tbuckley/cabot-search huggingface dataset:
Neutrophil-lymphocyte and platelet-lymphocyte ratio in patients after resection for hepato-pancreatico-biliary cancers.
Authors: Gaya Spolverato, Yuhree Kim, Georgios A Margonis, Martin Makary, Christopher Lee Wolfgang, Matthew J. Weiss, Kenzo Hirose, John L. Cameron, Timothy M. Pawlik
Journal: Journal of Clinical Oncology (2015)

378 Background: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) may be indicative of the immune response around the time of surgery. We sought to determine whether NLR or PLR were associated with outcomes of patients undergoing surgery for a hepatopancreatico-biliary (HPB) malignancy. Methods: Between 2010-2011, 289 patients who underwent an HPB procedure for a malignant indication were identified. Clinicopathological characteristics, NLR and PLR, as well as short- and long-term outcomes were analyzed. High NLR and PLR were classified using a cut-off value of 3 and 150, respectively, based on ROC analysis. Results: Median patient age was 63 years and 52.3% were female. The majority of tumors were pancreatic in origin (67.2%), while a subset were primary (10.3%) or secondary (22.5%) liver tumors. Patients with low vs. high NLR and PLR had similar baseline characteristics with regard to performance status and tumor stage (all P&gt;0.05). Operative interventions included pancreaticoduodenectomy (55.0%), ≤hemi-hepatectomy (29.1%), or extended hepatectomy (2.4%). Within 90-days of surgery, 143 patients experienced a complication for a morbidity of 49.5% (pancreas: 54.9% vs. liver: 40.0%). Patients with either an elevated NLR (OR=1.72) or PLR (OR=2.15) were at higher risk of a postoperative complication (both P&lt;0.05). Among patients with a pancreatic, primary or secondary liver tumor, 3-year survival was 38.6%, 43.0%, and 65.0%, respectively. While elevated NLR was not associated with long-term outcome (HR=1.36)(P=0.14), patients with an elevated PLR had a higher risk of death (HR=2.14)(P=0.01). Conclusions: Patients with a high NLR or PLR had an increased risk of a perioperative complication. Elevated PLR was also a predictor of worse survival among patients with HPB malignancy undergoing resection.
Interim results from ASCENT: A double-blinded randomized study of DN-101 (high-dose calcitriol) plus docetaxel vs. placebo plus docetaxel in androgen-independent prostate cancer (AIPC)
Authors: T. M. Beer, C. W. Ryan, P. M. Venner, D. P. Petrylak, G. Chatta, J. D. Ruether, W. M. D. Henner, K. N. Chi, S. Cruickshank
Journal: Journal of Clinical Oncology (2005)

4516 Background: High doses of calcitriol enhance the antitumor activity of multiple classes of chemotherapy in preclinical models and showed encouraging Phase 2 results in combination with docetaxel for AIPC. DN-101 is a new high-dose oral formulation designed to conveniently and reliably deliver the high calcitriol concentrations required for cancer therapy. Methods: Patients (pts) had metastatic AIPC, testosterone < 50 ng/ml, adequate organ function, clinical or PSA progression after anti-androgen withdrawal. Pts received weekly docetaxel 36 mg/m2 iv for 3 weeks of a 4-week cycle with standard dexamethasone and either 45 μg DN-101 or placebo orally 1 day prior to docetaxel. The study was powered at 85% to detect a 20% improvement in the fraction of patients with a ≥ 50% decline in serum PSA confirmed at least 4 weeks later (PSA response rate). Results: An interim analysis with a data cut-off of 6 months (June 2004) and median follow-up of 8 months is presented. 250 pts were randomized 1:1 at 48 sites in the US and Canada. Baseline characteristics were similar for both arms. PSA responses within 6 months (the primary endpoint) occurred more frequently in pts receiving DN-101 (58%) than placebo (49%), however this trend did not reach statistical significance (Cochran-Mantel-Haenszel chi square p=0.16). 102 patients had measurable disease. Objective response rate was 28% (3 CR, 10 PR of 46) vs. 20% (1 CR, 10 PR of 56) for DN-101 vs. placebo-treated patients. Most common grade 3/4 toxicities in the DN-101 and placebo-treated arms were neutropenia (8% vs. 8%), fatigue (7% vs. 15%), and hyperglycemia (6% vs. 11%). Serious adverse events occurred less frequently in DN-101 treated pts (24% vs. 36%, p=0.038). A similar trend was observed for AEs resulting in discontinuation of docetaxel (14% vs. 22% p=0.07). Conclusions: Early results show trends that favor DN-101 with respect to PSA and measurable tumor response rate and toxicity but do not reach statistical significance. Recommendations regarding further studies of DN-101 and docetaxel in AIPC will be made when the secondary endpoints of overall and progression-free survival are mature. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novacea Aventis, Novacea Aventis, Aventis Speakers Bureau, Novacea Novacea
Predictors and Impact Of 30-Day Readmissions On Patient Outcomes and Healthcare Costs After Allogeneic Hematopoietic Cell Transplantation
Authors: Abraham Sebastian Kanate, Sherri Rauenzahn, Sonia Leadmon, Quoc V. Truong, Aaron Cumpston, Londia Goff, Kim Evans, Jianjun Zhang, Sijin Wen, Michael Craig, Mehdi Hamadani
Journal: Blood (2013)
Prognostic value of pathological nodal status and tumor regression grade in patients with rectal cancer (RC) treated with pre-operative chemoradiotherapy
Authors: F. Bertolini, F. Iachetta, P. Giacobazzi, R. Depenni, S. Zironi, F. Bertoni, A. Frassoldati, G. Luppi, P. Conte
Journal: Journal of Clinical Oncology (2006)

13524 Background: The main objective of this study is to clarify the correlation between pathological nodal status and Dworak tumor regression grade (TRG) (Dworak et al. Int Colorectal Dis 1997, 12:19–23) after pre-operative chemoradiotherapy. Methods: From May 1998 to February 2005, 112 patients with locally advanced rectal cancer were diagnosed at Centro Oncologico Modenese and treated with pre-operative concomitant pelvic irradiation (50 Gy in 25 fractions) and chemotherapy with 5-FU in continuous infusion (225 mg/msq/daily). We considered for our analysis only pathological stage III cases. Results: Clinical positive nodal status (by CT scan or ultrasonography) was present in 71 patients on 106 (66.9%) at diagnosis. Among all radically resected patients (106), pathologic assessment of lymph nodes in surgical specimens was performed; average number of nodes examined was 11 (range: 2–22). Thirty patients (28.3%) had a positive nodal status at pathological examination: 19 (63.3%) were pN1 (≤3 lymph nodes) and 11 (36.7%) were pN2 (&gt;3). The nodal status changed from 66.9% (clinical evaluation) to 28.3% (pathologic evaluation). Among stage III patients 5 (16.7%) had a TRG 3, 12 (40%) TRG 2, 11 (36.7%) TRG 1 and 2 (6.6%) TRG 0. At a median follow-up of 32,3 months, 20/106 patients relapsed (18.8%); of these 20, 10 (50%) had a positive pathologic nodal status. In this subset recurrence occurred in 5/10 (50%) pN1 patients (1 local and 4 with distant metastases) and 5/10 (50%) pN2 patients (2 local and 3 with distant metastases). The 3-y DFS was 63% (68% pN1 and 54% pN2) (p=0.32). The 3-y OS was 84% (94% pN1 and 68% pN2, p=0.72). The 3-y DFS in post-operative stage III patients according to tumor regression grade was 81% for TRG 2–3 and 38% TRG 0–1 (p&lt;0.026). Conclusions: In stage III patients, TRG is confirmed as a relevant prognostic factor in locally advanced rectal cancer treated with neo-adjuvant chemo-radiotherapy. In the same subset of patients the number of positive nodes seems to impact on the prognosis, even not reaching a significant relevance. No significant financial relationships to disclose.
Response at Three Months Is a Good Predictive Factor for Newly Diagnosed Chronic Myeloid Leukemia Patients Treated by Recombinant Interferon-
Authors: F.X. Mahon, C. Fabères, S. Pueyo, P. Cony-Makhoul, R. Salmi, J.M. Boiron, G. Marit, C. Bilhou-Nabera, A. Carrère, M. Montastruc, A. Pigneux, Ph. Bernard, J. Reiffers
Journal: Blood (1998)
Sixty seconds on . . . bed blockers
Authors: Nigel Hawkes
Journal: BMJ (2016)

They have reason to be. The think tank the King’s Fund has reported that what worries them most is missing the four hour target for emergency department patients to be seen and delayed transfers of care.1

They’re strongly related. Both are symptoms of flow problems through the hospital: if you can’t move patients through emergency departments because beds are occupied by …
2016 ACC Lifelong Learning Competencies for General Cardiologists
Authors: Eric S. Williams, Jonathan L. Halperin, James A. Arrighi, Eric H. Awtry, Eric R. Bates, Salvatore Costa, Rosario Freeman, John A. McPherson, Lisa A. Mendes, Thomas Ryan, Chittur A. Sivaram, Howard H. Weitz
Journal: Journal of the American College of Cardiology (2016)
S54 Cognitive function in adults with and without cystic fibrosis related diabetes (CFRD) attending a large UK cystic fibrosis unit
Authors: HK Chadwick, AM Morton, A Driffill, A Wood, L Gillgrass, L Dye, CL Lawton, MW Mansfield, DG Peckham
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> On reaching adulthood many cystic fibrosis (CF) sufferers develop cystic fibrosis related diabetes (CFRD). CFRD shares clinical characteristics with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Impaired glucose tolerance (IGT), T1DM and T2DM have deleterious effects on cognitive performance. Hence, patients with CFRD are hypothesised to show similar impairment. This study aimed to elucidate the nature and severity of any cognitive impairment in patients with CFRD compared to non-diabetic patients with CF and healthy controls matched as closely as possible for age, gender and education level. Patients with CF were also matched as closely as possible on CFTR genotype. <h3>Methods</h3> Adult (&gt;16 years old), pancreatic insufficient patients registered to a large UK CF unit who had adequate verbal and written English were eligible. 49 patients with insulin-treated CFRD and 49 CF non-diabetics who had received a normal oral glucose tolerance test (OGTT) within the past 12 months were recruited. 46 healthy matched controls were recruited from relatives of patients and the general population. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjective measures of sleep, stress, mood and cognitive functioning were also collected. <h3>Results</h3> Matched controls performed better than both groups of patients with CF on tests of visual memory and learning, verbal memory, visual sustained attention, processing speed and executive function. Patients with CFRD performed significantly worse than controls on tests of mental flexibility and processing speed, which is consistent with the pattern of impairment shown in T1DM, and on verbal memory and learning, which is consistent with the pattern of impairment shown in T2DM. Compared to non-diabetic patients with CF, those with CFRD performed worse on tests of visual sustained attention, verbal memory, working memory, and processing speed. <h3>Conclusion</h3> CFRD has a negative impact on cognitive performance akin to T1DM and T2DM. Non-diabetic patients with CF also show impaired cognition but to a lesser degree than CFRD. Even modest cognitive impairment in adults with CF may impact upon their self-management skills, health and quality of life.
Novel early stopping rule uses early progression rather than lack of response as rapid assessment for futility.
Authors: Y. Wong, S. Litwin, D. J. Vaughn, E. R. Plimack, S. M. Cohen, H. Tuttle, G. R. Hudes
Journal: Journal of Clinical Oncology (2010)

TPS227 Background: Median survival for patients (pts) with metastatic (met) urothelial cancer (UroCa) is approximately 15 months due to the lack of active salvage agents. With the exception of gemcitabine, which is now used in first-line therapy, treatments following failure of platinum-based chemotherapy (chemo) have shown limited benefit, with median progression-free survival (med PFS) ≤ 3 months and objective response rates ≤ 10%. High-grade UroCa overexpress epidermal growth factor receptor (EGFR). Cetuximab (CET) is a monoclonal antibody against the EGFR. We are conducting a randomized, noncomparative phase II study to measure the efficacy of CET ± paclitaxel chemo-refractory met UroCa. Trials in advanced UroCa have been difficult to complete due to poor accrual. Investigators may lose interest in a study when initial pts progress quickly, or if it is closed awaiting response evaluation. We use a novel design that uses early progression to rapidly assess futility (Litwin, Stats Med 2007). Methods: Pts with met UroCa who received one line of chemo in the perioperative or met setting were randomized to CET 25 0mg/kg weekly (after 400 mg/kg load) ± paclitaxel 80 mg/m2 weekly. A cycle is 4 weeks (wks). Response is assessed by imaging every 8 wks. Based on the activity of other salvage therapies, we consider a new agent interesting if the med PFS ≥ 16 wks, and uninteresting if the med PFS is ≤8 wks. Therefore, early stopping rules state that either arm will close if 7 of the first 15 pts in that arm progress by 8 wks. The probability of stopping early if the agent is effective and ineffective are 5% and 50% respectively. Unlike other 2-stage phase II designs, this study does not close for response evaluation. Since futility is declared once 7 pts progress, the decision to close may occur prior to enrolling the full first stage. This may shorten the study and limit the number of pts exposed to inactive drugs. If either arm continues to full accrual (28 pts/arm), it will be considered positive if at least 9 pts are progression free at 16 wks. Final efficacy evaluation may occur if the endpoint is met prior to enrolling the full cohort. The study has 90.4% power to detect an improvement in med PFS from 8 to 16 wks with a 7.1% Type 1 error. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Phase II trial of radiation therapy/temozolomide followed by temozolomide/sorafenib in the first-line treatment of glioblastoma multiforme (GBM)
Authors: R. E. Lamar, D. R. Spigel, H. A. Burris, T. M. Markus, M. Kuzur, T. Ervin, L. Fichtel, F. A. Greco, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2009)

2018 Background: Anti-angiogenesis agents have recently shown activity in the treatment of patients (pts) with GBM. We added sorafenib, a multi-targeted TKI, to the standard first-line treatment of patients with GBM. Methods: Pts with histologically documented GBM were eligible at diagnosis or after resection. Additional entry criteria: ECOG PS 0 or 1; adequate organ function; ability to swallow pills; standard exclusions for antiangiogenesis agents. All pts initially received radiation therapy (total 60 Gy, 2 Gy by single daily fractions) plus temozolomide (75mg/m 2 po daily). Four weeks after completion of radiation therapy, pts received temozolomide (150mg/m 2 po days 1–5, repeated every 21 days for 6 cycles) plus sorafenib (400mg po bid daily x 24 weeks). Pts were evaluated every 8 weeks during temozolomide/sorafenib therapy, and every 3 months after therapy ended, until tumor progression. Median PFS was the primary endpoint. Results: Between April 2007 and July 2008, 45 pts were enrolled. The median age was 54 years; 30 pts (67%) had previous partial or complete surgical resection. 39 pts (87%) completed concurrent RT/temozolomide therapy, while 6 pts were removed from treatment (PD 4, toxicity 1, intercurrent event 1). 39 pts began treatment with temozolomide/sorafenib; 3 have completed all planned treatment, 8 remain on treatment, and 28 stopped treatment early (PD 22, toxicity 2, intercurrent event 1, pt decision 3). Best responses are as follows: CR, 1 pt (2%); PR, 5 pts (11%); stable disease, 22 pts (49%); progressive disease, 14 pts (31%). After a median follow-up of 9 months, median PFS for all pts was 6 months (95% confidence intervals, 2.7–7.8 months). Median PFS for pts who received at least 1 dose of sorafenib is also 6 months. The median overall survival is 16 months (95% CI, 7.2-NR months). Grade 3/4 toxicity during temozolomide/sorafenib was uncommon; 7 pts (16%) required dose reductions of sorafenib during their treatment course. Conclusions: The addition of sorafenib to standard treatment with RT/temozolomide is feasible and well tolerated by most pts. Preliminary efficacy is similar to standard therapy; updated results will be presented. [Table: see text]
Phase II study of oxaliplatin, docetaxel, and sargramostim (GM-CSF) in patients with previously treated advanced melanoma
Authors: F. L. Locke, J. I. Clark, T. F. Gajewski
Journal: Journal of Clinical Oncology (2007)

8570 Background: Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. Methods: Eligibility included intact organ function, PS=2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes, and no chremophor allergy. After premedication, docetaxel was administered day 1 at 85 mg/m 2 , then oxaliplatin on day 2 at 85 mg/m 2 . GM-CSF (5 μg/kg) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every 2 cycles by RECIST criteria. Results: 20 patients were enrolled, 13 with 1 prior therapy, 5 with 2 prior therapies, and 2 previously untreated. Six patients did not complete 2 cycles and were not formally evaluable for response. One patient who failed 2 prior treatment regimens experienced a minor response and received 10 cycles of therapy, and 4 patients had stable disease. The rest showed PD after 2 cycles. Notable toxicities included 7 cases of grade III/IV neutropenia and 2 hypersensitivity reactions. Conclusions: This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naive patients may still be warranted. No significant financial relationships to disclose.
Can the Q-TWiST method provide information on patients' preferences without collecting preference data from the patients? Quality-Adjusted Time Without Symptoms or Toxicity.
Authors: A Messori, S Trippoli
Journal: Journal of Clinical Oncology (1998)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.11.3716 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9817298 Can the Q-TWiST method provide information on patients' preferences without collecting preference data from the patients? Quality-Adjusted Time Without Symptoms or Toxicity. A MessorixA MessoriSearch for articles by this author , S TrippolixS TrippoliSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.11.3716 First Page PDF © 1998 by American Society of Clinical Oncology
Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure
Authors: Kenneth C. Bedi, Nathaniel W. Snyder, Jeffrey Brandimarto, Moez Aziz, Clementina Mesaros, Andrew J. Worth, Linda L. Wang, Ali Javaheri, Ian A. Blair, Kenneth B. Margulies, J. Eduardo Rame
Journal: Circulation (2016)

Background— The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. Methods and Results— We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate. Conclusions— These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart.