tbuckley/cabot-search huggingface dataset:
Molecular profiling of advanced refractory prostate cancer.
Authors: Rebecca A. Feldman, Gargi Dan Basu, Joanne Xiu, David Arguello, Sherri Z. Millis, Ryan Bender, Zoran Gatalica, Les Paul, Charles E. Myers
Journal: Journal of Clinical Oncology (2014)

107 Background: Prostate cancer is the second leading cause of cancer-related death among men in the U.S. Forty percent of men diagnosed will develop metastatic disease, which has few treatment options. We aim to describe the molecular profile of prostate cancer tumors and potential for novel therapeutic options. Methods: We reviewed profiling data of over 330 patients from a large referral laboratory (Caris Life Sciences, Phoenix, AZ) for biomarkers of drug response. Multiple methodologies were employed: sequencing (NGS, Sanger, pyrosequencing), in-situ hybridization (fluorescent and chromogenic), and immunohistochemistry. Results: High expression was observed for AR, MRP1, TOPO1, TLE3 and EGFR, with positivity rates of 89%, 87%, 63%, 48%, and 47%, respectively. Low expression was observed for TS, PGP, TUBB3, RRM1, PTEN and MGMT, with negativity rates of 94%, 87%, 75%, 69%, 54%, and 45%, respectively. Gene copy number increases for EGFR and cMYC were observed in 13% of patients. Sequencing data showed a 48% mutation rate for TP53, 18% for PTEN, 9% for CTNNB1, 8% for PIK3CA, 5% for RB1, ATM, and cMET, and approximately 2% for K/HRAS, ERBB4, ALK, BRAF, and cKIT. Targeted therapy options include imatinib for patients with high cKIT or PDGFRA (9 to 10%) and cetuximab for patients with EGFR positivity (13 to 47%). Promising agents may be considered, including cabozantinib, based on 4% of cohort with cMET aberrations or PAM pathway inhibitors (BEZ234, everolimus) based on approximately 30% of cohort with PIK3CA pathway activation. Lastly, HDAC inhibitors have recently been linked to cMYC driven cancers (13% amplified). 5-FU, gemcitabine, and temozolomide chemotherapies may be options, as approximately 70% of cohort with low TS, RRM1, or MGMT. Biomarker guidance for common prostate cancer drugs such as cabazitaxel is also provided, based on approximately 70% of cohort with low TUBB3 or PGP, or high TLE3. Also, continued dependence on androgen signaling is exhibited by 89% of cohort with high AR, indicating potential utility of anti-androgen agents like enzalutamide. Conclusions: Tumor profiling identified small subsets of patients that may benefit from targeted agents approved for other solid tumors (imatinib, cetuximab), promising therapies in clinical trials (cabozantinib) or agents not routinely used for prostate cancer (gemcitabine).
Coping with cancer treatment-related financial burden.
Authors: Ryan David Nipp, Leah L. Zullig, Gregory Samsa, Jeffrey M. Peppercorn, Deborah Schrag, Donald H. Taylor, Amy Pickar Abernethy, Yousuf Zafar
Journal: Journal of Clinical Oncology (2014)

161 Background: Growing evidence suggests that financial distress is a side effect of cancer care needing attention. Little is known about how patients cope with treatment-related financial distress. This study describes how patients with cancer cope with treatment-related costs and identifies those at greatest risk for using potentially harmful cost-coping strategies. Methods: Eligible patients for this cross-sectional, survey study were adults being treated for solid malignancies enrolled June 2010 to May 2011 in a national copay assistance program. Coping strategies were grouped as lifestyle-altering or care-altering. Descriptive statistics and analysis of variance assessed coping strategies and relationships between covariates. Results: Among 174 participants, 89% used at least one lifestyle-altering strategy to cope with costs, while 39% used a care-altering strategy. Most common care-altering coping strategies included: not filling a prescription (28%); and taking less medication than prescribed (23%). Lifestyle-altering strategies included: spending less on leisure activities (77%); spending less on basics (57%); borrowing money (54%); and spending savings (50%). The mean number of coping strategies was higher for patients &lt; 65 than for those ≥ 65 (Table). Lower-income patients used more care-altering strategies than higher-income patients. Patients with more education and shorter duration of chemotherapy adopted more lifestyle-altering strategies than their counterparts. Conclusions: Patients were generally more likely to use lifestyle-altering approaches to cope with treatment-related financial burden, but more than one-third adopted care-altering strategies. Younger patients and those with lower incomes were more likely to alter their care. Screening for and anticipating potentially harmful cost-coping behavior in the oncology clinic is important to reduce patient distress and promote optimal care. [Table: see text]
Biweekly cetuximab and irinotecan as second-line therapy to patients with platinium-resistant gastroesophageal cancer
Authors: J. K. Bjerregaard, K. R. Schønnemann, H. A. Jensen, L. W. Vestermark, T. P. Hansen, P. Pfeiffer
Journal: Journal of Clinical Oncology (2009)

e15624 Background: There is no established 2 nd line therapy for patients (pts) with advanced gastroesophageal (GE) cancer. In 2004, the Danish government initiated a national health programme for pts with advanced cancer. Non- proven therapy may be offered after approval by an expert panel appointed by the National Board of Health that subsequently finances the cost of treatment. This programme has had a major impact on the management of cancer pts in Denmark and has accelerated the introduction and implementation of new therapies. Inspired by the excellent results in colorectal cancer a combination of cetuximab and irinotecan (CetIri) was chosen for platinum-resistant GE cancer. While awaiting approval of a phase II protocol CetIri was offered at a single institution. We report our preliminary experience with biweekly CetIri as 2 nd line therapy in pts with GE cancer. Methods: All pts had histologically confirmed GE cancer (adeno- or squamous cell carcinoma) and all pts had previously received first line platinum based therapy. Pts received CetIri (cetuximab 500 mg/m 2 and irinotecan 180 mg/m 2 day 1) every 2 nd week until progression or unacceptable toxicity. Response rate was evaluated by the investigator according to RECIST every 8 th week. Toxicity was prospectively evaluated according to NCIC-CTC 3.0. Results: From December 2007 to August 2008, 31 consecutive pts was treated with CetIri. Median age was 62 years (33–76). Median performance status was 1 (0–2). Localisation of primary was: Esophagus 10%, GE junction 64%, gastric 26%. Twenty-seven pts (87%) had adenocarcimona. Median number of cycles were 6 (1–21). Most important grade 2–4 toxicities were non-haematological toxicity as diarrhea (25%), nausea (21%) and vomiting (11%). Three pts (11%) had grade 3 leukopenia, 1 had febrile neutropenia. Two pts had PR. Median PFS was 3.2 months. Fourteen pts (45%) received at least 6 courses (3 month of therapy). After a median follow-up of 6 month 5 pts continue CetIri without sign of PD. Conclusions: Biweekly CetIri is a convenient and well-tolerated 2 nd line regimen in pts with GE cancer. Predictive factors are needed to select which pts will benefit from therapy. A confirmatory phase II study is ongoing. [Table: see text]
Bivalirudin in the treatment of acute coronary syndrome
Authors: Stephen P Hoole, Nick E J West
Journal: BMJ (2016)

Is beginning to look like expensive dilute heparin

Bivalirudin was heralded as the successor to heparin. It is a direct thrombin inhibitor with a more predictable dose response than heparin, a short half life of 22 minutes, and the ability to bind circulating and clot bound thrombin. But does it have genuine advantages over heparin in patients having percutaneous coronary interventions (PCI) for acute coronary syndrome or is it just expensive dilute heparin? 

Bivalirudin is the market leader among anticoagulants used in PCIs in the United States and is endorsed with class I recommendations by national society guidelines.1 2 Global market revenues are estimated to be worth billions of dollars, with bivalirudin costs in the UK ranging from £300 (€400; $440) to £1000 per patient episode, depending on duration of infusion. By comparison, heparin costs only a few pounds.

Bivalirudin was established as the anticoagulant of choice in PCI during an era when glycoprotein IIb IIIa inhibitors were often coadministered with heparin. When compared with this combination, large trials such as HORIZONS-AMI, ACUITY, and EUROMAX confirmed that patients treated with …
Improvements in data collection through physician use of a computer-based chemotherapy treatment consultant.
Authors: D L Kent, E H Shortliffe, R W Carlson, M B Bischoff, C D Jacobs
Journal: Journal of Clinical Oncology (1985)

The impact of a computer-based data management system on the completeness of clinical trial data was studied before and after the system's introduction in an oncology clinic. Physicians use the system, termed ONCOCIN, to record data during patient visits and to receive advice about treatment and tests required by experimental cancer protocols. Although ONCOCIN does not force the user to enter all data expected by the protocol, after its introduction there was improvement in the recording frequency of such data. The percentage of expected physical findings recorded increased from 74% to 91% (P less than .05), toxicity history from less than 1% to 45% (P less than .01), general chemistry results from 36% to 82% (P less than .01), x-ray results from 44% to 73% (P less than .01), and physicians' assessments of overall disease activity and Karnofsky performance status from 73% to 91% (P less than .05). Analysis of the steps in data collection and their contribution to loss of data suggests that observations or test ordering which are dependent on the physician are most improved by the system. Furthermore, analysis of post-ONCOCIN visits when the system was unavailable suggests that the recording of physician-dependent data (physical findings and assessments of disease activity and performance status) is likely to revert to pre-ONCOCIN levels if the system is not used routinely. The results show that ONCOCIN can greatly enhance recovery of those data expected for chemotherapy protocol patients. The program's interaction with the physician is central to its effectiveness in data collection, especially for data that arise directly from the patient-physician encounter.
Association of cancer and stroke: A population-based study
Authors: M. P. Frenay, V. Bourg, C. Lebrun, M. Mahagne
Journal: Journal of Clinical Oncology (2008)

20672 Background: Cancer is considered as a risk factor of stroke. We tried to compare cardiovascular risk factors in patients with cancer and stroke and in patients with isolated stroke. Demographic, clinical and biological data were analyzed. Methods: A data-base was initialized prospectively including all patients hospitalized for stroke in our neurological unit since January, 2004. Patients with intra-tumoral and post-traumatic hemorrhage were excluded. The analysis was realized when 700 patients were included and separated in 2 groups: absence of cancer (group 1), report of cancer (group 2). For every patient, were collected: demographic data, medical history, type, location and mechanism of stroke, cardiovascular risk factors, treatment. When cancer was reported we collected date of diagnosis, location, date and type of reductive treatment (surgery, chemotherapy, radiotherapy, hormonotherapy) and status of neoplasia. Results: On 700 patients (292 women, 408 men, mean age: 65.8 years), 78 (11%) had a history of cancer (group 2). These patients were older (mean age: 70.7 years versus 64.8 years, p=0.036), mostly women (51% versus 41%, p<0.001). No difference was found concerning type and location of stroke. Stroke of unknown origin was more frequent in group 1, lacunar type in group 2. The cardiovascular risk factors were identical in the 2 groups with the exception of type II diabetes (more frequent in the group 1) and biological abnormalities (more frequent in the group 2). In group 2, specific data were collected: aseptic endocarditis (1 case), venous thrombosis with carcinomatous meningitis, intra vascular coagulation, stroke during chemotherapy or hormonotherapy, radiation-induced carotid stenosis, concomitant diagnosis of cancer. Conclusions: The prevalence of the association stroke-cancer was 11% and corresponds to the literature. The simultaneous discovery of a cancer remained exceptional (6/700). Cardiovascular risk factors were similar in the 2 groups. The role played by biological abnormalities and cancer treatments is discussed. Association of cancer and stroke is a frequent phenomenon but the role of cancer is not always obvious. Our study fits with the literature. No significant financial relationships to disclose.
How do mechanical insufflation:exsufflation (MI:E) settings influence flow rates and sputum movement? A bench study using a paediatric lung model
Authors: Ema Swingwood, Alex Harvey, Sarah Rand
Journal: European Respiratory Journal (2014)

Background:Cough is an essential defence mechanism. Paediatric patients with neuromuscular disease may have reduced cough effectiveness, causing an increased risk of regular chest infections. Cough augmentation strategies are essential to maintain health; MI:E is one such technique used in this patient group. To date studies have examined the effects of MI:E pressure and time settings. It is not known what the effect of repeated insufflations has on generated flow rates. There are no studies to date that have used the NIPPY Clearway MI:E device.

Objectives: To examine the effects of repeated insufflations on generated flow rates and sputum movement, using the NIPPY Clearway in a paediatric test lung model.

Methods: MI:E was attached to a paediatric test lung. Resulting flows, pressures and volumes, and sputum movement were measured at the airway opening of the test lung at 3 set I:E ratios (1:1, 3:1 and 5:1). The effects of repeated insufflations on generated flow rates and sputum movement were analysed using ANOVA and regression analysis.

Results: A significant reduction was found between set and generated insufflation pressures (p<0.001). Repeated insufflations had a significant influence on generated flow rates (p<0.001), and a non significant influence on sputum movement.

Conclusions: Increasing insufflation repetitions during MI:E created an inspiratory flow bias; this has the potential to further embed secretions when tested in a paediatric test lung model. Whether these results can be extrapolated into a clinical environment is an area that requires further investigation.
Return-to-work issues in outpatient palliative care.
Authors: Paul A. Glare, Tanya Nikolova, Alberta Alickaj, Victoria Susana Blinder, Sujata Patil
Journal: Journal of Clinical Oncology (2014)

35 Background: Early integration of palliative care (PC) with oncologic care means return to work (RTW) issues will apply to some patients. There is an extensive literature on RTW after completing definitive treatment but much less is known about RTW in patients with active disease and on treatment. Methods: Cross-sectional survey of patients in two Pain &amp; Palliative Care (PC) clinics at a comprehensive cancer center. Respondents were aged 25-65 and had been in paid employment prior to or during their treatment. The survey consisted of 37 items covering three domains: clinical details and demographics; work status, occupation, and work ability; importance of work and factors interfering with work. Results: 105 surveys were completed. 54% respondents were females, median age 53. 79% had been working at the time diagnosis. The commonest primaries were breast, colorectal, lung, GYN, and melanoma/sarcoma. 80% reported having active disease, median 2 years since diagnosis, and 73% were currently on treatment. In patients with active disease (n=86), 47% were currently working, 63% of them full time, typically RTW after taking &lt; 6 months off. Work was important to 80% them, making 83% "feel normal", and 58% feel like they are “beating the cancer”. 35% would have liked to work more hours. Fatigue interfered with work in 49%, pain in 38%, and side effects of pain medicines in 31%. Almost ¼ were anxious or depressed about their work situation. More than 20% experienced discrimination in the work place, although usually minor. Conclusions: It is not uncommon for patients with advanced cancer to RTW even when they are on treatment and are sick enough to need to be followed in a PC clinic. Work is important to them and many would like to work more. Symptoms and side effects may interfere with their work ability. Some may be experiencing discrimination in the work place. Interventions to overcome these problems should be part of comprehensive, interdisciplinary PC.
Improving care in ovarian cancer: Role of the weekly clinico-pathological meeting
Authors: P. Ganesan, L. Kumar, R. Hariprasad, A. Gupta, M. Vijayaragvan
Journal: Journal of Clinical Oncology (2008)

16542 Background: Ovarian tumors are characterized by marked heterogeneity in their clinical presentation- an accurate histopathological diagnosis is vital in their management. We evaluated the impact of a weekly clinico-pathological meeting on the management of ovarian cancer at a tertiary center in North India. Methods: In 2005 and 2006, around 400 cases of suspected or confirmed ovarian cancer were evaluated at our gynecology tumor clinic. Of these, 108 cases were referred for discussion in the weekly clinico-pathology meeting. These cases were retrospectively analyzed for the following: 1) the initial clinical impression,2) the initial pathologist’s diagnosis,3)the reason for referring the case for discussion in the meeting, 4) the final diagnosis after the meeting and 5) alterations in management (if any) as a result of the meeting. The alterations in diagnosis which impacted management were classified as major and those which did not were called minor. Results: Of the 108 cases, 91 had full data for analysis. 70 were initially diagnosed as epithelial ovarian cancers. There was an alteration in diagnosis in 48 cases (52%)- 34 cases of epithelial cancers were given a histopathological grade, 3 cases had a changed histopathological diagnosis (yolk sac tumor re-diagnosed as papillary carcinoma, Sertoli-Leydig cell tumor re- diagnosed as germ cell tumor, serous cystadenocarcinoma re-diagnosed as Clear cell carcinoma), 2 cases initially labeled as undifferentiated tumors had their diagnosis clarified and in 9 cases, in which the primary site was not known, a possible site of primary could be assigned( with the help of clinical, radiological and pathological reviews). Among the 14 cases with alterations other than grading, the change was contributed by slide review alone in 6 cases and in the rest- by a combination of slide review and clinical and radiological inputs from the clinicians. As a direct outcome, 20 cases (21%) had their management plan modified as a result of the meeting (major change). Conclusions: Weekly clinico-pathological meetings between clinicians and pathologists leads to improved care of patients with suspected ovarian cancer. No significant financial relationships to disclose.
Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning
Authors: Zhenyu Gao, Martina Proietti-Onori, Zhanmin Lin, Michiel M. ten Brinke, Henk-Jan Boele, Jan-Willem Potters, Tom J.H. Ruigrok, Freek E. Hoebeek, Chris I. De Zeeuw
Journal: Neuron (2016)

Highlights•Cerebellar nuclei provide modular corollary discharge to the cerebellar cortex•Nucleocortical afferents have unique molecular and ultrastructural features•Eyeblink conditioning induces structural plasticity of nucleocortical mossy fibers•Nucleocortical afferents amplify the amplitude of conditioned eyeblink responsesSummaryClosed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning.
A topotecan-containing induction regimen for treatment of high risk neuroblastoma
Authors: J. R. Park, C. F. Stewart, W. B. London, V. M. Santana, P. J. Shaw, S. L. Cohn, K. K. Matthay
Journal: Journal of Clinical Oncology (2006)

9013 Background: We assessed the toxicity and feasibility of adding dose-intensive topotecan and cyclophosphamide to a multi-agent chemotherapy induction regimen for treatment of newly diagnosed high-risk neuroblastoma. Methods: Patients received 2 cycles of topotecan (starting dose 1.2 mg/m 2 /day for 5 days) and cyclophosphamide (400 mg/m 2 /day for 5 days) (T/C) followed by an additional 4 cycles of chemotherapy; cisplatin, etoposide alternating with vincristine, doxorubicin, cyclophosphamide. Pharmacokinetically guided topotecan dosing (target systemic exposure of AUC 50 - 70 ng/ml*hr determined by single day topotecan lactone levels) was performed. Chemotherapy cycles were scheduled every 21 days, PBSC harvest occurred after T/C cycles and surgical resection of residual primary tumor after cycle 5. Results: Thirty-one patients, 3 with INSS Stage 3 and 28 with Stage 4, were enrolled between April 2004 and November 2005. Median age at diagnosis was 2.5 years (range 0.9 - 9.35 years). Ten of 25 patients had tumor cell MYCN amplification and 21 of 22 tumors were classified as unfavorable Shimada histology by central review. Targeted topotecan systemic exposure was achieved in 87% (27/31) of patients during T/C cycle 1 and in 85% (23/27) of patients during T/C cycle 2. PBSC collections occurred as intended in 95% of patients (21/22 patients), median harvest 30.8 × 10 6 CD34+cells cell/kg (range 2.24 - 542). No dose limiting toxicities occurred. All patients experienced Grade 3 or 4 hematopoietic toxicity. Febrile neutropenia occurred in 79% (19/24) of patients during T/C cycles and 78% (18/23) of patients during subsequent cycles of induction therapy. Documented infection occurred in 12.5% (3/24) patients during T/C cycles and 26% (6/23) during subsequent induction cycles. Dose intensity of all chemotherapy agents was maintained in 95.8% (23/24) of patients. Conclusions: This pilot induction regimen was well tolerated with expected and reversible toxicities. Dose intensity of standard induction chemotherapy agents was not limited by the addition of dose-intensive topotecan. These data support investigation of efficacy in a Phase III clinical trial for newly diagnosed high-risk neuroblastoma. [Table: see text]