tbuckley/cabot-search huggingface dataset:
Management of venous thromboembolism (VTE) in melanoma patients with brain metastasis
Authors: G. C. Alvarado, A. Y. Bedikian, W. J. Hwu, N. E. Papadopoulos, K. B. Kim, J. Homsi, R. L. Bassett, R. M. Kuhn, P. Hwu
Journal: Journal of Clinical Oncology (2008)

9522 Background: Venous thromboembolism (VTE) is a frequent complication in melanoma pts with brain metastases (BM). Because these pts are at very high risk of intracranial bleeding, treating VTE in this population is challenging. Limited data is available regarding the safety of anti-coagulation therapy (TX). Herein we evaluate the clinical outcome of our pts. Methods: Data was collected retrospectively on pts with BM that had deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Eight-one pts were included in the analysis. The purpose of the study was to assess whether TX with anticoagulation would affect the development of hemorrhage post-VTE. Two endpoints are of interest: 1) Overall survival and 2) Development of hemorrhage post-VTE. Cox proportional hazards regression methodology was used for analyses of survival. Analyses of hemorrhage were performed using logistic regression or Fisher’s exact tests. The covariates of interest included VTE therapy (IVC filter vs. anticoagulant vs. both vs. neither), VTE event (DVT vs. PE vs. both), VTE symptoms, DVT location and/or PE, pattern and location of BM (solitary, multiple, hemorrhagic), size of largest BM lesion, co-morbidities, and systemic chemotherapy. Results: 60/81 pts were given anticoagulation. 6/60 pts receiving anticoagulation developed hemorrhage within 1 month (4 intracranial, 1 GI tract, 1 bladder), which was not statistically different from 5 of 21 pts who developed hemorrhage within 1 month in the absence of anticoagulation (3 intracranial, 1 GI tract, 1 adrenal). Of the 6 pts who developed hemorrhage on anticoagulation, 2/6 pts remain alive after 5 and 6 months post VTE and 4 died due to PD. Regimens that included low molecular weight heparin (LMWH) vs. heparin or vitamin K antagonists alone or in combination, showed improved overall survival p=0.033. Hazard ratios (HR) for IVC filter, anticoagulant, and the combination ranged from 0.17 to 0.37. No statistically significant differences in survival were seen between pts treated with anticoagulation alone, IVC filter alone, or the combination of the two. Conclusions: Anticoagulants did not increase the risk of hemorrhage. The presence of BM without evidence of hemorrhage is not a contraindication for the use of anticoagulation therapy. No significant financial relationships to disclose.
Phase I study of combined vorinostat (V), lenalidomide (L), and dexamethasone (D) in patients (pts) with relapsed or refractory multiple myeloma (MM).
Authors: P. G. Richardson, D. M. Weber, C. S. Mitsiades, M. A. Dimopoulos, J. Harousseau, J. Howe, T. Graef, C. Byrne, K. C. Anderson, D. S. Siegel
Journal: Journal of Clinical Oncology (2010)

8031 Background: MM remains incurable despite recent therapeutic advances. Although novel treatment combinations have improved outcome, new combinations are urgently needed. V, an oral histone deacetylase inhibitor, enhances anti-MM activity of other small molecule pro-apoptotics, with preclinical synergy seen when combined with L. This ongoing phase I multicenter, open-label study evaluated V plus L and D. Maximum tolerated dose (MTD; primary objective), safety, tolerability, and response rate (RR) were assessed. Methods: Relapsed and/or refractory MM pts were enrolled into 1 of 5 escalating doses of combination regimen using standard 3+3 design. Toxicity and response were evaluated using NCI c3.0 CTC and EBMT/UC. Results: Median prior therapies was 3 (range 1-12, N=31). Most pts received prior bortezomib (65%), thalidomide (68%), or L (45%). The majority ofadverse events(AEs) were mild/moderate; most common ≥G3 drug-related AEs (all cycles) were neutropenia (23%), thrombocytopenia (16%), diarrhea (13%), and fatigue (10%). One dose-limiting toxicity was seen (Table), with MTD not reached. Of 30 pts evaluable for efficacy, 26 (87%) experienced ≥ stable disease (SD); best single responses were 2 complete, 2 very good partial (VGPR), 10 partial (PR), 5 minimal (MR), 7 SD, and 4 progressive disease, for RR (≥ MR) of 63%. Of 13 evaluable pts who received prior L, ≥ SD was seen in 9 (69%), with 1 VGPR, 3 PR, 1 MR, and 4 SD, for RR (≥MR) of 38%. Conclusions: Preliminary results suggest V, L, and D may be a convenient, effective, and generally well tolerated oral regimen for relapsed/refractory MM pts. Activity was also seen in pts who received prior L. Further analysis of this study is ongoing and a phase II study is planned. Dosing Dose level (DL) V(mg qd)7 days on 7 off(days 1-7 and 15-21) L(mg qd)× 21 days(day 1-21) D(mg qd)(days 1, 8, 15, and 22) Evaluable for DLT† Maximum cycles‡ DLT 1 300 10 40 3 19 0 2 400 10 40 3 15 0 3 400 15 40 3 11 0 4 400 20 40 3 12 0 5 400 25 40 6 (+10§) 12 Diarrhea (G3) Cycles: 28 days. Concomitant daily aspirin recommended. † 10/31 pts (across all DLs) remain ongoing. ‡ Maximum treatment cycle for which ≥1 pt received ≥1 dose. § 10-pt expansion cohort enrolled at DL 5 with no formal DLT assessment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Dana-Farber Cancer Institute, Merck Bristol-Myers Squibb, Celgene, Merck, Millennium, Novartis, Ortho Biotech, Pharmion Merck Celgene, Janssen-Ortho, Merck, Millennium, Novartis, Onyx, Ortho Biotech, Pharmion Celgene, Gloucester Pharmaceuticals, Merck, Merck Serono, Millennium, Novartis
Patterns of planned post-operative management among U.S. medical oncologists (USMO) after neoadjuvant chemoradiotherapy (nCRT) and surgery for stage III rectal cancer (RC)
Authors: S. A. Ashraf, G. Vugman, L. Daniels, S. Britton, L. Lovino, R. Leff, M. R. Green, C. J. Allegra
Journal: Journal of Clinical Oncology (2008)

6602 Background: Oxaliplatin containing regimens are the standard of care in the adjuvant therapy (ACT) of high risk stage II & III colon cancer however, its role in the adjuvant rectal setting is less clear. In addition, there are currently no studies designed to clarify the role of ACT in patients with RC who initially have abnormal nodes by ultrasound but found to have pathologic T1–2N0 disease following nCRT. We examined the patterns of practice by USMO concerning these two issues. Methods: Between 2004-2007 we studied the treatment plans of 2,719 USMO. Using two specific clinical scenarios, we assessed plans for post operative ACT in a patient presenting with uT3N1 RC treated with nCRT who has one of two pathologic findings following surgery: setting 1: T2N1 (3/11 nodes +) or setting 2: T1N0 (0/7nodes +). Results: In setting 1, >99% of USMO plan ACT. After the MOSAIC adjuvant colon data were published in June 2004, > 80% planned to use FOLFOX as their ACT regimen in RC as well. The increase in FOLFOX use was matched by a concurrent decrease in the use of single agent fluoropyrimidines. During 2006 and 2007 between 7–9% of USMO planned to add bevacizumab to the FOLFOX ACT. In setting 2, 83% of USMO planned post operative ACT, again primarily FOLFOX, while no post operative management was the plan for 17% (range 12% - 23%) of USMO studied. Post operative observation was somewhat more commonly planned by academic (20%) than community (16%) oncologists and was equally commonly selected by female (16%) and male (17%) USMO. Conclusions: USMO plan to use post operative ACT in uT3N1 RC, largely a FOLFOX regimen, following nCRT as long as residual tumor remains either in the primary itself (83% ACT) or in both tumor and nodes (> 99% ACT). While these data clearly demonstrate a “standard of care,” there is no level 1 evidence to support the use of oxaliplatin in this setting. Observation (17% of USMO) for the pathologic node negative patient (setting 2) is neither supported by level 1 evidence nor consistent with established national guidelines; thus, clinical investigations are clearly needed in this setting. Finally, the use of bevacizumab in the rectal adjuvant setting should await the results of ongoing clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NMCR, NMCR Analytics
Sharing Clinical Trial Data
Authors: Darren B. Taichman, Joyce Backus, Christopher Baethge, Howard Bauchner, Peter W. de Leeuw, Jeffrey M. Drazen, John Fletcher, Frank A. Frizelle, Trish Groves, Abraham Haileamlak, Astrid James, Christine Laine, Larry Peiperl, Anja Pinborg, Peush Sahni, Sinan Wu
Journal: JAMA (2016)

The International Committee of Medical Journal Editors (ICMJE) believes that there is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk. In a growing consensus, many funders around the world — foundations, government agencies, and industry — now mandate data sharing. Here we outline the ICMJE’s proposed requirements to help meet this obligation. We encourage feedback on the proposed requirements. Anyone can provide feedback at www.icmje.org by 18 April 2016. The ICMJE defines a clinical trial as any research project that prospectively assigns people or a group of people to . . .
A dose-escalation study of tositumomab and iodine I 131 tositumomab (Bexxar) in pts with previously treated non-Hodgkin's lymphoma (NHL) with > 25% bone marrow involvement
Authors: J. Mones, M. Coleman, L. Kostakoglu, J. M. Fiore, D. Muss, R. Furman, P. Stewart, S. Kroll, S. J. Goldsmith, J. P. Leonard
Journal: Journal of Clinical Oncology (2004)

6575 Introduction: The Bexxar therapeutic regimen can produce durable and complete responses in patients with relapsed/refractory low-grade NHL. Virtually all previous studies of radioimmunotherapeutic agents (including Bexxar therapy) for NHL excluded patients with extensive bone marrow involvement (BMI) with tumor (>25% intertrabecular space) due to risk of excess hematologic toxicity. Therefore, we evaluated Bexxar therapy specifically in this patient population to assess safety and toxicity in a dose-escalation study. Methods: Subjects were required to have baseline BMI of >25% and platelet count of 150,000/mm3. A patient-specific dose of Iodine 131 Tositumomab was administered to deliver a defined amount of total body radiation. Dose escalation began at a total body dose of 45 cGy (subsequently increased in increments of 10 cGy). Dose limiting toxicity (DLT) was defined as ANC < 500/mm3 or platelets <25,000/mm3 for >17 d; or ANC <750/mm3 or platelets <50,000/mm3 for >24 d. Results: Eleven patients were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI was 30% to 65%, with median of approx 40%. Subjects had a median of 3 prior chemotherapies (range: 1–6). One of 6 evaluable patients treated at 45 cGy experienced hematologic DLT. Three patients (estimated BMI 40–60%) received 55 cGy, with 1 having hematologic DLT concurrent with lymphoma progression with extensive BMI. Three of 11 (27%) subjects received hematologic supportive care. Non-hematologic toxicities were minimal and were similar to previous studies. Two patients responded with durations of 1 and 43.6+ months. Conclusion: Treatment of patients with >25 % bone marrow involvement with Bexxar therapy was well tolerated at 45 cGy total body dose and can result in lymphoma responses. Further studies with additional patients and at higher doses are required to further characterize the MTD and to establish efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Corixa Corp. Corixa Corp. Corixa Corp. Corixa Corp.
High dose chemotherapy with peripheral blood stem cell (P.B.S.C.) rescue in metastatic Ewing’s sarcoma at diagnosis
Authors: A. Tienghi, S. Ferrari, M. Mercuri, P. Giovanis, E. Barbieri, R. Luksch, F. Fagioli, P. Picci, K. Sundby Hall, S. Smeland, T. Alvegard
Journal: Journal of Clinical Oncology (2005)

9004 Background: Metastates at diagnosis are the worst prognostic factor in Ewing’s sarcoma. To ameliorate the prognosis of patients (pts) with lung-pleural and/or solitary bone metastases, ISG-SSG have designed a trial with high dose chemotherapy (HDCT) and PBSC support. Methods: Since June 1999, 70 pts were registered, median age 15 yrs (2–34), 43 males, 27 females. Sites of primary were pelvis-sacrum in 30%, extremities in 22%, axial in 24%, soft tissue in 10%, others in 14%. Metastatic disease was in the lungs in 83%, pleural in 10%, solitary bone in 7%. The treatment consisted in 4 cycles of induction chemotherapy with VCR 2 mg, ADM 90 mg/ sqm, IFO 3 g /sqm x 3 days (VAI) alternate to CTX 4 g/sqm, Etoposide 200 mg/sqm x 3 days (CE) supported by G-CSF. Harvest of PBSC was planned after the 2° cycle CE. Then the pts. underwent local treatment (surgery and/or radiotherapy) and 4 cycles of VCR 2 mg, ADM 80 mg/sqm, CTX 1200mg/sqm (VAC) alternate to IFO 1800 mg/sqm x 5 days and Etoposide 100 mg/sqm x 3 days. Responsive patients received HDCT with Busulfan 4 mg/kg x 4 days orally and Melphalan 140 mg/sqm with support of P.B.S.C. and G-CSF. Total Lung Irradiation (TLI) 15 Gy was planned two months later. Results: We collected a median of 9.6 x 106/kg CD34+ cells (5–50) on day 14°; only one pt. did not mobilise after CE but with G-CSF alone and he had bone marrow harvest. So far 60 pts. underwent local treatment: surgery in 35%, RT in 53% and both in 12%. Ten pts. had progressive disease during the treatment, 41 responsive pts. received HDCT with PBSC support: regarding toxicity, they had a neutrophil count <0.5 x 109/l for 10 days (4–20), platelet count <50 x 109/l for 12 days (5–20), severe stomatitis in 12 adult pts. One toxic death occurred for multiple organ failure. Nineteen pts. relapsed. At a median follow up of 21 months (2–62), 40 pts. are without evidence of disease, 21 died of disease, 8 are alive with disease, with a 3 years progression free survival (PFS) of 42%. The 3 years PFS is 52% for the 41 pts. who received HDCT and TLI. Conclusions: This schedule of intensive chemotherapy is feasible, with encoraging results regarding survival in this subset of poor prognosis pts; longer follow up is needed to confirm the efficacy and to monitor late sequaele. No significant financial relationships to disclose.
Comparative expression profiling with kinetic RT-PCR in paired fresh frozen and archived formalin-fixed, paraffin-embedded renal cell cancer and normal tissue
Authors: G. Hennig, H. Paus, D. Atkins, S. Störkel
Journal: Journal of Clinical Oncology (2006)

4606 Background: It would be a substantial progress if gene expression of tumor markers could be accurately analyzed on RNA isolated from formalin fixed paraffin-embedded (FFPE) tumor tissue which is routinely collected. To prove equivalence between fresh frozen and archived FFPE tissue RNA profiles, we quantified 12 different genes with kinetic RT-PCR in renal tumor and paired adjacent normal tissue archived for 8–14 years. Methods: We had access to a set of 32 clear cell renal cell cancers and its adjacent normal tissue (HELIOS Clinic, Wuppertal). Each sample existed as a FFPE tissue block and as paired fresh frozen tissue both stored over 8–14 years at RT or -80 o C, respectively. RNA from FFPE tissue was isolated with a Bayer HealthCare internal silica bead-based isolation method. Each sample was analyzed with kinetic one-step RT-PCR for the gene expression of 3 housekeepers (RPL37A, GAPDH, CD63) and 9 candidate genes (EGFR, Her2/neu, Her3, Her4, EGF, TGFα, NRG1, HIF1α, VEGFα). Results: The comparative FFPE/fresh frozen expression data showed a good correlation over all data points (r = 0.87 for Ct values) and the tumor specific up- and down regulation of EGFR family genes and its ligands could be detected in both tissue types equally. We could clearly demonstrate the tumor specific up-regulation of EGFR (2-fold), TGFα (2-fold), VEGFα (4-fold) and down-regulation of EGF (60-fold), Her2/neu (4-fold), Her3 (2-fold) and Her4 (30-fold) in renal cell cancer for both tissue entities (fixed and fresh frozen). In addition a 3-dimensional Principal Component Analysis completely separated the renal tumor population from paired normal tissue in both tissue entities based on the differential gene expression. Conclusions: Here we demonstrate that a small set of genes from the EGFR family and their ligands is specifically up-/down-regulated in renal cell cancer tissue and therefore can be clearly distinguished from normal renal tissue. Furthermore, these data prove that the internal Bayer HealthCare isolation/kinetic RT-PCR detection protocol for RNA from FFPE tissue allows accurate retrospective expression profiling and validation of marker panels in archived tissue material stored for more than a decade. [Table: see text]
Evidence of Respiratory Syncytial Virus Spread by Aerosol. Time to Revisit Infection Control Strategies?
Authors: Hemant Kulkarni, Claire Mary Smith, Dani Do Hyang Lee, Robert Anthony Hirst, Andrew J. Easton, Chris O’Callaghan
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Respiratory syncytial virus (RSV) is a highly contagious pathogen with a huge global health impact. It is a major cause of hospital-acquired infection; a large number of those exposed develop infection. Those infected in hospital are at increased risk of a severe clinical course. Prevention of nosocomial spread currently focuses on spread by hand and large droplets. There is little research evidence to determine if aerosol spread of infectious RSV is possible.Objectives: To determine if the air surrounding infants with RSV-positive bronchiolitis contains RSV in aerosolized particles that remain capable of causing infection.Methods: The amount of RSV contained in aerosolized particles produced by infants with bronchiolitis due to RSV was measured using viable impactor sampling. The ability of RSV contained in these particles to infect healthy and chronic obstructive pulmonary disease (COPD) human ciliated respiratory epithelium was determined.Results: We showed for the first time that infants with RSV-positive bronchiolitis nursed in a ward setting or ventilated in intensive care produced large numbers of aerosol particles containing RSV that remained infectious and were capable of infecting healthy and COPD human ciliated epithelium. A significant amount of RSV was found in particles with aerodynamic diameters less than 5 μm.Conclusions: Many of the aerosolized particles that contained RSV in the air surrounding infants with bronchiolitis were sufficiently small to remain airborne for a significant length of time and small enough to be inhaled and deposited throughout the respiratory tract. It is likely that this leads to spread of infection to others, with dissemination of infection throughout the respiratory tract.
Increased Recruitment of Hematopoietic Progenitor Cells Underlies the Ex Vivo Expansion Potential of FLT3 Ligand
Authors: David N. Haylock, Martyn J. Horsfall, Tracey L. Dowse, Hayley S. Ramshaw, Silvana Niutta, Sandra Protopsaltis, Li Peng, Christopher Burrell, Irene Rappold, Hans-Jorg Buhring, Paul J. Simmons
Journal: Blood (1997)
Prognostic influence of clinical biomarkers in patients (pts) with advanced hepatocellular carcinoma (HCC) receiving sorafenib: A single institution experience.
Authors: Omar Abdel-Rahman, Angela Lamarca, Ismail Salu, Mairead G McNamara, Juan W. Valle, Richard Hubner
Journal: Journal of Clinical Oncology (2016)

304 Background: Identification of HCC pts with higher probability of benefit from sorafenib warrants investigation. Hypertension (HTN) and hand foot syndrome (HFS) are sorafenib-specific toxicities; the development of these toxicities is prognostic in pts with renal cell cancer receiving sorafenib, their significance in HCC remains uncertain. Methods: HCC pts treated with sorafenib at the Christie NHS Foundation Trust (Nov-09-Feb-15) were identified. The primary end-point was overall survival (OS). Kaplan-Meier and Cox regression models were employed for identification of prognostic factors. Results: Eighty-five eligible pts were identified [median follow-up 6.2 months (range: 0.4-31.4)].Median age 68 yrs (range 29-89); 87% male; 80% background liver cirrhosis ;88% ECOG performance score 0/1; Child-Pugh (CP) A5 (64%), A6 (29%) and B (7%); 41% baseline AFP &gt; 400 IU/L; 45% previous liver-directed therapy. Sorafenib (400mg BD),was started in 68% (median dose intensity 49.9% (range 0.7-100)), remaining patients started at reduced dose. Fifty-one percent had pre-existing HTN (91% treated).The most common grade ≥ 3 treatment-related toxicities were HTN (42% no prior history of HTN), fatigue (8%), and HFS (8%);59% of pts developed any grade HFS and/or worsening HTN (HFS/HTN). Toxicity-related dose reduction/cessation was required in 46 (54%) pts (15% due to HFS, 7% due to HTN). Estimated median progression-free (PFS) and OS were 5.5 (95% CI 4.1-7.0) and 6.5 (95% CI 4.9-8.0) months, respectively. Age at diagnosis, previous liver-directed therapy, CP score, baseline AFP and development of HFS/HTN were included in multivariable analysis: CP-A (vs. B; p-value &lt; 0.001) and development of HFS/HTN (vs. no; HR 0.4 [95% CI 0.2-0.7] p-value 0.001) were independent prognostic factors. The prognostic influence of HFS/HTN was preserved when limiting analysis to pts developing worst grade HFS/HTN in the first 3 months of treatment (53 pts; HR 0.5 [95% CI 0.3-0.9] p-value 0.030) making time-on-treatment bias unlikely. Conclusions: The development of sorafenib-specific toxicities, HFS and HTN, are prognostic factors associated with prolonged OS.
Composite risk assessment of cervical cancer and precancer by learning algorism of single nucleotide polymorphisms and HPV genotypes
Authors: T.-Y. Chu, K. C. Hu, H.-C. Lai, J.-T. Horng
Journal: Journal of Clinical Oncology (2004)

9713 Background: While multiple environmental and host factors are involved in cancer development, the carcinogenesis of uterine cervix stand for a relatively simplified model to unveil the complex city, by the fact that virtually all cervical cancers are related to HPV. However, genetic susceptibilities of host response to viral infection and oncogenesis also play important roles. Previously, we have dissected the relative risks of individual viral genotype and host single nucleotide polymorphisms (SNP) in cervical cancer development (Int J Cancer, 1999; Gyn Oncol, 2001; Int J Cancer, 2003). However, gene-gene and gene-environmental interactions must be taken into account before the global risk assessment can be realized. Methods: Three HPV genotype groups (type 16, 18 and 58) and 11 SNP (MCP1 G2518A, IL10 G592T, IL10 C819T, IL10 G1082A, P53 R72P, IL4 C590T, IL4 C34T, MMP1 G1607GG, FAS A670T, IL4RA C3223T and IL12B A1188C) were analyzed in a cohort of 92 high grade squamous intraepithelial lesion (HSIL), 135 squamous cell carcinoma (SCC) of uterine cervix, and 70 normal controls. The Bayesian probabilistic network was generated to classify the degrees of relationship of the biomarkers toward the diagnosis. A decision tree was defined by the key biomarkers was then computed by using the J48 learning algorism. Results: The J48 algorithm gave an overall sensitivity of 60.3%, specificity of 77.7%, PPV of 56.8% and F measure of 58.5%. A decision tree with a hierarchy order of HPV group, MMP1, IL4RA/P53 and IL12B/MCP1 polymorphisms was generated. As shown in the table, this model more accurately predicted normal and SCC than HSIL. Conclusions: This study showed a promising feasibility of assessing cervical cancer risk by multiple host SNP and HPV genotypes. No significant financial relationships to disclose.