Relapsed Immune Thrombocytopenia
Authors: Howard A. Liebman, Mansoor N Saleh, James B. Bussel, O George Negrea, Heather Horne, William Wegener, David M Goldenberg
Journal: Blood (2012)
Structural modification of titanium surface by octacalcium phosphate via Pulsed Laser Deposition and chemical treatment
Authors: I.V. Smirnov, J.V. Rau, M. Fosca, A. De Bonis, A. Latini, R. Teghil, V.I. Kalita, A.Yu. Fedotov, S.V. Gudkov, A.E. Baranchikov, V.S. Komlev
Journal: Bioactive Materials (2017)

In the present study, the Pulsed Laser Deposition (PLD) technique was applied to coat titanium for orthopaedic and dental implant applications. Calcium carbonate (CC) was used as starting coating material. The deposited CC films were transformed into octacalcium phosphate (OCP) by chemical treatments. The results of X-ray diffraction (XRD), Raman, Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM) studies revealed that the final OCP thin films are formed on the titanium surface. Human myofibroblasts from peripheral vessels and the primary bone marrow mesenchymal stromal cells (BMMSs) were cultured on the investigated materials. It was shown that all the investigated samples had no short-term toxic effects on cells. The rate of division of myofibroblast cells growing on the surface and saturated BMMSs concentration for the OCP coating were about two times faster than of cells growing on the CC films.
Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).
Authors: Julie R. Brahmer, Leora Horn, Scott Antonia, David R. Spigel, Leena Gandhi, Lecia V. Sequist, Jon Wigginton, Dan McDonald, Georgia Kollia, Ashok Kumar Gupta, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2012)

7509 Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. We report here that BMS-936558 mediates antitumor activity in heavily pretreated patients (pts) with advanced NSCLC, a tumor historically not considered to be responsive to immunotherapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors, including NSCLC, at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts with advanced NSCLC previously treated with at least 1 prior chemotherapy regimen were eligible. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 75 NSCLC pts were treated at 1 (n=17), 3 (n= 19), or 10 mg/kg (n=39). ECOG performance status was 0/1/2 in 24/49/2 pts. Tumor histology was squamous (n=17), non-squamous (n=52), or unknown (n=6). The number of prior therapies was 1 (n=9), 2 (n=20), ≥3 (n=45), or unknown (n=1). Ninety-five percent of pts had received platinum-based chemotherapy and 40% had a prior tyrosine kinase inhibitor. Sites of metastatic disease included lymph node (n=50), liver (n=12), lung (n=62), and bone (n=13). Median duration of therapy was 10 wk (max 100 wk). Common related AEs were fatigue (17%), nausea (11%), pyrexia (7%), pruritus (7%), dizziness (7%), and anemia (7%). The incidence of grade 3-4 related AEs was 8%. There was 1 drug-related death due to pulmonary toxicity. Clinical activity was observed at all dose levels (Table) and in multiple histologies. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. At the time of data lock, of 10 OR pts, 3 had responses lasting ≥6 mo and 5 were on study with response duration of 1.8-5.5 mo. Conclusions: BMS-936558 is well tolerated and has encouraging clinical activity in pts with previously treated advanced NSCLC. Further development of BMS-936558 in pts with advanced NSCLC is warranted. [Table: see text]
Higher Interleukin-10 (IL-10) and Lower Interferon-Gamma (IFN-γ), Tumor Necrosis Factor Alpha (TNF-α), IL-6, IL-8 Serum Levels in Patients Undergoing Reduced Intensity Versus Conventional Intensity Conditioning Hematopoietic Cell Transplantation (HCT).
Authors: H. Stradmann, Ute Hegenbart, M. Bruegel, Haifa K. Al-Ali, Dietger W. Niederwieser
Journal: Blood (2005)
Individual risk prediction of major cardiovascular events after cancer: A Childhood Cancer Survivor Study report.
Authors: Eric Jessen Chow, Yan Chen, Gregory T. Armstrong, William L. Border, Lillian R. Meacham, Daniel A. Mulrooney, Kevin C. Oeffinger, Charles A. Sklar, Marilyn Stovall, Leslie L. Robison, Yutaka Yasui
Journal: Journal of Clinical Oncology (2014)

10080 Background: Childhood cancer survivors are at increased risk of cardiovascular (CV) events. Models that combine information on cancer treatment exposures and conventional CV risk factors to estimate an individual's probability of developing major CV events would be clinically important. Methods: Cohort study of 10,521 five-year survivors of childhood cancer diagnosed 1970-86, free of CV disease at initial baseline survey, and who were followed with longitudinal surveys. Poisson regression models estimated the risk of the developing severe, life-threatening, or fatal CV events: 1) congestive heart failure (CHF), 2) coronary heart disease (CHD), 3) stroke, and 4) any CV-related death. Models accounted for sex, age at cancer diagnosis, and select chemo- and radiotherapy exposures. Secondary models accounted for late relapse and second cancers occurring beyond 5 years, and the effect of conventional CV risk factors (current smoking, alcohol use, physical activity, obesity, and any treatment for hypertension, dyslipidemia, or diabetes). Model prediction and discrimination were assessed via area under the curve (AUC) and the concordance (C) index. Results: After a median follow-up period of 25.8 years (range 7.4-39.2) since cancer diagnosis, the cohort experienced 182 (1.7%) CHF, 186 (1.8%) CHD, 159 (1.5%) stroke, and 66 (0.6%) deaths related to CV events. Models based on primary cancer treatment exposures predicted CHF, CHD, stroke, and CV death risk at/through age 40 with AUC and C-statistics ranging from 0.71-0.77. Adjusting for late relapse/second cancers and conventional CV risk factors further improved prediction (AUC/C-statistics 0.73-0.78; improvement in model prediction, p=0.01 to 0.07). The predictive weights assigned to hypertension and diabetes were similar to those assigned to high-level anthracycline or chest radiotherapy exposures. Conclusions: The predictive models we generated offer the potential for individual risk assessment of serious CV diseases at/through age 40. Once validated in other cohorts, these models may become important clinical tools in helping care for long-term childhood cancer survivors.
Validation of a prognostic classification system for mediastinal nonseminomatous germ-cell tumors (MGCT).
Authors: Lance C. Pagliaro, Agnes Laplanche, Aude Flechon, Jozef Mardiak, Lionnel Geoffrois, Pierre Kerbrat, Christine Chevreau, Remy Delva, Frederic Rolland, Christine Theodore, Guilhem Roubaud, Gwenaelle Gravis, Jean-Christophe Eymard, Jean-pierre Malhaire, Claude Linassier, Muriel Habibian, Florence Journeau, Maria Reckova, Stephane Culine, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

4562 Background: The anterior mediastinum is the most common location for extra-gonadal germ-cell tumors. MGCT has poor prognosis (International Germ Cell Consensus Classification); overall survival (OS) is 45–50% with standard treatment. Based on a prior study (Urol Oncol 2012, 30:879-85) we hypothesized that men with MGCT have favorable (Fav), intermediate (Int) or very poor (VP) prognosis when grouped by number of risk factors (RF). Methods: To validate the RF scoring system, we applied it to a prospectively collected subset of 66 men with MGCT who were registered on the GETUG-13 phase III trial (ASCO 2013, abstr #LBA4500). Patients (pts) were registered 11/2003–5/2012 and received bleomycin/etoposide/cisplatin (BEP) in the first cycle. Pts with unfavorable marker decline in cycle 1 were randomized to BEP (N=28) or an intensified regimen (paclitaxel-BEP-oxaliplatin x2 cycles and cisplatin/ifosfamide/bleomycin x2 cycles; N=29); the other 9 pts remained on BEP. One point was assigned for each of 3 RF at diagnosis: hCG ≥ 1,000 mg/ml, histology other than yolk sac tumor, and extra-mediastinal dissemination. Pts were then scored as Fav (0 RF), Int (1 RF), or VP (2–3 RF). We performed Kaplan-Meier analysis of OS and progression-free survival (PFS) for these groups and prognostic analyses (univariate and multivariate) for each RF. Results: Median age was 28 (18–65). Biopsy results were available for 30 pts (45%) and 36 (55%) had been diagnosed clinically. 27 pts died; 34 progressed and/or died. Median OS and PFS were not reached in the Fav (N=26) and Int groups (N=24). By contrast, the VP group (N=16) had median OS and PFS of 13 months and 4 months, respectively (log-rank P=.03; P<.001). Hazard ratios (HR) for RF are shown in the table. Conclusions: RF score predicted OS and PFS in this validation cohort of men with MGCT. Histology alone was not a strong RF, but the data were incomplete because a biopsy was not always clinically indicated. HR (95% CI) Univariate Multivariate RF N (%) OS PFS OS PFS Metastasis 26 (39) 2.3* (1.1–4.9) 2.8* (1.4–5.6) 2.1 (0.9–4.5) 2.5* (1.2–5.2) hCG ≥ 1,000 12 (18) 2.5* (1.1–6.1) 3.3* (1.5–7.1) 2.1 (0.9–5.2) 2.7* (1.2–6.0) Non-yolk sac 21 (32) 1.4 (0.6–3.1) 1.2 (0.6–2.4) 1.5 (0.7–3.3) 1.2 (0.6–2.4) *P<.05
Informed decision making (IDM) for prostate cancer (PCa) screening in a high-risk population.
Authors: Puneet Dhillon, Petros Grivas, Paola Raska, Devon Hickman, Paul Elson, Ann Awadalla, Jame Abraham, Kathy N. Smolenski, Hui Zhu, Thomas Schalcosky, Charles Modlin, Kimberly Bell, Samir Abraksia
Journal: Journal of Clinical Oncology (2017)

112 Background: PCa incidence and mortality in African Americans (AA) is higher than in Caucasians. Health-education programs and culturally appropriate outreach to high-risk groups in accordance with American Cancer Society IDM guidelines can reduce disparities. Data show that it is hard to provide comprehensive unbiased education about screening to patients (pts). This study aims to examine whether IDM guidelines in a large high risk group setting can improve knowledge on PCa and screening decision, and whether such education program is overall beneficial to pts. Methods: Pts were included in one-day outreach event and were given a 15-question pre and post- test focused on standard informative educational PowerPoint and then were offered screening (PSA + DRE). Components of IDM were reviewed during this educational intervention. Demographics and family history was collected and UCSF 10-year mortality index was assessed to help IDM. Pre- and post- test number of correct answers were compared (Wilcoxon signed rank); pts were surveyed on their opinion on the program. The decision regarding screening after the intervention was tracked as well as the % of PCa diagnosed. Pts were tracked via an established navigation system to ensure follow up care. Results: 106 pts were included in the current analysis. Median number of correct answers at pre and post test was 8 and 11 (p &lt; 0.001). Overall, 86% responded that they wanted screening. Of those, 92% were AA and 21% had family history of PCa; 21 pts had PSA only, 60 had PSA + DRE. 13 pts (16%) had abnormal PSA per NCCN guidelines, 5 (8%) had abnormal DRE. 5 PCa were biopsy-diagnosed, 4 had abnormal DRE + PSA; 1 had only abnormal DRE. Overall, 82% pts favored IDM before screening, 18% would prefer screening without IDM. 75% of all pts found the information “very helpful” in decision-making (within a 5-point Likert scale). Conclusions: Our education-based IDM led to significant improvement in knowledge about PCa screening. Most pts preferred education prior to screening. Our approach paired with the use of navigation program is feasible and was positively received by a large high risk group. Project is ongoing with more pts and follow up, and further validation is pending. Clinical trial information: NCT02419846.