tbuckley/cabot-search huggingface dataset:
Association between trial registration and positive study findings: cross sectional study (Epidemiological Study of Randomized Trials—ESORT)
Authors: Ayodele Odutayo, Connor A Emdin, Allan J Hsiao, Mubeen Shakir, Bethan Copsey, Susan Dutton, Virginia Chiocchia, Michael Schlussel, Peter Dutton, Corran Roberts, Douglas G Altman, Sally Hopewell
Journal: BMJ (2017)

<h3>Abstract</h3> <h3>Objective</h3> To assess whether randomised controlled trials (RCTs) that were registered were less likely to report positive study findings compared with RCTs that were not registered and whether the association varied by funding source. <h3>Design</h3> Cross sectional study. <h3>Study sample</h3> All primary RCTs published in December 2012 and indexed in PubMed by November 2013. Trial registration was determined based on the report of a trial registration number in published RCTs or the identification of the trial in a search of trial registries. Trials were separated into prospectively and retrospectively registered studies. <h3>Main outcome measure</h3> Association between trial registration and positive study findings. <h3>Results</h3> 1122 eligible RCTs were identified, of which 593 (52.9%) were registered and 529 (47.1%) were not registered. Overall, registration was marginally associated with positive study findings (adjusted risk ratio 0.87, 95% confidence interval 0.78 to 0.98), even with stratification as prospectively and retrospectively registered trials (0.87, 0.74 to 1.03 and 0.88, 0.78 to 1.00, respectively). The interaction term between overall registration and funding source was marginally statistically significant and relative risk estimates were imprecise (0.75, 0.63 to 0.89 for non-industry funded and 1.03, 0.79 to 1.36 for industry funded, P interaction=0.046). Furthermore, a statistically significant interaction was not maintained in sensitivity analyses. Within each stratum of funding source, relative risk estimates were also imprecise for the association between positive study findings and prospective and retrospective registration. <h3>Conclusion</h3> Among published RCTs, there was little evidence of a difference in positive study findings between registered and non-registered clinical trials, even with stratification by timing of registration. Relative risk estimates were imprecise in subgroups of non-industry and industry funded trials.
Disproportionate representation of unexpected cancer origins in CUP population evident through microRNA profiling.
Authors: Mats Olot Sanden, Eran Goren, Alexis Smith, Robert Wassman
Journal: Journal of Clinical Oncology (2014)

e22102 Background: MicroRNA profiling of tumors can accurately identify the cancer of origin in CUP patients. The distribution of cancers observed in CUP patients and can aid overall understanding of this clinical dilemma. Methods: MicroRNA analysis using a previously described method was performed on 435 consecutive real-world clinical specimens referred for identification of cancer origin. Frequencies of diagnoses were compared to published, gender specific rates of these tumors. Results: Sufficient tumor material and successful analysis was possible in 336 cases with a mean TAT of 7 days. The age was 63 years with 54% female and 46% male. Pancreatic/Biliary/Cholangiocarcinoma (P/B/C) (17.2%) was the most common diagnosis, followed by colorectal (14.2%), breast (8.7%), upper body squamous cell (7.9%), and mesothelioma (7.3%). A significant proportion of breast cancers were in males (3.5% of total). Compared to published rates, some significant differences were observed. P/B/C is highly over-represented in the CUP population comprising 17%, compared to an expected 3.6%. Male breast cancer is expected in 0.26% versus the observed rate of 3.5%. Female breast cancer (5.2%) is low compared to breast cancer overall, however prior diagnostic work-up generally restricted our cases to triple-negative cases (TNBC) which comprise only 3-6% of female cancers. Similarly, the observed rate of mesothelioma is much higher in the CUP population (7.3% versus 0.21%), and the gender ratio is shifted from the published 4:1 Male: Female to 2:1 in our series. Finally, the observation of exceedingly rare cancers in a small (16 cases) series (Islet cell, Pheochromocytoma, GIST, Thymomas, Germ cell, and NET) is striking. Conclusions: Failure to consider rarer tumor types and gender presentations, hard to localize primaries, and tendency toward poorly differentiated histology may contribute to being called CUP. Cancer frequencies in CUP is distorted from the expected rates in the population, and may give insight into factors leading to failure to diagnose a specific cancer type in CUP. The failure to think of an unlikely diagnosis can be overcome through the use of this profiling and result in better treatment choices.
UTILIDAD DEL PATRON DE CRIPTAS PARA IDENTIFICAR DISPLASIA EN UN PROGRAMA DE SCREENING CON CROMOENDOSCOPIA EN LA EII
Authors: N Fernández Fernández, F Muñoz Nuñez, M Garcia Alvarado, M Sierra Ausín, P Suárez Álvarez, D João Matias, MJ Fernández Gundín
Journal: Endoscopy (2015)

Introducción: La cromoendoscopia detecta más lesiones que las biopsias a ciegas en los programas de cribado de cáncer de colon en EII.
Proportion of BRCA mutation frequency in young black women with breast cancer.
Authors: Tuya Pal, Devon Bonner, Deborah Cragun, Sharland Johnson, Mohammad R Akbari, Lily Servais, Steven Narod, Susan Thomas Vadaparampil
Journal: Journal of Clinical Oncology (2014)

1506 Background: Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. Prior studies suggest BRCA mutations account for ~5% of breast cancers in young breast cancer survivors. We evaluated the prevalence of BRCA mutations and variants detected through full gene sequencing and large rearrangement testing in a population-based sample of young Black women with breast cancer. Methods: Black women diagnosed with invasive breast cancer < age 50 between the years 2009-2012 were recruited through the Florida Cancer Registry. Participants completed genetic counseling, a study questionnaire, and consent for medical record release. Saliva specimens were collected for BRCA sequencing and large rearrangement testing through MLPA. Data analysis included frequencies and Pearson Chi-square tests. Results: Of 283 participants, 28 (9.9%) had BRCA mutations (including 26 through sequencing and 2 through MLPA) and 93 (32.9%) had detection of one or more variant of unknown significance (VUS). Of 28 carriers, 18 (64.3%) had a BRCA1 mutation and 10 (35.7%) had a BRCA2 mutation. Among all participants, 94 (33%) were clinically tested prior to enrollment; those with prior clinical testing were more likely to have insurance at diagnosis than those not tested previously (p<0.001). Compared to those without an identified mutation, those with a BRCA mutation were significantly more likely to have: 1) triple negative (TN) cancer (20% vs. 48%); 2) a >10% prior probability of having a mutation based on the Myriad Prevalence Table (31% vs. 54%); and 3) previous genetic testing (31% vs. 50%) (all p<0.05). Conclusions: Our findings suggest that a higher than expected BRCA mutation frequency may partially account for the disproportionately higher incidence of breast cancer observed in young Black women. Furthermore, the high VUS rate is partly attributed to the disparity in BRCA testing in Blacks. Thus our results further highlight the importance to increase awareness and access to genetic testing services in Blacks, to help address the growing health disparities in clinical cancer genetics.
Cancer stem cells with increased metastatic potential as a therapeutic target for esophageal cancer
Authors: D. Wang, J.Th.M. Plukker, R.P. Coppes
Journal: Seminars in Cancer Biology (2017)

Esophageal cancers (EC) are highly aggressive tumors, commonly presented in a locally advanced stage with a poor prognosis and survival. Up to 50% of the patients are eligible for treatment with curative intent and receive the standard treatment with neoadjuvant chemoradiotherapy (nCRT) and surgery. Currently, pathologic complete response to nCRT is 20–30%, with a partial or no response in about 50% and 20%, respectively. EC recurrences occur frequently even after successful anti-cancer treatment, suggesting high aggressiveness with increased metastatic potential. A tumor sub-population of so-called cancer stem cells (CSCs), is known to display a high metastatic potential and resistance to conventional anti-cancer therapy, hereby being responsible for the unbeneficial clinical features. In this review, a concise overview will be given of the current literature on esophageal CSCs and related metastases. Esophageal CSC markers will be discussed followed by the pathways that initiate and sustain these cells. In addition, the cellular processes, epithelial-mesenchymal transition (EMT), hypoxia and autophagy, known to contribute to cancer stemness and metastasis will be explained. Finally, potential options for treatment also related to cancer genome atlas (TCGA) data on EC will be discussed.
Demographic, clinical, and outcomes characteristics associated with screening colonoscopy in colorectal cancer patients.
Authors: Samantha Ann Armstrong, Safi Shahda, Amikar Sehdev
Journal: Journal of Clinical Oncology (2017)

554 Background: Screening colonoscopy has well established role in CRC prevention. Factors associated with underutilization of screening colonoscopy, and how underutilization affects the CRC outcomes is unclear. We conducted a retrospective study with an aim to identify demographic, clinical and outcome characteristics associated with screening colonoscopy in patients with CRC. Methods: The Indiana Network for Patient Care (INPC) was used to identify patients diagnosed with CRC between 2001-2015. The INPC is the largest and longest tenured clinical data warehouse of the Indiana Health Information Exchange in the USA. Patient demographic (age, race, gender, median household income, insurance type, geographical location), clinical (BMI, year of diagnosis, stage, tumor location, CEA, surgery, chemotherapy, comorbidity) and outcome characteristics were obtained. Only patients who had colonoscopy prior to diagnosis were included, and divided those who received screening colonoscopy versus diagnostic colonoscopy. Chi-square was used for univariate analysis. Multivariate logistic regression was used to model the association of colonoscopy with overall mortality, and CRC-specific mortality. Results: A total of 1546 patients were identified, of which 361 (23.3%) and 1185 (76.6%) had screening and diagnostic colonoscopy, respectively. On univariate analyses, older age, female gender, Caucasian race, lower BMI and lack of insurance, were significantly associated with screening colonoscopy (P &lt; 0.05). Additionally, patients receiving screening colonoscopy had higher likelihood to undergo surgery and receive chemotherapy (P &lt; 0.05). Multivariate analyses adjusted for age, gender, race, surgery, chemotherapy and insurance status showed that screening colonoscopy (as compared with diagnostic colonoscopy) is associated with a 38% lower odds of overall mortality (adjusted OR = 0.62, 95% CI, 0.46-0.83, p &lt; 0.001), and 68% lower odds of CRC-specific mortality (adjusted OR = 0.32, 95% CI, 0.19-0.51, p &lt; 0.001). Conclusions: Screening colonoscopy is associated with decreased odds of overall and CRC-specific mortality and individuals with older age are more likely to receive it.
A functional procedure using fresh samples to select patients with acute myeloid leukemia prior to treatment with the novel targeted cytotoxic agent F14512
Authors: J. Barret, C. Dumontet, J. Annereau, V. Brel, F. Breillout, Y. Guminski, T. Imbert, N. Guilbaud, C. Bailly
Journal: Journal of Clinical Oncology (2009)

11087 Background: The Polyamine Transport System (PTS) is an energy-dependent machinery generally hyper-active in cancer cells with a high demand for polyamines. This system can be viewed as a suitable molecular gate to deliver selectively polyamine-based molecules into cancer cells. We exploited this strategy to target to PTS-positive cancer cells, F14512 , a novel polyamine-epipodophyllotoxin conjugate, that exhibits significant anti-tumor activity and has been selected for further clinical development. This study was undertaken to investigate the potential of N-methyl-spermine-NBD, a proprietary fluorescent polyamine conjugate, designed to select patients with PTS-positive leukemic cells. Methods: The uptake of this probe was first measured by flow cytometry in a panel of human leukemia cell lines. The procedure was then adapted and optimized to measure N-methyl-spermine-NBD fluorescence in blood samples from healthy donors. After the selection of the optimal CD gating, median value of fluorescence of our probe was measured by flow cytometry in lymphocytes and blastes of each patient. Results: Data showed that high level of fluorescence was detected in F14512 -sensitive cancer cell lines whereas leukemia cells responding poorly to F14512 generally exhibited very low levels of PTS. We then demonstrated that human leukocytes incorporate N-methyl-spermine-NBD in a time, concentration and temperature dependent manner, confirming the active transport of polyamines in these cells. The incorporation in lymphocytes was found low and with a weak inter-individual variation. A panel of 50 fresh human acute myeloid leukemia samples showed a larger inter-individual variation and, interestingly, incorporation of the fluorescent probe was generally higher in leukemia blasts than in lymphocytes. Median values of fluorescence intensity were similar in blood and bone marrow samples, suggesting that these two sources might be used for this analysis. Conclusions: The data show that the PTS can easily be evaluated in fresh AML blasts and provides a simple means to identify patients for future enrollment in clinical trials with F14512. [Table: see text]
Treatment failure in endometrial cancer.
Authors: Yun-hsin Tang, Angel Chao, Chyong-Huey Lai, Cheng-Tao Lin, Gingin Lin, Feng-yuan Liu
Journal: Journal of Clinical Oncology (2013)

e16537 Background: To evaluate the clinical features and the outcomes of endometrial cancer with treatment failure after primary definitive surgery. Methods: A total of 89 patients who received primary definitive surgery between 2000 and 2010 with treatment failure were retrospectively reviewed. The correlation of clinicopathological features, primary treatment, failure pattern, and salvage treatment with outcomes were analyzed. Results: Twenty of the 89 patients with persistent or progressive diseases died at a median of 7.6 months (range, 1.9-14.0 months). The remaining 69 patients with initial disease controlled but subsequent relapse had a median time to recurrence of 13.9 months (range, 3.2 – 97.1). Assessable failure patterns included vaginal only in 14.5%, pelvic in 2.9%, distant in 59.4%, distant and loco-regional in 23.2%. The median survival after recurrence (SAR) was 25.5 months (range 1.5-121.7 months). The 5-year SAR rate was 52.7%. By univariate analysis, FIGO stage, grade of differentiation, histologic cell type, cervical invasion, adnexal metastasis, and status of lymph node metastasis when initial diagnosis, and bone or/and lung metastasis, radiotherapy after recurrence, and CA-125 ≥ 35 U/mL at recurrence were significant factors of 5-year survival after recurrence. By multivariate analysis, high-grade cancer (HR 3.05, 1.17-8.01; p = 0.023), bone and/or lung metastasis at recurrence (HR2.81, 1.15-6.85; p = 0.023), and CA-125 ≥ 35 U/mL (HR 2.85, 1.18-6.87; p = 0.013) were significantly poor prognostic factors for SAR. Six patients achieved long-term survival with more than one recurrence after aggressive multimodal salvage therapy along with deliberate restaging and post-therapy surveillance. Conclusions: High-grade, bone and/or lung metastasis and CA-125 ≥ 35 U/mL at recurrence were significantly poor prognostic factors for SAR. After intensive treatment, patients with recurrent endometrial cancer may have long-term survival.
Polymorphisms in adipokine-related genes to predict treatment outcomes in patients (pts) with metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy.
Authors: Yuji Miyamoto, Sebastian Stintzing, Wu Zhang, Shu Cao, Yan Ning, Satoshi Okazaki, Martin D. Berger, Mitsukuni Suenaga, Marta Schirripa, Shivani Soni, Satoshi Matsusaka, Dongyun Yang, Roel Gopez, Diana L. Hanna, Afsaneh Barzi, Hideo Baba, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2017)

600 Background: The molecular effects of obesity are mediated by alterations in the levels of adipokines, which are produced mainly by adipose tissue. Adipokines have multiple effects, including insulin sensitivity, cell proliferation, inflammation, and angiogenesis. We previously reported that single-nucleotide polymorphisms (SNPs) in obesity-related genes were associated with the recurrence probability of CRC treated with 5-FU based adjuvant chemotherapy. This study aimed to evaluate whether SNPs in adipokine-related genes may predict clinical outcomes in bevacizumab treated mCRC pts. Methods: Genomic DNA was obtained from mCRC pts receiving bevacizumab plus FOLFIRI as first-line treatment and analyzed by using PCR-based direct sequencing. Eleven functional SNPs in 7 genes ( LEP, LEPR, ADIPOQ, ADIPOR1, RETN, TNFa and NAMPT) were tested in 291 pts in FIRE3 trial bevacizumab cohort (NCT00433927). Main characteristics were the following: male/female = 193/98; median age = 65; High BMI pts (BMI ≥ 25 Kg/m 2 )/low BMI pts (BMI &lt; 25 Kg/m 2 ) = 162/129; median PFS = 10.1 months; median OS = 24.2 months, median follow-up time = 40.8 months. Results: LEPR rs1137100 G/G variants (n = 24) showed worse PFS than any A variants (n = 246) in univariate (10.4 months (M) vs. 9.2 M, HR = 1.75, 95%CI = 1.12-2.74, P = 0.011) and multivariate analyses (HR = 1.75, 95%CI = 1.11-2.74, P = 0.016). NAMPT rs61330082 T/T (n = 24) showed worse PFS than any C variants (n = 243) in multivariate analysis (HR = 1.65, 95% = 1.02-2.67, P = 0.042). RETN rs1862513 C/C (n = 23) showed worse OS than any G variants (n = 246) in univariate analysis (14.1 m vs. 25.1 M, HR = 1.65, 95%CI = 1.04-2.60, P = 0.029). In subgroup analyses of high BMI pts, the prognostic effect of LEPR rs1137100 G/G and RETN rs1862513 C/C was confirmed and no association was observed among low BMI pts. Conclusions: Our study showed for the first time that genetic variations in adipokine-related genes are associated with prognosis of mCRC pts treated with bevacizumab based chemotherapy.
Risk factors predicting recurrence patterns and prognosis in gastric cancer patients after curative gastrectomy and adjuvant chemotherapy.
Authors: Chun-Xia Du, Ai-Ping Zhou, Quan Xu, Yu-Xin Zhong
Journal: Journal of Clinical Oncology (2015)

e15105 Background: To explore the risk factors associated with recurrence patterns and prognosis in gastric cancer patients who underwent curative gastrectomy and adjuvant chemotherapy in China. Methods: 293 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or a subtotal gastrectomy with at least D1 lymph nodes dissection between Jan, 2006 and Dec, 2011, followed by 1 to 12 cycles of adjuvant chemotherapy. Clinicopathologic characteristics and cancer-relevant treatments were selected as risk factors. Lymph node ratio (LNR) was defined as the number of metastatic LNs divided by the total number of excised LNs, and divided into four category: 0%, 1-30%, 31-60%, > 60%. Results: On multivariable analyses, LNR (p < 0.001)and perineural invasion (PNI)(p = 0.001)were independently correlated with overall survival (OS). Factors including primary site(p = 0.005),LNR(p < 0.001),PNI(p = 0.003),and vascular/lymphatic invasion (p = 0.041)were independently correlated with disease-free survival (DFS). Higher LNR ( > 60%) was shown to be strongly correlated with locoregional lymph node metastases (LNMs) (p = 0.006). Risk factors associated with peritoneal plantation included young age ( < 50 years) (p = 0.017), positive vascular/ lymphatic vessels invasion (p = 0.048), higher LNR (p = 0.024) and positive PNI ( < 0.001). More than 6 cycles of adjuvant chemotherapy reduced the risk of distant LNMs (p = 0.037), and displayed a tendency to reduce haematogenous metastases. Conclusions: LNR and PNI were both independent risk factors for DFS and OS in gastric patients after radical surgery and adjuvant chemotherapy, and were useful to predict recurrence patterns.
Patterns of cancer-related health information seeking and receipt among Hispanic and non-Hispanic childhood cancer survivors.
Authors: Kimberly A Miller, Cynthia N Ramirez, Katherine Wojcik, Anamara Ritt-Olson, Lourdes Baezconde-Garbanati, Stefanie Marie Thomas, David Robert Freyer, Ann S. Hamilton, Joel Milam
Journal: Journal of Clinical Oncology (2017)

197 Background: Because childhood cancer survivors (CCS) report a high number of unmet cancer-related information needs, knowing where CCS access information may provide insights into appropriate delivery systems to address information deficits. Active seeking of health information among CCS is associated with positive health behaviors, including adherence to follow-up care. This study examined patterns of cancer-related health information seeking as an indicator of health care engagement. Methods: Participants (N = 193) were young adult CCS diagnosed with any cancer type in Los Angeles County, 54% Hispanic, with a mean age of 19.87, and at least two years from treatment. CCS were asked where they accessed health information related to their cancer with 8 response options which were categorized into four information domains: hospital resources, social media, other survivors, and family members. Multivariable logistic regression was used to assess correlates of each information domain, including sociodemographic information, post-traumatic growth, and health care engagement, controlling for age, ethnicity, sex, education, and health insurance status. Results: Hospital resources were the most frequently endorsed information domain (65.3%), and Hispanic CCS (vs. non-Hispanic) were more likely to access this source. Online sources were more likely accessed by female CCS. Seeking information from other cancer survivors was associated with follow-up care and post-traumatic growth after cancer. Hispanic CCS were less likely to seek information from other survivors and their family than non-Hispanics. Conclusions: While CCS obtain information from a variety of sources, hospital resources were the most commonly accessed, particularly for Hispanics. Information sharing between survivors may promote positive health care engagement; however, Hispanics may be less likely to pursue this resource. Future work should address barriers Hispanic CCS face in information sharing with other cancer survivors. [Table: see text]