tbuckley/cabot-search huggingface dataset:
Discussions about clinical trials among patients with lung and colorectal cancer.
Authors: Kenneth L. Kehl, Neeraj K. Arora, Deborah Schrag, John Ayanian, Steven Clauser, Carrie N. Klabunde, Katherine Leslie Kahn, Robert H. Fletcher, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2014)

6509 Background: Clinical trials are essential for evaluating new cancer therapies, but less than 5% of adults with cancer enroll in trials. Barriers to enrollment may include patient-provider communication factors, such as lack of patient awareness or understanding about the option of participation. Methods: We surveyed a population- and practice-based sample of patients (or their surrogates) 3 to 6 months after diagnoses of lung or colorectal cancer. We assessed whether respondents learned that clinical trial participation might be an option, and if so, with whom they first discussed this possibility. We used multivariable logistic regression to assess the association of patient characteristics with clinical trial discussions and enrollment. Results: Of 7,887 respondents, 1,114 (14.1%) reported discussing clinical trial participation. Most (92.7% of participants, 75.8% of nonparticipants) learned about trials from their physicians. 287 patients (3.6% of all patients, 25.8% of trial discussants) enrolled. Among 2,173 patients who received chemotherapy for advanced (stage III/IV lung or stage IV colorectal) cancer, 25.7% discussed trials, and 7.6% (29.5% of discussants) enrolled. In adjusted analyses among all patients, discussion of clinical trials was more common among college-educated patients (OR 1.9, 95% CI 1.5-2.5 vs <high school education) and those with incomes >$60,000/year (OR 1.7, 95% CI 1.4-2.2 vs <$20,000/year), and less common among older patients (OR 0.96, 95% CI 0.95-0.97/year). These factors were not significantly associated with enrollment among patients discussing trials. Enrollment was higher among patients reporting shared vs. physician–driven decisions (P<0.05). Conclusions: In this population-based cohort, less than one-sixth of cancer patients discussed clinical trials. Discussions were more frequent in the setting of advanced disease but were still reported by a minority of patients. Older age and lower education and income levels were associated with less discussion of clinical trials but not with enrollment in trials following discussions. Strategies to broaden access to trials and facilitate patient-provider communication about participation may improve enrollment rates.
A phase II study of neoadjuvant chemotherapy with S-1 and cisplatin for stage III gastric cancer: KUGC03.
Authors: Hiroshi Okabe, Hiroaki Hata, Shugo Ueda, Masazumi Zaima, Atsuo Tokuka, Tsunehiro Yoshimura, Shuichi Ota, Yousuke Kinjo, Kenichi Yoshimura, Yoshiharu Sakai
Journal: Journal of Clinical Oncology (2014)

e15058 Background: Surgery followed by adjuvant chemotherapy is the recommended treatment for advanced gastreic cancer in Japan, where D2 gastrectomy is standard. However, for highly advanced disease, neoadjuvant chemotherapy (NAC) followed by D2 gastrectomy is a promising approach to further improve survival. We conducted a phase II study to evaluate the safety and efficacy of NAC with S-1 plus cisplatin for patients (pts) with clinical stage III gastric cancer. Methods: Eligibility criteria included histologically proven gastric cancer; cT3(SE)/T4(SI) or cN2, not Stage IV; P0 and CY0 confirmed by laparoscopy; age between 20 and 80 years old; PS of 0 or 1; capable of oral administration. Pts received two 35-day cycles of SP regimen (S-1 of 80 mg/m2 from day 1 to 21 and cisplatin of 60 mg/m2 on day 8), and then underwent D2 gastrectomy, followed by adjuvant chemotherapy with S-1 for one year. Primary endpoint was 3-year progression free survival (3YPFS). Key secondary endpoint was ratio of R0 resection. Other secondary endpoints included response rate, adverse events, and overall survival. Sample size was determined to have 80% power for detecting 15% improvement in 3YPFS over 55% baseline at one-sided alpha of 0.1. Results: Between January 2009 and June 2011, 53 pts were enrolled. All pts were eligible and 44 pts completed two cycles of SP (83%). Among 33 pts with target lesions, clinical response was observed in 69.7%. The most frequent grade 3/4 toxicity was appetite loss (15.1%). Gastrectomy was performed in 50 pts (94%), and R0 resection was achieved in 48 pts (91%; 95% CI, 79-97%). Postoperative complications occurred in 20 pts (40%), and one patient died (1.9%). Pathological response, defined as disappearance of more than one third of the primary tumor, was confirmed in 24 pts (45%) and complete response was observed in 4 pts (8%). 3YPFS was 53.1% (95% CI, 38.4-67.8%), while 3-year overall survival was 74.9%. Conclusions: Although 3YPFS did not reach the expected value, NAC with SP regimen for pts with clinical stage III gastric cancer was safe and led to R0 resection at a high rate. Clinical stage III could be a candidate target to evaluate the superiority of NAC by a phase III study. Clinical trial information: UMIN000001584.
Abstract 156: Involvement of β-adrenergic System in Myocardial Dysfunction Induced by Obesity
Authors: Ana Paula Lima-Leopoldo, Artur Ferron, Bruno Jacobsen, Dijon Campos, Renata Luvizotto, Márcia R Cunha, Antonio Cicogna, Andre Leopoldo
Journal: Circulation Research (2014)

Several structural and functional changes of the heart have often been associated with human and experimental models of obesity. Some factors have been suggested as responsible for possible cardiac abnormalities in models of obesity, among them β-adrenergic system, an important mechanism of regulation of myocardial contraction and relaxation. The objetive of present study was to evaluate the . Thirty-day-old male Wistar rats were assigned to one of two groups: control (C) and obese (Ob). The C group was fed a standard diet and Ob group was fed cycles of four unsaturated high-fat diets for 15 weeks. The body fat was measured from the sum of the individual fat pad weights and the obesity was defined by adiposity index. Isolated papillary muscle preparation was performed under basal conditions and after inotropic and lusitropic maneuvers. β-adrenergic system was evaluated by using cumulative concentrations of isoproterenol and Western Blot. After 15 weeks, the Ob rats developed higher adiposity index than C rats. Obesity promoted comorbities such as glucose intolerance, insulin resistance, hyperleptinemia, and dyslipidemia; however, were not associated with changes in systolic blood pressure. The cardiac structure results post-death showed that obesity caused cardiac hypertrophy. Furthermore, Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. The obesity was not accompanied by changes in protein expression of Gsα, β1 and β2 adrenergic receptors. In conclusion, the myorcardial dysfunction caused by unsaturated high-fat diet-induced obesity, after 15 weeks, is not related to β-adrenergic system impairment.
Endometrial cancer outcomes in hypertensive women treated with beta-blocker.
Authors: Dario R. Roque, Stuart Pierce, Kemi Morenikeji Doll, Brittany Davidson, Amanda Lynn Jackson, Emily Meichun Ko, Dominic T. Moore, Paola A. Gehrig, Angeles Alvarez Secord, Laura Jean Havrilesky, Victoria Lin Bae-Jump
Journal: Journal of Clinical Oncology (2014)

e16545 Background: Hypertension (HTN) is a comorbidity frequently found in women with endometrial cancer (EC). While evidence suggests a protective benefit of beta-blockers in other malignancies, the impact of HTN on survival outcomes in EC remains unclear. Our goal was to evaluate survival outcomes in hypertensive women with EC on beta-blockers. Methods: In an IRB-approved retrospective analysis, women treated for EC at two academic institutions between January 2005 and July 2012 were identified. Clinical data, including medication use at the time of diagnosis, was abstracted from medical records. A cohort of EC patients with HTN treated with a beta-blocker was identified. Cox regression modeling was used to analyze progression free survival (PFS), time-to-progression (TTP) and overall survival (OS). Results: Of 1,964 diagnosed with EC in the study period, 1,172 (60%) women had HTN, comprising the study cohort. Of these, 429 (37%) were using beta-blockers. On univariate analysis, HTN was significantly associated with worse OS (HR 1.7, 95% CI: 1.3-2.1, p=0.0001) and PFS (HR 1.4; 95% CI: 1.1-1.7, p=0.03) but not TTP. However, in multivariate analysis controlling for age, grade, stage, race, BMI and adjuvant treatment, HTN was only significantly associated with worse OS (HR 1.4; 95% CI: 1.02-1.8, p=0.04). Within the HTN cohort, beta-blocker use, on univariate analysis, was significantly associated with worse OS (HR 1.5, 95% CI: 1.1-1.9, p=0.002), PFS (HR 1.5, 95% CI: 1.2-1.8, p=0.0006) and TTP (HR 1.4, 95% CI: 1.03-1.8, p=0.03). On multivariate analysis, beta-blocker use continued to be associated with worse OS (HR 1.5, 95% CI: 1.1-2.0, p=0.01), and PFS (HR 1.4, 95%CI: 1.1-1.8, p=0.02) but not TTP. Conclusions: When accounting for other known prognostic factors in women with EC, hypertension was significantly associated with worse OS but not PFS or TTP. In contrast to other cancers, beta-blocker use does not appear to provide a protective effect in EC patients with HTN and may potentiate negative outcomes with increased risk of recurrence and death. Our results suggest a complicated association between HTN, adrenergic receptor blockade, and endometrial cancer pathogenesis and may have implications for the management of HTN in women with EC.
Pain management (PM) continuing medical education (CME) changes physician practice patterns
Authors: L. A. Leong, R. Morgan, N. Slatkin, M. Rhiner, L. Schroeder, B. Pritt
Journal: Journal of Clinical Oncology (2004)

6155 Background: Society is recognizing the importance of education in improving treatment of pain and suffering. California Bill AB487 requires all practicing physicians to obtain 12 hours of CME in PM before 2006 for license renewal. The effectiveness of this mandate has not been systematically evaluated Methods: We conducted the first of five annual PM seminars. Topics included management of malignant and non-malignant pain, pharmacology and management of side-effects of opiate and non-opiate analgesics, and adjunctive therapies (depression management, spirituality issues). Immediate post-attendance and 4-month follow-up questionnaires were sent to participants. Results: Of the 81 physicians representing 17 medical specialties, 51 responded to the immediate questionnaire. 31 responses were received to the 4 month follow-up questionnaire: Responses were as follows: (Early, 4 months) I will change my practice 34 (67%), 28 (90%) I see no need to change my practice 6 (12%), 2 (6%) I will await further information 7 (14%), 1 (3%) No Response regarding practice change 4 (8%) Responses of those who changed their practices included: Increased use of known modalities for pain control 21 Earlier referrals to specialists 14 More attention to psychosocial aspects 14 Use of new drugs/modalities of care 11 Specific comments regarding practice changes are consistent with topics presented at the seminar. Conclusions: These results indicate that this cohort of physicians was overwhelmingly open to changing practice patterns in the area of PM and palliative care. 67% expressed an interest in changing their practice immediately following this intensive educational experience. 90% responding to the follow-up evaluation indicated that their practices had changed. These data show that CME can effectively influence physician practice patterns. (Supported by CA62505) No significant financial relationships to disclose.
Multicentric survey on dose reduction in cancer drug therapy: Detection and measurement of critical phenomena as potential indicators of suspected adverse reactions.
Authors: Elena Tenti, Andrea Casadei Gardini, Dino Amadori, Paola Fiacchi, Alessandra Stancari, Alessandra Zanardi, Chiara Cherubini, Stella Sferra, Simonetta Sara, Cristina Rondoni, Antonio Maugeri, Silvia Restuccia, Maria Laura Gallani, Simonetta Palazzini, Erika Bianchini, Silvia Menozzi, Eleonora Musi, Martina Minguzzi
Journal: Journal of Clinical Oncology (2013)

e13579 Background: The antineoplastics are considered drugs with a high number of side effects. Paradoxically, in the National Network of Pharmacovigilance the number of reported adverse reactions of these medicine is proportionally lower than that of normal drugs. In the field of pharmacovigilance programs promoted by the Region Emilia Romagna and funded by AIFA (Italian Medicines Agency) a project of multicenter surveillance of cancer drugs and their effect has been developed aimed at improving patient safety. The project joined 7 centers: IRCCS IRST (Coordinating Center) and the Hospitals of Ravenna, Parma, R. Emilia, Bologna, Ferrara and Rimini. Methods: All centers except one used the management software Log80 and therefore shared a database of information of analogous structure (the data presented come from the database of medication prescription). The survey included patients that started therapy in 2011 and reduced it in the same year. It was analyzed dose reduction from 10% to 50% during the first 90 days of therapy (dose reduction was counted from the actual administred dose to patient). The first 90 days of therapy have been considered as a significant time frame to intercept critical phenomena. Results: Out of a total of 12,389 patients, 1,320 have reduced the dose in the firts 3 mounth of treatment (10.7%). The drugs that have mostly resulted in a reduction of dose were Paclitaxel and Oxaliplatin (with a reduction of respectively 17.4% and 17.3% in term of number of patients ), Docetaxel (14.8%), Carboplatin (15%), Fluorouracil (10.7%) and among oral medications Capecitabine (6.9%). Conclusions: This survey has shown that patients treated with chemotherapy have had a dose reduction lower than compared to published studies. With regards to these reduction it must be highlighted that approximately 20% of patients have reduced by 30% the dose within three months of therapy. The dose reduction may underlie suspected adverse reactions; in this perspective, further investigations could show if the patients had severe adverse drug reactions.
Letter by Koh Regarding Articles, “Predicting the 10-Year Risks of Atherosclerotic Cardiovascular Disease in Chinese Population: The China-PAR Project (Prediction for ASCVD Risk in China)” and “Distribution of Estimated 10-Year Risk of Recurrent Vascular Events and Residual Risk in a Secondary Prevention Population”
Authors: Kwang Kon Koh
Journal: Circulation (2017)
Next-generation sequencing of serum microRNA (miRNA) in hepatocellular carcinoma (HCC) patients on targeted therapy.
Authors: Robin Kate Kelley, Aaron N. Chang, Esperanza Anguiano, Jimmy Hwang, Hubert J. Stoppler, Ryan M. McWhirter, Anna L. Parks, Bilal Hameed, Oren K. Fix, Elizabeth M. Wayne, Halla Sayed Nimeiri, Pamela N. Munster, Alan P. Venook, Andrei Goga
Journal: Journal of Clinical Oncology (2014)

4096 Background: Circulating biomarkers are urgently needed in HCC. miRNA are noncoding RNA that regulate mRNA expression and are detectable in tumor tissue and extracellular compartments. This pilot study explored the feasibility of using next-generation RNA sequencing to characterize miRNA abundance in serum from HCC patients at baseline and on targeted therapy. Methods: Banked serum samples (400µL) were obtained from HCC patients enrolled on a phase I clinical trial of sorafenib plus the mTOR inhibitor, temsirolimus. Control sera were obtained from patients with non-malignant liver diseases (NMLD). Total RNA was purified using Trizol-LS and miRNeasy kit. Mature miRNA were size-selected by gel electrophoresis. Samples were sequenced by Illumina HiSeq 2500, 5M reads per sample. Raw reads were mapped using Novoalign, quantified, and normalized to total reads and exogenous spike-in miRNA recovery. Comparisons between HCC vs. NMLD and baseline vs. on treatment cohorts were performed using one-way ANOVA and false discovery rate (FDR) correction. Candidate signature miRNA were derived by fold change, p-value, and abundance cutoffs and cross-referenced to literature. Results: Cohorts: HCC baseline (n=23) and paired on treatment (n=20 cases, 30 samples), NMLD (n=12). HCC cohort: HBV+/dual 40%, HCV+ 32%. NMLD cohort: HCV+ 83%. 38 of 65 (58%) total samples qualified. Candidate miRNA were identified which showed up-regulation in HCC vs. NMLD (non-significant) and in elevated vs. normal alpha-fetoprotein (AFP) (FDR p<0.05). Multiple miRNA families showed a trend toward down-regulation on treatment with temsirolimus plus sorafenib including Let-7 and miR-17/92 family members. Serum signatures for HCC vs. NMLD and elevated AFP overlapped with miRNA expression in a published dataset of HCC tumors. Conclusions: Serum miRNA in HCC patients can be characterized by next-generation sequencing. Differences in miRNA abundance were observed between HCC cases and NMLD controls, and within HCC cases according to clinical covariates including treatment status and AFP. Serum miRNA warrant further study as novel biomarkers in HCC.
Letter to the editor: Pre-exposure prophylaxis for HIV in Europe: The need for resistance surveillance
Authors: Carla van Tienen, David van de Vijver, Teymur Noori, Anders Sönnerborg, Charles Boucher
Journal: Eurosurveillance (2017)

__To the editor:__ In a recent paper by Hauser et al. in this journal, a prevalence of 10.8% of transmitted drugresistant viruses was reported among newly diagnosed HIV cases in Germany in 2013 and 2014.  
The authors conclude that genotypic resistance testing remains important for treatment as well as HIV prevention. We comment on the use of pre-exposure prophylaxis (PrEP) in relation to drug resistance in HIV infections and the need for European surveillance of drug resistance.
A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients
Authors: E. Chatelut, A. Schmitt, A. Lansiaux, C. Bobin-Dubigeon, M. Etienne-Grimaldi, M. Boisdron-Celle, F. Pinguet, A. Floquet, E. Billaud, C. Le Guellec
Journal: Journal of Clinical Oncology (2009)

2527 Background: It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), body weight (BW), age, and sex. This multi-center pharmacokinetic study was performed to evaluate prospectively the benefit of using cysC for carboplatin individual dosing. Methods: The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was performed using the NONMEM program. Seven covariates were studied: Scr, cysC, age, sex, BW, ideal body weight, and lean body mass. Results: The best covariate equation was: carboplatin clearance (mL/min) = 105. (Scr/75) -0.433 . (cysC/1.00) -0.290 . (BW/65) +0.547 . (age/56) -0.351 . 0.855 sex , with Scr in μmol/L, cysC in mg/L, BW in kg, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +2% and 15% respectively on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index. Conclusions: For the first time, a unique formula is proposed for carboplatin individual dosing to patients which is shown to be equally valid for underweight, normal weight, and obese patients. No significant financial relationships to disclose.
Incidence of pseudo-progression in low-grade gliomas treated with radiotherapy.
Authors: Sophie E. van West, Hein G. de Bruin, Bart van de Langerijt, Annemarie T. Swaak-Kragten, Martin J. Van Den Bent, Walter Taal
Journal: Journal of Clinical Oncology (2015)

2051 Background: Pseudo-progression (psPD) is a well-known phenomenon in high-grade gliomas (HGG) after treatment with radiotherapy/temozolomide. However the incidence of psPD in low-grade glioma (LGG) after radiotherapy (RT) is unknown. Therefore, we retrospectively investigated the occurrence of psPD in a cohort of low grade glioma patients treated with RT. Methods: All patients with histologically proven LGG treated with RT between 2000 and 2011 were reviewed. MRI scans were reviewed by two independent reviewers before and after RT in periods of 3-6 months until progression leading to the start of a new treatment as judged by the treating physician. Furthermore clinical data including dexamethasone dose and epileptic activity was taken into account. Pseudo-progression was scored when a new enhancing lesion occurred after RT, and this disappeared or remained stable for at least a year without therapy. Results: Seventy-one patients were treated with RT for LGG. Sixty-four patients were deemed eligible for evaluation (3 were lost to follow up and 4 patients were not evaluable, due to a missing scans). The median follow-up was 7 years (range 1- 22 years). The median progression free survival was 3.1 years. The median overall survival time was 5.3 years. Sixty-three patients were evaluable for psPD (1 patient was evaluated for response only, because of gadolinium allergy). psPD was seen in 13 patients (20.6%). In two of these patients epilepsy may have played a role. Pseudo-progression occurred after a median of 10 months in a period of 3 – 78 months. The median duration of psPD was 6 months with a range of 2 – 26 months. It always occurred within the RT fields. The area of the enhancement at the time of pseudo-progression was significantly smaller compared to the area of enhancement during ‘true’ progression (median size 54 mm2 (range 12 – 340 mm2) versus 270 mm2 (range 30 – 3420 mm2), respectively; p = 0.009). Conclusions: psPD occurs frequently in LGG patients treated with RT. This supports the policy to postpone a new line of treatment until further progression is evident, especially when patients have small contrast enhancing lesions in the RT field.