tbuckley/cabot-search huggingface dataset:
Differing complications of hyperleukocytosis in children with acute lymphoblastic or acute nonlymphoblastic leukemia.
Authors: N J Bunin, C H Pui
Journal: Journal of Clinical Oncology (1985)

We assessed the frequency and outcome of complications associated with hyperleukocytosis in children who had received remission induction therapy for either acute lymphoblastic leukemia (ALL) or acute nonlymphoblastic leukemia (ANLL). Among 234 consecutive patients with a leukocyte count of 100 X 10(9)/L or greater at diagnosis, the frequency of early death was significantly higher in those with ANLL (23% v 5% for patients with ALL, P less than .001). The risk of early death increased with increasing leukocyte count, especially when it exceeded 300 X 10(9)/L in patients with ANLL (P less than .001). Intracerebral hemorrhage occurred in eight (11%) of the ANLL patients and accounted for six of the 17 early deaths; in all but two instances, the complication was associated with coagulopathy. Respiratory failure, presumably from pulmonary leukostasis, resulted in six other early deaths in ANLL patients. By contrast, intracerebral hemorrhage occurred in only two of the ALL patients (1.2%); both had normal coagulation studies, but leukocyte counts greater than 400 X 10(9)/L. Severe metabolic derangements from blast cell lysis accounted for three of the eight early deaths among patients with ALL. Leukapheresis or exchange transfusion effectively lowered the leukocyte counts of all 15 patients who received the procedures. Either method may be preferable to emergency cranial irradiation for preventing the complications of hyperleukocytosis in children with acute leukemia.
Phase II study of nab-paclitaxel, bevacizumab, and gemcitabine for first-line therapy of patients with HER2-negative metastatic breast cancer (MBC)
Authors: S. Gluck, C. Lobo, I. Reis, G. Lopes, C. Carmody, K. Tukia, J. Hurley, P. Seo, O. Silva, J. Slingerland, C. Welsh
Journal: Journal of Clinical Oncology (2008)

1089 Background: Nab-paclitaxel (nab-pac) demonstrated an overall response rate almost double that of solvent-based paclitaxel (p=0.001) in a phase III study in patients with MBC. Combination therapies including gemcitabine or bevacizumab and solvent-based paclitaxel demonstrated improved time to progression and response rates compared with solvent-based paclitaxel alone. This was the first study initiated to examine the efficacy of combination therapy with nab-pac, bevacizumab, and gemcitabine as first-line treatment for patients with MBC. Methods: Patients (≥18 years with untreated HER2-negative MBC or metastases diagnosed ≥6 months after primary systemic treatment) received gemcitabine 1,500 mg/m2, nab-pac 150 mg/m2, and bevacizumab 10 mg/kg (each administered intravenously over 30 minutes) on days 1 and 15 of 28-day cycles. Cycles were repeated for the duration of therapy. Progression-free survival is the primary endpoint; secondary endpoints include rates of complete or partial response (CR or PR), overall survival, safety, and toxicity. A total enrollment of 30 evaluable patients and a 2.5-year study duration are planned. Results: To date, 15 patients (14 female; mean age, 54 years) have been enrolled, of whom 11 were evaluated for efficacy (received ≥2 cycles), 13 for safety, 15 for estrogen receptor (ER) status, and 12 for progesterone receptor (PR) status. All patients were HER2-negative; 80% were ER+, and 58% were PR+. Ten (91%) patients achieved PR, and 1 (9%) patient had progressive disease. All adverse events were grade 1 or 2, and the most commonly reported side effects were alopecia (62%) and fatigue (38%). Two patients were hospitalized because of port site infection and hematotoxicity. Conclusions: This interim analysis demonstrates a 91% overall response rate to first-line combination therapy with nab- pac, bevacizumab, and gemcitabine in patients with MBC. Despite the small sample size, this data suggests that this regimen may represent an important new option for the first-line treatment of patients with MBC. Complete response, survival, and safety results will be reported. The study is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech
Analysis of Overall Survival (Os) for Patients (Pts) with Different Prognostic Risk Factors Treated with Cabazitaxel and Prednisone (Cbz + P) After Docetaxel (D) in the Tropic Trial
Authors: K.N. Chi, J.S. de Bono, A. Bahl, S. Oudard, B. Tombal, M. Özgüroğlu, S. Hansen, I. Kocak, G. Gravis, L. Shen, Z. Su, O. Sartor
Journal: Annals of Oncology (2014)
Chemotherapy of advanced non-small-cell lung cancer: A comparison of three active regimens. A randomized trial of the Italian Oncology Group for Clinical Research (G.O.I.R.C.)
Authors: L Crinò, M Clerici, F Figoli, P Carlini, G Ceci, E Cortesi, A Carpi, A Santini, F Di Costanzo, C Boni
Journal: Annals of Oncology (1995)
General practitioner (GP) communication with potential lung cancer patients; review of practices prior to onward secondary care referral
Authors: Selva Selvaraj, Kate Garbett, Julia McAdam, Koottalai Srinivasan, Harmesh Moudgil
Journal: European Respiratory Journal (2011)

Background: Anecdotally, there is heterogeneity in what patients understand as to why they are being asked to urgently attend respiratory clinics for suspected lung cancer; this is partly because of accelerated referral pathways after initial abnormal radiology and potentially bypassing direct contact in primary care.

Aim: We investigated patients referred to our urgent lung cancer referral pathway and report (1) how and what patients are told prior to attending secondary care clinics, (2) how these findings relate to subsequent outcomes, and (3) the performance status of patients at the point of initial review.

Results: Over a 4 month period to August 2010, of 107 referrals, 95 (89%) had complete data available for analysis. Mean (range) age was 65.8 (29-95) years. 51 (54%) are male. 79/95 (83%) had prior information from their GP with no home consultations, 15 (19%) had been contacted by telephone, 4 (5%) had received letter, and 60 (76%) had attended the GP surgery. 8 (10%) had been told that they had a possible or definite lung cancer, 54 (68%) had been told they had abnormal chest x-ray findings, and 17 (22%) had been told they were being referred for investigation. Performance status was, respectively from 0 to 4, 36 (38%), 34 (36%), 18 (19%), 6 (6%), and 1 (1%).

Conclusions: Results confirm the variation in referral routes and methods as well as the wide age range referred under this urgent system, but with only 23 (24%) patients with an eventual outcome of lung cancer. Results further emphasize the need to balance any direct and early information from the GP priming the patient before subsequent consultation in secondary care.
Abstract P4-01-02: Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer
Authors: Ian E Krop, Erin Macrae, Sarah R Galler, Farideh Bischoff, Romeo Fauni, Edgar Sales, Lan Huynh, Christine Mitchell, Trisky Clarin-Tamayo, Mark Anderson, Leslie Abad, Eric Winer
Journal: Cancer Research (2015)

Abstract Background: We have previously shown feasibility by CLIA validation of HER2 FISH on circulating tumor cells (CTCs). Several small retrospective studies have identified HER2 amplification in CTCs in a subset of patients (pts) with clinically HER2 negative metastatic breast cancer (MBC). While these findings potentially have profound implications for CTCs as a predictive biomarker, prospective validation and functional characterization of this subgroup is necessary. Methods: We enrolled a prospective cohort of pts with MBC that was HER2 negative by IHC and/or FISH on all available primary and metastatic biopsies. Pts had ≥1 line of prior chemotherapy for MBC. Blood samples were collected at study entry. CTCs were enumerated based on standard criteria (Cytokeratin (CK)+/CD45- staining) as well as by FISH for HER2 using the OncoCEE-BR™ CTC test (Biocept, Incorporated). This test employs a proprietary antibody cocktail for capture followed by CK/CD45 staining, and FISH analysis directly within a microfluidic device. Samples were reported as positive if the HER2/CEP17 ratio was ≥ 2.0. HER2+ CTCs were classified into two categories: CK+/CD45-/HER2+ and CK-/CD45-/HER2- Results: CTCs were observed in 208 out of 323 pts (64%). Median number of CTCs was 10 (range 1 to &amp;gt; 34195). 75 pts (23%) had HER2+ CTCs, with a median number of 3 HER2+ CTCs (range 1 to 21). 36% (27/75) of these pts had CK+/HER2+ CTCs and 43% (32/75) of pts had only CK-/HER2+ CTCs. The remaining pts (21%) had both CK+/HER2+ and CK-/HER2+ CTCs present. Conclusion: HER2 amplified CTCs are present in a subset (23%) of pts with clinically HER2-negative breast cancers. Interestingly, we observed a high prevalence of pts with only CK-/HER2 amplified CTCs (32 out of 323; 10%). The unique multi-antibody CTC capture method used here thus allows for detection of a prevalent population of CK-/HER2+ CTCs that may be largely undetected by other current adopted technologies. The functional significance of CK-/HER2+ and CK+/HER2+ CTCs in patients with clinically HER2 negative breast cancer is currently being evaluated in a prospective study with HER2-directed therapy. Citation Format: Ian E Krop, Erin Macrae, Sarah R Galler, Farideh Bischoff, Romeo Fauni, Edgar Sales, Lan Huynh, Christine Mitchell, Trisky Clarin-Tamayo, Mark Anderson, Leslie Abad, Eric Winer. Prospective characterization of HER2-positive circulating tumor cells in patients with HER2-negative metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-02.
Use of a Balanced Test to Resolve Competing Best Interest and Liberty Claims When Parents Refuse Consent for Neonatal Pulse Oximetry
Authors: Allan J. Jacobs, Kavita Shah Arora
Journal: The American Journal of Bioethics (2016)

"Use of a Balanced Test to Resolve Competing Best Interest and Liberty Claims When Parents Refuse Consent for Neonatal Pulse Oximetry." The American Journal of Bioethics, 16(1), pp. 28–29
A randomized phase I clinical and biologic study of two schedules of BAY 43–9006 in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML): A National Cancer Institute of Cancer Clinical Trials Group Study
Authors: M. Crump, B. Leber, J. Kassis, D. Hedley, M. Minden, R. Buckstein, L. McIntosh, E. Eisenhauer, L. Seymour
Journal: Journal of Clinical Oncology (2004)

6611 Background: Components of the Ras pathway are becoming important targets in AML therapy. BAY 43–9006 (BAY) is a small molecule inhibitor of CRAF and BRAF kinases and the receptor tyrosine kinases VEGFR-2, PDGFR-β and flt-3 and is currently in phase II and III testing in solid tumors. This randomized phase I trial was initiated to establish optimal dose and schedule in patients (pts) with AML or MDS. Methods: Pts with AML or MDS (1 prior regimen or elderly or secondary high risk AML) were randomized to BAY for 28 days (continuous) or 14 days followed by a 14-day rest period, escalated at 100, 200 and 400 mg bid orally. Phospho-ERK levels were assessed in bone marrow (BM) blasts at baseline, day 15 and 28 by immunohistochemistry and in stem cell factor (SCF) stimulated peripheral blood (PB) blasts by a flow cytometry assay. Results: 36 pts have been enrolled (4 MDS, 32 AML; median age 70 range 50–82; prior chemotherapy: 17 pts) and received 100 mg bid (7 pts); 200 mg bid (12 pts); 400 mg bid (17 pts). Dose-limiting toxicity was seen in 0/7 pts at 100 mg bid, 2/12 pts at 200 mg bid and 1/17 pts at 400 mg bid. At 400 mg bid, 6 pts received <14 days of treatment due to gr 1 and 2 toxicity (abdominal pain, nausea, vomiting, rash, stroke, thrombocytopenia), indicating this dose was above tolerability. Accrual to an intermediate dose of 300 mg bid for 28 days is ongoing. Clinical effects (reduction in PB and BM blasts) have been seen in 4/27 evaluable pts: 2 at 200 mg bid (one 28 d, one 14 d schedule) and 2 at 400 mg bid (both on 28 d schedule). One pt at 400 mg bid with AML and a 30 bp internal tandem duplication in flt-3 had a confirmed CRp lasting 3 cycles. Biologic activity (inhibition of pERK in SCF stimulated PB blasts) has been assessed in 14 pts and shows drug-related inhibition in 5/14, all at 400 mg bid. Assessment of flt-3 mutational status, BM pERK staining and gene expression by 19K microarray will be presented. Conclusions: BAY appears to be well-tolerated when given continuously at 100–300 mg bid to pts with relapsed or high risk AML/MDS. Early clinical and biological activity is evident. No significant financial relationships to disclose.
Locoregional failure rates after mastectomy for breast cancer patients with T1-2 tumors and axillary nodal microscopic metastases.
Authors: Lonika Majithia, Jose Bazan, Allison Marie Quick, Alicia Maria Terando, Doreen Marie Agnese, Ewa Mrozek, William Blair Farrar, Julia R. White
Journal: Journal of Clinical Oncology (2015)

64 Background: The indications for postmastectomy radiotherapy (PMRT) are expanding to include patients 1-3 axillary nodal metastases (ALN). Improvements in diagnostic evaluation have led to increasing numbers of breast cancer (BC) patients who are found to have microscopic nodal metastases (N1mic). The challenge today is whether these BC patients have risk that warrants the routine delivery of PMRT. Methods: We reviewed patients with pathologic T1-2N1 BC treated with initial mastectomy (mast) and adjuvant systemic therapy (ST) from 2000-2013. The primary endpoint was locoregional failure (LRF), defined as a recurrence in either the ipsilateral chestwall or regional lymphatics (axillary, internal mammary, or supraclavicular). Secondary endpoints were disease-free survival (DFS, failure or death) and overall survival (OS). The log-rank test was used to compare survival between groups. Results: We identified 550 eligible patients from our prospectively maintained cancer registry with 5 year median follow-up. 95 patients (17%) had N1mic disease. Baseline characteristics include: median age 53 yrs, 61% pathologic T2, 39% grade 3, 72% hormone receptor positive, 16% HER2+, 12% triple-negative. Treatment included chemotherapy in 78% (n = 428), PMRT in 15% (n = 82), and anti-endocrine therapy in 70% (n = 385). A median of 18 ALN (range, 1-68) were removed. Among the patients with N1mic disease, 81 had 1+ node, 13 had 2+ nodes, and 1 had 3+ nodes. The 5 yr LRF was 0% for patients with N1mic disease vs. 4.6% in those macro metastases (p = 0.84). The 5 yr LRF rate for the entire cohort was 3.9%; patients with 1+, 2+, and 3+ nodes had 5 yr LRF of 2.6%, 4.7% and 6.4%, respectively (p = 0.79). Patients with N1mic disease had a trend towards improved DFS (91.6% vs. 82.3%, p = 0.07) and significantly improved OS (96.9% vs. 87.6%, p = 0.03) compared to patients with macrometastases. Conclusions: In a cohort of patients with T1-2,N1 BC treated with modern therapy, we found overall low rates of LRF. Patients with N1mic disease had no LRF events and improved OS compared to patients with macrometastases. These findings support that PMRT should not be routinely recommended for N1mic BC patients with T1-2 tumors.
Commentary on “Autonomic and behavioural thermoregulation in tennisAutonomic and behavioural thermoregulation in tennis”
Authors: Timothy Noakes
Journal: British Journal of Sports Medicine (2008)

Over 100 years ago, biologist Charles Morris proposed the revolutionary idea that humans evolved as hot weather hunters. Today it is increasingly accepted that we Homo sapiens owe our big brains (and our ability to undertake science) to our sweaty, hairless, long-legged torsos that allowed our (then small-brained) ancestors to outrun antelope in the midday heat on the sultry African savanah starting perhaps 2 million years ago. Studies of modern hunters in the Kalahari desert in Southern Africa suggest that these hunts were most successful when held in dry- bulb temperatures of 40–46°C. Often these hunts can …
Plasma trough imatinib levels and molecular response in patients of chronic myeloid leukemia (CML): A single institution study from India.
Authors: Hemant Malhotra, Pratibha Sharma, Shipra Bhargava, Om Singh Rathode, Bharti Malhotra, Vikram Gota
Journal: Journal of Clinical Oncology (2013)

7079 Background: One of the reasons proposed for suboptimal responses in Chronic Myeloid Leukemia (CML) patients receiving standard-dose Imatinib has been low blood levels of the drug. Our study aimed to determine the correlation between mean trough Imatinib plasma levels and molecular response in CML chronic phase patients at our centre. We also attempted to compare imatinib plasma levels in patients receiving Gleevec (Novartis) versus patients who were on the generic version of the drug. Methods: One hundred and thirty one (131) CML Chronic phase patients were included in this study. All patients had received 400 mg of imatinib for more than 2 year. Plasma Imatinib trough levels were estimated by high-performance liquid chromatography (HPLC). In order to estimate a threshold for plasma imatinib level that correlates with a favorable response, a receiver operating characteristic (ROC) curve was constructed. Patients were divided into two groups: those with Major Molecular Response (MMR) [bcr/abl : abl ratio &lt;1% as assessed by RQ-PCR] or better (Responders) and those without MMR (bcr/abl : abl ratio =/&gt; 1% as assessed by RQ-PCR) [Non Responders]. Imatinib plasma levels were also compared in patients who were on Gleevec versus those who were on the generic version of the drug. Results: The mean trough imatinib plasma level in the responders was significantly higher (2.10±1.18µg/ml) than in the non responders (1.31±0.72µg/ml) with p value of 0.001. The area under ROC curve was 0.733, with best sensitivity (51.85%) and specificity (89.42%) at a plasma threshold of 0.988 µg/ml. There was no significant difference between the mean trough plasma imatinib levels of the patients who were on Gleevec as compared to those who were on generic Imatinib (p value &gt; 0.05). Conclusions: Plasma Imatinib trough levels were statistically similar in the Gleevec and generic Imatinib groups. These levels showed a statistically significant correlation with molecular response. Trough plasma imatinib levels may be a marker for suboptimal response to Imatinib and may identify patients in whom increase of drug dose or change to second generation tyrosine kinase inhibitors may be indicated.
Abstract 092: Transgenic Expression of Heat Shock Protein 60 Results in Neonatal Death and Adult Heart Failure
Authors: Shan-Wen Liu, Tsung-Hsien Chen, Yen-Ling Chen, Mei-Ru Chen, Ching-Han Hsu, Kurt M Lin
Journal: Circulation Research (2013)

Heat shock proteins (HSPs) are known for their enhanced expression and pro-survival role in cells under noxious stress. Only recently was it discovered that aberrant expression of HSPs was linked to the onset of cardiovascular diseases. HSP60, originally identified as one of the mitochondrial chaperonins, was shown involved in autoimmune, metabolic, and cardiovascular diseases, but the roles of HSP60 remain unclear in part due to the lack of HSP60 transgenic mouse models. This study aims to investigate the outcome of expressing HSP60 in cardiac tissues to elucidate the role of HSP60 in initiating apoptotic cardiomyopathy. By using a conditional HSP60 transgenic mouse line (G-Lox-HSP60) and a Cre mouse line, human HSP60 expression in most mouse tissues, driven by the ubiquitous CAG promoter, was achieved. The ubiquitous expression of HSP60 was found to cause neonatal death during postnatal day one. In HSP60 expressing newborn mice, hemorrhagic cardiac myopathy was found, and some of these mice exhibited atrium septal defects. A greatly increased rate of apoptosis was found in cardiac tissues with HSP60 overexpression, suggesting a pro-apoptotic role for HSP60. A tamoxifen-inducible Cre mouse (Myh6-Cre/ESR) was used to induce HSP60 expression in the adult mouse heart, and the results showed that dilated heart failure developed within 8 weeks after the induction of HSP60 expression. By employing an isolated perfusion model, the basal contractility was found to be significantly enhanced by HSP60, and a cardiac protection against simulated ischemia and reperfusion injury was found in mice with the HSP60 induction for 4 weeks. Both increased contractility and cardiac protection were lost in mice 6 to 8 weeks after HSP60 induction. Our results showed that HSP60 expression led to heart failure in neonatal mice and likely involved developmental defects and induced apoptosis. While expressing HSP60 in adult cardiac tissues only temporally improved cardiac function and exerted cardiac stress protection, hypertrophy and heart failure eventually occured in these mice. The G-Lox-HSP60 model that achieves expression of HSP60 in an inducible and tissue-specific manner will be useful in studies to investigate the roles and molecular details of HSP60 in various diseases.
Activity and Safety of Everolimus in Combination with Octreotide Lar and Metformin in Patients with Advanced Pancreatic Well-Differentiated Neuroendocrine Tumors (Pwdnets): a Single–Center, Open-Label, Phase Ii, Proof-Of-Concept Study (Metnet1 Trial)
Authors: F.G.M. De Braud, S. Pusceddu, B. Formisano, P. Consonni, M. Pacifici, J. Pulice, L. Concas, F. Festinese, C. Bregant, A. Martinetti, R. Buzzoni
Journal: Annals of Oncology (2014)
Abstract 11084: Coronary Artery Bypass Graft Surgery in Elderly Patients With Multivessel Coronary Artery Disease is Associated with Better Outcomes
Authors: John T Posenau, Daniel M Wojdyla, Linda K Shaw, Karen P Alexander, E. M Ohman, Manesh R Patel, Peter K Smith, Sunil V Rao
Journal: Circulation (2014)

Introduction: The appropriate revascularization strategy for elderly patients with multivessel CAD is unclear. Hypothesis: We hypothesized that the rate of death, MI, and revascularization would be lower in elderly patients with multivessel CAD who receive revascularization with CABG. Methods: We used the Duke Databank for Cardiovascular Disease from 10/01/2003 through 06/30/2013 to identify patients ≥ 75 years old with multivessel disease, and treatment with PCI or CABG within 30 days of index catheterization. Exclusions included STEMI, left main disease, and significant valvular disease. The primary outcome was a composite of all-cause death, MI, and coronary revascularization through latest follow-up. The outcomes were examined across initial revascularization therapies including bare metal stents, drug-eluting stents, and CABG. Unadjusted estimates were assessed with Kaplan-Meier time-to-event methods. Multivariable Cox proportional hazards modeling was used to assess adjusted relationships with outcome. Results: We identified 763 patients who met criteria (BMS n=202, DES n=411, CABG n=150). The median age was 79 years and the median follow up time was 6.28 years. Unadjusted primary outcome rates per 100 patient-years of follow up were 22.41% for BMS, 16.97% for DES, and 12.39% for CABG. After adjustment, both BMS and DES were associated with a higher risk of the primary outcome. BMS versus CABG HR=1.58 (1.15-2.19, p=0.01). DES versus CABG HR=1.45 (1.08-1.95, p=0.01). The adjusted event rate for PCI with DES versus BMS was not significant, HR=0.92 (0.71-1.19, p=0.51). Conclusions: In this retrospective single center analysis of 763 elderly patients with multivessel coronary disease, CABG was associated with a significantly lower rate of death, MI, and revascularization when compared with initial revascularization with bare metal or drug-eluting stents. This may reflect selection of healthier patients taken for bypass surgery.