tbuckley/cabot-search huggingface dataset:
Timely referral of cancer patients from oncology-hematology to palliative care: Qatar experience.
Authors: Azza Adel Hassan, Mufid M. El Mistiri, Reham Negmeldin, Saad Jobran Eziada, Akhtari Begum, Kamal Aboudi, Amra Alkhalil, Hanadi Al Ayoubi
Journal: Journal of Clinical Oncology (2014)

e20548 Background: As evidenced based, early palliative care access can improve quality of life and improve symptoms control, as well as improve metrics perceived for high quality cancer care. In Qatar, the timing of referral to palliative care service was late, around 55% stayed for a period of time of less than 30 days, while almost 15% stayed for no more than 48 hours from the time of referral. Methods: This Project was held from March 2012 until September 2012 as a well-structured Clinical Care Improvement initiative where the problem was clearly defined as a) the Cancer patients of National Center for Cancer Care and Research (NCCCR) are not referred from acute care to palliative care on time. b) ‘End of life patients’ care was being provided at acute care rather than palliative setting, which compromised patients’ quality of care and Quality of good death. An objective one-page scoring tool (adopted from NCCN Palliative Guidelines Referral Criteria) was developed and used to review medical records. Quality Improvement methodologies as PDSA and tools as process mapping, brainstorming, cause and effect analysis, prioritization tools as pareto & lean/six sigma methodology evident in value analysis, eliminating waste and reducing variation were all used to embrace a well evidenced change concept and build PDSA cycles successively to improve the current process. Results: A physician survey showed that more than 30% of barrier for palliative care consultation and referral stemmed from unawareness of referral criteria. The process value analysis did confirm that adding a subjective scoring tool to guide referral eliminated the 40% waste in the process. We reduced the percentage of patients with score ≥ 5 without palliative consultation from mean of 68% to 16% and ≥ 7 without care in palliative setting from mean of 32% to 2%. Aim was achieved and sustained. Conclusions: Our project proved that standardizing referral process and objective referral tools are needed to facilitate the transfer of care from one level to another.
Prospective survey on patient satisfaction and quality-of-life impact concerning the administration of fentanyl pectin nasal spray for breakthrough pain in cancer: Qualipec study.
Authors: Ignacio Delgado, Luis Antón-Aparicio, Philippe Poulain, Alain Serrie
Journal: Journal of Clinical Oncology (2014)

TPS6639 Background: Previous clinical trials have confirmed the efficacy and safety of fentanyl pectin nasal spray (PFNS), as a rapid analgesic agent in cases of Breakthrough pain in cancer (BTPc), characterized by intermittent episodes of intense pain of limited duration. Here we present two QUALIPEC studies aimed to assess patient satisfaction after early administration and dose titration of PFNS for BTPc. The surveys intend to describe patients’ quality of life improvement along the four week observational period and the effects of PFNS treatment on their everyday activities. Concurrently, they expect to analyze the clinicians’ therapeutic management in real practice. Methods: These are two multicenter, open-label, prospective, observational studies conducted in different hospitals in France and Spain. The current numbers of enrolled patients are 253 and 42 patients, for France and Spain, respectively. Major eligibility criteria were patients over 18 that were taking at least 60 mg/day morphine (or equivalent) for chronic background pain in cancer. The BTPc diagnosis was evaluated through patient medical interrogation and/or visual analog scale (VAS). Patients started PFNS treatment during the inclusion visit. The first criterion for prescribing PFNS treatment was the BTPc intensity, associated with the daily number and/or duration of the episodes. Patients initially entered a dose-titration training phase which was primarily done during the first treatment prescription and evaluated during the following medical consultation. The primary objective was the measurement of early treatment satisfaction after PFNS titration. Also additional quality of life criteria were evaluated and the effect on daily activities. Clinical trial information: NCT01693328 (France) and NCT01698645 (Spain).
Effect of beta-hydroxy beta-methylbutyrate/arginine/glutamine (HMB/Arg/Gln) on lean body mass (LBM), in patients with advanced lung cancer.
Authors: Jennifer S. Pascoe, Joyce Thompson, Julie Joseph, Claire Gaunt, Sarah Jane Bowden, Aimee Houlton, Lucinda Billingham, Cassandra Brooks, Amanda Irwin, Neil Matthew Steven
Journal: Journal of Clinical Oncology (2014)

e20684 Background: Cancer cachexia is a multi-factorial syndrome causing loss of LBM, functional impairment and death. HMB/Arg/Gln attenuates skeletal muscle degradation in animal studies. Cancer trials have been limited by poor compliance possibly due to advanced cachexia at entry. Earlier intervention may be effective. Primary objective; to determine whether HMB/Arg/Gln delays onset of cachexia sufficiently to justify a phase III trial in advanced lung cancer patients (pts). Methods: A multicentre, phase II, two-arm, open-label, randomized trial comparing HMB/Arg/Gln (BD) or no HMB/Arg/Gln for 12 weeks . Pts received standard treatment, structured nutritional and symptom support. Inclusion criteria: newly diagnosed lung cancer; oral nutrition, WHO PS 0-2; life expectancy >4 months. Exclusion criteria: curative treatment. Weight loss not required for entry. Primary endpoint: no. of pts alive without significant (5%) LBM loss at week 12 (successes). A difference in no. of successes ≥5 in favor of HMB/Arg/Gln arm would support a phase III trial. Based on Jung design assuming two-sided α≤0.2 and β≤0.15, 48 pts per arm required given null hypothesis of failure free survival rate of 40% with detectable absolute increase of 20% in experimental arm. Protocol planned interim analysis with independent statistical review at ~ 50% recruitment. Results: Interim analysis conducted following randomization of 38 pts. Baseline characteristics were well balanced. Fourteen pts (74%) withdrew or discontinued treatment in HMB/Arg/Gln arm versus 3 (16%) in control. Commonest reasons; unpalatable treatment, unable to take treatment or disease progression. Primary outcome: 10 pts (53%) in treatment arm and 13 pts (68%) in control arm were eligible for primary outcome analysis (had baseline and week 12 LBM/death). There were 3 successes in the HMB/Arg/Gln arm versus 9 in control. Futility analysis showed very low probability of a positive outcome at trial completion. Trial closure was recommended. Conclusions: Compliance with HMB/Arg/Gln was poor. There is no evidence that it delays onset of cachexia in pts with advanced lung cancer. Further investigation in this setting is not indicated. Clinical trial information: ISRCTN 39911673.
Palliative radiotherapy for bone metastases: Population-based utilization near end of life in a Canadian province.
Authors: Manpreet Singh Tiwana, Mark Barnes, Andrew Kiraly, Stacy Miller, David Hoegler, Ivo Olivotto, Robert Anton Olson
Journal: Journal of Clinical Oncology (2014)

9523 Background: Palliative radiotherapy (RT) plays an important role in the care of patients dying with bone metastases (BM) and is guided by life expectancy . We sought to determine the patterns of RT fractionation in patients with BM towards their end of life in a population-based, publicly funded health care system. Methods: Consecutive patients with BM treated with RT between 2007 through 2011 were identified in a provincial Canadian cancer registry database. Associations between choice of RT fractionation, patient and provider characteristics were analyzed. Results: A total of 16,898 courses of palliative RT were delivered to 8,601 patients from 2007 through 2011. Of these RT courses 1,734 (10%) and 709 (4%) were prescribed to patients in the last 2-4 weeks and <2 weeks of their life, respectively. Multiple fraction RT was prescribed 52%, 46%, and 36% for patients who died >4, 2-4, and <2 weeks of receiving palliative RT, respectively (p<0.001). Fifteen percent of courses were planned for ≥5 RT fractions in patients who died within 2 weeks of receiving palliative RT. The proportion of patients who died within 4 weeks of RT varied by primary tumour site; lung 25%, gastrointestinal 23%, genitourinary 11%, lymphoma 9%, breast 6%, and other 19.4% (p < 0.001). The proportion of patients who died within 4 weeks of RT varied by treatment site; spine 17%, extremity 14%, pelvis 12%, other 13% (p < 0.001). After controlling for gender, age, tumour type, and treatment site, patients were less likely to receive multiple fraction RT in the last 4 weeks of life (OR 0.54; 95% CI 0.49 – 0.59; p <0.0001). Conclusions: This population-based analysis found that 14% of patients with bone metastases received radiotherapy during the last 4 weeks of their life. There was significant variability by primary tumour type, with approximately ¼ of lung and gastrointestinal patients receiving RT with the last 4 weeks of life, suggesting physicians treating these sites should consider benefits of RT versus the short prognosis in these tumour sites. Appropriately, patients who received RT with the last 2 or 2-4 weeks of life were less likely to receive a multiple fraction RT course compared to patients alive >4 weeks since RT.
Abstract 17600: Improved Iterative Reconstruction Reduces Artifacts and Results in Larger Measurements of Ileofemoral Artery Size on Computed Tomography in Patients Referred for Transcatheter Aortic Valve Replacement
Authors: Anum Minhas, Smita Patel, Ella Kazerooni, Antonio Conte, Troy Labounty
Journal: Circulation (2015)

Background: Computed tomography (CT) is typically used to measure ileofemoral artery size in patients considered for transcatheter aortic valve replacement (TAVR). However, these patients often have significant arterial calcification, which can introduce artifacts and limit measurement accuracy. We hypothesized that improved iterative reconstruction would improve image quality and reduce artifacts, resulting in larger measured size. Methods: We examined 56 patients undergoing CT for possible TAVR, and compared image quality and ileofemoral arterial size between separate reconstructions of the same studies, comparing standard (STD) advanced statistical iterative reconstruction and improved model-based iterative reconstruction (MBIR). A blinded reader identified the sites with the smallest luminal diameter, and provided identical short-axis reformats for both reconstructions. A separate blinded reader graded image quality and made measurements in a random sequence. We compared mean and minimal diameters, image quality (1 poor, 4 excellent), and signal and noise. Results: Mean age was 77 ± 10 years and 54% were male. Table 1 compares measured diameters and image quality between STD and MBIR reconstructions. Between STD and MBIR images, ≥moderate beam-hardening artifacts were observed in 30% (17/56) and 9% (5/56) of patients, respectively (p=0.008); severe artifacts were seen in 23% (13/56) and 5% (3/56) of patients, respectively (p=0.01). Overall image quality of STD and MBIR images was graded as good or excellent in 70% (39/56) and 91% (51/56) of cases, respectively (p=0.008). Conclusion: In patients referred for TAVR, improved iterative reconstruction resulted in higher image quality, fewer beam-hardening artifacts, and larger measurements of ileofemoral artery size.
Comparison of angiopoietin-1 and -2 and VEGF expression in bone marrow and peripheral blood leukemic cells of patients with acute promyelocytic leukemia.
Authors: Mariana Scaranti, Jose Mauricio Segundo Correia Mota, Ana Silvia Gouveia de Lima, Barbara Amelia Santana Lemos, Antonio Roberto Lucena-Araujo, Eduardo Magalhaes Rego
Journal: Journal of Clinical Oncology (2014)

7079 Background: Angiogenesis is a well-known hallmark of solid cancer, but its relevance in acute leukemia genesis is controversial. Kini et al. (2001) reported that VEGF is secreted by acute promyelocytic leukemia (APL) cells, which also express VEGF receptor 2 (VEGFR2, or KDR). Moreover, arsenic trioxide, which is the most effective agent in the treatment of refractory APL, was shown to have anti-angiogenesis effect in vitro and to reduce microvascular density in bone marrow cells of APL-treated patients (Alimoghaddam et al., 2006). Considering that VEGF has paracrine and autocrine effects and the microenvironment has an important role in VEGF signaling, we decided to determine whether circulating and bone marrow APL cells differ regarding pro-angiogenic factors expression. Methods: We assessed VEGF, angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) gene expression through quantitative PCR (RT-qPCR) in peripheral blood (PB; n=14) and bone marrow (BM; n=24) cells of PML-RARα positive APL patients. BM (n=7) and PB (n=3) samples from healthy donors were used as controls. Statistical analysis was performed using STATA 12. The Student t-test was used to compare means between two groups and the Kruskal-Wallis test followed by Dunn’s post-test to compare three or more groups. Results: ANG1 presented lower expression in BM when compared to PB samples of APL patients (BM = 10.6 ± 0.97, PB = 7.3 ± 1.06, p=0.03). ANG2 expression was not detected in all samples. VEGF expression was not differentially expressed between PB and BM of control and APL samples. VEGF and ANG1 gene expression did not show any differences when we compared PB and BM of APL patients and healthy donors. Conclusions: ANG1 has a lower expression in BM of APL patients when compared to PB.This could be of importance for leukemia spread from BM to PB, since ANG1 is described as a regulator of endothelial monolayer integrity.
A population-based analysis of changes in therapy of metastatic renal cell carcinoma (mRCC).
Authors: Hannes Jurgens, Rena Tiigi, Kristiina Ojamaa, Helis Pokker, Kaire Innos, Peeter Padrik
Journal: Journal of Clinical Oncology (2014)

e15586 Background: The main therapy of mRCC before the era of targeted agents was immunotherapy with interferon-alfa (INFa) or interleukin-2. Current therapies include various sequencies of sunitinib, bevacizumab, INFa, sorafenib, pazopanib, axitinib, temsirolimus and everolimus. The aim of the study was to perform a population-based analysis of implementation of targeted therapies in everyday practice and survival. Methods: All patients with mRCC who started medical therapy in Estonia during the years 2004-2010 were identified using the database of Estonian Health Insurance Foundation. Patients’ clinical data were specified from their clinical records. Survival data were obtained from the Estonian Population Registry. The only available therapy before 2008 was INFa. From 2008 sorafenib became routinely available as a second-line therapy. Sunitinib, bevacizumab plus INFa and temsirolimus became available as a first-line therapies from 2009. For survival analysis patients were divided into 2 groups: INFa therapy only ( group 1) and INFa followed by targeted agents or targeted agents therapy only ( group 2 ). Results: A total of 295 patients were identified, 276 were eligible for analysis. 48% of patients were identified in group 1 and 52% in the group 2. 67% of patients were male and 33% female. First-line treatments were INFa (79%), sunitinib (15%), INFa+bevacizumab (4%), sorafenib (1%) and temsirolimus (1%). 37% of patients received 2nd-line therapies: sorafenib (69%), sunitinib (11%), INFa (8% ), pazopanib (4%), others (8%). Third-line treatment was applied to 21% of patients and 3% received 4th –line treatment. Median survival of all patients was 1.24 years ( 95% CI 0.95-1.59), 0,67 years (0.57-0.76) for group 1 and 2.18 years (1.70-2.94) for group 2. Median survival for men was 1.0 year (95% CI 0.76-1.47) and women 1.71 years (1.1-2.28). 1, 2 and 3 year survival rates for group 1 were 33%, 18% and 10% compared to 74%, 55% and 40% for group 2. Hazard ratio(HR) for group 2 was 0.35 (p= 0.000; 95% CI 0.26-0.46). Conclusions: There are changes in natural history and treatment of mRCC. Patients who receive targeted therapies have a significant prolongation of median survival and reduction in risk of death compared to INFa treatment only.
microRNA expression in circulating samples of pancreatic ductal adenocarcinoma patients: A search for circulating biomarkers.
Authors: Barbara Alemar, Cleandra Gregorio, Patricia Izetti, Alessandro Bersch Osvaldt, Ursula Matte, Patricia Ashton-Prolla
Journal: Journal of Clinical Oncology (2014)

e22111 Background: Pancreatic ductal adenocarcinoma (PDAC) is a rare disease, whose incidence rates are very close to mortality rates. Part of the high mortality of PDAC is due to its difficult (often only possible with pancreatic tissue analysis) and late diagnosis. The discovery of noninvasive diagnostic biomarkers emerges as a possibility to perform a safe diagnosis. MicroRNAs (miRNAs - non-coding RNAs involved in initiation/maintenance of tumors) were discovered as stable molecules in circulating samples. Several studies have shown that the difference in their expression levels between cases and controls can accurately discriminate the presence or absence of certain diseases. Methods: In this study, we evaluated the expression levels of six miRNAs (miR-21, -34a, -155, -196a, -200b and -376a) in serum (24 PDAC and 9 healthy patients) and saliva (10 PDAC and 10 healthy patients) samples. The aim of our study was to investigate the presence of diagnostic and/or prognostic biomarkers. Expression levels were measured by relative quantification using real-time quantitative PCR. Results: In serum, miR-21 and miR-34a were significantly more expressed in samples from patients with PDAC (P < 0.001 and P = 0.001) and both were able to distinguish patients with and without disease with clinically acceptable sensitivity and specificity: AUC for miR-21 and miR-34a of 0.894 (P = 0.001) and 0.865 (P = 0.002), respectively. Our study also showed that there is a strong correlation between the expression levels of these two miRNAs in serum (rs = 0.681; P < 0.001; and Kappa tests: 0.477; P = 0.022). In salivary samples, generally, miRNA levels were very low, and no difference in miRNA expression levels was seen between cases and controls. Conclusions: Serum miR-21 and miR-34a are potentially useful PDAC diagnostic biomarkers and their expression appears to be correlated. However, the mechanism related to this correlation remains unknown. In saliva, our findings suggest that the chosen miRNAs are not adequate as diagnostic biomarkers. Further studies in a larger subset of patients should be undertaken to confirm these findings and to investigate the mechanisms that regulate miRNA expression in pancreatic cancer.
Minichromosome maintenance (MCM) family expression correlation with grade and prognosis in human gliomas.
Authors: Li Bie, Xianfeng Zhang, Michael McClelland
Journal: Journal of Clinical Oncology (2014)

e13002 Background: Gliomas are the most common type of all central nervous system tumors. Almost all patients diagnosed with these tumors have a poor prognostic outcome. We aimed to identify novel glioma prognosis-associated candidate genes. Methods: We applied WebArrayDB software to span platform integrate and analyze 771 glioma microarray datasets (WHO II-IV) derived from The Cancer Genome Atlas (TCGA) and GEO by WebArrayDB software. We focused on a subset of the significantly up-regulated genes, the minichromosome maintenance (MCM) family. We used 59 glioma frozen samples (F/M 18/21, age 38.9±14.3y, 14 II grade, 21III grade and 24 IV grade). The samples consisted of AO (n = 27), AA (n = 9) and GBM (n = 23). 6 control samples, trauma (n = 4) and epilepsy (n = 2). The frozen samples predict the relationship between the expression of MCMs and patients outcome by qPCR. Results: We found that MCMs expression was significantly up-regulated in glioma samples. High MCM2 mRNA expression appeared to be strongly associated with poor overall survival in high grade glioma. Furthermore, we reported that MCM7 is strongly correlated with patient outcome in WHO grade II-IV. MCM3 expression was to be up-regulated in glioma and correlate with overall survival in WHO grade III. MCM2, MCM3 and MCM7 expression level were of greater prognostic relevance than histological diagnosis according to the current WHO classification system. Conclusions: The results suggest MCM2, MCM3 and MCM7 aberrations in glioma tumors portended a particularly aggressive clinical behavior.
Development of a <i>CYP1B1*3</i> genotyping assay and mechanism of action studies related to docetaxel treatment in CRPC.
Authors: Carol Swartz, Leslie Recio, Suzanne Phillips, Timothy Maynor, William Douglas Figg
Journal: Journal of Clinical Oncology (2014)

e16036 Background: Prostate cancer is the most common cause of cancer death in men over age 75, with most cases progressing to castration resistant prostate cancer (CRPC). Docetaxel remains the standard of care for patients with CRPC, yet a significant number of CRPC patients do not respond to docetaxel. A recently identified CYP1B1 genotype, CYP1B1*3 (4326C>G; L432V), may be useful to predict survival in patients with CRPC prior to treatment with docetaxel. Men carrying two copies of the CYP1B1*3 variant had a poor prognosis after docetaxel-based therapies. The CYP1B1*3 allele can be rapidly determined in blood and is potentially useful as a diagnostic tool to predict response to docetaxel. A hypothesized mechanism for docetaxel failure is increased estradiol quinone formation, associated with activity of the CYP1B1*3allele, resulting in direct binding to docetaxel or interference with microtubule stabilization. Methods: ILS has designed a PCR-based TaqMan allelic discrimination assay for determining CYP1B1 genotype from patient samples. The assay has been tested on cell lines of known CYP1B1genotype and on commercially available matched blood and tumor samples. MCF-7 cells with enhanced estrogen quinone levels are being used to study the mechanism of docetaxel interference. Endpoints include GSH:GSSG ratios, free versus bound tubulin, expression of genes related to DNA damage and repair, and induction of chromosomal damage. Results: The assay has correctly determined genotypes in cells of known CYP1B1status and we have successfully determined identical genotypes in matching blood and FFPE tumor samples. Sequencing of the tumor and blood samples to confirm genotype status and mode of action studies are underway. Conclusions: ILS has developed a robust allelic discrimination assay that can determine CYP1B1 genotype status from cultured cells, tissues, blood, and FFPE tissue samples. Confirmation of the mechanism of docetaxel interference could lead to further improvements in therapy for CRPC patients carrying the CYP1B1*3 genotype.