tbuckley/cabot-search huggingface dataset:
Serum markers of angiogenesis in patients with von Hippel-Lindau Disease
Authors: J. Spaulding, R. Brekken, L. Robinson, K. Koeneman, B. Mickey, J. Cadeddu, C. Croft, A. Sagalowsky, N. Ahmad, G. E. Tomlinson
Journal: Journal of Clinical Oncology (2004)

1033 Background: Von Hippel-Lindau disease is an autosomal dominant genetic cancer predisposition syndrome characterized by hemangioblastomas of the retina and cerebellum, renal cell carcinoma, and other tumors. The disease results from a mutation in the 3p25–26 region and this gene conforms to Knudson's two-hit hypothesis of carcinogenesis. The protein product of the VHL gene participates in ubiquitin-mediated proteolysis of hypoxia inducible factors 1 and 2, which upregulate the expression of a variety of proteins. Mutations in the VHL gene lead to decreased proteolysis of HIF, in turn leading to upregulation of downstream products, including VEGF. The tumors associated with this syndrome are often not detected until the second decade of life or later; by this time, damage to organs has already occurred and the only treatment available is surgical. The development of pre-clinical serum markers would be of important clinical utility in detecting at-risk individuals. Methods: This study examines the use of the angiogenic factor VEGF and its soluble receptor sVEGFR1 as serum markers in Von Hippel-Lindau disease in patients with mutations of the VHL gene with varying levels of active disease, compared with the same number of mutation negative family controls. Results: In our preliminary analysis, data has been collected from a total of 27 subjects. 18 (66.7%) of them are affected with VHL, 9 (33.3%) non-affected. The mean concentration of VEGF is 213.7 (SD 148.1) pg/ml in VHL affected subjects, and 88.3 (SD 87.4) pg/ml in non-affected subjects. The difference in VEGF levels in mutation positive and mutation negative individuals was highly significant (p=0.008) A trend was observed towards increasing VEGF levels and number of disease sites involved. Levels of sVEGFR1 did not differ between the two groups. Conclusion: The results suggest preliminarily that subjects affected with VHL disease have significantly higher concentrations of VEGF, as compared to those non-affected with VHL disease (Mean of 213.7 +/− 148.1 vs. 88.3 +/− 87.4; p = 0.008). No significant financial relationships to disclose.
Correlation of FDG-PET results after one cycle and after two cycles of chemotherapy in Hodgkin lymphoma.
Authors: M. Hutchings, L. Kostakoglu, A. Loft, M. Coleman, L. Specht
Journal: Journal of Clinical Oncology (2010)

8061 Background: FDG-PET after two cycles of chemotherapy is highly predictive of treatment response and progression-free survival in Hodgkin lymphoma (HL). Early interim PET after two therapy cycles is used to direct early PET-response adapted therapy in numerous clinical trials. However, due to the risk of early chemoresistance, a treatment escalation should be considered as early as possible to non-responding patients. The purpose of this trial is to study the correlation of PET results after one cycle and after two cycles of chemotherapy, and to investigate if the high predictive value of PET after two cycles is obtainable already after one cycle of chemotherapy. Methods: Two institutions take part in this trial. In Copenhagen, all enrolled HL patients had PET scans at baseline, after one cycle and after two cycles of chemotherapy (29 patients). In New York, all patients are scanned at baseline and after one cycle of chemotherapy, while only patients who are PET-positive after one cycle have a repeat PET after two cycles (7 patients). 34 patients were treated with ABVD and two patients with BEACOPPesc. Results: From a total of 36 patients, 22 were PET-negative after both one and two cycles. 11 patients were PET-positive after both one and two cycles. Three patients were PET-positive after one cycle and became PET-negative after two cycles. No PET-negative patient after one cycle turned PET-positive after the second cycle of therapy. The median follow-up time is short and does not yet allow for a survival analysis. Conclusions: There is a very high correlation between the results of FDG-PET after one cycle and after two cycles of chemotherapy for HL. These results show that the negative predictive value of PET is at least as high after one cycle as after two cycles of chemotherapy. A few patients who still have pathological FDG uptake after one cycle turn PET-negative after two cycles. A higher risk of false positive results after one cycle than after two cycles or alternatively a better positive predictive value after one cycle is yet to be determined with longer follow-up data. Patients with unsatisfactory PET-response to ABVD could benefit from having an escalation of therapy already after the first cycle of chemotherapy. No significant financial relationships to disclose.
Abstract 298: Evaluation of Physiological Feedback-Based CPR in a Swine Model of Cardiac Arrest
Authors: Matthew Sundermann, David Salcido, Allison Koller, James J Menegazzi
Journal: Circulation (2014)

Introduction: Chest compressions (CC)s are given to cardiac arrest patients at a fixed depth and rate during cardiopulmonary resuscitation (CPR), regardless of patient chest size, patient age, or cardiac arrest etiology. Mechanical CC devices help automate CCs, but are still limited by their fixed rate and depth settings. We investigated the feasibility of a CC device to respond to physiologic signals during a cardiac arrest by changing CC rate and depth. Methods: A custom-built chest compression device for CPR was built by linking a linear actuator with a SmartMotorTM and writing MATLAB® code to control the actuator. The device was tested in a swine model of cardiac arrest where 3 sixty-pound female swine were instrumented with Millar pressure catheters in the aorta, shocked into ventricular fibrillation, left untreated for 8 minutes, and then treated with our device. The physiologic signals we investigated were central arterial pressure (CAP) and quantitative electrocardiogram (QECG). Median slope (MS) ...
Effects of omeprazole on the pharmacokinetics and toxicities of irinotecan in cancer patients: A prospective open-label cross-over drug-interaction study
Authors: J. M. van der Bol, J. Verweij, F. A. de Jong, W. J. Loos, M. H. Lam, E. van Meerten, R. H. Mathijssen
Journal: Journal of Clinical Oncology (2009)

2502 Background: The proton pump inhibitor omeprazole (Losec) is one of the most extensively prescribed medications worldwide and within its class, omeprazole is most frequently associated with drug interactions. In vitro studies have shown that omeprazole can alter the function of metabolic enzymes and efflux transporters that are involved in the metabolism of irinotecan, such as UGT1A1, CYP3A, and ABCC2. In this open-label cross-over study we investigated the effects of omeprazole on the pharmacokinetics and toxicities of irinotecan. Methods: Fourteen patients were treated with one course (C1) of single agent irinotecan (600 mg i.v., 90 min) followed three weeks later by a second course (C2) with concurrent use of omeprazole 40 mg once daily, which was started 2 weeks prior to C2. Plasma samples were obtained up to 55 hours after infusion and analyzed for irinotecan, and its metabolites SN-38, SN-38 glucuronide (SN-38G), NPC, and APC by reversed-phase high-performance liquid chromatography with fluorescence detection. Non-compartmental modelling of pharmacokinetic data was performed with WinNonLin. Toxicities were monitored during both courses and graded according to the CTCAE criteria v3.0. Paired statistical tests were performed with SPSS. Results: The mean AUCs of irinotecan and all metabolites were not significantly different between both courses (p&gt;.151; see table). In addition, no differences were seen in C max and clearance of irinotecan and all metabolites between C1 and C2 (p&gt;.072). The nadir ANC and WBC and the percentage decrease in ANC and WBC from baseline were not different between both courses (p&gt;.529). Neither were there significant differences in the severity of neutropenia, febrile neutropenia, diarrhea, nausea, and vomiting. Conclusions: Omeprazole 40 mg did not alter the pharmacokinetics and toxicities of irinotecan. This widely used drug can therefore be safely administered during a 3-weekly single agent irinotecan schedule. [Table: see text] No significant financial relationships to disclose.
PDGFR inhibition using imatinib (I) combined with docetaxel (D), a potential new treatment strategy in the treatment of recurrent non-small cell lung cancer (NSCLC): Preliminary efficacy results
Authors: C. H. Huang, S. K. Williamson, P. J. VanVeldhuizen, C. T. Hsueh, A. Allen, H. Smith, M. Mayo, O. Tawfik, A. M. Uypeckcuat, K. Kelly
Journal: Journal of Clinical Oncology (2008)

19055 Background: Anti-angiogenesis is the new paradigm in the management of non-small cell lung cancer. Platelet Derived Growth Factor Receptor alpha (PDGFR-alpha) is involved in angiogenesis and its expression has been found in lung cancer. Preclinical models have shown that I inhibit PDGFR and may subsequently inhibit angiogenesis. Second line D monotherapy for NSCLC produces a response rate of 8- 10% and a median survival of 6–8 months. Weekly D had similar efficacy compared with every 3 week schedule with better tolerability. In addition, I + D have additive anticancer activity. We initiated a phase II trial of I +D to evaluate the efficacy and safety of this regimen in recurrent NSCLC. The primary endpoint was response rate using Simon two-stage design. A total of 32 patients is planned. Methods: Patients (pts)with pathologically confirmed NSCLC, measurable disease, no more than 1 previous platinum-based chemotherapy regimen, PS 0–1, clinically stable brain metastases and adequate organ function were eligible. Tumor samples, when available, were tested for PDGFR expression by immunohistochemistry. All pts received D 30 mg/m2 intravenously weekly × 3 every 4 weeks and oral I 600 mg daily for 4 cycles. Non-progressors after 4 cycles continued with I alone for a total of 12 months or until progression. Tumor response was assessed every 2 cycles. Results: Currently, we have enrolled 23 patients, 18 are evaluable (per protocol definition: completion of 2 cycles of therapy), and 5 are not evaluable. Patient characteristics and toxicity is summarized bellow. Further toxicity data will be presented. We have observed partial response in one patient (5.5%), stable disease in 5 (27.8%) and progressive disease in 12 (66.7%). Conclusions: PDGFR inhibition may be a potential new strategy in the treatment of patients with recurrent lung cancer. The combination of docetaxel with imatinib produced mostly stable disease. Patient Characteristics and Toxicity Summary Number of patients enrolled 23 Median age (range) 67 (52–80) M:F 21:2 PS0: PS 1 0:23 Adeno: Squamous: Non-specified 6:3:14 ≥ Grade 3 Hematological Toxicity 2 ≥ Grade 3 nonhematological toxicity (possibly, probably or definitely treatment related) 15 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis Novartis
A phase I study of capecitabine (CAP), carboplatin (CARB), paclitaxel (TAX) and external beam radiation therapy (EBRT) for patients with esophageal carcinoma (EC)
Authors: C. R. Kelsey, B. G. Czito, J. C. Bendell, C. G. Willett, M. A. Morse, T. A. D’Amico, W. Honeycutt, A. Franklin, D. Yu, H. I. Hurwitz
Journal: Journal of Clinical Oncology (2006)

14044 Background: Chemoradiotherapy is used to treat esophageal cancer with curative intent or local symptom control. A phase I study of 5-FU + CARB + TAX + EBRT showed 100% RR and 50% pCR rate. CAP allows for fluoropyrimidine treatment without the inconvenience of an infusion pump. CARB allows for platinum treatment with less toxicity than cisplatin. We evaluated this combination of agents in a phase I study. Methods: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus requiring local therapy received CAP (825 mg/m 2 bid on radiation days) + CARB (AUC 2 qweek) + TAX (60 mg/m 2 qweek) + EBRT (1.8 Gy qd to 50.4 Gy). DLT was defined as any grade 4 heme toxicity, grade 3 heme toxicity lasting ≥ 7 days, ≥ grade 3 N/V, diarrhea, or esophagitis lasting ≥ 4 days despite optimal medical management, grade 3 other toxicity, inability to deliver 75% of scheduled CAP dose, or treatment delay &gt; 3 days. Results: 13 pts were enrolled (10M, 3F). Median age was 62 (R- 48–78). EUS stage was uT3N0 (n=1), uT2N1 (n=1), or T3N1 (n=11). 2/3 pts had DLT at dose level 1 (both grade 4 esophagitis). Esophagectomy was performed in 2/3 patients, both pCR. Three pts were then enrolled at dose level -1 (CAP 600 mg/m 2 bid + CARB AUC 1.5 + TAX 45 mg/m 2 ). One patient developed DLT (grade 3 esophagitis) so 7 more pts were added at this dose level. Overall, 3/10 patients at dose level -1 developed DLT (two grade 3 esophagitis, one grade 3 hypotension). Esophagectomy was performed in 6/10 pts - 2/6 had pCR; 6/6 had pathologic downstaging. Conclusions: MTD for this regimen was CAP 625 mg/m 2 bid + CARB AUC 1.5 + TAX 45 mg/m 2 with EBRT to 50.4 Gy. However, at the MTD, this regimen is relatively toxic with no significant improvement in rate of pCR. [Table: see text]
Endogenous heat-shock protein vaccines for metastatic melanoma.
Authors: J. M. Heun, W. K. Nevala, M. R. Callstrom, T. D. Atwell, M. A. Farrell, E. Galanis, L. Erickson, V. Suman, W. J. Charboneau, S. Markovic
Journal: Journal of Clinical Oncology (2010)

TPS175 Background: Heat shock proteins (hsp) are a family of molecules critical for normal cell survival. HSP can be induced at elevated temperatures and when released into the extracellular environment following cell necrosis, act as immunomodulatory molecules attracting antigen- presenting cells (APCs) to the sites of immunogenetic peptides. Previous studies have isolated hsp from autologous melanoma tumor cells in vitro and then re-inoculated into patients as exogenous therapeutic vaccines. Heating of cells by radiofrequency ablation (RFA) has been shown to upregulate hsp expression in vivo. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a commercially available cytokine that works as an immune adjuvant by mediating dendritic cell (DC) maturation, increasing surface expression of MHC class I and II molecules of DCs, and enhancing antibody responses to known immunogens. In this feasibility study, we attempt to create an endogenous hsp vaccine in patients with metastatic melanoma through the use of sublethal radiofrequency treatment (RFT) supplemented with intra-lesional GM-CSF plus or minus subsequent cell killing with either RFA or cryoablation. Methods: With institutional review board approval, consenting HLA-A2 positive patients with metastatic melanoma (liver or soft tissue) are sequentially placed into one of three cohorts with three patients in each cohort. Cohort 1 receives sublethal RFT (42°C for 30 minutes) to the target lesion followed by intra-lesional injection of 500 mcg of GM-CSF. Cohort 2 receives sublethal RFT to the target lesion, followed by standard RFA to the target lesion, followed by intra-lesional injection of 500 mcg of GM-CSF. Cohort 3 receives sublethal RFT to the target lesion, followed by cryotherapy, followed by intra-lesional injection of 500 mcg of GM-CSF. In all cohorts, hsp70 (and multiple cytokines) are measured in the peripheral blood at baseline and every three hours for the first 24 hours post procedure. Melanoma specific tetramer analysis is performed on peripheral blood prior to procedure, 3 weeks and 6 weeks postprocedure to evaluate for the primary endpoint of melanoma specific cytotoxic T lymphocyte (CTL) production. Clinical outcomes will be correlated with laboratory findings. No significant financial relationships to disclose.
A Novel Asn344 Deletion in the Core Domain of Coagulation Factor XIII A Subunit: Its Effects on Protein Structure and Function
Authors: Sasichai Kangsadalampai, Gareth Chelvanayagam, Rohan T. Baker, Pa-thai Yenchitsomanus, Parichat Pung-amritt, Chularatana Mahasandana, Philip G. Board
Journal: Blood (1998)
Initial report of Radiation Therapy Oncology Group (RTOG) 9802: Prospective studies in adult low-grade glioma (LGG)
Authors: E. G. Shaw, B. Berkey, S. W. Coons, D. Brachman, J. C. Buckner, K. J. Stelzer, G. R. Barger, P. D. Brown, M. R. Gilbert, M. Mehta
Journal: Journal of Clinical Oncology (2006)

1500 Background: Treatment of adult LGG is controversial. Favorable patients (pts) (age &lt;40 years [yrs] who undergo gross total resection [GTR]) are typically observed. Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B]) are usually given initial radiation therapy (RT), reserving chemotherapy (historically procarbazine, CCNU and vincristine [PCV]) for recurrence. In 1998, the RTOG, in conjunction with SWOG, NCCTG, and ECOG initiated prospective studies of adult LGG, the results of which are reported herein. Methods: Favorable pts were observed postoperatively in a single arm Phase II study (Arm 1). Unfavorable pts were stratified by age, histology, KPS, and presence/absence of contrast enhancement on preoperative magnetic resonance imaging and randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3). Reported results include overall survival (OS) rate, median overall survival time (MOST), progression-free survival (PFS) rate, and median progression-free survival time (MPFST). Survival data are compared using Wilcoxon p-values. Results: A total of 362 eligible/analyzable pts were accrued between 1998 and 2002. Median follow-up time is 4 years. For the 111 favorable pts observed on Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%. For the 251 unfavorable pts on Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72). MOST was not reached in RT alone pts and was 6.0 yrs in RT+PCV pts. PFS at 2- and 5-yrs was 73% and 39% with RT alone vs 72% and 61% with RT+PCV (p=0.38). MPFST was 4.0 yrs with RT alone vs 6.0 yrs with RT+PCV. Acute grade 3–4 toxicity occurred in 9% of pts who received RT alone, 67% who received RT+PCV (mostly hematologic). There were no treatment deaths on either arm. Conclusions: 5-yr PFS was poor in all three arms ranging from 39% to 61%. Only half of favorable pts were disease-free at 5 yrs. In unfavorable pts, there was no OS advantage with the addition of PCV to RT. Both PFS and MPFST were better with the addition of PCV, but not significantly. Analysis of outcome by 1p19q status is pending. No significant financial relationships to disclose.
Randomized controlled trial comparing efficacy of oral amoxicillin-clavulanate and ofloxacin with intravenous ceftriaxone and amikacin as outpatient therapy in pediatric low risk febrile neutropenia
Authors: A. Gupta, C. Swaroop, S. Agarwala, S. Bakhshi
Journal: Journal of Clinical Oncology (2008)

10020 Background: Inpatient therapy is recommended in pediatric low risk febrile neutropenia (LRFN) since there is insufficient data regarding efficacy of outpatient therapy. Methods: This is a single institutional, prospective, randomized control trial in pediatric LRFN patients age 2–15 years with absolute neutrophil count (ANC) <500/mm3 and without evidence of pneumonia and hypotension. Patients on growth factors, recipients of intensive leukemia/lymphoma treatment or stem cell transplantation were excluded. Total of 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/ kg 8 hourly or intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures. Results: Out of 117 evaluable episodes, 1/3rd were leukemia patients in maintenance and rest were solid tumors. 1 patient had a central line. Success was achieved in 55/59 (93.22%) and 54/58 (93.1%) in oral and IV arms respectively (p-NS); of the successes, modification (fluconazole/acyclovir) was required in 5 (9.1%) and 2 (3.7%) episodes respectively. There was no mortality and 1 hospitalization. Median days to resolution of fever, ANC >500/mm3 and antibiotic use were 3, 5 and 6 days in both arms. Documented infections were 73% and 76% in oral and IV arms respectively; rest were fever of unknown origin. There were 5 blood culture isolates (3 gram positive and 2 gram negative bacteria). Failure was associated with perianal infections (p=.037), positive blood cultures (p=.037) and FN onset before day 9 therapy in solid tumors (p=.015) on univariate analysis; positive blood cultures (p=.004) and perianal infections (p=.007) on multivariate analysis. All gram positive isolates were successes while both gram negative isolates were failures. Diarrhea in IV arm (p=.03) & vincristine, actinomycin D, cyclophosphamide therapy for rhabdomyosarcoma in oral arm (p=.02) predicted failure in sub-group analysis. Conclusions: Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxicillin-clavulanate and ofloxacin may be the oral regimen of choice. No significant financial relationships to disclose.
Preoperative platelet-derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation in high-risk localized prostate cancer
Authors: P. Mathew, C. Pettaway, L. Pisters, D. Williams, P. Troncoso, C. Logothetis
Journal: Journal of Clinical Oncology (2007)

5141 Background: Reduction in tumor interstitial fluid pressure with platelet-derived growth factor receptor (PDGFR) inhibitor therapy in experimental systems improves drug delivery and the therapeutic index of taxane chemotherapy (Pietras, Cancer Research, 2002). We hypothesized that PDGFR inhibitor therapy with imatinib mesylate combined with androgen ablation (AA) and docetaxel (D) induces pathological complete responses (pCR) in high-risk localized prostate adenocarcinoma (PC) prior to radical prostatectomy and pelvic lymph node dissection (RP). Methods: Thirty six men with PC ≥T2 disease or Gleason grade 8–10 or serum prostate-specific antigen (PSA) &gt; 20 ng/ml or cT2b and PSA &gt;10 ng/ml and Gleason 7 disease (AJCC, 1992), without radiological evidence of metastases, were planned to receive intramuscular leuprolide, imatinib 600mg orally daily, and weekly D 30 mg/m 2 on D1, 8, 15, 22 q42 for three cycles (18 weeks) before RP [β (0.02, 1.98) prior on the possibility of pCR]. Unresectable pelvic nodal disease, post-operative PSA &gt; 0.2 ng/ml or administration of post-operative radiation or AA were defined as treatment failure. Results: Between 6–03 and 9–04, 39 men were registered; median age 57 years (range, 44–71); 35 Caucasian, 2 Hispanic, 4 African-American. Risk factors included T3 disease (22/39), Gleason 8–10 disease (31/39), PSA &gt; 20 ng/ml (12/39). Three men were ineligible or declined therapy; 29/36 (80%) received three cycles of therapy; 7/36 (20%) discontinued therapy related to toxicity. Grade 3–4 toxicity included rash (n=3), diarrhea (n=5), fatigue (n=3), neutropenia (n=2), hepatic (n=1). Severe or unexpected surgical complications were not encountered. No pCRs were defined; 15/36 (42%) have PSA &lt; 0.2 ng/ml [12/36 (33%), &lt;0.1 ng/ml] at 24 months and 13/36 (36%) met definition for treatment failure. Conclusions: The addition of the PDGFR inhibitor imatinib to pre-operative AA and D, although feasible, did not induce pCR in PC. [Table: see text]