tbuckley/cabot-search huggingface dataset:
Improving the rate of influenza vaccination in pediatric patients with cancer.
Authors: Jason Lawrence Freedman, Anne F. Reilly, L. Charles Bailey
Journal: Journal of Clinical Oncology (2013)

49 Background: Pediatric patients with cancer are at increased risk of influenza, with high mortality, morbidity, and delay of cancer therapy. CDC guidelines support yearly vaccination in these patients. In prior years at our center, only 53-56% of pediatric cancer patients received at least one dose of the vaccine. Our objective was to increase the rates of influenza vaccination in pediatric cancer patients through a multi-faceted QI initiative. Methods: Five interventions were instituted concomitantly, in eligible patients (&gt;6 months old, &gt;100 days from BMT if applicable, and within 1 year of chemotherapy) over a 6-month period (9/1/12 to 3/31/13). 1) Family education: provision of influenza/vaccine handouts to families in clinic waiting rooms; 2) Health informatics intervention: via electronic health records, generation of daily lists of patients due for doses with automated email lists to triage and nurses; 3) Clinical process interventions: standardization of triage process to identify patients needing vaccination and provision of colored wristbands to such patients alerting providers to order the vaccine, or document refusals, during the encounter; 4) Inpatient orders: influenza vaccine order built into computerized physician admission order set to trigger vaccination upon discharge; and 5) Provider education: printed materials and tutorials for staff at conferences on proper screening of patients, vaccine ordering/dose, and correct documenting of refusals/contraindications. These processes were iteratively refined over the 6-month timeframe. Results: Influenza immunization rates increased by 20% after the changes were implemented; this was seen across all tumor subgroups. Overall, 74% of patients received at least one dose as compared with 52% in the prior year. 61% of patients were fully immunized (vs. 42% in 2011-12). Immunizations were deferred due to allergy/refusal in 8% of patients (vs. 7% in 2011-12). Consequently, only 18% of eligible patients were unimmunized as compared to 41% in the prior year. Conclusions: Technology, education, and clinical process changes led to a successful increase in influenza vaccination rates. Ongoing efforts will target subgroups with lowest overall rates of immunization.
Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate resistant prostate cancer (mCRPC): Results from an expanded access program.
Authors: David Thomson, Natalie Charnley, Omi Parikh
Journal: Journal of Clinical Oncology (2014)

188 Background: Abiraterone or enzalutamide are licensed for use post-docetaxel in metastatic castrate resistant prostate cancer (mCRPC). Both target the androgen receptor signalling pathway. There is little information describing their sequential use. Methods: Patients with mCRPC who had failed treatment with docetaxel and abiraterone received enzalutamide as part of an expanded access program. Patients were reviewed four weekly and post-treatment PSA used to determine efficacy. Results: Twenty three patients, median age 76 (range, 65 to 82), performance status of 1 (15/23) or 2 (8/23) with mCRPC (22/23 bone and 4/23 visceral disease) were enrolled. All had received prior docetaxel and abiraterone as well as cabazitaxel (35%), dexamethasone (30%), and stillboestrol (52%). Median biochemical progression free survival (bPFS) was 11.9 weeks. Nine (39%) patients showed sensitivity to enzalutamide, defined as a greater than 50% reduction in PSA. There was a correlation between PSA response to abiraterone and enzalutamide (R=0.45, p=0.03). In 10 out of 23 and 13 out of 23 patients who were sensitive and insensitive to abiraterone, 60% and 23% had a great than 50% reduction in PSA, respectively. There was a trend to improved bPFS in those sensitive to abiraterone (15.7 vs. 11.4 weeks, p=0.40) and in those who showed any PSA response to abiraterone (15.9 vs. 5.3 weeks, p=0.06). Conclusions: Enzalutamide has activity following failure of docetaxel and abiraterone in mCRPC. The effectiveness is more pronounced in those who have responded to abiraterone.
High-Dose Melphalan Re-Induction with or without Stem Cell Support Prior to Myeloablative Allogeneic Stem Cell Transplantation in Patients with Advanced Relapsed or Refractory Acute Myeloid Leukemia.
Authors: Alix O'Meara, Thomas Pabst, Dominik Heim, Christoph Bucher, Joerg Halter, Caroline Arber, Alicia Rovò, André Tichelli, Alois Gratwohl, Martin Stern
Journal: Blood (2009)
Prostate cancer considered low or intermediate risk for biochemical failure according to the rtog-astro phoenix definition: Results of the use of neoadjuvant androgen deprivation before high-dose rate brachytherapy and external beam radiotherapy
Authors: A. C. Pellizzon
Journal: Journal of Clinical Oncology (2008)

16121 Background: Patients treated with radiation therapy have a significantly better outcome as the dose to the prostate is increased. Conformal high dose rate brachytherapy (HDR) is a successful method for delivering higher dose of radiation. This is a retrospective analysis of patients presenting with low (LR) or intermediate (IR) risk features, who were submitted or not to neoadjuvant androgen deprivation (NAAD). Methods: Charts of patients treated with HDR and localized 3DRT between 1997 and 2005 were reviewed. At the discretion of the referral urologist patients had NAAD (goserelin +/− flutamide or ciproteron acetate). 3 to 6 months. Results: 142 patients were eligible for study entry, 84 (59.1%) had no NAAD. Median age of the patients was 70 years (range, 53–81 years). Median follow-up was 6 years. There were 77 (54.2%) of patients into the LRG and 65 (45.8%) into IRG. The dose of EBRT ranged from 40 to 54 Gy (median 47 Gy). The HDR dose ranged from 16 to 24 Gy given in 4 fractions, BID, in two days. Median HDR dose was 20 Gy. Of the patients who had NAAD, 38 (26.8%) of the patients had central or total androgen blockage and 20 (14.1%) patients had peripheral blockage only. The crude overall survival (OS) rate at 4-year was 95.1%. The 5- and 10-year actuarial OS rates were 93.6% and 85.8%, respectively. The crude biochemical control (BC) rate at 4-year was 79.2%. Actuarial BC rates at 5- and 10-year were 91.4% and 59.6% for LRG and for IRG were 89.2% and 45.4%, respectively (p=0.308). NAAD did not influence the BC rates (p=0.477). Conclusion: dose of radiation prescribed seems to be an important factor related to BC. So far in our own experience, HDR and 3DRT are successful forms of treatment combination, but data from prospective randomized trials are still missing. We favour the use of adjuvant androgen deprivation over NAAD for patients presenting with adverse prognostic factors. No significant financial relationships to disclose.
Sorafenib (Sor) and mTOR inhibitors (mTORinh) combination for hepatocarcinoma recurrence after liver transplantation.
Authors: E. Garralda, J. F. Castroagudin, J. Bustamante, M. Salcedo, B. Sangro, I. Herrero, M. Testillano, A. Matilla, H. Cortes-Funes, C. Gomez-Martin
Journal: Journal of Clinical Oncology (2011)

e14574 Background: Tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC) remains a mayor clinical challenge. The PI3K/Akt/mTOR pathway has been linked to hepatocarcinogenesis and mTOR inhibitors exhibit antineoplastic activity in preclinical models of HCC. Sorafenib, a multi-tyrosine kinase inhibitor, is the only targeted therapy approved for treatment in patients with unresectable HCC. The rationale for the use of Sor and mTORinh based immunosuppression is the enhanced efficacy that could be achieved through dual inhibition of these key signaling pathways. The aim of our study was to evaluate the efficacy and security of this combination in the treatment of patients with relapsed HCC not amenable to local therapy. Methods: A retrospective review of a multicenter database identified 31 patients receiving mTOR inh and Sor for HCC recurrence, 26 in the palliative setting. Clinic/pathologic variables were analyzed and efficacy was measured in terms of global survival, progression free survival and objective response. Results: Median time to recurrence was 25.3 months. The most common site of recurrence were lungs (41%). 29 pts were on calcineurin inhibitor therapy prior to recurrence and switched afterwards to everolimus (n=22) or sirolimus (n=7). After a minimum of 8 weeks of treatment with Sor, there were 2 non evaluable patients, 1 partial response, 13 stable disease and 10 pts with disease progression. Median progression free survival was 6.77 months (2.35-11.18). Overall survival was 19.33 months. (13.47-25.19). mTOR inh related toxicities were dislipemia (58%), ionic alterations (16%) and hiperglycemia (12.9%). Sor related toxicity was mainly grade 1 or 2, being the most common diarrhea (83.8%), fatigue (58%), hand-foot skin reaction (54%), and hypertension (32%). 4 severe adverse events were reported: 2 upper gastrointestinal bleedings 1 SNC haemorrhage and 1 Heart failure. 2 out of 4 graft dysfunctions required lowering sorafenib dose. Conclusions: In patients with HCC recurrence after liver transplantation not suitable for curative therapy, the Sor/mTOR inh combination seems an effective and safe treatment approach. Full data analyses will be presented.
Characteristics and treatment of 35 patients affected by advanced medullary thyroid carcinoma
Authors: H. Koussis, A. Scola, S. Tonello, P. Karahontzitis, C. Pagetta, A. Toniato, M. R. Pelizzo, D. Casara, A. Archonti, S. Monfardini
Journal: Journal of Clinical Oncology (2005)

5558 Background: MTC is an interesting model of endocrine tumor arising from parafollicular C cells of thyroid. MTC shows two distinct tumour types, sporadic variety (75%) and familial feature (25% in MEN and non MEN). Surgery is the treatment of choice. 50–70% of patients at diagnosis have lymph node metastasis and recurs in approximately 50%. Prognosis of unresectable disease or with distant metastasis is poor and treatment still remains controversial. Chemotherapy (CT) trials have been limited by the scarcity of these tumors. Response rate is usually low. Methods: 35 patients with advanced disease followed during the last 10 yrs are presented. Twenty pts were female and 15 male, 4 were affected by MEN II A. Median age at diagnosis was 48 yrs (range 19–72). All cases underwent total thyroidectomy plus lymphoadenectomy of central neck compartment; 3 patients were operated on for local recurrence. The pattern of disease spread was the following: neck and/or meadiastinum lymph nodes in 21 pts, bone in 14, liver in 11 and lung in 10. Four of 35 patients, all with sporadic disease developed a second metachronous cancer (breast, rectum, oesophagous and lung). Thirteen underwent external radiotherapy and 22 were treated by means of chemotherapy (eight patients with DTIC/5FU and 14 with Adriamycin, Cisplatin and Bleomycin (BAP)). Eleven patients were treated with Somatostatin analogues (Octreotide 30mg or Lanreotide 30mg). Results: No complete remission was observed, stabilization of disease for 6 months in 20 cases and partial remission was recorded in 2 patients treated by CT (one with DTIC/5-FU and another with BAP regimen). With the BAP regimen nausea was common; myelosuppression grade 4 in 1 pt and gastrointestinal grade 4 in 2 pts were observed. DTIC and 5-FU was usually well tolerated. Eight deaths were recorded because of disease progression. In our cases CEA resulted more effective in an early prediction of disease progression compared to Calcitonin and Chromogranin A. Patients treated by Somatostatin analogues obtained only stabilization of disease for twelve months (all except one). Conclusion: In MTC patients with advanced disease, chemotherapy and somatostin analogues resulted only palliative treatments. No significant financial relationships to disclose.
Myocardial Recovery in Patients With Systolic Heart Failure and Autoantibodies Against β 1 -Adrenergic Receptors
Authors: Yuji Nagatomo, Dennis M. McNamara, Jeffrey D. Alexis, Leslie T. Cooper, G. William Dec, Daniel F. Pauly, Richard Sheppard, Randall C. Starling, W.H. Wilson Tang, Dennis M. McNamara, Karen Janosko, Charles McTiernan, Barry London, Karen Hanley-Yanez, John Gorcsan, Hidekazu Tanaka, Mathew Suffoletto, Randall C. Starling, Cynthia Oblak, Leslie T. Cooper, Annette McNallan, LuAnne Koenig, Paul Mather, Natalie Pierson, Sharon Rubin, Yanique Bell, Alicia Ervin, John Boehmer, Patricia Frey, Jeffrey Alexis, Janice Schrack, Pam LaDuke, Guillermo Torre-Amione, Jeannie Arredondo, Daniel F. Pauly, Pamela C. Smith, Richard Sheppard, Stephanie Fuoco, Ilan S. Wittstein, Elayne Breton, Vinay Thohan, Deborah Wesley, G. William Dec, Diane Cocca-Spofford, David W. Markham, Lynn Fernandez, Colleen Debes, Mark J. Zucker, Laura Adams, Peter Liu, Judith Renton, Jagat Narula, Byron Allen, Elizabeth Westberg
Journal: Journal of the American College of Cardiology (2017)
Comparative effectiveness of panitumumab (P) and cetuximab (C) in metastatic colorectal cancer (mCRC) with wild-type KRAS (WTKRAS).
Authors: Yifan Xu, Joel W Hay, Heinz-Josef Lenz, Sarmad Sadeghi, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2016)

652 Background: In 2015, 140,000 patients will be diagnosed with colorectal cancer (CRC) with 20% diagnosed with mCRC and another 20% developing mCRC during their course. In recent years the outcome of mCRC has improved with survival reaching 30 months in clinical trials. P and C have similar effectiveness as reported in ASPECCT, though their administration and toxicities are different. Availability of more than one agent for one indication makes cost a variable in selection process. We aimed to evaluate the comparative effectiveness of P and C as monotherapy in chemo-refractory mCRC with WTKRAS from a societal perspective. Methods: We developed a Markov model with three states: stable disease, progressive disease and death. Probabilities of each state and transitions were extracted from the ASPECCT trial report. Costs of drug and administration were based on the Veteran Affairs Federal Supply Schedule and Medicare reimbursement rates for a base case of a 61-year-old male. We conducted a literature review to obtain data regarding the costs and utilities of toxicities. All costs are in 2015 US dollars. The model was constructed using a 1-month cycle length and 3-year time horizon, discounted at an annual rate of 3%. The model used quality-adjusted life-year (QALY) to measure the health outcomes for each treatment option. Results: P produced 9.8 months life-years gain and 0.56 QALYs at the cost of $74,827 per patient. C produced a 9.2 months life-years gain and 0.53 QALYs, at the cost of $79,916 per patient. The incremental net monetary benefit of P is $10,168 when compared to C under a societal willingness-to-pay threshold of $150,000 per QALY. The model showed robustness to the one-way sensitivity analysis and various alternative scenarios, and was found to be most sensitive to the cost of C. P and C are equivalent when cost of C drops from $1,038 to $782 per 100mL vial. Conclusions: In the US, effectiveness and toxicities are the main variables for choice of treatment regimen. The rising cost of care is forcing providers and policy makers to consider other data points in treatment selection. Our results indicate that P has a cost advantage over C and provide a strong argument to use P in lieu of C in mCRC.
Associations between <i>MDM2</i> SNP309 and SNP285C haplotypes and ovarian cancer risk in <i>BRCA1</i> mutation carriers.
Authors: M. Bjørnslett, S. Knappskog, P. E. Lonning, A. Dørum
Journal: Journal of Clinical Oncology (2011)

5030 Background: While BRCA mutation carriers possess a 20-40% lifetime risk of ovarian cancer (OC), genetic modifying factors that influence the individual phenotypic expression, remains obscure. Recently, we reported the MDM2 promoter polymorphisms SNP309T>G (enhancing MDM2 transcription) and the recently discovered SNP285G>C (reducing MDM2 transcription) to enhance versus reduce risk of sporadic OC in Caucasians (Knappskog et al. Cancer Cell 2011; doi:10.1016/j.ccr.2010.12.019). We now report the distribution of two MDM2 polymorphisms in Norwegian BRCA1 related ovarian cancer. Methods: Blood from 135 OC patients carrying a BRCA1 mutation were analyzed for MDM2 SNP285 and SNP309 status. Distribution of the polymorphisms was compared to 1465 sporadic OC patients and 2465 healthy controls. Results: Among healthy controls, 43% harbored the 309TT genotype, 44% were 309TG, while 12% were 309GG. In contrast, the three genotypes accounted for 37%, 50% and 12% among sporadic OC patients and 32%, 49% and 19% among BRCA1 mutated OC patients, respectively (distribution difference between the three cohorts: p < 0.001). The frequency of 309GG and 309TG was significantly increased among OC patients with BRCA1 mutations as compared to healthy controls (GG: OR 2.16; CI 1.31-3.58, TG: OR 1.51; CI 1.02-2.23, combined: OR 1.65; CI 1.14-2.39) and moderately increased as compared to sporadic OC (GG: OR 1.83; CI 1.10-3.07, TG: OR 1.15; CI 0.77-1.71, combined OR 1.28; CI 0.88-1.87). Removing individuals harboring the SNP285C from the analyses strengthened the effect of SNP309G on OC risk among BRCA1 carriers compared to healthy controls (GG + TG combined: OR 1.80; CI 1.24-2.62) and sporadic OC (GG + TG combined: OR 1.34; CI 0.92-1.96). SNP285C was found to be a risk reducing factor in BRCA1 related OC as compared to healthy controls carrying the 309G allele (OR 0.36; CI 0.15-0.90). Conclusions: The MDM2 SNP309G increases while the SNP285C reduces the risk of OC development in BRCA1 mutations carriers, resembling their effects on risk of sporadic OC. The finding that SNP285C has a counteracting effect on SNP309G may have implications for genetic counseling with respect to prophylactic risk-reducing oophorectomy in BRCA1 carriers.
Physician–investigator (PI) and patient communication regarding altruism and non-therapeutic benefits in phase I trials.
Authors: C. Daugherty, F. J. Hlubocky, N. E. Kass, D. Roter, S. Larson, J. Sugarman, K. Wroblewski, M. J. Ratain
Journal: Journal of Clinical Oncology (2011)

e16579 Background: Prior research indicates that altruism is not a motivating factor for ACP participation in phase I trials. However, how much altruism and non-therapeutic and/or nonpatient-related benefits are discussed in Phase I clinical trials between PIs and ACP participating in phase I trials has not been described. Methods: Clinical encounters between 131 ACP entering phase I trials and 29 PIs at three institutions (University of Chicago; Johns Hopkins; and Duke University) were audio-taped. ACP completed a follow-up questionnaire one week later to assess understanding of Phase I informed consent elements. Audiotapes were analyzed using the Roter Interaction Analysis System (RIAS). Results: To date, 101 ACP-PI encounters have been analyzed using RIAS. Average length of encounters: 30.4 min (range: 5.7-77.8 min). ACP demographics include: median age 61 y (33-83); 54% female; 89% Ca; 55% <college educ; 53% income <$60,000. The PIs were coded as making statements regarding therapeutic benefits of ACP participation in Phase I trials in 48% of encounters. The PIs discussed altruistic benefits to ACP in 27% of encounters. The proportion of encounters where the PIs reported that the PI or trial sponsor may gain financial or other benefits ( fame and publication) from ACP participation in the trial occurred in 2.2% of the encounters. The PI was never recorded describing any potential financial benefit that could be gained by the institution. Within these encounters, no ACP was recorded as inquiring regarding PI or trial sponsor benefits. ACP statements related to altruistic benefits (e.g. advance science, benefit future patients) occurred in 12% of discussions. In follow-up questionnaires, although 75% ACP reported that participation in a Phase I trial was a way to “help others” and “advance science”, 48% ACP reported their primary reason for enrolling in a Phase I trial was to “do everything I could”. Conclusions: Despite some evidence of PI discussion of the potential for altruistic benefits, little evidence is present regarding altruism as a motivating factor for ACP phase I trial participation.
Effect of MiR-32 on gastric carcinoma tumorigenesis by targeting Kruppel-like factor 4.
Authors: Chao Yan, Jianchun Yu, Weiming Kang
Journal: Journal of Clinical Oncology (2016)

76 Background: Gastric cancer (GC) is a prevalent malignant cancer worldwide and is highly lethal because of its fast growth. Currently, the comprehensive treatment is the combination of surgery, chemotherapy and radiotherapy, which has made progress in the treatment of advanced GC. However, the accuracy of current diagnostic methods is not very satisfactory. To address these limitations and improve the survival rate and reduce mortality it is necessary to identify sensitive early diagnostic markers. MiR-32 has been reported as an oncogenic microRNA in many cancers, but its role in GC is unclear. Methods: We detected miR-32 expression in clinical gastric carcinoma tissue samples and adjacent normal tissue samples from the same patient. The expression of miR-32 was also detected in 40 gastric carcinoma patients’ plasma, as compared with the plasma of 40 healthy individuals. The proliferation ability of cells was monitored by the xCELLigence Real-Time Cell Analyzer (RTCA)-MP system. Transwell insert chambers with an 8 μm diameter porous membrane (Neuro Probe, MD, USA) were used for the migration/invasion assays. Also, the plasmid construction and luciferase reporter assay, western blotting analysis and immunofluorescence cell staining were performed. Data were analyzed with SPSS v.17.0 software. Results: We detected the expression level of miR-32 in two normal gastric tissue, the GES-1 cell line, and eight gastric carcinoma cell lines. The expression of miR-32 was significantly higher in tumor tissues as compared with normal tissues, p = 0.0016. The expression of miR-32 was significantly higher in 40 gastric carcinoma patients’ plasma, as compared with the plasma of 40 healthy individuals, p = 0.004.MiR-32 promotes the proliferation, migration and invasion of GC cells. The expression of KLF4 is negatively regulated by miR-32. Knockdown of KLF4 promotes cell proliferation, migration and invasion in GC cell-lines. Conclusions: In addition to identifying upregulated miR-32 as a diagnosis biomarker in clinical GC tissue and plasma, we have defined the biological functions of miR-32 as an oncogene in GC cells and explored the molecular mechanism of miR-32 in GC cells’ aggressive phenotype.