tbuckley/cabot-search huggingface dataset:
The treatment of limb soft tissue sarcoma with TNF-alfa and pegylated liposomal doxorubicin (PLD): Phase I-II study
Authors: F. Di Filippo, M. Anzà, R. Garinei, P. Perri, S. Di Filippo, G. Citro, S. Disegni, P. Di Angelo, C. Sofra, R. Pasqualoni
Journal: Journal of Clinical Oncology (2008)

10583 Background: Hyperthermic isolation perfusion (HILP) has been employed for STS as limb salvage procedure. Fifty-eight patients affected with unresectable STS have been treated with doxorubicin and 1 mg of TNF-alfa. The CR and PR were 34% and 48% respectively, with a limb salvage rate of 84%. Unfortunately, the limb toxicity was quite high, therefore we decided to employ PLD. Methods: Fourteen patients have been treated with escalating dose of liposomal doxorubicin, starting from 10 mg/L of limb volume up to 18 mg/L, at mean muscle temperature of 41.5C. During HILP blood samples were taken from both systemic and perfusional circulation at 10 minutes intervals. At the end of HILP a tumor and muscle biopsy was carried out in order to evaluate the doxorubicin concentration. A total of 18 STS patients have been treated with PLD. All the patients were monitored in terms of grade of limb toxicity (Wieberdink classification) and systemic toxicity (WHO classification). Eleven patients have been later treated with PLD and TNF-alfa. As soon as muscle and tumor temperature reached 41C, 1 mg of TNF-alfa was injected in the arterial line of the perfusional circuit. After 30 minutes PLD (16 mg/L) was administered and HILP lasted 60 minutes. Results: The MTD of PLD was 16 mg/L because at 18 mg/L two grade IV limb reactions were observed. This dosage is twice as much that employed with free doxorubicin. Despite this high dosage a grade I or II limb reaction was always observed in all patients, even in patients treated with PLD and TNF-alfa. Pharmacokinetics showed that liposomes, despite the short time of circulation (60 minutes), release the drug molecules that enter preferentially the tumor cells and not the healthy tissue. As a matter of fact a grade III-IV was recorded in 8 out 23 patients (35%) treated with free doxorubicin and TNF-alfa. In 11 patients treated with PLD and TNF-alfa an OR of 82% was obtained with a limb salvage rate of 100%. Conclusions: The study demonstrated that the association of PLD and TNF- alfa strongly reduces the limb toxicity due the particular pharmacokinetics of liposomes. The therapeutic effectiveness is satisfactory but warrants to be confirmed in a larger patient population. No significant financial relationships to disclose.
Construction and Characterization of a Fusion Protein of Single-Chain Anti-CD20 Antibody and Human β-Glucuronidase for Antibody-Directed Enzyme Prodrug Therapy
Authors: Hidde J. Haisma, M. Fleur Sernee, Erik Hooijberg, Ruud H. Brakenhoff, Ida H. v.d. Meulen-Muileman, Herbert M. Pinedo, Epie Boven
Journal: Blood (1998)
Hematological Improvement during Deferasirox Treatment in Patients with Myeloproliferative Neoplasms (MPN)
Authors: Roberto Latagliata, Chiara Montagna, Ambra Di Veroli, Raffaele Porrini, Sabrina Leonetti Crescenzi, Pasquale Niscola, Fabrizio Ciccone, Antonio Spadea, Massimo Breccia, Angela Rago, Francesca Spirito, Michele Cedrone, Marianna De Muro, Marco Montanaro, Alessandro Andriani, Antonino Bagnato, Francesco Lo Coco, Enrico Montefusco, Giuliana Alimena
Journal: Blood (2014)
Abstract 19420: Epicardial Paracoronary Chemical Ablations Using Endocardial Approach Preserve Coronary Patency
Authors: Yoav Dori, Aravindan Kolandaivelu, Roy Beinart, Henry R Halperin, Nazarian Saman, Menekhem M Zviman
Journal: Circulation (2012)

Background: Epicardial ablations are often neccesary to treat ventricular tachycardia (VT). However, this procedure carries significant risk of damage to coronary vessels. We hypothesized that paracoronary epicardial ablations can be performed safely using intra-myocardial injection of alcohol from the endocardial approach. Methods: 5 swines underwent 3D rotational angiography guided intra-myocardial injection of 1 cc of ethanol at a depth of 5 mm into the myocardium. Lesions were placed at 1-3 locations under the LAD. The animals were survived for 3 days and then sacrificed and the myocardium stained with TTC. Hearts were excised and sectioned for lesion analysis and for histological evaluation. Results: Injections resulted in lesions that engulfed the coronary vessels, but by angiography and histology did not cause coronary stenosis. In 5/5 (100%) animals the lesions extended to the epicardial surface and were not transmural. Average lesion volume was 325.4 ± 73.5 mm3 and average epicardial scar area was 48.3 ± 23.9 mm2. Injections caused transient ST and blood pressure (BP) changes that return to baseline with a mean time to BP normalization of 159 ± 74 sec. Histological analysis demonstrated disruption of the paracoronary myocardium and the coronary tunica adventitia as well as partial disruption of the tunica media. There were no visible changes in the tunica intima. Conclusions: Paracoronary epicardial ablations can be performed safely using injection of alcohol from endocardial approach. This novel approach mitigates many of the risks of epicardial RF ablations and should be considered as an alternative to the current methods. Further studies are warranted to determine the long term efficacy of this method. Figure 1. Injection catheter was placed underneath the LAD (A) and alcohol mixed with contrast was injected. (B) Angiography shows that the arteries were patent post injection. (C) Epicardial view reveals epicardial lesions. (D) section through the LV wall
Smoking and prognostic factors in advanced non-small cell lung cancer (NSCLC)
Authors: S. Altug, C. Li, M. Marek, S. Guclu, Y. Kim, M. Meshref, S. Qin, K. Krejcy, W. Reece
Journal: Journal of Clinical Oncology (2007)

18048 Background: The aim of this prospective, multi-country, observational study (B9E-AA-B004) is to estimate the effect of prognostic factors, including continued smoking during therapy, on treatment outcomes in patients (pts) with advanced NSCLC receiving first- line chemotherapy with a gemcitabine (gem)-platinum combination as part of their routine care. Methods: Major eligibility criteria included: tissue diagnosis of advanced stage IIIB/IV NSCLC not amenable to curative surgery/radiotherapy; no prior chemotherapy; ECOG performance status (PS) 0 or 1; and written informed consent. A predictive model was constructed and validated by splitting the data at random by centre into two datasets in a ratio of 3:1 Construction:Validation. The primary and secondary endpoints are the effect of prognostic factors on survival and selected adverse events (AEs), respectively. The association of smoking with outcomes was tested in the Construction dataset. Results: This interim analysis to assess the effect of prognostic factors on AEs occurred when all pts had completed treatment. 1214 pts were enrolled: 75.1% male; mean age 60.5 yr, range 23–86 yr; 57.1% Stage IV; 66.2% PS 1; 69.4% received gem-cis, 30.5% gem-carb; 25.7% had never smoked, 70.8% had ever smoked and 11.2% continued smoking during therapy. 22.0% of pts had =1 AE. After variable selection in the Construction database (891 pts) the following factors were associated with an AE possibly related to therapy: disease stage (IV vs III, odds ratio (OR) =1.48, p=0.034), weight loss &gt;10% (OR=0.60, p=0.017), age (&lt;70 vs =70, OR=0.66, p=0.046), treatment (gem- carb vs gem-cis, OR=1.5, p=0.04), pain at baseline (present vs absent, OR=1.5, p=0.03), country (OR vs Taiwan ranged from 0.32 (Israel) to 4.2 (Egypt), p&lt;0.0001). Sex (F vs M, OR=0.86) was then added to the model because of its clinical importance. There was a trend towards a higher probability of an AE with continued smoking during therapy (OR=1.4), but this was not statistically significant (p=0.28). Conclusions: This model can be used to improve the prediction of whether patients are likely to experience treatment-related AEs. While the trend was for a greater AE rate in pts who continued to smoke during therapy, this was not proven. [Table: see text]
Abstract 16668: The Effects of Dabigatran on Fibrin Network Structure and Lysis: A Simple Technique to Monitor Efficacy of Treatment?
Authors: Francesco Franchi, Rhodri King, Fladia Phoenix, Fabiana Rollini, Jung Rae Cho, Mona Bhatti, Christopher DeGroat, Antonio Tello-Montoliu, Valeria Duarte, Estela Thano, Gabriel Faz, Martin M Zenni, Luis A Guzman, Theodore A Bass, Dominick J Angiolillo, Ramzi Ajjan
Journal: Circulation (2014)

Background: Thrombus formation represent the final step in the atherothrombotic process and occurs secondary to a complex interaction between platelets and coagulation factors. Increased platelet reactivity and enhanced clot formation can both determine predisposition to vascular events. Direct platelet inhibition by modern antiplatelet therapy is now effective at controlling the cellular component of coagulation but the fibrin network is not generally targeted in arterial disease. Our aim was to investigate the effects of dabigatran on fibrin network characteristics in individuals dual antiplatelet therapy (DAPT). Methods: This was a prospective, randomized, double-blind study conducted in 30 patients on maintenance (at least 30 days) DAPT with aspirin (81mg/day) and clopidogrel (75mg/day). Patients were randomized to receive either dabigatran 150mg bid or matching placebo for 7 days. Fibrin clot properties were studied using a validated turbidimetric assay and the following parameters were recorded: lag phase and time to full clot formation, both of which measure clotting potential; clot maximum absorbance, representing fibrin network density and fibre thickness; clot lysis time to assess fibrinolytic efficiency. Results: Dabigatran treatment was associated with an increase in lag phase, compared with baseline, of 1013±167 sec , whereas no difference was detected in placebo treated patients (-17±14 sec, p&lt;0.001 for dabigatran vs placebo). Similar results were obtained for clot formation time with an increase of 240±37 sec in dabigatran treated patients with no change following placebo treatment (-24±18 sec; p&lt;0.001 comparing the two groups). The change in clot maximum absorbance after dabigatran and placebo treatment showed no differences (-0.02±0.01 and 0.00±0.01 au, respectively; p=0.2) and clot lysis time was similar. Conclusions: In patients on DAPT with aspirin and clopidogrel, additional treatment with dabigatran delays fibrin clot formation without affecting fibrinolysis. Therefore, triple therapy with dabigatran may be one option to reduce thrombosis potential in high risk individuals. Moreover, our assay, which can be conducted on stored samples, offers the opportunity to monitor response to dabigatran therapy.
Response to Letters Regarding Article, “Segmental Aortic Stiffening Contributes to Experimental Abdominal Aortic Aneurysm Development”
Authors: Uwe Raaz, Alexander M. Zöllner, Isabel N. Schellinger, Ryuji Toh, Futoshi Nakagami, Moritz Brandt, Fabian C. Emrich, Yosuke Kayama, Suzanne Eken, Matti Adam, Lars Maegdefessel, Thomas Hertel, Alicia Deng, Ann Jagger, Michael Buerke, Ronald L. Dalman, Joshua M. Spin, Ellen Kuhl, Philip S. Tsao
Journal: Circulation (2015)
Principles of Immunotherapy
Authors: Anthony J Olszanski
Journal: Journal of the National Comprehensive Cancer Network (2015)

With recent success stories in melanoma, breast cancer, gastric cancer, renal cell carcinoma, prostate cancer, Hodgkin's lymphoma, squamous cell lung cancer, and other malignancies, immunotherapy has emerged as perhaps the most paradigm-changing treatment strategy to occur on the oncologic front in the last 35 years. At the NCCN 20th Annual Conference, Dr. Anthony J. Olszanski offered a primer on immunotherapeutic basics, featuring the complex interplay between the immune system and cancer; a comparative look at innate and adaptive immunity; and the topics of immune surveillance, tumor escape mechanisms, and immune suppression. Several examples of cancer immunotherapies in action are briefly presented.
Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform
Authors: Glenn M. Chertow, Jiannong Liu, Keri L. Monda, David T. Gilbertson, M. Alan Brookhart, Anne C. Beaubrun, Wolfgang C. Winkelmayer, Allan Pollock, Charles A. Herzog, Akhtar Ashfaq, Til Sturmer, Kenneth J. Rothman, Brian D. Bradbury, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2016)

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005–2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: −0.24 [−0.08 to −0.37] for stroke, −2.43 [−1.35 to −3.70] for VTE, and −0.77 [−0.28 to −1.27] for heart failure), although non–ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.
<i>In Vivo</i>Visualization and Characterization of Epithelial–Mesenchymal Transition in Breast Tumors
Authors: Zhen Zhao, Xiaoping Zhu, Kemi Cui, James Mancuso, Richard Federley, Kari Fischer, Gao-jun Teng, Vivek Mittal, Dingcheng Gao, Hong Zhao, Stephen T.C. Wong
Journal: Cancer Research (2016)

The activation of the epithelial-to-mesenchymal transition (EMT) program is a critical step in cancer progression and metastasis, but visualization of this process at the single-cell level, especially in vivo, remains challenging. We established an in vivo approach to track the fate of tumor cells based on a novel EMT-driven fluorescent color switching breast cancer mouse model and intravital two-photon laser scanning microscopy. Specifically, the MMTV-PyMT, Rosa26-RFP-GFP, and Fsp1-Cre triple transgenic mouse model was used to monitor the conversion of RFP-positive epithelial cells to GFP-positive mesenchymal cells in mammary tumors under the control of the Fsp1 (ATL1) promoter, a gate-keeper of EMT initiation. RFP-positive cells were isolated from the tumors, sorted, and transplanted into mammary fat pads of SCID mice to monitor EMT during breast tumor formation. We found that the conversion from RFP- to GFP-positive and spindle-shaped cells was a gradual process, and that GFP-positive cells preferentially localized close to blood vessels, independent of tumor size. Furthermore, cells undergoing EMT expressed high levels of the HGF receptor, c-Met, and treatment of RFP-positive cells with the c-Met inhibitor, cabozantinib, suppressed the RFP-to-GFP conversion in vitro Moreover, administration of cabozantinib to mice with palpable RFP-positive tumors resulted in a silent EMT phenotype whereby GFP-positive cells exhibited reduced motility, leading to suppressed tumor growth. In conclusion, our imaging technique provides a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. Cancer Res; 76(8); 2094-104. ©2016 AACR.
Results of the IFCT 0002 phase III study comparing a preoperative and a perioperative chemotherapy (CT) with two different CT regimens in resectable non-small cell lung cancer (NSCLC)
Authors: V. Westeel, B. Milleron, E. Quoix, J. L. Breton, D. Braun, M. Puyraveau, L. Bigay-Game, J. L. Pujol, F. Morin, A. Depierre
Journal: Journal of Clinical Oncology (2009)

7530 Background: Association of surgery and CT is standard for early-stage NSCLC. Meta-analyses showed comparable efficacy of adjuvant and neoadjuvant CT. The primary objective was to compare survival between two different CT strategies: all before surgery (PRE) versus perioperative (PERI). Methods: Between 2001 and 2005, 528 patients with a stage IA-II resectable NSCLC were randomized to 4 parallel arms (A: 2 GP + 2 GP in responders, then surgery, B:2 GP - surgery + 2 GP in responders, C: 2 TC + 2 TC in responders then surgery, D: 2 TC - surgery + 2 TC in responders; GP: Gemcitabine 1250 mg/m 2 /d1, 8 and cisplatin 75 mg/m 2 /d1 q3 wk; TC: Paclitaxel 200 mg/m 2 /d1 and carboplatin AUC 6, q3 wk). Results: 501 patients were operated on, 96.2% in the preoperative CT arms (PRE: A+C) and 95.8% in the perioperative CT arms (PERI: B+D). Ninety- day postoperative mortality was 4.9% and 4.2%, respectively. Pathological complete response was not significantly influenced by the number of preoperative cycles (PRE:8.6%, PERI:6.4%). In an intent-to-treat analysis, 3-yr survival was 67.8% and 68.6%, respectively (p=0.96). In responders, despite a dramatic difference in CT compliance (90.4% and 75.2% having received the 4 cycles, respectively, p=0.001), 3-yr survival was 75.1% and 79.5%, respectively (p=0.82). Survival did not differ with the CT regimen (GP versus TC, p=0.84). Three-yr survival increased from 68.1% in the PRE arms to 77.2% in the PERI arms in squamous cell carcinomas (SCC), and decreased from 67.7% to 61.6% in non SCC, respectively (Cox model interaction, p=0.35). Three-yr survival was 74.6% in the GP arms and 70.7% in the TC arms, in SCC, and was 64.2% and 65.4%, in non SCC, respectively (interaction, p=0.51). There was no interaction between CT strategy and stage. In stage II patients, 3-yr survival was 59.1% but 76.5% in responders, comparable to that of all stage I patients (72.9%). Conclusions: Despite an increased compliance of the all preoperative chemotherapy strategy, no difference was observed between the PRE and PERI arms. There might be an advantage for perioperative CT and for gemcitabine-based in SCC and for preoperative CT and for taxane-based in non SCC. No significant financial relationships to disclose.
Abstract 288: Predicting Return of Spontaneous Circulation Using Cerebral Oximetry and End Tidal CO2
Authors: Thomas Engel, Craig J Thomas, Patrick Medado, Brian Reed, Scott Millis, Brian J O’Neil
Journal: Circulation (2013)

Background: Previous literature has identified ETCO2 as a good predictor of ROSC. Cerebral Oximetry (CerOx) utilizes near infrared spectroscopy to non-invasively measure regional O2 saturation of the frontal lobes of the brain. Objectives: The objective of this study is to compare the predictive value of simultaneously measured ETCO2 and CerOx for ROSC during CPR. Methods: We conducted an IRB approved, prospective study on a convenience sample of subjects suffering cardiac arrest. Subjects were monitored with ETCO2 and CerOx simultaneously during CPR performed in the ED. We analyzed the data using logistic regression modeling and ROC curve analysis. Results: We analyzed 135 events. Mean age was 64.5±15.6 years. 90 (66.7%) were witnessed arrests with 78 (57.8%) receiving bystander CPR. Average downtime was 24.9±15.0 minutes. ROSC was achieved in 39 (28.9%) of these subjects. Initial rhythm presented as 58 (43.0%) asystole, 52 (38.5%) PEA and 25 (18.5%) VF/VT. A series of binary logistic regression models were run in which various derivations of ETCO2 and CerOx were simultaneously entered into the model to predict ROSC. CerOx, but not ETCO2, proved to be a significant predictor in determining ROSC for the following variables: regression slope during the full code [CerOx p&lt;0.000, ETCO2 p&lt;0.386], regression slope during the last 5 minutes of the resuscitation [CerOx p&lt;0.000, ETCO2 p&lt;0.749], maximum value recorded during resuscitation [CerOx p&lt;0.000, ETCO2 p&lt;0.858]. Both CerOx and ETCO2 proved to be significant predictors of ROSC for the following variables: last value recorded during resuscitation [CerOx p&lt;0.000, ETCO2 p&lt;0.009], the change from first value recorded to last value recorded [CerOx p&lt;0.000, ETCO2 p&lt;0.000]. CerOx also proved to be a better predictor of ROSC than ETCO2 when utilizing a ROC curve analysis: last values recorded [CerOx, AUC=0.856; ETCO2, AUC=0.761] and maximum values recorded [CerOx, AUC=0.802; ETCO2, AUC=0.630]. Conclusions: CerOx is a better predictor of ROSC than ETCO2 when analyzed by the whole resuscitation effort, the last five minutes, the maximum value, the last value recorded, and the change in values from first to last recordings during CPR. The maximum and last values of CerOx are good diagnostic tests for predicting ROSC.
Phase II study of capecitabine (C) in combination with docetaxel (D) as neoadjuvant treatment in patients with locally advanced breast cancer (IIIA and IIIB stage)
Authors: M. Bellet, M. Muñoz, A. Pelegri, J. Corominas, B. Bellosillo, I. Tusquets, X. Fabregat
Journal: Journal of Clinical Oncology (2004)

752 Background: C and D have demostrated antitumor synergy in preclinical setting and superiority to D in pretreated metastatic breast cancer patients This synergy is thought to occur from D-mediated upregulation of thymidine phosphorylase (dThdPase) The 1° endpoint was to assess the efficacy and feasibility of this combination in chemo-naive locally advanced breast cancer patients. 2a aims included analysis of prognostic and predictive factors, including those specific for C-D combination (dThdPase, dihydropyrimidine dehydrogenase and thymidylate synthase) Methods: Eligible patients had stage IIIA or IIIB disease, adequate organ functions and ECOG performance status (PS) 0–2. Neoadjuvant regimen: C 1250 mg/m2 twice daily, 1–14d and D 75 mg/m2 d1/3w x4 cycles. Adjuvant AC every 3 weeks x 4, followed by radiotherapy + tamox. x5y if ER+ and/or PGR+, were planned postoperatively. Results: From March 2002, 8 patients with BC stage IIIA (61.5%) and 5 IIIB (38.5%) have been enrolled. Age 51.2 years (37–67). Mean tumor size 6,7 cm. A total of 47 cycles of (C) and (D) were administered (median 4, range 1–4). Median relative dose intensity: C= 0.88 (range: 0.77–1.01), D= 0.97 (range: 0.80–1.03). 13 pts were evaluable for safety. Hemat toxicity consisted of G4 neutr: (30%) and G2 leucop (7.7%). The most severe non-hematol toxicit: G3 diarrhea: (7.7%), G3 infection: (7.7%) and G3 cerebelar syndr (7.7%). G 1–2/3–4 hand and foot syndr was seen in 9 pts (69.2%) and 2 pts (15.3%), respectively. There were no toxic deaths. 2 pts were prematurely withdrawn due to AE and were not evaluable for response. Clinical response: 9/11 (2 CR [18.2%], 7 PR [63.6%]), stable disease 2/11 (18.2%). Pathological PR in breast (invas tumor < 1 cm):4/11(36%), in nodes (<3 afected axillary nodes):5/11 (45%).8 pts have started adjuvant chemotherapy Conclusions: C-D has clinical activity as a neoadjuvant treatment for locally advanced breast cancer with an acceptable toxicity profile. The study is ongoing. Detailed data about pathological responses and analysis of prognostic/predictive factors will be available at the meeting. No significant financial relationships to disclose.