tbuckley/cabot-search huggingface dataset:
Integrin genetic variants and risk of thromboembolic events in patients with colorectal cancer.
Authors: Gerald Prager, Alexandra Schuler, Cihan Ay, Clemens Pausz, Heinz-Josef Lenz, Ingrid Pabinger, Christoph Zielinski
Journal: Journal of Clinical Oncology (2014)

462 Background: Patients with colorectal cancer are at increased risk of venous thromboembolism (VTE). Integrin beta-3 are involved in tumor biology as well as platelet aggregation, thus, we tested as a primary endpoint whether a comprehensive panel of germline single nucleotide polymorphisms (SNPs) in the integrin beta-3 gene could predict the risk of VTE in colorectal cancer patients. Methods: The study population comprises patients recruited into the Vienna Cancer and Thrombosis Study (CATS) (Ay, C et al; JCO 2011 vol. 29 no. 15), an ongoing prospective observational cohort study initiated in October 2003 at the Medical University of Vienna. In 114 out of 139 patients diagnosed with colon cancer DNA was assessable for integrin beta-3 germline SNPs rs3809865, rs5918, rs4642 characterization. Whole blood samples were analyzed using PCR-RFLP or direct DNA-sequencing. VTE events were statistical analyzed using one-way Anova testing. Results: The patient’s demographics and tumor characteristics were balanced between groups. VTE occurred in 14 patients (12.28%). In colorectal cancer patients with an rs3809865 A/A allele profile a statistical significant (p=0.0015) increased risk of VTE events was observed as 12 (25%) of 48 patients experienced VTE. Only 2 of 52 patients (3.85%) harboring an A/T allele VTE was diagnosed. None (0%) of the T/T subgroup had any VTE. Other SNPs revealed no predictive value for VTE. In multivariable analysis including age, sex, chemotherapy, and anti-VEGF therapy rs3809865 A/A allele profile remained a statistical significant risk factor for VTE. Conclusions: This study identifies germline polymorphisms in integrin genes as independent prognostic markers for VTE in colorectal cancer. These data may help to select subgroups of patients who may benefit from an enforced prophylaxis of venous thromboembolism (VTE).
Stereotactic body radiotherapy (SBRT) with or without surgery for primary and metastatic liver tumors.
Authors: Alexander V. Kirichenko, David S. Parda, Angela Sanguino, Olivier Gayou, Moses S. Raj, Dulabh K. Monga, Ngoc Thai
Journal: Journal of Clinical Oncology (2016)

360 Background: We report on the outcome and toxicity of liver SBRT alone or in combination with surgery for inoperable primary and metastatic liver tumors. Methods: Patients with up to four isolated hepatic metastases (sum of tumor diameters ≤ 8cm) and individual tumor diameter ≤ 9 cm received SBRT at 46.8Gy ± 3.7 in 4-6 fractions. In patients with hepatic cirrhosis, liver dose constraints were imposed exclusively on residual functional liver volume defined on SPECT during SBRT treatment planning. The primary end point was local control with at least 6 months of radiographic followup, and secondary end points were toxicity and survival. Results: Between 2007-2014, 120 lesions in 91 patients with either unresectable primary (n = 43) or metastatic liver cancer (n = 48) completed liver SBRT to 36-60 Gy delivered in 4 to 6 treatment fractions, with a mean BED of 197 Gy 3 (range 108 – 300 Gy 3 ). Median followup was 20.3 months (range 1.9 - 64.1). Fourteen patients underwent liver transplant with SBRT as a bridging therapy or for tumor downsizing. Eight patients completed hepatic resections in combination with planned SBRT for unresectable tumors. Two-year local control was 96% for hepatoma and 93.8% for metastases; it was 100% for lesions ≤ 4cm. Ten of 14 transplanted patients developed complete pathological response with median time to transplant of 5.7 months (range 1.7 – 23.3). No incidence of grade &gt; 2 treatment toxicity was observed. There was no accelerated Child-Pugh class migration from A to B or from B to C. There were no operative or perioperative complications in patients who received SBRT prior to liver transplant or in combination with planned hepatectomy. Two-year overall survival was 82.3% (hepatoma) and 64.3% (metastases). Conclusions: In this retrospective analysis we demonstrate that liver SBRT alone or in combination with surgery is safe and effective for the treatment of isolated inoperable hepatic malignancies and provides excellent local control rates with minimal toxicity.
Clinical outcome of GBM long-term survivors.
Authors: B. Flechl, M. Ackerl, C. Sax, K. Dieckmann, R. Crevenna, G. Widhalm, M. Preusser, C. Marosi
Journal: Journal of Clinical Oncology (2011)

e12507 Background: An increasing number of patients with Glioblastoma mulitforme (GBM) are alive up to three years after diagnosis (long-term survivors). Hence there is an urgent need for data about their clinical outcome and quality of life to optimize the medical management and function of patients. Methods: In this cross sectional study we studied 16 GBM long-term survivors treated at the outpatient clinic of the Medical University Hospital Vienna. The patients have been treated there since their diagnosis. We assessed patient's clinical outcome to get global information about the circumstances under which they live. Results: We assessed 8 female and 8 male GBM long-term survivors with a median age of 52 years (71-30). 14 of them lived together with their partner (and children) while two lived single. The mean of the summary-score of the Neuro Cog-Fx, a computerized instrument for neurocognitive assessment of patients with neurological diseases, was 88 and ranged from 70 to 111, whereas results from 61-79 are defined conspicuous, 80-89 borderline and results up to 90 normal. The global health score ranged from 17% to 100% with a mean of 68%. Drowsiness, weakness in both legs and a headache were the most stated physical problems. The Independent Activities of Daily Living – Score ranged from 0-8 points; mean was 7 points and Barthel Index resulted in 35-100 with a mean of 92 points. Six patients showed impairment in their manual dexterity, one patient in their mobility. Three patients showed conspicuous depression scores, two had conspicuous anxiety results. Furthermore, future uncertainty was stated in 12 patients. Conclusions: GBM long-term survivors show moderate impairment in their cognitive functions and often suffer from physical problems. However, the majority of the GBM long-term survivors is able to manage their activities of daily living independently. Nevertheless, global health and future prospects remain poor.
Efficacy and toxicity of sorafenib in patients with advanced renal cell cancer in northeast China: A multicenter study.
Authors: X. Xie, F. Guo, X. Song, Q. Zhang, X. Kong, C. Li, Z. Li, S. Qu, Z. Liu, Y. Piao, Z. Zheng
Journal: Journal of Clinical Oncology (2011)

e15046 Background: The objective was to observe efficacy and toxicity of sorafenib in patients with aRCC in China Methods: 103 consecutive patients were eligible from Dec. 2006 to Dec. 2009. All cases were diagnosed as aRCC histopathologically without exception. 400mg sorafenib was orally taken twice daily until PD or the occurrence of intolerable toxic reaction. The primary efficacy end points were OS and treatment-induced toxicities. PFS and 1-year survival rate were observed as the secondary end points. Results: All patients were available for assessment of efficacy and safety. The total RR, DCR and SAR was 35.9%, 86.5% and 84.5%, respectively. Especially, there was obviously remission on pulmonary symptoms such as coughing and brachypnea. Compared to patients with multiple metastases in different organs, the DCR of 44 patients with purely pulmonary metastases was better. The main toxicity was I-II grade and was tolerable to patients. The DCR of patients with grade III-IV toxicity was 40.0%, which was much higher than that of patients with grade I-II toxicity. However, both of them were no statistical significance on one-year OS. Conclusions: Sorafenib has good effects on patients with aRCC in Northeast China. It can remarkablely improve DCR and survival time of patients with minor or tolerable toxicities.
Identification of hTid1 as a Molecular Partner and a Negative Regulator of the Transcription Factor Stat5B
Authors: Remy Nyga, Isabelle Dhennin-Duthille, Saliha Yahiaoui, Karl Munger, Aline Regnier, Valerie Gouilleux-Gruart, Kaiss Lassoued, Fabrice Gouilleux
Journal: Blood (2008)
Effects of Retinoids on Augmentation of Club Cell Secretory Protein
Authors: Yin Chen, Monica M. Vasquez, Lingxiang Zhu, Rosa E. Lizarraga, Mary Krutzsch, Janine Einspahr, David S. Alberts, Peter Y. P. Di, Fernando D. Martinez, Stefano Guerra
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Association of HER2/neu subtype with ipsilateral breast tumor recurrence after breast-conserving surgery in young-age breast cancer.
Authors: H. J. Kim, S. Ahn, D. Noh, O. V. Yi, H. Moon, S. K. Ahn, W. Han
Journal: Journal of Clinical Oncology (2011)

e21099 Background: To determine whether breast cancer subtype and age is associated with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS). Methods: Using information from Asan medical center and Seoul National University Hospital databases in Korea, we assessed IBTR related to the breast cancer subtype using immunohistochemical (IHC) staining. We also compared the IBTR in young age patients with those in older age patients. Results: In an analysis of 2,235 breast cancer patients who got a breast conserving surgery, 548 patients were ≤40 years old (young age group) and 1,687 patients were over 40 years old (old age group). Median follow up was 61 months. In young age group patients, The Overall 5 year cumulative incidence of IBTR was 2.2%; 1.5% (0.8-2.2) for luminal A, 1.7 % (0.0-3.4) for luminal B, 6.6% (3.0-10.2) for HER2/neu, and 2.8% (1.4-4.2) for triple negative subtype. On multivariate analysis with luminal A as baseline in young age group, only HER2/neu type was associated with increased IBTR (HR=9.9; 95% CI, 1.8-53.3). on Multivariate analysis, IBTR of HER2/neu type of old age group was similar to the those of Luminal A type of young age group (HR 1.04; 95% CI, 0.1-8.3) Conclusions: Overall, the 5 year IBTR after BCS was low, but HER2/neu subtype was associated with increased risk of IBTR only for young breast cancer. future study about the survival effect of IBTR of HER2/neu target agent is warranted.
Development of a comprehensive registry of gastrointestinal stromal tumors (GIST) patients in eastern Ontario.
Authors: E. Marginean, T. R. Asmis, R. A. Auer, D. Soulieres, S. Verma
Journal: Journal of Clinical Oncology (2010)

e12049 Background: GISTs are the most common GI mesenchymal neoplasms, highly resistant to conventional chemotherapy and radiotherapy. Surgery is the mainstay of therapy; however targeted therapy with imatinib mesylate has revolutionized therapy of recurrent and metastatic tumors, and recently in adjuvant setting. Subclassification of GISTs according to kinase mutation status has both biological and clinical implications, since it predicts response to imatinib and prognosis following resection. Methods: We have undertaken a study of all patients diagnosed with GISTs in eastern Ontario between 2004-2009. Collected data include pts demographics, clinical characteristics and outcomes and therapy provided. Pathology of all cases was centrally reviewed by a single pathologist. Pathological parameters include tumor size, location, classification into spindle cell, epithelioid and mixed types, number of mitoses/50HPF, tumor necrosis and nuclear atypia. An IHC panel was performed including CD117, DOG1, CD34, vimentin, S100, desmin, SMA and caldesmon. Risk stratification was performed using AFIP criteria. Molecular classification was performed in all cases at a central molecular laboratory. DNA was obtained from fixed archived material. PCR amplification and sequencing was done for exons 9, 11, 13, 17 of KIT and exons 12 and 18 of PDGFRA genes. Results: A total of 57 cases have been identified thus far; 48 (84% of whom remain alive. 34 (60%) involved stomach, 17 (30%) small bowel, 3 (5%) rectum, 1 (2%) each of esophagus and colon and 1 (2%) unknown primary. Of these, 82% showed spindle cell morphology, and 9% each were mixed and epithelioid. By IHC, 100% cases were CD117 and DOG1 positive. Mutation frequencies in 42 pts were: KIT exon 11: 22 (52%) – including 16 deletions, 5 point mutations and 1 insertion, KIT exon 9 : 2(5%), KIT exon 17: 1(2%), wild type: 15 (36%) and PDGFRA mutations: 2(5%), 1 each in exons 12 and 18 D842V. Conclusions: In rare tumors such as GISTs, with rapidly shifting treatment paradigms, comprehensive, centralized regional and collaborative databases are feasible and compulsory to assess short and long term outcomes of interventions. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Quality of transurethral resection in patients with bladder cancer: A process-outcomes link.
Authors: Eric Christian Ballon-Landa, Karim Chamie, Jeffrey C. Bassett, Timothy J. Daskivich, Meryl Leventhal, Dennis Deapen, Mark S. Litwin
Journal: Journal of Clinical Oncology (2014)

292 Background: Detrusor muscle at diagnostic transurethral resection of a bladder tumor (TURBT) is often used as a surrogate of resection quality. We examined whether surgical and pathologic quality at the time of initial resection was associated with improved cancer-specific survival among subjects diagnosed with non-muscle-invasive bladder cancer. Methods: We retrospectively reviewed the operative and pathology reports of all individuals ≥18 years of age within the Los Angeles SEER registry, with an incident diagnosis of urothelial non-muscle-invasive bladder cancer between 2004-2005. We recorded patient age, gender, race, marital status, socioeconomic status, insurance type, institution type, surgeon and pathologist volume, tumor stage and grade, detrusor muscle presence/mention, and vital status. After adjusting for confounding using competing-risks regression analysis, we determined whether surgical and pathologic quality was associated with cancer-specific survival. Results: We identified 1,865 patients, 335 urologists, and 278 pathologists. Muscle was reported as present in 972 (52.1%), reported as absent in 564 (30.2%), and was not mentioned in 329 (17.7%) of the initial pathology reports. The incidence of detrusor muscle sampling did not differ according to grade or stage. However, bladder cancer death was more likely with higher stage disease (Tis: HR=5.00, 95% CI 2.38-10.50; T1: HR=5.44, 95% CI 3.00-9.88) and lower quality staging (muscle absent: HR=1.50, CI 1.00-2.27; muscle not mentioned: HR=2.01, CI 1.14-3.56). This pattern was enhanced among those with high-grade disease. For this group, the 5-year cancer-specific mortality was 8.0%, 13.0%, and 21.5% when muscle was present, absent, or not mentioned, respectively. Conclusions: Nearly half of all diagnostic TURBTs do not include muscle. This omission is associated with increased mortality, particularly in high-grade disease—yet few of these patients undergo treatment to correct this error. Because urologists cannot discern between high- or low-grade disease, we contend that all patients with bladder cancer should undergo endoscopic resection with detrusor muscle sampling (and appropriate pathology reporting) at diagnosis.
Smaller, faster trials: The right way to assess new targeted agents? A simulation study.
Authors: M. Le Deley, K. V. Ballman, D. J. Sargent
Journal: Journal of Clinical Oncology (2011)

6062 Background: Traditional clinical trial designs strive to definitively establish the superiority of an experimental treatment, which results in risk adverse criteria and large sample sizes. Increasingly, common cancers are recognized to consist of small subsets with a specific aberration for targeted therapy, making large trials infeasible. We compared different trial design strategies to determine which performs best over a 15 yr research horizon. Methods: We simulated a series of two-treatment superiority trials over 15 yrs using different trial design parameters. Trial parameters examined were number of positive trials to establish superiority (1 vs 2), α-level, and number of trials over 15 yrs (thus trial sample size, SS). Different disease scenarios (median survivals), accrual rates, and distributions of treatment effect were studied. Metrics used: gain in survival rate (Hazard Ratio yr 15 vs yr 0), risk of an overall effect of harm (HR > 1), and number of false positive trials. Results: For all scenarios, overall gains were greater using the criterion of 1 positive trial (vs 2) and as α increased from .025 to .20. Gains in survival were achieved with SSs smaller than required under traditional criteria. Reducing the SS and increasing α increased the mean gain but also the likelihood of having a poorer survival rate at yr 15, but the chance was < 7% in all scenarios. The avg number of false positive trials was < 0.5 trials over 15 yrs. Results were consistent under different assumed distributions for treatment effect. For example, median survival 1 yr, accrual rate 100/yr, historical scenario (mean HR 0.95). Conclusions: A traditional trial design strategy yields smaller expected gains over a 15 yr horizon compared to strategies using larger α and small SSs. As patient populations become more specific (and thus smaller), the current risk adverse trial design strategy may slow long term progress and deserves reexamination. Decision criterion Optimal strategy Performance No. of positive trials α No. of trials SS Mean HR (at 15 yr) Risk of HR > 1 Avg No. of false-positive trials 1 .025 7 114 0.59 0.5% 0.02 1 .05 8 88 0.55 1% 0.05 1 .10 10 50 0.50 3% 0.19 1 .20 10 50 0.42 3% 0.42 2 .025 5 200 0.69 <0.1% <0.001 2 .05 7 114 0.65 <0.1% 0.002 2 .10 8 88 0.60 0.5% 0.02 2 .20 9 66 0.53 1% 0.08
Irrational numbers in surgical training
Authors: Jonathan Glass
Journal: BMJ (2017)

I enjoy numbers. I enjoy the accuracy they provide and the guidance they give in the practise of clinical medicine. In medicine we should not allow numbers to be arbitrarily bandied about, yet this still happens.

If you were applying for a certificate of completion of training (CCT) in urology in 2015 you had to have seen or assisted in at least 20 radical prostatectomies before being signed off as competent. A year later, for no apparent reason, it appears that 10 will do.

Changes to the required numbers of various procedures to which a trainee needs to be exposed are often made year on year, and yet failure to achieve these “indicative numbers” is …
Insurer pre-authorization and copayment for palliative patients with cancer receiving opioids other than morphine.
Authors: Marieberta Vidal, Akhila Sunkepally Reddy, Eden Mae Rodriguez, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

217 Background: Uncontrolled pain is one of the main fears for patients with cancer and their families. Opioid analgesics are highly effective agents, but the choice of type, route, and dose needs to be personalized. The highly cost of some of them can make it difficult for patients to received adequate pain control without appropriate insurance coverage. There is a lack of information regarding the frequency of denials or heavy copayments by insurers. Methods: We evaluated 143 continuous opioid test claims for prescriptions by our palliative care providers for opioids other than morphine, including transdermal fentanyl, extended release oxycodone, hydromorphone and oxymorphone. We will categorize the test claims in 4 different groups: Approved with $0 to $49 dollars co-pay, Approved with high co-pay ($50 or more), Preauthorization required, and Direct Denial. Results: Among the 143 collected test claims 102 were for hydromorphone ER, 27 Oxycodone ER, Fentanyl TD 6 and Oxymorphone ER 8: 4 (3%) were rejected, 65 (46%) had a $0-50 copay , 28 (20%) had $50 or more copay and 46 (31%) needed prior authorization.). Conclusions: Only 65 ( 46%) of the prescriptions for opioids other than morphine had a copayment of 0-50$. Insurers’ copayment and requirements pose a major barrier for patients and physicians.
Patient-centered outcomes with post-approval nivolumab in metastatic NSCLC at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Marc A. Shapiro, Katherine Glass, Alicia M Redden, Nathan A. Pennell, James Stevenson, Vamsidhar Velcheti, Emily Van Wagoner, Chad W Cummings, Brian James Bolwell
Journal: Journal of Clinical Oncology (2016)

29 Background: Patient-centered outcomes are important quality metrics of value-based cancer care. For NSCLC, these include chemotherapy administration within 30 days of death and end of life hospitalizations. Nivolumab was initially FDA approved in March 2015 for second-line therapy of squamous NSCLC and subsequently for non-squamous NSCLC. To evaluate the impact of post-approval nivolumab use on patient-centered outcomes, a retrospective review was performed of patients (pts) with metastatic NSLCC receiving nivolumab at TCI main campus and regional centers. Methods: All pts with NSCLC receiving nivolumab from 3/4/15 to 10/5/15 were identified (cohort A) and treatment characteristics were collected from pharmacy, billing, and tumor registry databases and manual chart review. Similar data for a cohort of NSCLC pts (cohort B) initiating care with 4 academic thoracic and 12 community TCI oncologists from 1/1/12 to 7/1/13 and who received second-line therapy were used for comparison. Results: 113 cohort A pts received nivolumab with a median follow up of 101 days. 82 (73%) were alive at the time of evaluation. 70 (62%) received ≤ 1 prior chemotherapy regimens for metastatic disease. 19 of 52 (37%) cohort A pts completing nivolumab received drug within 30 days of death, 13 (68%) of whom had received ≤ 1 prior chemotherapy regimens. 3 of 50 (6%) cohort B pts completing second-line therapy received drug within 30 days of death. In patients with a known date of death, median time from first dose of nivolumab in cohort A and second-line therapy in cohort B and death was 41 and 145 days respectively. 28 (25%) cohort A pts and 18 (36%) cohort B pts were hospitalized at a TCI facility during therapy. Conclusions: This study shows the brisk uptake of nivolumab to clinical practice, but with potential for inappropriate utilization. Continued evaluation of practice patterns is necessary including cost analysis. Further research is needed to better understand outcomes in patients with EGOG PS ≥ 2, front-line use, and cost effectiveness.