tbuckley/cabot-search huggingface dataset:
BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients
Authors: J. Kim, E. Kim, B. Sohn, D. Yoon, C. Yoo, S. Kim, D. Lee, S. Kim, J. Lee, C. Suh
Journal: Journal of Clinical Oncology (2009)

7097 Background: The objective of this study was to compare the efficacy and toxicity of two high-dose regimens for autologous stem cell transplantation (ASCT) in patients with non-Hodgkin's lymphoma (NHL): BEAM (BCNU, etoposide, cytarabine, and melphalan) and BuCyE (busulfan, cyclophosphamide, and etoposide). Methods: We analysed 65 NHL patients, who underwent high-dose chemotherapy with BEAM (N=43) or BuCyE (N=22), followed by ASCT, at the Asan Medical Center. BEAM was used from February 2002 to October 2005, and BuCyE was used from November 2005 to April 2008. Results: Median age was 46 years (range: 15–68), and baseline characteristics, such as gender, International Prognostic Index (IPI), age adjusted IPI, stage and status of disease at ASCT, and median number of infused CD 34+cells/kg were well balanced between groups. The incidence of mucositis, nausea/vomiting, diarrhea and bleeding, and the number of events clinically important infections during ASCT did not differ between groups. Median follow-up for survivors was 49.3 months in the BEAM group and 21.5 months in the BuCyE group. Median overall survival (OS) was 30.6 months (95% confidence interval [CI], 8.19–53.0 months) and 22.6 months (95% CI, 12.1–33.1 months) and median event-free survival (EFS) was 16.1 months (95% CI, 0.0–53.6 months) and 11.2 months (95% CI, 0.0–22.5 months) in the BEAM and BuCyE group, respectively. There were no significant differences in OS (p=0.636) and EFS (p=0.575) between the two groups. Conclusions: In our analysis, BuCyE appeared to be not inferior to BEAM for survival. And we found that regimen-related toxicities did not differ significantly between the two groups. No significant financial relationships to disclose.
PROSPER: A phase 3 study of enzalutamide in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) patients.
Authors: Maha Hussain, Karim Fizazi, Fred Saad, Neal D. Shore, Axel Heidenreich, Mohammad Hirmand, Frank Perabo, Zakaria Khondher, Katharina Modelska, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2014)

TPS5094 Background: There is no standard of care for patients with M0 CRPC. In a recent study, patients with a PSA ≥8 ng/mL or PSA doubling time of ≤10 months had a median time to bone metastasis of only 2 years (Smith et al. Lancet 2012; 379: 39–46). Prostate cancer growth is dependent on androgen receptor (AR) signaling. Enzalutamide (formerly MDV3100) is a novel oral AR inhibitor that targets multiple steps in the AR signaling pathway. In two large Phase 3 studies, enzalutamide was shown to prolong overall survival and radiographic progression-free survival in patients with metastatic CRPC. The objective of the PROSPER trial is to evaluate the efficacy and safety of enzalutamide in M0 CRPC patients. Methods: PROSPER is a randomized, double-blind, placebo-controlled, international Phase 3 study (NCT02003924) initiated in December 2013 and involving more than 200 sites globally. Eligibility criteria include: asymptomatic M0 CRPC; PSA doubling time ≤10 months; screening PSA ≥2 ng/mL; and adequate hematologic, hepatic, and renal function. Approximately 1560 patients will have continued androgen deprivation therapy and will be randomized 2:1 to enzalutamide 160 mg/day or placebo. Patients will be stratified by PSA doubling time (<6 vs 6-10 months) and baseline use of bone-targeting agent (yes vs no).The primary endpoint is metastasis-free survival (MFS) based on central independent review of whole-body radionuclide bone scans for bone disease assessment and CT or MRI scans for soft tissue disease assessment. Imaging will be undertaken at screening and every 16 weeks post randomization till radiographic progression. The study has 90% power to detect a target hazard ratio of 0.75 based on a 2-sided log-rank test at an overall significance level of 0.05. Secondary endpoints include: overall survival; time to pain progression; time to opiate use for prostate cancer pain; time to first use of cytotoxic chemotherapy; time to first use of new antineoplastic therapy; time to PSA progression; PSA response; time to functional status deterioration as assessed by the FACT-P global score; and quality of life as assessed by EQ-5D-5L and QLQ-PR25. Clinical trial information: NCT02003924.
Constitutively Activated and Hyper-Sensitive Basophils in Patients with Polycythemia Vera: Role of JAK2V617F Mutation and Correlation with Pruritus
Authors: Alessandro M. Vannucchi, Lisa Pieri, Costanza Bogani, Paola Guglielmelli, Maria Zingariello, Rosa Alba Rana, Alberto Bosi
Journal: Blood (2008)
Fifteen year follow up of the first cohort of localized prostate cancer patients treated with brachytherapy
Authors: J. E. Sylvester, J. C. Blasko, P. D. Grimm, R. Meier, J. F. Spiegel, J. A. Malmgren
Journal: Journal of Clinical Oncology (2004)

4567 Background: The role of external beam radiation in addition to brachytherapy continues to be scrutinized for long term disease free survival. Methods: A cohort of 223 localized prostate cancer patients treated with iodine125 or palladium103 brachytherapy and neoadjuvant external beam radiation therapy were followed for biochemical failure, local or distant disease recurrence, and vital status. Biochemical failure (BF) was assigned if there were two consecutive PSA rises with the second greater than the first after a nadir post implant. Vital status was obtained from chart review, the social security death index, the SEER registry, and death certificate records. Time to BF was calculated and compared using Kaplan-Meier plots. Risk categories were derived from multivariate modeling and are defined as low = PSA ≤10 ng/mL, Gleason score (GS) <7, and stage <T2c; intermediate PSA >10 ng/mL or GS ≥7 or stage ≥T2c; and high = 2 or more intermediate risk factors. Results: Implants were conducted from 1987 to 1994 with average patient age at implant equal to 69 years. Median follow up time was 10 years (range 1.4 to 16.3). Twenty seven percent were low risk (n=61), 41% were intermediate (n=91) and 32% were high risk (n=71). The disease specific death rate from prostate cancer was 14% (29/212) for the sub group with known cause of death. Cause of death was unknown for 11 of 115 decedents. Fifteen year biochemical relapse free survival by risk category was the following: low = 86%, intermediate = 72% and high = 47% (log rank test score = 30.76, p=.000). Fifteen year survival was 93% for low risk, 86% for intermediate risk and 59% for high risk (log rank test score = 31.64, p = .000). Conclusions: Excellent long term biochemical and disease specific survival outcomes are achievable with prostate brachytherapy in low and intermediate risk groups. High risk patients could possibly benefit from additional adjuvant therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Proqura; Seattle Prostate Institute Education Bard; Oncura Proqura Oncura; Seattle Prostate Institute Education Bard; Oncura; Theragenics Amersham
Does timing of androgen deprivation influence radiation-induced toxicity? A secondary analysis of Radiation Therapy Oncology Group protocol 9413
Authors: J. Bahary, K. Bae, D. Taussky, M. Roach, H. M. Sandler, W. U. Shipley
Journal: Journal of Clinical Oncology (2006)

4655 Background: We conducted a secondary analysis of RTOG 9413 to compare if the timing of antiandrogen-therapy, concomitant versus adjuvant, influences the incidence of rectal toxicity in whole pelvic radiotherapy. Methods: For the purpose of this secondary analysis, we analyzed the 2 of the 4 arms of the study, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate and excluded the two arms that received prostate only radiotherapy. The 2 arms differed only in the timing of the total of 4 months of total androgen deprivation (TAD): arm I (320 patients), TAD was begun 2 months before the start of radiotherapy and continued during radiotherapy. Arm III (319 patients), TAD started immediately after the completion of radiotherapy. Both acute rectal and acute urinary toxicities (CTC v.2.0), testosterone (measured at baseline and yearly after) and other patients data were modeled using the multivariate logistic regression and the multivariate Cox-proportional hazards regression. Results: Median follow up for all patients is 6.0 and 5.8 years (arm I and II, resp.). 43 (13%) patients in each arm had abnormally low testosterone before start of TAD. Late grade 2 - 5 rectal toxicity occurred in 16% and 13% and urinary toxicity in 18% and 20% (arm I and II, resp.). Frequency (or occurrence) of late rectal toxicity (grade 0–1 vs. 2–5, p = 0.2170) and late urinary toxicity (grade 0–1 vs. 2–5, p = 0.4204) are not significantly different between the two arms. The only risk factors for late rectal toxicity in a multivariate regression model was acute rectal toxicity (OR 1.48, p = 0.025), but not abnormal testosterone level at baseline (p = 0.718) or treatment arm (p = 0.874). For late urinary toxicity: age (OR = 1.588, p = 0.010), RT field size (OR 1.004, p &lt; 0.025), baseline testosterone (OR 1.718, p = 0.028), and acute (grade 2–4) toxicity (OR = 1.664, p = 0.006) but not treatment arm (p = 0.928) were risk factors. Conclusions: While late toxicity was not different for concomitant vs. adjuvant hormonal therapy, an abnormally low testosterone level at baseline is a risk factor for late urinary toxicity and not late rectal toxicity. No significant financial relationships to disclose.
FASs/FASLs ratio: A marker of chemoresistance in advanced colorectal cancer (CRC)
Authors: C. Nadal, J. Maurel, R. Gallego, A. Castells, M. Marmol, S. Sanz, R. Molina, P. Gascon
Journal: Journal of Clinical Oncology (2004)

3583 Background: Oxaliplatin (OXL) or Irinotecan (CPT11)-5-fluorouracil (FU) combinations have improved responses up to 40% in advanced CRC. Unfortunately, those patients who will respond are unknown and, initially sensitive patients become rapidly resistant to current therapies. Fas (CD95) has been implicated in DNA-damage sensitivity. Whereas the pro-apoptotic role of Fas and FasL are well characterized, the function of their soluble forms remains unknown. Methods: We designed a prospective study to evaluate the role of sFas, sFasL and their ratio in CCR chemoresistance. From July 2001 to September 2003, seventy-three patients with advanced CRC(median age= 61; PS 0=25,1=35, 2=13; 1 organ=46; >1=27) received either OXL 85mgr/m2, LV 200 mgr/m2 and FU 3gr/m2, c.i., bi-weekly (group A, n=51) or OXL-FU/CPT11-FU combinations (group B, n=22) in first-line therapy. CT scans were done every 3 months and responses were evaluated by RECIST. ELISA sFas and sFasL analysis were done before treatment and every 3 months, until disease progression. Results: Total extractions, n=179. There were no differences in responses (A=53%, B=46%, p: 0.62). We found a significant increase in sFas levels at 3 m. compared to baseline (13.6 vs 10.2 ng/ml; p=0.001) and a significant increase in the sFasL levels up to 9 m. of therapy compared to 1st-3rd extractions (0.26 vs 0.10 ng/ml; p=0.002). A random effect regression statistical model evaluated the effects of time/therapy on response. We determined that >500 basal sFas/sFasL ratio values and/or a >5 increase in sFas/sFasL ratio were markers of chemosensivity (p=0.014). In addition, we have found a predictor of chemoresistance in a subgroup of patients who despite presenting a high ratio at baseline and a CT response after treatment, they developed decrease ratio. Conclusions: These data strongly indicates that high sFas/sFasL ratio and its increase after treatment could be an excellent marker of chemosensivity in CRC. On the other hand, a decrease ratio after treatment can be a predictor of chemoresistance despite a radiological response. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Grant: "Emili Letang" (Hospital Clinic Barcelona)
A randomized phase II trial of irinotecan plus oxaliplatin versus oxaliplatin, fluorouracil (5 FU), leukovorin (LV) as first-line treatment in advanced gastric cancer
Authors: I. Boukovinas, N. Androulakis, A. Polyzos, N. Vardakis, K. Amarantidis, V. Bozionelou, C. Kouroussis, S. Giassas, C. Christophyllakis, D. Mavroudis
Journal: Journal of Clinical Oncology (2009)

4536 Background: To compare the efficacy and tolerance of two oxaliplatin-based regimens as first-line treatment of advanced gastric cancer. Methods: Chemotherapy-naïve patients with measurable recurrent or metastatic gastric adenocarcinoma, PS (ECOG) 0–2 and adequate organ functions were randomly assigned to receive either irinotecan 200mg/m2 and oxaliplatin 80mg/m2 (IO), every 21 days or oxaliplatin 85mg/m 2 on day 1, 5-FU 400 mg/m 2 (over 1 hour infusion) + 600mg/m 2 (over 22 hours infusion) on days 1 and 2, leucovorin (LV) 200mg/m 2 on days 1 and 2 (FOLFOX4) every 2 weeks. Study endpoints: Overall Response Rate (ORR), Toxicity Time to Progression (TTP) and Survival (S). Results: 138 patients were enrolled and all were evaluable for response. Median number of cycles administered was 5.5 (range 1–10) for IO and 7 (range 1–18) for FOLFOX4. In an intent-to treat analysis the ORR (RR+CR) was 29.4% for IO arm and 34.3 % for FOLFOX4 arm (p= 0.587). The median response duration was 5.63 months (mo) for IO arm and 6,6mo for FOLFOX4 arm. Median TTP was 4.2mo and 6,1mo for IO and FOLFOX4 arm respectively (p= 0.012). Median OS was 9.4mo for IO and 11.97mo for FOLFOX4 (p= 0.456). Toxicity was acceptable, with one toxic death in each arm. Grade 3–4 vomiting (7.3%), diarrhea (11.8%), neutropenia (22%) and febrile neutropenia (5.9%) occurred more frequently in IO arm, while anaemia (4.3%) and grade II neurotoxicity (11.4%) was more frequent in FOLFOX4 arm. Conclusions: Both regimens are well tolerated and active in advanced gastric cancer. Based on the TTP and toxicity profile, the FOLFOX4 regimen merits to be further evaluated in prospective phase III trials. No significant financial relationships to disclose.
Analysis of serum biomarkers and tumor genetic alterations from a phase II study of lenvatinib in patients with advanced BRAF wild-type melanoma.
Authors: Pallavi Sachdev, Omid Hamid, Kevin Kim, Axel Hauschild, Steven O'Day, Corina Andresen, Yasuhiro Funahashi, Tadashi Kadowaki, James P. O'Brien, Keith Flaherty
Journal: Journal of Clinical Oncology (2013)

9058 Background: Lenvatinib is an oral receptor tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFRβ. Phase I and II studies of lenvatinib demonstrate that a subset of advanced melanoma patients (pts) appears to derive benefit from lenvatinib treatment (tx), prompting a need to identify predictive biomarkers for response to lenvatinib. Methods: Serum and archival tumor samples were collected from 93 enrolled pts in the BRAF wild-type (wt) cohort of the lenvatinib phase II study of advanced melanoma. Concentrations of 50 factors were measured in pre- and post-tx serum samples; 58 archival tumor tissues were obtained and gene mutation (mut) (n=53) and gene expression profiling (GEP) (n=39) analyses were performed. For mut analysis, targeted resequencing was performed on a select panel of genes using the Ion PGM Sequencer and mut validation studies were performed. For GEP analysis, the nCounter Analysis System was used to measure the expression level of 330 genes. Results: Clinical benefit rate (32%) and objective response rate (9%) by independent radiologic review were observed in the BRAF wt cohort. In serum biomarker analysis, lenvatinib tx resulted in a decrease in soluble VEGFR2 and increase in VEGF and PlGF levels consistent with target engagement. Correlation with clinical outcome demonstrated that baseline (BL) levels of Ang-2, IL8, PlGF, and PDGFBB associated with OS, but only pts with low BL Ang-2 levels also demonstrated improved response. High BL levels of FLT3LG and eotaxin associated with longer OS and improved response. In GEP analysis, expression levels of a set of genes including TARBP2, ZNF544, and NF1 (targets identified in phase I and preclinical studies) associated with OS. In gene mut analysis, NRAS mut showed a trend towards longer OS. Pts with NRAS mut along with wt PIK3CA status demonstrated longer OS. Conclusions: Lenvatinib demonstrated limited response in BRAF wt advanced melanoma pts. A subset of pts may derive extended clinical benefit. NRAS mut/PIK3CA wt status and low BL Ang-2 levels appear to associate with improved clinical outcome in this pt population and require further study to assess their predictive value. Clinical trial information: NCT01136967.
Size-dependent Effects of Gold Nanoparticles on Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells
Authors: Yangheng Zhang, Na Kong, Yuanchao Zhang, Wenrong Yang, Fuhua Yan
Journal: Theranostics (2017)

Gold nanoparticles (AuNPs) have been reported to promote osteogenic differentiation of mesenchymal stem cells and osteoblasts, but little is known about their effects on human periodontal ligament progenitor cells (PDLPs).In this study, we evaluated the effects of AuNPs with various diameters (5, 13 and 45 nm) on the osteogenic differentiation of PDLPs and explored the underlying mechanisms.5 nm AuNPs reduced the alkaline phosphatase activity, mineralized nodule formation and expression of osteogenic genes, while 13 and 45 nm AuNPs increased these osteogenic markers.Compared with 13 nm, 45 nm AuNPs showed more effective in promoting osteogenic differentiation.Meanwhile, autophagy was up-regulated by 13 and 45 nm AuNPs but blocked by 5 nm AuNPs, which corresponded with their effects on osteogenic differentiation and indicated that autophagy might be involved in this process.Furthermore, the osteogenesis induced by 45 nm AuNPs could be reversed by autophagy inhibitors (3-methyladenine and chloroquine).These findings revealed that AuNPs affected the osteogenic differentiation of PDLPs in a size-dependent manner with autophagy as a potential explanation, which suggested AuNPs with defined size could be a promising material for periodontal bone regeneration.
Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.
Authors: Mary O'Brien, Rabab Mohamed Gaafar, Sanjaykumar Popat, Francesco Grossi, Allan Price, Denis Charles Talbot, Tanja Cufer, Christian H.H Ottensmeier, Sarah Danson, Athanasios G. Pallis, Baktiar Hasan, Jan P. Van Meerbeeck, Paul Baas
Journal: Journal of Clinical Oncology (2012)

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m 2 /3 wks and bortezomib 1.3mg/m 2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P 0 =0.50 and P 1 =0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.
ARRHYTHMIAS IN HOSPITALIZED HEART TRANSPLANTED PATIENTS: A UNITED STATES NATIONAL STUDY
Authors: Srikanth Yandrapalli, Sohaib Tariq, Venkat Lakshmi Kishan Vuddanda, Prakash Harikrishnan, Viswajit Reddy Anugu, Zeeshan Solangi, Wilbert Aronow, Sachin Sule, Alan Gass, Chhaya Aggarwal, William Frishman, Gregg Fonarow, Ali Ahmed, Jason Jacobson, Sei Iwai, Howard Cooper, Julio Panza, Gregg Lanier
Journal: Journal of the American College of Cardiology (2017)
PROGNOSTIC RISK FACTORS FOR HEART FAILURE HOSPITALIZATION IN WOMEN WITHOUT OBSTRUCTIVE CORONARY DISEASE: AN ANCILLARY STUDY FROM THE WOMEN'S ISCHEMIA SYNDROME EVALUATION (WISE)
Authors: Parham Zarrini, Derek Leong, Janet Wei, Galen Cook-Wiens, Ahmed Al Badri, Carl Pepine, Sheryl Kelsey, Eileen Handberg, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2017)
BIMODAL PROGNOSIS OF PATIENTS HOSPITALIZED WITH SUSPECTED ACUTE CORONARY SYNDROME IN WHOM THE DIAGNOSIS IS NOT CONFIRMED
Authors: Jose A. Barrabes, Alfredo Bardaji, Javier Jiménez-Candil, Vicente Bodí, Roman Freixa, Rafael Vazquez, Jesus-Gabriel Sánchez-Ramos, Andrés May, Maria-Jesús Rollán, Antonio Fernandez-Ortiz
Journal: Journal of the American College of Cardiology (2017)
Prophylaxis Against Cytomegalovirus Infections with Oral Maribavir in Allogeneic Stem Cell Transplant Recipients: Results of a Randomized, Double-Blind, Placebo-Controlled Trial.
Authors: Drew Winston, Jo-Anne van Burik, Vinod Pullarkat, Genovefa Papanicolaou, Ravi Vij, Estil Vance, George Alangaden, Roy Chemaly, Finn Petersen, Nelson Chao, Jared Klein, Kellie Sprague, Carolyn Dougherty, Stephen Villano, Michael Boeckh
Journal: Blood (2006)
Combination of Fludarabine (FAMP) Cyclophosphamide (CTX) and Alemtuzumab for Patients with Relapsed Chronic Lymphocytic Leukemia (CLL).
Authors: Alessandra Tedeschi, Marco Montillo, Sara Miqueleiz, Michela Draisci, Francesca Ricci, Barbara Scarpati, Mariangela Mura, Monica Crugnola, Enrica Morra
Journal: Blood (2005)
ONLY EIGHT PERCENT OF VERY HIGH-RISK FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS ACHIEVE LDL-CHOLESTEROL TARGET DESPITE BEING ON MAXIMAL CONVENTIONAL LIPID-LOWERING THERAPY
Authors: Martin Prøven Bogsrud, Asgeir Græsdal, Dan Johansen, Gisle Langslet, Anders Hovland, Kirsten Holven
Journal: Journal of the American College of Cardiology (2017)