bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating an orally available small-molecule inhibitor (vemurafenib) of BRAFV600E in a novel preclinical model of human papillary thyroid cancer.
Authors: Duquette Mark , Sadow Peter M. , Priolo Carmen , Fischer Andrew , Hodin Richard , Parangi Sareh , Lawler Jack , Nucera Carmelo 
Published: March 2020

e17014 Background: Patients with BRAFV600E-positive human papillary thyroid cancer (PTC) have poorer prognosis, higher rates of metastases and mortality, and resistance to radioiodine treatment. The goal of this study was to assess the therapeutic efficacy of vemurafenib (a new orally available BRAFV600E selective inhibitor) in a translational therapeutic model of BRAFV600E human nonmetastatic or metastatic PTC. Methods: We have established in vitro cultures of human primary PTC cells with or without heterozygous BRAFWT/V600E, primary normal thyroid (NT) cells, and used previously established human PTC cell lines with BRAFV600E. Immunocytochemistry was used to characterize markers of differentiation. Genotyping (over 500 genes analyzed) by mass spectrometry was performed to determine genetic alterations. Cell viability assays were performed upon different concentrations of vemurafenib: 0.01, 0.1, 1, 5, and 10 µM. Phosphorylation (p) of ERK1/2 (downstream BRAFV600E) was used to measure BRAFV600E activity. Results: We have isolated 8 independent batches of primary human non-metastatic or metastatic PTC cells from total thyroidectomy patients with PTC >1.1 cm, and 4 independent batches of primary NT cells from normal matched thyroid tissue specimens. 62.5% of the isolated batches of PTC cells were heterozygous BRAFWT/V600E and expressed epithelial markers and thyroid differentiation markers (e.g. PAX8, TSH-receptor). The NT cells showed no mutations. BRAFWT/V600E nonmetastatic PTC cells showed decreased viability (IC50: 5 µM) and pERK1/2 levels (IC90: 10 µM) when exposed to vemarufenib, with no toxic effects. PTC cells with BRAFWT, or NT cells showed no change in viability and pERK1/2 levels when exposed to vemarufenib. Importantly, BRAFWT/V600E metastatic PTC cells showed a partial suppression of viability and inhibition of pERK1/2 but only at a higher dose (10 µM) of vemurafenib. Conclusions: We have established the first translational therapeutic model of heterozygous BRAFWT/V600E-PTC. Testing of PTC samples for BRAFWT/V600E and testing in vitro will help predict therapeutic efficacy of Vemurafenib in patients with BRAFWT/V600E-PTC.
A phase IB trial of 5-azacitidine (5AC) and suberoylanilide hydroxamic acid (SAHA) in patients with metastatic or locally recurrent nasopharyngeal carcinoma (NPC) and NK-T cell lymphoma.
Authors: Hsieh Wen Son , Tan Eng Huat , Lim Wan-Teck , Soo Ross A. , Chan Anthony T. C. , Hui Edwin P. , Lee Soo-Chin , Low John Soon Wah , Lim Pei Li , Loh Thomas Kwok Seng , Ames Matthew M. , Reid Joel M. , Murray Paul Gerard , Tao Qian , Goh Boon C. , Ambinder Richard F. 
Published: March 2020

e17017 Background: Epigenetic up-regulation of EBV and cellular genes via demethylation and histone deacetylase inhibition can induce EBV lytic replication enhancing immune mediated tumor killing and up-regulation of tumor suppressor genes resulting in tumor apoptosis. Methods: Patients (Pt) with relapsed or refractory NPC and NK-T cell lymphomas were enrolled to determine safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor activity using a dose escalation design. 5AC was administered on days 1 to 10 sub-cutaneously while SAHA was administered on days 1 to 14 orally. PK for SAHA, EBV viral load, characterization of circulating EBV, Immunohistochemistry (IHC) and EBV promoter methylation analysis in tumor tissue were performed. Results: 11 pt have been treated (M:F 8:3, median age 48, R: 35-71) at 3 dose levels – 5AC 50 mg/m2 and SAHA 200 mg b.i.d. (dose level 1), 5AC 37.5 mg/m2 and SAHA 200 mg q. am and 100 mg q. pm (dose level 2), and 5AC 25 mg/m2 and SAHA 100 mg b.i.d (dose level 3). Median number of previous treatment regimens was 3 (R:1-6). Dose limiting toxicities (DLT) were seen in 2/2 pts at dose level 1: grade 4 thrombocytopenia (1 pt), grade 3 nausea, vomiting and fatigue (2 pts), and grade 5 hepatic failure (1 pt). Two of six patients at dose level 2 experienced DLT: grade 3 fatigue (1 pt) and worsening of pre-existing Sweet’s Syndrome (1 pt). Common AEs (G1/2) included fatigue (73%), cough (64%), anorexia (55%), and injection site reaction (45%). One minor response was seen and 5 pt had prolonged stable disease (>16 weeks), including one patient for 88 weeks. Analysis of post-treatment tumor biopsies showed demethylation of EBV lytic cycle gene promoters after treatment. SAHA PK, IHC results for EBV gene expression in tumor tissue, EBV viral load and characterization of circulating EBV will be presented. Conclusions: 5AC/SAHA appears to be tolerable at dose level 3 with suggestion of clinical benefit. Analysis of post-treatment tumor and blood samples suggests that modulation of EBV gene expression may play a role in the mechanism underlying clinical benefit. Continued accrual at dose level 3 is ongoing. Clinical trial information: NCT00336063.
Acute toxicity of neoadjuvant chemotherapy in oral cavity cancers: Can it be predicted?
Authors: Poladia Bhavesh , Patil Vijay , Noronha Vanita , Joshi Amit , Bhosale Bharatsinha Baburao , Punatar Sachin , Sharama Vibhor , Prabhash Kumar 
Published: March 2020

e17027 Background: Neoadjuvant chemotherapy administration is associated with significant amount of morbidity and around 2-3% mortality in the Western world protocol settings. In developing countries where malnourishment is prevalent, the same data might not apply. Methods: This analysis was performed on a database of patients undergoing NACT for oral cancers at our center from 2010- 2012. The toxicity was graded according to CTCAE version 4.02 scale. Descriptive analysis, univariate and multivariate analysis were performed to determine factors affecting toxicity. Results: There were 528 patients, the median age was 45 years (22-78 years). The regimens administered were TPF in 35 patients (6.6%) and taxane with platinum in the rest. At least one cycle of chemotherapy was taken at our center by 94.8% (494). The median number of cycles were 2. The any grade toxicity after 1st cycle of chemotherapy were vomiting, diarrhea, mucositis, fatigue, febrile neutropenia (FN), peripheral neuropathy, hyponatremia, hypokalemia, hperkalemia, transaminitis were in 41.3% (204), 43.9% (217), 44.3% (219), 47.2% (233), 7.2% (35), 3.0% (15), 33.8% (167), 14.4% (71), 4.9% (24) and 12.3% (61).Toxicity details of second cycle of chemotherapy were available for 390 patients. The any grade toxicity after 2nd cycle of chemotherapy were vomiting, diarrhea, mucositis, fatigue, febrile neutropenia, peripheral neuropathy, hyponatremia, hypokalemia, hyperkalemia, transaminitis were in 28.6% (113), 37.3% (108), 31.3% (124), 39.3% (116), 3.1 % (12), 3.2% (13), 19.7 % (74), 7.4% (30), 3.1% (12) and 4.9% (19). For diarrhoea, female sex, nutrition (BMI below 18.5 KG/m2) and use of 3 drug regimen were predictive. For development of mucositis only nutrition was predictive. Use of 3 drug regimen and overnourishment were predictive of FN. Use of 3 drug regimen and use of docetaxel were predictive for hyponatremia. On multivariate analysis for diarrhoea only nutrition was predictive (p=0.017), for FN both drug regimen (p=0.003) and over nutrition (p=0.035) were predictive and for hyponatremia only use of 3 drug regimen was significant (p=0.017). Conclusions: 3 drug regimen, malnourishment and use of docetaxel are important predictors of acute toxicity associated with NACT in oral cancers.
Highly sensitive C reactive protein (hsCRP) as a surrogate marker of head and neck cancer.
Authors: Lakshmangowda Preethi Bangalore , K Adarsh , Ponni T.R Arul 
Published: March 2020

e17034 Background: High-sensitivity C-reactive protein (hsCRP) an acute phase inflamatory reactant protein, has been used to predict the risk of cardiovascular disease healthy individuals and to monitor treatment responses. Epidemiological evidence also points to link between inflammation and development of cancer, i.e. long-term inflammation and dysplasia. Worldwide ~ 15 % of the cancer incidence is associated with microbial infection. NSAIDs have been used for cancer preventionin familial adenomatous polyposis. The objective of study is to evaluate the association between hs-CRP and head and neck cancer (SCCHN). Methods: Prospective, cross sectional case-control study was under taken involving 36 SCCHN (cases) and 36 normal volunteers age matched (controls). Cases staged as per UICC TNM. The study subjects 4ml clotted blood, centrifuged, serum stored at -20°C. hsCRP (mg/L) determined using Quantitative Immunoturbidimetric method. Statistical analysis was performed using SPSS. Results: Evaluable subjects = 72, Cases (Cancer patients) = 36 & Control = 36. Age group range 18 to 80 yrs. Mean Age Cases 59.5+9.9 v/s Control 59+96. M: F Cases- 25:9 v/s Control 27:9. In Cases Oral Ca – 22(61.1%) & Oropharynx - 14 (38.9%).T4 – 20(55.6%), T3-8(22.2%) & T2-8(22.2%). N3-3(8.3%), N2-14(38.9%), N1-5(13.9%) & N0-14(38.9%). The hsCRP of Control group v/s Cancer Case group = 3.03 ± 2.61 v/s19.23 ± 19.003 respectively (P < 0.0001). hsCRP for Oral Cancer – 15.07+7.66 & OPX – 25.77+28.31. In the case group, the mean hsCRP levels with tumor size T2 was 119.36 ± 7.0, T3 was 21.32 ± 23.27 , T4 was 18.3350 ± 21.0915 and with Node size N0- 20.3 ± 35.07, N1- 13.8 ± 5.37, N2 -21.6 ± 25.022, N3 - 122.1 ± 1.7. Conclusions: Inflammatory responses play decisive roles at different stages of tumor development, initiation, promotion, malignant conversion, invasion, and metastasis. This study shows serum hsCRP levels were significantly elevated in SCCHN cases compared to age matched normal control subjects. hsCRP Can be used as a surrogate marker of SCCHN. Measuring and charting hsCRP values can prove useful in determining disease progress or the effectiveness of treatments, Furthers studies are contemplated.
A discrete choice experiment to examine preferences and willingness to pay for prophylactic granulocyte colony-stimulating factors (G-CSF) in previously treated breast cancer patients.
Authors: Johnson Phaedra , Bancroft Tim , Barron Richard L. , Legg Jason C. , Li Xiaoyan , Watson Holly , Naeim Arash , Marshall Deborah 
Published: March 2020

e17509 Background: As patient-centered care becomes more prominent, a better understanding of patient preferences and tradeoffs amongst treatment alternatives and outcomes is needed. This study used a discrete choice experiment to examine the preferences and willingness to pay for prophylactic G-CSF to decrease the incidence of chemotherapy (CT)-induced febrile neutropenia in breast cancer patients who previously received CT. Methods: An online survey was developed with 16 paired treatment choice scenarios comparing 3 alternative G-CSF options (11 versus 1 or 6 versus 1 injections per CT cycle) with a follow-up “no treatment” option. Each scenario had 4 attributes: risk of disruption to CT schedule due to neutropenia, risk of infection requiring hospitalization, frequency of G-CSF administration, and total out-of-pocket (OOP) cost for G-CSF during a CT cycle. Patients’ preferences and willingness to pay (as OOP cost) were estimated using logistic regression. Results: Patients’ (n = 296) preferred G-CSF options with the lowest OOP costs, the fewest injections, and improved outcomes (lowest risk of disruption to CT schedule and lowest risk of infection requiring hospitalization). In the context of this discrete choice experiment, OOP costs and risk of disruption to CT schedule were the most important attributes to patients; risk of infection requiring hospitalization and frequency of G-CSF administration affected patients’ choice of G-CSF option to a smaller but similar degree. Patients were willing to pay OOP $1,076 per cycle to reduce the risk of disrupting the CT schedule from high to low, $884 per cycle to reduce the risk of developing an infection requiring hospitalization from 24% (high) to 7% (low), and $851 and $667 per cycle to decrease the number of G-CSF injections per cycle from 11 to 1 and 6 to 1, respectively. Conclusions: With a current focus on patient-centered approaches in decision-making, physicians need to consider patient preferences when making decisions about therapy, including supportive care agents.
Prevalence, risk factors, treatment and outcomes of catheter-related thrombosis in patients with malignancies.
Authors: Cote Julie , Dumas Olivier , Demers Christine , Lemieux Julie 
Published: March 2020

e17517 Background: Tunnelled catheters (Leonard, BARD) and peripherally inserted central catheters (Piccline, BARD) are used for intravenous therapies in patients with malignancies. Thrombosis is a well known complication, but risk factors are not clearly established. The objective the incidence, risk factors, therapeutic approaches and complications of catheter-related thrombosis among patients with malignancies. Methods: Medical charts of patients with malignancies and Leonard or Piccline inserted, from August 2002 to December 2006 at Hôpital de l’Enfant-Jésus (Québec City, Canada), were retrospectively reviewed. Results: A total of 618 catheters were inserted in 361 patients. Eighty-six percent of the catheters were placed in patients with hematologic malignancies and most were Piccline (70%). Sixty-one thromboses were identified (incidence of 10%). Fourteen percent of the patients had more than one episode of catheter-related thrombosis. The majority of thromboses was related to a Piccline (93%) and occurred at a mean time of 34 days after the insertion. At the time of thrombosis, the mean platelet count was 169 x 109/L. Previous history of a catheter-related thrombosis (OR = 4.30 (1.48-12.50); p = 0.0075) as well as lymphoma (OR = 3.29 (1.22-8.87); p = 0.0185) were associated with superficial thromboses. The Piccline was associated with both types of thromboses (OR = 5.78 (1.69-19.74); p = 0.0051), especially with superficial thromboses. Most of the catheters (88%) were removed once a thrombosis was identified. The management of anticoagulation varied considerably. No complication associated with thromboses was reported. Conclusions: The incidence of central venous catheter-related thrombosis was 10%. The thrombosis occurred on average 34 days after the insertion. The Piccline was associated with all types of thromboses, especially the superficial ones. A previous history of catheter-related thrombosis and lymphoma were risk factors for superficial thromboses. Further studies are necessary to better define characteristics and optimal management of central catheter-related thrombosis.
Awareness and attitude of cancer patients about participation in clinical research (CR) in Saudi Arabia.
Authors: Sheblaq Nagham Ramzi , Traifi Sara , Al Sakiani Moahmmed , Gasmelseed Ahmed , Abolfotouh Mostafa A , Jazieh Abdul Rahman 
Published: March 2020

e17528 Background: Enrollment of patients in CR may be impacted by their levels of awareness and attitude toward participation. Our study aims at assessing the awareness and willingness to participate in CR and identifying the barriers and influencing factors for participation. Methods: A cross-sectional study was performed using an interview-based questionnaire composed of close-ended questions conducted by trained research coordinators. Descriptive statistics, univariate and multivariate analyses were applied. Results: A total of 300 patients were enrolled in the study with a median age of 53.6 (42.2 - 64.0), and 188 patients (62.67%) were females. The majority of patients 289 (97.31%) were not aware of what is institutional review board. On the other hand, 226 (75.33%) showed interest in CR participation, if offered. The trust in treating physician (88.33 %) and the belief that participation in CR offers a better chance of cure (73.14%) were the two most important influencing factors to participate, while the preference of receiving standard treatment (43.13%) and the unknown efficacy of treatment (40.32%) were the top two barriers to participate. In univarate analyses, patients younger than 45 years (p<0.015) and those with higher education (more than middle school) (p<0.022) were significantly more interested in CR participation. However; in a multivariate analysis, higher education was the only significant predictor of interest to participate (p<0.023). Conclusions: There is an apparent gap in cancer patients’ awareness about CR. However, there is an obvious interest in participation in CR especially in patients with higher education level. Enhancing public awareness is crucial to improve CR participation.
Insufficient involvement of the family physician (FP) in the care of chemotherapy-treated cancer patients: A barrier to comprehensive medical care.
Authors: Ben-Ami Eytan , Merom Hadar , Sikron Fabienne , Livneh Jessica , Sadetzki Siegal , Wolf Ido 
Published: March 2020

e17536 Background: Following advancement in the oncology field, increasing numbers of patients are receiving ambulatory active treatment for prolonged periods of time. Many of these patients suffer from additional comorbidities and require comprehensive medical care. We aimed to assess the perception of cancer patients regarding the role of the FP and the oncologist in their care during times of active cancer treatment. Methods: A survey was conducted among 265 consecutive chemotherapy-treated patients at the day care clinic of the Oncology Institute at Sheba Medical Center in Israel. Results: Median age was 60 years (range 22-86), 184 (69%) were woman and 147 (55%) were Israeli born. All patients belonged to one of four Israeli HMOs, 96% had a regular FP and 70% met with him during the prior month. While 78% of the patients evaluated that their FP had sufficient time to devote to them, only 32% and 27% thought their FP was trained to or wished to treat medical problems occurring while receiving chemotherapy. Yet, a majority of patients (76%) stated that involvement of the FP is important to them. Surprisingly, 85% perceived the oncologist as having enough time to devote to their care and 60% perceived him as being capable of dealing with non-oncological problems. However, only 30% stated that the oncologist communicates with the FP. Accordingly, 72% of the patients stated that in the case of an urgent problem they will turn first to the oncology institute and only 9% will turn to their FP. Indeed, 46% had unscheduled visits to the day care facilities during the prior month. Conclusions: Our data indicate lack communication between team members and inadequate medical training as major barriers for comprehensive medical care for chemotherapy-treated cancer patients. This may adversely affect medical care, decrease satisfaction among physicians and increase unnecessary workload. A change of the current situation requires collaboration between FPs and oncologists at the local and national levels and should include standardization of communication measures as well as implementation of required aspects in educational programs of both specialties.
The economic assessment of eribulin compared to treatment of physician's choice (TPC) in Australia.
Authors: Jones Trefor , Simons W. Robert 
Published: March 2020

e17552 Background: The Eisai Metastatic Breast Cancer Study Assessing Physician’s Choice Versus E7389 (EMBRACE) established clinical benefits. This study evaluates its translation into comparative economic value. Methods: Because of superior survival benefits and a non-inferior safety profile, we use a cost-effectiveness analysis. Costs include medication and administration costs, cost of toxicity management, and indirect cost. The primary endpoint is the ratio of incremental means of costs and quality adjusted life years (QALY) yielding an incremental cost effectiveness ratio (ICER). Partitioned survival analyses were evaluated using a log-logistic function for overall survival, progression free survival, response duration, and toxicity time. Health state utilities or quality weights are applied to each component and aggregated. Sensitivity analyses assessed the influence of variability in a number of parameters. Results: Overall survival based on the log-logistic extrapolation was 686 days in the eribulin group compared to 550 days in the TPC group for a difference of 136 days. Mean time without progressive disease was 214 days and 160 days, respectively, for a difference of 59 days. Time spent with Grade 3 and 4 toxicity were 3.62 and 2.25 days in the eribulin group versus 2.25 and 0.98 days in the TPC group. Response times were 15.62 and 9.64 days, 5.98 days longer in the eribulin group. After weight components of overall survival with corresponding utilities and converting to years, the QALY were 1.166 in the eribulin group compared to 0.926 in the TPC group for a mean incremental improvement of 0.24 years. Mean treatment costs were $14,302.80 AUD and $1,672.02 AUD for a difference of $12,630.78 AUD. Total incremental cost is $13,794.35 AUD. The ICER with and without discounting is $48,134.29 AUD and $45,770.97 AUD, respectively. Survival time and drug cost were the most influential variables on the ICER. Conclusions: At a threshold of $50,000 AUD per QALY, eribulin is good value at $48,134 AUD per QALY. Clinical trial information: NCT00388726.
A review of the Inuit oncology patients treated at the Ottawa Hospital Cancer Centre.
Authors: Febbraro Michela , Spaans Johanna , Alvarez Gonzalo G , Asmis Timothy R. 
Published: March 2020

e17563 Background: Cancer is a major health concern among Canada’s northern Inuit population. Limited Inuit specific data exists on the geographical isolation and the effect on treatment outcomes of Inuit referred to urban hospitals for cancer treatment. Methods: A retrospective chart review of all Inuit referred to the Ottawa Hospital Cancer Centre from Nunavut, Canada (distance: 1298 miles) between 2001-2011 was conducted. Demographic, diagnostic and treatment related information was collected on all patients, including the number of visits made by each Inuit patient from Nunavut to OHCC for treatment. Results: 234 Inuit (male: 74, female: 160) were referred to OHCC with a diagnosis of cancer. Mean age at diagnosis was 58.5 years (sd 14.61). Over half the patients were current smokers (54%) and 39% of patients had a history of tuberculosis (TB). Among Inuit men, lung (n=32, 43%), colorectal (n=11, 14%) and nasopharyngeal (n=9, 12%) cancer were the most common diagnosis. Among Inuit women, the most common cancers were lung (n=72, 45%), colorectal (n=32, 20%), breast (n=21, 13%), cervical (n=11, 7%) and nasopharyngeal (n=7, 4%). Metastatic disease at presentation was common (n=76, 38%). Primary cancer was amenable to surgery in n=57 patients. An equivalent number of patients (n=82) received adjuvant/definitive radiation therapy (RXT) and adjuvant chemotherapy, with n=52 receiving chemoradiation. Palliative RXT and chemotherapy was received by 64 and 51 patients, respectively. Among patients receiving chemotherapy, there were no cases of TB reactivation and no treatment related serious adverse outcomes or deaths. Average number of trips made to Ottawa for treatment was n=7 (sd 7.90) with the upper quartile averaging n=10 trips. Conclusions: Lung, colorectal and nasopharyngeal cancers are over-represented among Canadian Inuit, who often present with advanced disease. Travel burden is significant among patients receiving treatment. Improved cancer screening and oral molecularly targeted therapies that can be delivered in remote northern communities are likely to improve the experience and treatment outcomes among Canadian Inuit.