tbuckley/cabot-search huggingface dataset:
The positive predictive value of PI-RADS 4 lesions stratified by lesion number in biopsy naïve men.
Authors: Jamil Syed, Juan Javier-desloges, Kevin Nguyen, Alison Sheridan, Angelique Levi, Jeffrey Weinreb, Preston Sprenkle
Journal: Journal of Clinical Oncology (2017)

29 Background: To assess the positive predictive value (PPV) of PI-RADS 4 lesions stratified by suspicion for tumor multi-focality. Methods: Between April 2015 and July 2016, 62 biopsy naïve men with at least one PI-RADS 4 lesion underwent mpMRI/US fusion biopsy. Patients were placed into group 1 if they had a single lesion, group 2 if they had an additional PI-RADS 3 or 2 lesion, and group 3 if they had an additional PI-RADS 4 or 5 lesion. Image interpretation was performed prospectively and assessed using PI-RADS version 2. The ANOVA and chi-square tests were used to assess differences between continuous and categorical variables, respectively. Results: Using systematic and targeted biopsy combined, the overall and GS ≥ 7 cancer detection rate for the entire cohort was 80.6% (50/62), and 53.2% (33/62), respectively. There were a total of 88 lesions with 26,14, and 48 lesions in groups 1,2, and 3, respectively. There were no significant differences in mean age, PSA density, race, or lesion location between groups; p = 0.107, p = 0.694, p = 0.511, and p = 0.558, respectively. The PPV for any prostate cancer was 65.4% (17/26), 100% (14/14), and 90% (43/48) for groups 1,2, and 3 respectively (p = 0.005). The PPV for GS ≥ 7 was 42% (11/26), 50% (7/14), and 75% (36/48) for groups 1,2, and 3, respectively (p = 0.001). Conclusions: Our data indicate that the PPV for a PI-RADS category assessment score of 4 may be influenced by tumor multi-focality on imaging. Further assessment with increased sample size will be useful to confirm our initial results.
Prognostic factors of overall survival of stage III or IV adrenocortical carcinomas (ACC): A multicenter ENS@T study.
Authors: Rossella Libe, Isabelle Borget, Cristina Lucia Ronchi, Arianna Ardito, Matthias Kroiss, Jerome Bertherat, Marcus Quinkler, Margarita Bala, Felix Beuschlein, Delphine Vezzosi, Harm Haak, Sophie Leboulleux, Barbara Zaggia, Martin Fassnacht, Eric Baudin
Journal: Journal of Clinical Oncology (2014)

4106 Background: Several reports suggest heterogeneity of advanced ACC.The primary objectives of our study were to provide evidence for an improved staging and grading system and refine the prognostic classification of stage III-IV ACC. Methods: 444 patients registered with the ENS@T ACC database (diagnosed 2000-2009) were enrolled (210 stage III; 234 stage IV). Inclusion criteria were: age>18 yrs, pathological review, synchronous stage III-IV, follow-up available. Primary endpoint was overall survival. Parameters captured were: age, modality of diagnosis, TNM, pathological grading (Weiss score,Ki 67%), R status at first surgery. Univariate and multivariate analyses were performed according two models. Model 1 “prior surgery”; model 2
A phase 1 mechanism of action study of intratumoral or intravenous administration of enadenotucirev, an oncolytic Ad11/Ad3 chimeric group B adenovirus in colon cancer patients undergoing resection of primary tumor.
Authors: Rocio Garcia-Carbonero, Marta Gil-Martin, Emiliano Calvo, Susana Prados, Fernando De la Portilla, Ramon Salazar, Cristina Santos, Amparo Sanchez-Gastaldo, Hipolito Duran, Xavier Sanjuan, Juan M. Bozada, Valentina Boni, Monica Jurado, Christopher Ellis, Simon Alvis, John William Beadle, Kerry Fisher, Christine Blanc, Antonio Cubillo
Journal: Journal of Clinical Oncology (2014)

TPS3112 Background: To date convincing clinical success with oncolytic viruses tends to be associated with intra-tumoral (IT) administration and evidence for successful systemic delivery of viruses to tumor cells by intravenous (IV) infusion remains sparse. Enadenotucirev (E or ColoAd1) is a tumor selective Ad11/Ad3 group B adenovirus that has demonstrated preclinical activity in a metastatic model of colorectal cancer (CRC) and in human tumor biopsies ex-vivo [Kuhn et al, PLoS ONE 2008; 3 (6):e2409]. Serological studies suggest that the prevalence of neutralising antibodies against group B adenoviruses is low, which may permit systemic delivery [Holterman et al, J Virol. 2004 Dec; 78(23):13207-15]. CRC patients (Pts) scheduled for resection of primary tumor present a pre-surgical window of opportunity to evaluate IV and IT delivery to tumor, lymph nodes and normal margins in resected tissues. Methods: Pts with histologically confirmed CRC scheduled for surgical removal of primary tumor receive E delivered either IV on day (D) 1, 3 and 5 at a dose of 1e12 viral particles (vp) over 5 min (5 pts); or IT at a dose of 1e11 vp/mL with a variable volume injected based on the tumor surface area (5 pts). Surgery is performed 7 – 15 days post first dose of E. The primary objective is to assess the pattern and extent of E spread in the tumor, normal tissue and draining lymph nodes as visualised by IHC staining of E hexon protein. Evidence of immune modulation associated with virus activity is assessed by co-staining for markers including CD8, CD11b, CD57 and CD25. Additional staining includes the primary uptake receptors of E (CD46, DSG-2) and markers of endothelial cells (CD31) and myofibroablasts (SMA) that may influence viral delivery or spread. Additional analyses include electron microscopy and qPCR. Other objectives are assessment of safety, viral kinetics and immune response following IV and IT administration. Correlation with routine tumor biomarkers e.g. K-ras, BRAF, PI3K, PTEN, SPARC will also be evaluated. To date 3 pts have been treated, 1 IT and 2 IV, and 3 pts are scheduled for treatment. Clinical trial information: EUDRACT 2013-000562-11.
Evaluation of a web-based cognitive rehabilitation programme (CRP) in cancer survivors reporting cognitive symptoms following chemotherapy.
Authors: Victoria J Bray, Haryana M. Dhillon, Melanie Bell, Michael Kabourakis, Holly Rice, Desmond Yip, Frances M. Boyle, Melanie Price, Janette L. Vardy
Journal: Journal of Clinical Oncology (2015)

9510 Background: Self-reported cognitive impairment is frequently seen in cancer survivors. We evaluated a CRP in cancer patients with cognitive symptoms. Methods: 243 adult cancer patients who had completed adjuvant chemotherapy within 6-60 months and reported changes in memory and/or concentration on EORTC-QLQ-CF, received a 30 minute phone consultation and were randomized to a 15-week, home-based CRP (Insight) or usual care (UC). Primary endpoint was self-reported cognitive function (FACT-COG Perceived Cognitive Impairment [PCI] subscale). Secondary endpoints included: neuropsychological (NP) testing (CogState), quality of life (QOL) and fatigue (FACT-F), anxiety/depression (GHQ), and stress (PSS). Primary analysis used linear mixed models comparing the difference in FACT-COG PCI between the 2 arms at each post baseline timepoint: post intervention (T2) and 6 months later (T3). Results: A total of 243 patients were randomized: median age 53 (range 23-74); 95% female; 89% breast cancer, 5% colorectal cancer. There were no significant differences between the groups at baseline. The CRP group had improvement in all FACT-COG domains including PCI at T2, which were sustained at T3. Individual NP test results were not significantly different at T2 or T3. Anxiety/depression was improved at T2 and T3, and stress at T3, in the CRP group. There were no differences between the groups in fatigue or QOL (global or in domains) at any timepoint. Conclusions: The web-based CRP Insight led to improvements in cognitive symptoms that were sustained at 6 months compared to phone consultation alone. Clinical trial information: ACTRN12609000683235. CRP (n=122) UC (n=121) p-value FACT-COG: PCI T2 23.8 33.6 <.0001 T3 23.5 32.6 <.0001 Impact on QOL T2 4.5 5.8 0.0241 T3 4.4 5.7 0.0385 Perceived cognitive abilities T2 17.1 14.0 <.0001 T3 16.8 14.2 0.0010 Comments from others T2 1.5 2.4 0.0010 T3 1.8 2.3 0.0578 GHQ: T2 22.5 24.4 0.0222 T3 23.1 24.7 0.0638 FACT-G: T2 82.5 81.2 0.5096 T3 82.9 79.8 0.1131 FACT-F subscale: T2 36.9 35.3 0.2809 T3 37.2 35.9 0.3687 PSS: T2 22.5 23.5 0.1332 T3 22.3 23.9 0.0246
Testosterone replacement for fatigue in male hypogonadic patients with advanced cancer: A preliminary double-blind placebo-controlled trial.
Authors: Kalyan Pulivarthi, Rony Dev, Jose Garcia, J. Lynn Palmer, Eduardo Bruera, Egidio Del Fabbro
Journal: Journal of Clinical Oncology (2012)

e19643 Background: Hypogonadism affects two thirds of men with advanced cancer. Uncontrolled studies show fatigue, anorexia, depression,and insomnia are associated with low testosterone in men with cancer. Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions. The primary goal of this study was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer, by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)at day 29. Methods: Randomized, double-blinded placebo controlled at two centers. Clinic outpatients with advanced cancer, bioavailable testosterone (BT) &lt;70ng/dL, hemoglobin&gt;9g/dL, and moderate to severe fatigue assessed by a score &gt;3/10 on the Edmonton Symptom Assessment Scale (ESAS) were eligible.Contraindications to testosterone therapy or other causes of fatigue such as hypothyroidism, hypercalcemia, or chronic kidney disease excluded subjects. Weight-based intra-muscular testosterone or a sesame seed oil placebo administered every 14 days to achieve a BT level 70-270ng/dL. Initial sample size was for fifty evaluable patients per group. One-sided t test was used to analyze differences in FACIT scores between arms. Results: Accrual was slower than anticipated with a final total of 43 eligible males randomized to testosterone(19) or placebo(24). Neither age nor site was statistically significant (&lt;0.05) between arms. 14 placebo and 12 testosterone treated patients were evaluable for the primary outcome.No statistically significant difference was found for FACIT-F total scores between arms, with a trend for testosterone to improve scores (-5.5±19 for placebo, 3.9±14 for testosterone, p=0.09) using a one-sided t test. Adverse events were similar between groups. There were no significant differences in secondary outcomes of ESAS scores, Hospital Anxiety and Depression Scale, hand-grip or 6 minute walk. Conclusions: Testosterone replacement in hypogonadal male patients with advanced cancer had a trend to improve fatigue and quality of life in this preliminary trial.
Evolutionary explanations for financial and prosocial biases: Beyond mating motivation
Authors: Anthony C Little
Journal: Behavioral and Brain Sciences (2017)

Abstract Mating motivation likely plays a role in bias to attractive individuals, but there are other complementary theories drawn from the evolutionary literature related to competition, friendship, and leadership selection that also make relevant predictions concerning biases towards attractive individuals. The relative balance of these factors will be context dependent and so help explain why the pattern of bias is sometimes variable.
Prognosis value of hormonal and HER2 receptors on overall survival (OS) and disease-free interval (DFI) in metastatic breast cancer (MBC)
Authors: L. Francis, T. Olivier, P. Frédérique, A. Catherine, M. Marie-Ange, R. Ines, D. Xavier, G. Pierre, C. Hervé, C. Philippe
Journal: Journal of Clinical Oncology (2007)

1077 Background: In MBC, positive HR constitute a favourable prognostic factor and predict response to an hormonal therapy. Conversely HER-2 overexpression is an adverse prognostic factor associated with a more aggressive tumor. In this retrospective study we analysed overall survival (OS) and disease-free interval (DFI) of three phenotypes: HR-/HER-2- (triple negative); HR+/HER-2- (luminal) and HER-2 overexpression (HER-2+). Methods: We evaluated 511 patients with a MBC treated at Centre Jean Perrin from 1973 to 2006. A comparative lecture of oestrogenic, progestative and HER-2 receptors was performed by IHC. At present, HR and HER-2 status were re-evaluated on 166 initial tumor sample of this data base by two pathologists (study currently ongoing). Median age of patients was 54.8 years. 120 (23.6%) patients were directly metastatic (M1), 391 (76.4%) relapsed distantly (M0). Metastatic patients received a median number of 2 lines of chemotherapy (range, 0–14) and/or a median number of 1 line (range, 0–8) of hormonotherapy. 92 (55.4%) patients had a luminal phenotype, 48 patients (28.9%) were HER-2+ and 26 patients (15.7%) were triple negative. Results: Among these 166 tumors, OS was significantly different between these three populations (p=0.00056). DFI variation was not signicant (p=0.083). These data showed that: - Luminal phenotype had the better OS (median survival of 36.5 months) and DFI (51.09 months) - HER-2+ phenotype (33 of 48 patients were treated with trastuzumab from 1999) had an intermediate prognostic on OS (median survival of 31.1 months) and DFI (42.2 months) - Triple negative phenotype had a poor prognostic on OS (median survival of 12.8 months) and the worse DFI (32.64 months) Conclusions: In metastatic breast cancer, luminal phenotype patients had the best OS; HER-2+ phenotype (treated by herceptin) had an intermediate OS, and triple negative phenotype had the worse OS. No significant financial relationships to disclose.
Vinorelbine plus cisplatin versus gefitinib in resected non-small cell lung cancer haboring activating EGFR mutation (WJOG6410L).
Authors: Hirohito Tada, Koji Takeda, Kazuhiko Nakagawa, Isamu Okamoto, Tetsuya Mitsudomi, Yukito Ichinose, Kenji Sugio, Masahiro Tsuboi, Yoichi Nakanishi
Journal: Journal of Clinical Oncology (2012)

TPS7110 Background: Vinorelbine plus cisplatin after completely resected stage II-III non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors (TKIs). Three randomized trials demonstrated that gefitinib is superior to platinum based chemotherapy in progression free survival. Retrospective analysis of adjuvant TKIs therapy for patient with resected lung cancer harboring EGFR mutation showed favorable trend toward improvement in disease free survival (DFS) and overall survival (OS). (J Thorac Oncol. 2011;6: 569–575) BR19 comparing adjuvant gefitinib vs. placebo for completely resected NSCLC without any selection of biomarker was closed early and did not show any benefit of adjuvant gefitinib, even in the EGFR mutation positive cohort. The randomized trial in adjuvant therapy with erlotinib vs. placebo for patients with overexpression of EGFR protein has complete enrolment already. We conduct the first randomized phase III trial comparing adjuvant gefitinib with chemotherapy in patients with completely resected stage II-III NSCLC harboring EGFR mutations. Methods: Patients who have undergone complete resection and have EGFR mutation, deletions in exon 19, or L858R point mutation at exon 21 and without T790M mutation are randomly assigned gefitinib 250mg a day for 2 years or vinorelbine 25mg/m 2 days 1 and 8, plus cisplatin 80mg/m 2 day 1, every 3 weeks for 4 courses. The primary endpoint is DFS and secondary endpoints are OS and safety. On the basis of previous studies, we assume the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS, 230 patients in total would be needed during 3-year accrual period. This trial has begun from September 12 among 22 institutes in Japan. Until now (January 31. 2012), 13 cases have been enrolled. Five cases were enrolled in latest 1 month.
Intra-individual genomic diversity between circulating tumor cell-free DNA (cfDNA) and tumor tissue testing in metastatic renal cell carcinoma (mRCC).
Authors: Andrew W. Hahn, David Michael Gill, Jessica Streeter, Erin B. Bailey, Emma Carroll, Lubina Aryal, Julia A. Batten, Sumati Gupta, Neeraj Agarwal, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2017)

444 Background: Multiple approved targeted therapies are available for treatment of mRCC. Though some clinical trials guide treatment selection, there are many gaps without high-level evidence. Both tumor tissue and cfDNA based next-generation sequencing (NGS) testing are frequently performed to help guide treatment. Our objective was to assess type and number of genomic aberrations among tumor tissue and cfDNA. Methods: 14 sequential pts with both tissue and cfDNA NGS testing were selected and genomic profiles were compared. The total number of aberrations detected was statistically evaluated using comparison of the means. The Mann-Whitney test was used to compare the incidence of mutations in identified mutation pathways. Results: There was a discordance in the genetic aberrations detected among tumor versus cfDNA NGS tests, confirming intra-individual genetic diversity. Specifically, alterations in the DNA repair, PI3K, and epigenetic pathways were more common in tissue based testing (Table). Additionally, the median number of mutations identified was significantly lower for cfDNA based NGS testing (median 1.5) compared to tissue based NSG testing (median 10.0) (p &lt; 0.0001). Conclusions: Discordance in the type of genomic aberrations in tissue versus cfDNA testing suggests intra-individual genetic diversity and may have implications in treatment selection when using these tests. Lower number of aberrations detected by the cfDNA testing may have occurred due to lower sensitivity of NGS by cfDNA compared to the tissue based NGS. The higher frequency of aberrations on tissue based testing suggests that tissue based testing should be used preferentially in clinical trials and practice. This data is hypothesis generating and needs further investigation in a larger cohort. [Table: see text]
A Bayesian network meta-analysis of systemic regimens for advanced pancreatic cancer.
Authors: Kelvin K. Chan, Doug Coyle, Chris Cameron, Kelly Lien, Yoo-Joung Ko
Journal: Journal of Clinical Oncology (2013)

4015 Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) in randomized control trials (RCTs). Few have been compared with each other directly in RCTs and the relative efficacy and safety among them are unclear. Methods: A systematic review was performed through MEDLINE, EMBASE, Cochrane Central Register of Contorlled Trials and ASCO meeting abstracts up to Jan 2013 to identify RCTs that included metastatic pancreatic cancer comparing the following regimens: G, G+5-flourouracil (GF), G+capecitabine (GCap), G+S1 (GS), G+cisplatin (GCis), G+oxaliplatin (GOx), G+erlotinib (GE), G+Abraxane (GA) and FOLFIRINOX. Studies were reviewed by two authors and discrepancies were resolved by consensus or by a third author. Data including overall survival (OS), progression-free survival (PFS), response rate (RR), and side-effects were extracted. A Bayesian network meta-analysis with random effects was performed using WinBUGS to compare all regimens simultaneously. Results: Twenty-two studies involving 6,252 patients were identified, with 21 RCTs involving G, 4 with GF, 3 with GCap, 2 with GS, 6 with GCis, 3 with GOx, 1 with GE, 1 with GA and 1 with FOLFIRINOX. Median OS, PFS and RR for G arms from all trials were similar, suggesting the absence of significant clinical heterogeneity among RCTs. For OS, the results of the Bayesian network meta-analysis found that the probability that FOLFIRINOX was the best regimen was 71%, while it was 19% for GS, 7% for GA and 2% for GE respectively. The OS hazard ratio (HR) for FOLFIRINOX vs. GS was 0.82 (95% credible region (CR): 0.53-1.35), the OS HR for FOLFIRINOX vs. GA was 0.77 (95% CR: 0.51-1.23), and the OS HR for FOLFIRINOX vs. GE was 0.67 (95% CR: 0.45-1.08). Similar ranking and probabilities were observed for the best regimen for PFS. Conclusions: FOLFIRINOX appeared to be the best regimen for advanced pancreatic cancer probabilistically, with a trend towards improvement in OS and PFS when compared with GS, GA, or GE by indirect comparisons. In the absence of direct pairwise comparisons of these regimens from RCTs, network meta-analysis helps synthesize evidence and inform decision making.
Impact of prior knowledge of mutation status on tumor stage in BRCA1/2 mutation carriers with newly diagnosed breast cancer.
Authors: Clinton Yam, Jill Stopfer, Amanda Brandt, Jacquelyn Powers, Jessica M. Long, Kara Noelle Maxwell, Angela R. Bradbury, Katherine L. Nathanson, Susan M. Domchek
Journal: Journal of Clinical Oncology (2015)

1562 Background: BRCA1/2 mutation carriers have an elevated lifetime risk of developing breast cancer. Knowledge of one’s BRCA1/2 mutation status may aid earlier detection of breast cancers due to increased awareness and screening with breast MRIs. Methods: Retrospective analysis of tumor characteristics of BRCA1/2 mutation carriers known to our institution who were diagnosed with breast cancer from 1/1/2009 - 12/31/2013. Results: 106 BRCA1/2 mutation carriers were diagnosed with their first breast cancer during the study period. 82 patients received care primarily at our clinical sites and were included in the study. 19.5% (16/82) were known BRCA1/2 mutation carriers prior to breast cancer diagnosis and the remaining 66 patients had genetic testing after cancer diagnosis. There were no differences in the median age at cancer diagnosis (p = 0.87) or distribution of BRCA1 vs BRCA2 mutation carriers between the 2 groups (p = 0.18). 62.5% (10/16) of known carriers were diagnosed with breast cancer following an abnormal MRI vs 0/66 of those identified as carriers only after breast cancer diagnosis (Table 1). Patients who knew their BRCA1/2 mutation status were more likely to have smaller tumors (p = 0.008) and node negative disease (p = 0.004). There were no differences in the ER, PR or Her2 statuses between the 2 groups. Conclusions: BRCA1/2 mutation carriers who have knowledge of their genetic status are more likely to have early stage disease at the time of breast cancer diagnosis, demonstrating the utility of identifying unaffected carriers who benefit from enhanced screening for early detection. Summary of findings. Known at diagnosis (n = 16) Unknown at diagnosis (n = 66) p value Years (range) Median age 40 (25 - 70) 42.5 (28 - 74) 0.87 Number (%) BRCA BRCA1 11 (68.8) 33 (50) 0.18 BRCA2 5 (31.3) 33 (50) Method of diagnosis MRI 10 (62.5) 0 <0.001 Mammogram 2 (12.5) 21 (31.8) Physical exam 2 (12.5) 45 (68.2) Prophylactic Mastectomy 2 (12.5) 0 T stage Tis/T1 15 (93.8) 34 (51.5) 0.008 T2-4 1 (6.3) 31 (47.0) Tx 0 1 (1.5) Node negative 16 (100) 42 (63.6) 0.004 Stage 0 4 (25) 3 (4.5) 0.011 I - II 12 (75) 52 (78.8) III - IV 0 11 (16.7) ER+ 8 (50) 34 (51.5) 0.91 PR+ 7 (43.8) 32 (48.5) 0.73 Her2+ 1 (6.3) 6 (9.1) 0.73
Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors
Authors: Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Journal: Nature Genetics (2017)