tbuckley/cabot-search huggingface dataset:
Sterotactic body radiosurgery for primary small renal tumors: A retrospective analysis.
Authors: Irving D. Kaplan, Andrew Wagner, Anand Mahadevan, Rabia N Dagoglu
Journal: Journal of Clinical Oncology (2014)

475 Background: Small renal tumors are being diagnosed with increased frequency with the increasing use of axial imaging. Partial or total nephrectomy is the "gold standard" for management. Often patients are not candidates or refuse surgery. Stereotactic Radiotherapy (SBRT) is used to treat brain metastases from RCC. This study is aimed to evaluate the efficacy and toxicity of SBRT in the treatment of renal tumor. Methods: From June 2009 to December 2012, 21 patients with 22 lesions treated with 48Gy in 3 fractions were retrospectively evaluated. 21 patients had RCC and 1 had lymphoma. All patients had tracking during respiration. The Cyberknife system was used. All patients were with ondansetron and /or prochlorperazine to prevent nausea. Follow-up abdominal CT scans or MRI’s were used to evaluate efficacy. Blood Creatinine and urea values were used to track renal function. Clinical records were also evaluated for hypertension. Results: The median Follow up was 21 months (3-48 months). The median age was 82 (56-95). 4 patients had baseline chronic renal failure and 13 patients had baseline hypertension. 12 lesions (54.5%) were left sided and 10 lesions (45.5%) were right sided. 9 lesions (42.9%) were located at upper pole, 6 (28.5%) at lower pole, 5 (23.8%) at middle pole and 1 (4.8%) at renal pelvis. Median maximal tumor size was 3.8cm (1.9-7.7) and median treatment volume was 46cc (7.7-237cc). Five patients developed acute grade 1 fatigue and one patient developed pain which was attributed to inflammation and resolved. One patient developed worsening renal function and 1 patient developed hypertension. There were two local failures at 13 and 21 months. Two patients underwent surgery because one had progressive disease and one as a result of patient choice. 1y and 2y overall survival were both 95%. 1 y and 2 y local control rates were 92 and 84% respectively. Conclusions: This is the largest experience to report on the use of SBRT to treat small renal tumors. SBRT with a dose of 48Gy in 3 fractions of 16 Gy for small renal tumors seems to be an effective and a safe treatment with minimal acute toxicities. In addition tumors in locations not amenable to ablation (renal pelvis) can be safely treated with SBRT.
Long-term nasal tolerability of fentanyl pectin nasal spray in breakthrough pain in cancer.
Authors: N. Y. Gabrail, S. M. Weinstein, A. W. Burton
Journal: Journal of Clinical Oncology (2011)

e19604 Background: Previous randomized controlled studies have demonstrated that fentanyl pectin nasal spray (FPNS) offers pain improvement within 5 minutes with high patient acceptability. Given that FPNS is administered nasally, this report specifically evaluates long-term nasal tolerability. Methods: The 16-week, open-label study consisted of both newly titrated or rolled over patients with breakthrough pain in cancer (BTPc) from earlier controlled studies. Those experiencing 1–4 BTPC episodes/day while taking ≥60 mg/day oral morphine (or equivalent) were included. FPNS was used to treat ≤4 BTPc episodes/day. Nasal tolerability was assessed both by the clinician (nasal obstruction, inflammation, discharge, mucosal color) and by subjective patient assessments before the study at weeks 4, 8, 12, and 16, and at the final study visit to assess the following on a 4-point scale (0=absent, 3=severe): stuffy/blocked nose, runny nose, itching/sneezing, nose crusting/dryness, burning/discomfort, bleeding, cough, postnasal drip, sore throat, and taste disturbance. Results: This analysis included 403 patients. One hundred ten of those patients completed the study; 94% of 42,227 FPNS-treated episodes required no additional rescue medication. After titration to an effective dose, 90% of patients required no increase in FPNS dose over the study period overall. Of the newly enrolled patients, 87 had confirmed allergic/seasonal rhinitis; 72 (83%) were successfully titrated and entered the open-label study. Overall, objective and subjective nasal assessments showed no clinically significant effects. When subjective nasal assessments were averaged across BTPc episodes for each patient, all the parameters scored ≤0.2, with most symptoms rated absent to mild. Among treatment-related adverse events (TRAEs), nasal discomfort (2.2%) and rhinorrhea (1.2%) were reported by ≥1% patients. None of these TRAEs were considered severe. Conclusions: In a long-term, 16-week, open-label study, FPNS has been shown to provide consistent efficacy with no clinically significant nasal TRAEs. Such nasal tolerability has been confirmed through both objective and subjective assessments.
Weekly docetaxel plus estramustine for hormone-refractory prostate cancer (HRPC) with intermittent repetition: Preliminary results of a multicenter phase II study (AUO AP33/02)
Authors: K. Miller, C. Wülfing, J. Lehmann, M. Johannsen, A. Heidenreich, A. Hegele, B. Backhaus, U. Steiner
Journal: Journal of Clinical Oncology (2005)

4613 Background: Docetaxel is active in HRPC alone, with prednisone, and with estramustine. We investigated whether tumor control can be maintained with intermittent docetaxel-estramustine, which may have a favorable toxicity profile compared with standard dosing. Methods: Patients with HRPC and prostate-specific antigen (PSA) or clinical progression received weekly docetaxel 35 mg/m2 (30-minute intravenous infusion on Days 2, 9, and 16) with estramustine (140 mg orally, tid on Days 1–3, 8–10, and 15–17). Treatment was interrupted after 3 cycles (1 sequence) and monthly follow-up visits were performed (to assess PSA level, pain scores, white blood cell count). Treatment was restarted if PSA levels doubled (compared with the nadir during the previous sequence) or if progression was suspected for other reasons. The primary endpoint was best response (clinical and/or PSA) to treatment in Sequence 2. PSA response was defined as a ≥50% reduction in PSA from baseline, lasting ≥ 4 weeks. Assuming that 60% of enrolled patients would start Sequence 2 and a PSA response rate of 70%, ≥67 patients were required to confirm a response rate ≥50% (0.05 1-tailed type I error; 80% power). Results: Seventy-five patients (median age 66; range: 50–88 years) have been enrolled. Baseline ECOG PS was 0–1 in 95% of patients. Sequences 2/3/4 were started in 40/23/7 patients, respectively, and the median treatment-free intervals were 86.5/86.0/75.0 days. PSA levels were 105/96/179/232 ng/mL at the start of Sequences 1/2/3/4, respectively; PSA response (90% CI) was achieved in 76% (67–84%), 80% (67–90%) [primary endpoint], 57% (38–74%), and 29% (5–66%) of patients, respectively. Median follow-up was 9.1 (range: 0.7–21) months. So far, 21 patients (28%) have died. Main WHO grade 3–4 toxicities were: leukocytopenia (6.7%), pain (14.7%), and nail changes (5.3%). Conclusions: Intermittent docetaxel and estramustine is well tolerated and shows a high response rate in the second and third sequence of treatment in patients with HRPC. Further evaluation vs continuous treatment is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis, AstraZeneca AstraZeneca
Prevalence, patient characteristics and outcomes of a novel piperacillin/tazobactam-resistant, pan-β-lactam-susceptible phenotype in Enterobacteriaceae : implications for selective reporting
Authors: S.M. Stainton, A.K. Thabit, J.L. Kuti, J. Aslanzadeh, D.P. Nicolau
Journal: Clinical Microbiology and Infection (2017)
The underlying mechanism of prodromal PD: insights from the parasympathetic nervous system and the olfactory system
Authors: Shu-Ying Liu, Piu Chan, A. Jon Stoessl
Journal: Translational Neurodegeneration (2017)

Neurodegeneration of Parkinson's disease (PD) starts in an insidious manner, 30–50% of dopaminergic neurons have been lost in the substantia nigra before clinical diagnosis. Prodromal stage of the disease, during which the disease pathology has started but is insufficient to result in clinical manifestations, offers a valuable window for disease-modifying therapies. The most focused underlying mechanisms linking the pathological pattern and clinical characteristics of prodromal PD are the prion hypothesis of alpha-synuclein and the selective vulnerability of neurons. In this review, we consider the two potential portals, the vagus nerve and the olfactory bulb, through which abnormal alpha-synuclein can access the brain. We review the clinical, pathological and neuroimaging evidence of the parasympathetic nervous system and the olfactory system in the neurodegenerative process and using the two systems as models to discuss the internal homogeneity and heterogeneity of the prodromal stage of PD, including both the clustering and subtyping of symptoms and signs. Finally, we offer some suggestions on future directions for imaging studies in prodromal Parkinson's disease.
Decreased Telomerase Activity In CD4 Regulatory T Cells Is Associated with Severity of Chronic Graft-Versus-Host Disease (cGVHD) After Hematopoietic Stem Cell Transplantation (HSCT)
Authors: Yutaka Kawano, Haesook Kim, Ken-ichi Matsuoka, Suzan Lazo-Kallanian, John Daley, Joseph H. Antin, Robert Soiffer, Jerome Ritz
Journal: Blood (2010)
Treatment of relapsed or refractory non-hodgkin lymphoma with the oral isotype-selective histone deacetylase inhibitor MGCD0103: Interim results from a phase II study
Authors: M. Crump, C. Andreadis, S. Assouline, D. Rizzieri, A. Wedgwood, P. McLaughlin, E. Laille, Z. Li, R. E. Martell, A. Younes
Journal: Journal of Clinical Oncology (2008)

8528 Background: MGCD0103 is an orally available selective inhibitor of histone deacetylases (HDACs) with significant biological activity in preclinical models of both solid tumors and hematopoietic cancers. Methods: Open-label, Phase II trial in adults (Trial 008) with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Eligibility included: ≥1 site of measurable disease (≥2.0 cm), ECOG 0 or 1. MGCD0103 was given 3x/week starting at 110 mg; after 32 patients (pts) the starting dose was reduced to 85 mg. Tumor responses were determined every 2 cycles. PK was evaluated on Day 1, Cycle 1. Results: 50 pts received treatment; 33 DLBCL and 17 FL (median age [range], 61.5 years [32−80]; male, n=27; prior rituximab therapy: 96%; prior stem cell transplant: 33%). The response rate in pts with DLBCL met the protocol defined criteria for expansion beyond 21 pts, and enrollment of this cohort is now complete. Of 17 DLBCL pts with tumor reassessed by CT, most had tumor reduction, including 1 CR & 3 PRs (response rate 23.5%), with progression free survival (PFS) for responders ranging from 168 to >336 days. Five DLBCL pts with stable disease had PFS ranging from 112 to >336 days. One of 10 FL pts with tumor reassessment had a PR. All 50 pts were evaluable for safety: the most common toxicities grade ≥3 were fatigue (14%), neutropenia (12%), thrombocytopenia (10%), and anemia (6%). Comparison of data available to date of the 85 mg and 110 mg cohorts revealed 16% and 53% of patients, respectively, with ≥ grade 3 toxicity. MGCD0103 was rapidly absorbed (median Tmax = 1 hr), and disappeared biphasically (plasma t½, approximately 8 hrs). Similar exposures (Cmax & AUC) were observed at 85 (n=8) and 110 (n=17) mg, suggesting a trend towards saturable absorption. Inhibition of HDAC activity in PBMCs was seen in 13/18 pts (9/13 at 85 mg and 4/5 at 110 mg) and is similar between the group treated with 85 mg or with 110 mg. Conclusions: MGCD0103 demonstrated significant anti-cancer activity in relapsed or refractory NHL (DLCBL and FL subtypes) and had a manageable side effect profile. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MethylGene, Pharmion MethylGene MethylGene
Open-label, sequential, ascending, multi-dose, phase I study of KW-2450 as monotherapy in subjects with previously treated advanced solid tumors.
Authors: M. A. Dickson, P. LoRusso, E. A. Sausville, N. Rao, E. Kobayashi, M. R. Kurman, S. Akinaga, G. K. Schwartz
Journal: Journal of Clinical Oncology (2011)

3078 Background: KW-2450, a potent small molecule insulin-like growth factor receptor (IGF-1R)/insulin receptor (IR) antagonist, is under investigation for the treatment of solid tumors. It has shown efficacy against in vitro and in vivo malignant cells. The objectives of the current study were to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of KW-2450 in patients with advanced solid tumors. Methods: Patients received KW-2450 orally, once daily for 28 days followed by a 1-week observation period, followed by a continuous daily schedule. Plasma and serum samples were collected on Days 1, 2, 8, 15, 22, 28, and 29 for pharmacokinetic analysis and to evaluate the effects on plasma insulin, IGF-1, growth hormone (GH) and IGF binding protein 3 (IGFBP3) levels. Results: 13 patients (8 male) with metastatic disease and a median age of 56 years (range: 41-66) were treated at 2 dose levels: 50 mg (cohort 1) and 37.5 mg/day (cohort -1). The mean duration of therapy was 12.6 weeks (median: 9; range: 1.1-55.1). The maximum tolerated dose (MTD) was 37.5 mg/day since dose-limiting toxicities (DLTs) of Grade 3 non‐fasting hyperglycemia were observed in 2/6 patients treated at the starting dose of 50 mg/day. At the 37.5 mg dose, a 1/7 patients had a DLT of Grade 3 rash. Glucose levels typically returned to baseline by 24-hours post-dose. The most frequently reported adverse events (AEs) were fatigue (77%), nausea (69%), and pain (46%). There were no complete or partial responses. The half-life (t1/2) for KW-2450 averaged about 10‐13 hours and maximum concentration (Cmax) averaged 2.4-3 μg/mL, which was well above the IC50 for IGF-1R/IR inhibition. Increases in plasma insulin levels to above the maximum quantifiable limit of 300 μIU/mL were observed in 5 of 6 patients at 50 mg/day, and in 3 of 7 patients at the 37.5 mg/day dose group. Plasma IGF-1 and GH increases were observed in 2 patients each across both dose levels. Conclusions: The MTD for KW-2450 was 37.5 mg/day. The AE of note was non-fasting grade 3 hyperglycemia. Rapid oral absorption, peak concentrations in excess of IC50 for IGF1R and IR, and a t1/2 of 10-13 hours suggest KW-2450 is suitable for once-daily dosing.
H3B-8800, an Orally Bioavailable Modulator of the SF3b Complex, Shows Efficacy in Spliceosome-Mutant Myeloid Malignancies
Authors: Silvia Buonamici, Akihide Yoshimi, Michael Thomas, Michael Seiler, Betty Chan, Benjamin Caleb, Rachel Darman, Peter Fekkes, Craig Karr, Gregg F. Keaney, Virginia M. Klimek, Kaiko Kunii, Linda Lee, Stanley Chun-Wei Lee, Xiang Liu, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Sudeep Prajapati, Justin Taylor, John Wang, Markus Warmuth, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith
Journal: Blood (2016)
A mathematical model of diffuse low-grade gliomas treated with PCV chemotherapy.
Authors: F. Ducray, M. Peyre, D. Ricard, B. Čajavec-Bernard, E. Grenier, M. Tod, V. Calvez, D. Frappaz, M. Sunyach, A. Vasiljevic, J. Pallud, S. Cartalat-Carel, J. Honnorat, B. Ribba
Journal: Journal of Clinical Oncology (2011)

2065 Background: Several questions remain unanswered regarding the optimal use of first-line chemotherapy in low-grade gliomas (LGGs). Dynamic studies assessing the impact of first-line chemotherapy have shown that after the termination of chemotherapy, LGGs frequently continue to decrease in volume despite chemotherapy no longer being administered. Understanding this phenomenon is likely to be crucial to optimize chemotherapy for LGGs. The aim of the present study was to develop a mathematical model that could accurately describe the evolution of LGGs growth dynamics during and after first-line PCV chemotherapy. Methods: The model was formulated as systems of ordinary differential equations distinguishing between two cell populations: a proliferative treatment-sensitive cell population and a quiescent treatment-resistant cell population that spontaneously undergoes apoptosis. Model evaluation was performed in a series of 21 patients treated with first-line PCV chemotherapy. Results: Consistent with the biology of LGGs, the model estimated that LGGs consist largely of quiescent cells. Despite large inter-individual variability, the model correctly predicted individual tumor response profiles in the 21 patients. In analyzing evolution over time of proliferative and quiescent cell compartments, the model suggested that in some patients the six-week interval between PCV cycles might be suboptimal and that lengthening the time interval between cycles might improve the duration of response. Conclusions: We propose a mixed-effects model that accurately describes the evolution of LGGs during and after PCV chemotherapy. This model suggests that tailoring the time interval between PCV cycles according to the individual growth characteristics of LGGs may be a possible means by which to increase the efficacy of PCV chemotherapy.
Financial conflicts of interest (FCOIs) among the National Comprehensive Cancer Network (NCCN) clinical practice guideline panel members
Authors: K. Riggle, R. S. Go
Journal: Journal of Clinical Oncology (2008)

17570 Background: NCCN develops clinical practice guidelines that are considered authoritative, benchmarks for quality care, and widely adopted in the U.S. While every attempt is made to derive recommendations based on evidence, in many aspects of cancer care, high quality evidence are unavailable. Moreover, even evidence are subject to interpretation. Therefore, the potential for bias exists and full disclosure of FCOIs to the public among NCCN panel members is paramount. Currently, NCCN publishes only disclosures for the panel as a whole, but not individually. Objective: We wanted to determine the prevalence and nature of FCOIs among NCCN panel members of the top 10 cancers in 2007. Methods: Since NCCN would not disclose to the authors the individual FCOIs, we obtained FCOIs from alternate sources (2005–2007) in the following order of priority: American Society of Clinical Oncology (ASCO) annual meeting program books, continuing medical education (CME) websites (Research to Practice and Physicians’ Education Resource), and journal publications. Results: We were able to find disclosures for 220 of the 256 panel members (86%). The sources of disclosures were ASCO books (31%), journals (53%), and CME websites (4%). Among the top 10 cancers, the prevalence of FCOIs were: breast (52%), lung (50%), kidney (47%), colorectal (44%), bladder (40%), lymphoma (36%), melanoma (35%), leukemia (35%), prostate (24%), and uterine (12%). The distributions of FCOI categories were: consultancy (32%), honoraria (29%), research (29%), stocks (2%), employment (1%), testimony (2%), and other remunerations (6%). Among panel members with FCOIs, 32%, 39%, and 29% declared 1, 2, and >3 FCOIs, respectively. Conclusions: FCOIs are prevalent among NCCN panel members. Approximately 2/3 of FCOIs are unrelated to research funding or employment. Current method of financial disclosures of panel members by NCCN is inadequate and below the standard of leading medical journals. As NCCN considers its practice guidelines the standard for clinical policy in the oncology community, it must set a higher standard and be more transparent with its financial disclosures. No significant financial relationships to disclose.
Clusterin expression (CLU) as a prognostic marker in colorectal carcinoma (CCR).
Authors: Julia Alcaide, Antonio Rueda, Isabel Rodrigo, Teresa Tellez, Rafael Funez, Maria del Carmen Padilla, Irene Zarcos, Elisabeth Pérez-Ruiz, Rosa Villatoro, Diego Perez, Maximino Redondo
Journal: Journal of Clinical Oncology (2016)

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (&gt;10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p&lt;0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p&lt;0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p&lt;0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]
Liposomal cisplatin in cancer patients with renal failure.
Authors: G. Stathopoulos, S. Rigatos, J. Stathopoulos, S. Batzios
Journal: Journal of Clinical Oncology (2011)

7072 Background: One of the problems in chemotherapeutical agents administration is the renal failure. In general, when the grade of creatinine (and glomerular filtration data [GFR]) is of high level, chemotherapy is avoided in nearly all the cytotoxic agents or doses are reduced. Liposomal Cisplatin is a new agent, which has been tested in phase I, II, III trials and has shown no renal toxicity. In the present trial this agent was tested as a single agent and also in combination with gemcitabine mainly in lung and bladder cancer patients with renal insufficiency. Methods: 40 patients, with NSCLC 16 patients, bladder 14 and 10 with GT tract, were included. 36 were men and 4 women. Median age 65 (range 40-78). Gemcitabine was given at a dose of 1000 mg/m2 and Liposomal cisplatin 150-200 mg/m2 the first day, repeated every 2 weeks. Blood urea and serum creatinine were tested before each course of treatment and 1 week after. Full blood count was also tested the same dates. The number of courses were 6 the median (range 3-9). Serum creatinine was 1.6 mg/dl to 3.5 mg/dl. The median was 2.4 mg/dl. Myelotoxicity was observed in 30% of the patient but only of Grade I-II probably due to Gemcitabine. Anemia was observed in half of the patients (Grade I-II). Treatment delay for 1 week was done in only 2 patients (5%). Results: No serum creatinine increase was observed in any of the patients. In some patients serum creatinine levels were reduced, particularly in patients with bladder cancer. No serious side effects were seen apart of temporary fatigue. Conclusions: Liposomal Cisplatin is a new agent which according to the literature and the present study is the eligible cytotoxic agents for patients with renal insufficiency and in particular of bladder and NSCLC cancers.