tbuckley/cabot-search huggingface dataset:
Computerized textural analysis of DCE-MRI to enable identification of HER2-enriched breast cancers.
Authors: Nathaniel Braman, Prateek Prasanna, Donna Plecha, Hannah L. Gilmore, Lyndsay Harris, Vinay Varadan, Anant Madabhushi
Journal: Journal of Clinical Oncology (2016)

598 Background: HER2+ breast cancer is biologically and clinically heterogeneous. PAM50 profiling of HER2+ breast cancer reliably identifies the HER2-Enriched (HER2-E) subtype as most responsive to HER2-targeted antibody therapy (trastuzumab). As this subtype is currently only identifiable using molecular profiling of breast tumor tissue, a non-invasive HER2-E identification method could reduce future patient morbidity. We present initial findings involving a new computational imaging feature (CIF) that captures the disorder among pixel level gradient directions on dynamic contrast-enhanced (DCE) MRI. We show that this CIF is able to discriminate between HER2-E and other HER2+ breast cancer subtypes on DCE-MRI. Methods: 25 baseline DCE-MRI HER2+ breast cancer cases were split into two cohorts by PAM50-confirmed subtype (10 HER2-E, 15 non-HER2-E). 13 CIFs were computed on peak contrast image within expert-annotated lesions. This feature set was narrowed down to the 8 most differentially expressed features. Pharmacokinetic (PK) parameters (Kep, Ktrans, Ve), which quantify tumor-associated permeability changes, were also computed using Toft’s model. Consensus clustering was performed using 1) CIFs and 2) PK parameters and peak intensities. Results: Results of 2-group consensus clustering are shown in Table 1. CIFs yielded two distinct clusters, corresponding to HER2-E and non-HER2-E groups, with 70% sensitivity and 60% specificity. Studies sorted to the HER2-E cluster were characterized by under-expression of entropy and over-expression of texture homogeneity features relative to those of the non-HER2-E cluster. In contrast, PK parameters and peak intensities produced poorly defined groups that were uncorrelated with HER2 subtypes. Conclusions: CIFs more accurately identified HER2-E status compared with standard PK parameters on DCE-MRI. CIF expression patterns in HER2-E tumors suggest a less disordered imaging phenotype than other HER2+ tumors. Future validation studies of the HER2-E CIF signature identified here could potentially enable non-invasive prediction of response to trastuzumab. Feature Set Cluster % HER2-E Present % Non-HER2-E Present CIF A 70 40 B 30 60 PK + Intensity A 40 20 B 60 80
A phase II prospective trial correlating progression-free survival (PFS) with CYP2D6 activity in patients with metastatic breast cancer treated with tamoxifen: ECOG-ACRIN E3108.
Authors: Vered Stearns, Anne M. O'Neill, Bryan P. Schneider, David A. Flockhart, Todd C. Skaar, Minetta C. Liu, Caroline A. Lohrisch, Matthew P. Goetz, Carlos Vallejos Sologuren, Joseph A. Sparano, Diego Villa, Paula Silverman, Puneet S. Cheema, Dennis Frederic Moore, George W. Sledge
Journal: Journal of Clinical Oncology (2016)

546 Background: Genetic variants in the CYP2D6 gene or inhibition of the enzyme result in reduced concentrations of endoxifen in tamoxifen-treated individuals. Whether CYP2D6 activity or endoxifen concentrations lead to reduced tamoxifen efficacy has been debated. Methods: We enrolled patients with locally advanced or stage IV hormone receptor-positive breast cancer who were candidates for single agent tamoxifen (any line). The primary objective was to correlate CYP2D6 activity and PFS. This required enrollment of 204 of 240 patients where CYP2D6 score could be determined, at least 10% with score of 0, followed for at least 12 weeks (cycle 3, C3), 180 PFS events using a two-sided 0.05 level log-rank test to detect an HR of 1.95 between CYP2D6 scores 0 (poor metabolizer) and 1+2 (intermediate/extensive metabolizers). A secondary objective included endoxifen concentration and PFS. We performed CYP2D6 analysis at baseline (Roche Amplichip), and determined endoxifen concentrations (Quest Diagnostics) at C3 and end of treatment. Results: From September 2010 to June 2013, 124 individuals enrolled in the study. Median age 62, 86% Caucasians, 33% Hispanic, 86% postmenopausal,10% received prior adjuvant tamoxifen. The study was suspended due to a lower than expected initial rate of score 0 in 51 patient samples. Overall 6 month PFS was 52%. CYP2D6 scores were subsequently available in 90 (73%) patients. We did not observe significant correlations across the CYP2D6 phenotypes and PFS (Table). Endoxifen concentrations were available from only 41 (33%) patient samples for a C3 PFS landmark analysis. CYP2D6 activity correlated with C3 endoxifen concentrations. The association between endoxifen concentrations and PFS could not be assessed given missing data. Conclusions: Our study did not meet its accrual goal, and we encountered several barriers obtaining adequate samples. We therefore cannot determine whether CYP2D6 activity or endoxifen concentrations predict PFS in individuals with advanced breast cancer treated with tamoxifen. Clinical trial information: NCT01124695.CYP2D6 Score N (%) 6 month PFS (%) 0-0.5* 8 (9) 43 1 22 (24) 42 1.5-2 54 (60) 54 2.5-3 6 (7) 33 *n=2 score 0, n=6 score 0.5
What drives patient outcomes in brain metastases: Number, volume, or biology?
Authors: Rupesh Kotecha, Jacob A Miller, Samuel T. Chao, Alireza Mohammad Mohammadi, Erin Sennett Murphy, John H. Suh, Gene H. Barnett, Michael A. Vogelbaum, Lilyana Angelov, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2017)

2071 Background: To delineate the prognostic importance of number of brain metastases (BM), lesion volume, and biology on overall survival. Methods: Patients treated for BM with whole-brain radiation therapy (WBRT), surgery, and/or stereotactic radiosurgery (SRS) at a single tertiary care institution from 1997-2015 were reviewed. The primary outcome was overall survival. Multivariable proportional hazards regression was used to adjust for confounding factors. Results: 3,955 patients with 16,189 BM were included in the analysis. There was a reduction in median survival with increasing number of lesions [1 lesion, 10.2 months; 2-4 lesions, 7.2 months, Hazard Ratio (HR) 1.36; 5-10 lesions, 5.6 months, HR: 1.69; &gt; 10 lesions, 5.5 months, HR: 1.57, p&lt; 0.001]. Among 1,651 patients (35%) who underwent SRS, there was a similar reduction in median survival with increasing lesion number [1 lesion, 12.2 months; 2-4 lesions, 10.1 months, HR 1.20; 5-10 lesions, 8.4 months, HR 1.41; &gt; 10 lesions, 6.9 months, HR 1.19], p&lt; 0.001). Among patients who underwent upfront SRS, increasing number of BM did not adversely affect survival in those with the smallest intracranial disease volume (≤0.4 cc, 10 th percentile, p= 0.39), but was associated with inferior survival in patients with larger disease volumes (≤1.1 cc, 25 th percentile, p= 0.05; ≤2.6 cc, 50 th percentile, p= 0.005; ≤6.3 cc, 75 th percentile, p= 0.006, and ≤12.2 cc, and 90 th percentile, p =0.004). After partitioning the cohort into molecular subsets, patients with ALK+ disease had no difference in survival based on either lesion number or volume. Patients with EGFR+, HER2+, and luminal B disease had no difference in survival based on number of metastases, while patients with BRAF V600+and luminal A disease had no difference in survival based on intracranial disease volume. Conclusions: Number of BM closely correlates with survival in the majority of patients and intracranial disease volume impacts survival independent of number of metastases. For patients with certain tumor subtypes ( ALK+), intracranial disease burden appears to have no correlation with survival. Molecular profile characterization is important to identify patients with favorable subtypes given available treatment options.
The potential of circulating tumor DNA (ctDNA) to reshape the design of clinical trials testing adjuvant therapy in patients with early stage cancers.
Authors: Jeanne Tie, Yuxuan Wang, Cristian Tomasetti, Lu Li, Simeon Springer, Isaac Kinde, Rachel Wong, Suzanne Kosmider, Ben Tran, Jayesh Desai, Theresa M. Hayes, Andrew Mark Haydon, Desmond Yip, Michael Christie, Robert Strausberg, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs
Journal: Journal of Clinical Oncology (2016)

3511 Background: The conventional approach to testing the benefit of adjuvant therapies in patients (pts) with relatively favorable prognoses is to follow a large number of pts for long periods of time, hoping that mature outcome data will document an improved outcome compared to control pts. We reasoned that the design of such trials could be improved if pts with minimal residual disease could be identified a priori through the presence of ctDNA, and the effects of adjuvant therapy then assessed through serial ctDNA assays. Methods: We carried out a prospective trial in 231 pts with Stage II colon cancer. Serial plasma samples were collected every 3 months starting 4-10 weeks after surgery. Somatic mutations in pts' tumors were identified via sequencing of 15 genes commonly mutated in colon cancer. We then designed personalized assays to quantify ctDNA in plasma samples. Adjuvant chemotherapy was administered at clinician discretion, blinded to ctDNA analysis. Results: Somatic mutations were identified in 230 (99.6%) of tumors. Matching ctDNA was detected in the immediate post-operative period in 14 of 178 (8%) pts not treated with chemotherapy, 11 of whom had recurred (79%) at a median follow-up of 27 months. In contrast, recurrence occurred in only 16 (10%) of the 164 pts with negative ctDNA not treated with chemotherapy (HR 15.66, log-rank P<0.0001). ctDNA was detected in the immediate post-operative period in 6 of 52 pts who went on to receive chemotherapy. The ctDNA status turned from positive to negative during adjuvant treatment phase in all 6 pts (100%) but became positive again following completion of chemotherapy in 2 pts, both of whom have recurred. In patients with serial samples available, the median lead-time between ctDNA detection and radiologic-recurrence was 167 days. Conclusions: Detection of ctDNA in pts with resected stage II colon cancer provides direct evidence of residual disease. As well as defining pts at very high risk of later radiologic-recurrence, serial ctDNA analysis may provide an early readout of adjuvant treatment effect. Including ctDNA analyses would increase the efficiency of clinical trials testing the benefit of adjuvant treatment. Clinical trial information: ACTRN12612000326897.
当院におけるFilter device(Filtrap)の使用経験および有効性の検討
Authors: 小椋裕司, 永田武士, 山口宗孝, 千年忠佑, 小山洋史, 名幸久仁, 仲村佳典, 山下卓郎, 山田賢裕, 下村英紀
Journal: Circulation (2008)
Bevacizumab (Bev) to reduce the negative impact of glioblastoma (GBM) tumor size on survival from first recurrence.
Authors: Huy Tram N. Nguyen, Liang Yen Liu, Nhung T Nguyen, Daniel Lenchner, Laura Dovek, Robert J. Harris, Benjamin M. Ellingson, Byram H Ozer, Arliene Ravelo, Nicolas Sommer, Myung Shin Sim, Robert M. Elashoff, Richard M. Green, Phioanh Leia Nghiemphu, Timothy Francis Cloughesy, Albert Lai
Journal: Journal of Clinical Oncology (2017)

2052 Background: Bev was FDA approved for recurrent GBM in 2009. However, the survival benefit from Bev in GBM remains to be demonstrated. Methods: We retrospectively identified 168 primary GBM patients diagnosed between 2001-2015 at UCLA and Kaiser Permanente LA, who received upfront radio-chemotherapy, followed with Bev and/or Lomustine (CCNU) at 1st recurrence. We measured tumor size at 1st recurrent treatment initiation, using bi-dimensional (2D) and volumetric (3D) techniques. We analyzed overall survival (OS) from 1st recurrence by Kaplan-Meier analysis. Results: Three groups of patients diagnosed from 2009-2015 were identified: patients treated with Bev alone (n = 49), CCNU alone (n = 36), and concurrent Bev/CCNU (n = 53). Patients were statistically different in performance status at 1st recurrence and tumor size; the CCNU alone group had smaller tumor sizes at diagnosis compared to the Bev groups. The CCNU group showed substantially greater survival (median OS (mOS) = 14.1 mo) compared to the Bev and Bev/CCNU groups (mOS = 6.9 and 7.1 mo, respectively), which may be explained by the imbalance in tumor sizes among the groups, and high rate of crossover (69%) to Bev in subsequent recurrences. To minimize selection bias, we identified another control group (n = 30) diagnosed from 2001-2004 who received CCNU only (CCNU 01-04). These patients had tumor size and KPS more comparable to both Bev groups, and a low rate of crossover (7%). OS for CCNU 01-04 (mOS = 5.7 mo) was similar to the Bev groups. Across all patients, we observed poor OS associated with larger 2D size vs. those with small tumors (mOS = 6.7 vs. 8.8 mo; p = 0.003). In separate stratification of each treatment group by tumor size, this association was retained in the CCNU 01-04 group (mOS = 4.0 vs. 8.4 mo, p &lt; 0.001), but not in either Bev (mOS = 6.7 vs. 7.3 mo) or BEV/CCNU (mOS = 7.0 vs. 8.8 mo). Analysis of effect of tumor size by 3D measurement yielded similar results. Conclusions: Bev appears to reduce the negative impact of large tumor size on GBM patient survival from 1st recurrence. 2D and 3D measurements were correlated, suggesting the adequacy of use of conventional tumor bi-dimensional measurement to predict benefit of Bev in patients based on tumor size.
Rethinking the Hispanic advantage in cancer outcomes: Influence of birthplace.
Authors: Paulo Pinheiro, Karen Callahan, Hongbin Jin, Cyllene Morris
Journal: Journal of Clinical Oncology (2016)

1575 Background: In the United States, the Hispanic advantage in cancer outcomes over Non-Hispanic Whites (NHW) derives from studies aggregating heterogeneous Hispanic subgroups and ignoring birthplace. Here, for the first time, we provide a detailed analysis of cancer mortality by birthplace for the largest Hispanic subgroup, Mexican Hispanic (MH), which comprises 65% of all US Hispanics. Methods: Cancer-specific mortality rates, age adjusted to the 2000 US standard population, were calculated for NHW, US-born Mexican Hispanic (USB-MH) and Mexico-born Mexican Hispanic (MB-MH) residents of California. Age-adjusted mortality ratios obtained from Poisson regression models were used to compare rates. Results: 283,052 cancer deaths from 2008-2012 were analyzed, including 185,840 in NHW, 17,978 in USB-MH, and 18,593 in MB-MH. NHW males had the highest all-cancers-combined mortality rates, 201 per 100,000, followed by USB-MH and MB-MH, 191 and 131 per 100,000, respectively. Rates for females were 152 for NHW, 125 for USB-MH, and 96 for MB-MH per 100,000. Overall risk of cancer death was 1.57 and 1.49 times higher for NHW and USB-MH than MB-MH, (p< 0.01). For liver and colorectal cancer, US-born Mexican Hispanic males had a risk 2.48 and 1.82 times higher than Non-Hispanic Whites, and 2.85 and 1.30 times higher than Mexican-born Mexican Hispanics, (p< 0.01). Conclusions: Assumptions about the relative advantage of Hispanic ethnicity for cancer outcomes need to be re-examined. Mexican Hispanic populations born in the US have an increased risk of mortality compared to those born in Mexico; their overall risk of cancer mortality approaches that of Non-Hispanic Whites. The prototypical advantage of Hispanics - low smoking prevalence and low lung cancer rates - is counterbalanced by increases in mortality for most cancers; for males, the increases in liver and colorectal cancers are substantial. This bolsters evidence of a first generation Healthy Immigrant Effect, rather than an ethnicity-specific benefit for Hispanics. Crucial to cancer prevention and control efforts is the identification of factors that can halt this unfavorable convergence of rates from lower to higher risk among the largest growing minority population in the US, Hispanics.
The use of electronic-neutral penetrating peptides cyclosporin A to deliver pro-apoptotic peptide: A possibly better choice than positively charged TAT
Authors: Wei Gao, Xiucong Yang, Zhiqiang Lin, Bing He, Dong Mei, Dan Wang, Haoran Zhang, Hua Zhang, Wenbing Dai, Xueqing Wang, Qiang Zhang
Journal: Journal of Controlled Release (2017)
Measuring NHS activity
Authors: A. M Pollock, N. Vickers
Journal: BMJ (1995)

respondents were home owners and 6 1 % car owners, was recruitment principally from the upper social class?Furthermore, it would have been beneficial if the authors had described the sociodemographic characteristics of the non- respondents, thereby allowing comparison with those ofthe respondents.Secondly, respondents were asked whether particular services would currently be of some help, great help, or no help.to them personally.It was therefore no surprise that the "healthy" group gave higher rankings to health promotion activities than to symptomatic treatments compared with the "unhealthy group."III individuals may be best placed to put a utility value on their own state of health.Sick people, however, would not be able to give "informed" opinions about health states that they have not experienced, and their judgment may be consciously or subconsciously biased.It would have been more useful for prioritisation purposes to have invited respondents to be more altruistic, by asking them to value primary care services for society as a whole.This would be similar to Rawls's "original position," when subjects are asked to make judgments from behind a "veil of ignorance."I Thirdly, it was disappointing that Hopton and Dlugolecka dealt very superficially with ethical issues such as equality and equity and then only at the end of their paper.Equity is similar to Aristotle's concept of justice, whereby equals are treated equally and unequals unequally, in propor-3 tion to their relevant differences.While the respondents in this study are different in terms of health state, there may be other factors of moral worth that we wish to consider.In any case, Hopton and Dlugolecka do not indicate how the views of unhealthy people may be given more weight.We would prefer to appeal to the ethical principle of equal consideration of interests.Since we are all potential users of health care, we should all have a right to participate in decisions on prioritisation, even if this is biased towards conditions that we would be least likely to experience rather than actual experience of a reduction in quality of life associated with different health states.
Abstract 2350: Clinical Feasibility and Applicability of Measuring Pre-ejection Velocity in the Prediction of Myocardial Viability with Delayed-enhanced magnetic Resonance Imaging as a Reference in Patients with Myocardial Infarction
Authors: Hyung-Kwan Kim, Sung-A Chang, Jung-Im Shin, Su-Yeon Choi, Jin-Shik Park, Yong-Jin Kim, Byung-Hee Oh, Young-Bae Park, Yun-Shik Choi, Dae-Won Sohn
Journal: Circulation (2006)

Background- +Pre-ejection velocity(PEV) was reported to predict recovery of regional myocardial systolic function after revascularization(PCI) in patients with myocardial infarction(MI). We sought ...
Coloscopie de haute résolution avec chromoscopie versus coloscopie standard pour la détection des polypes. Résultats d'une étude prospective randomisée en groupes parallèles
Authors: M Le Rhun, E Coron, D Parlier, JM Nguyen, JM Canard, A Alamdari, D Sautereau, S Chaussade, JP Galmiche
Journal: Endoscopy (2005)

But La coloscopie de haute résolution avec chromoscopie (CHR) devrait théoriquement permettre une meilleure détection des lésions précancéreuses coliques. Cependant aucune étude contrôlée n'a établi la supériorité de cette nouvelle technologie sur la coloscopie standard (CS) en matière de détection des adénomes dans une population à risque. C'est l'objectif de cet essai prospectif, randomisé, en groupes parallèles, réalisé dans 4 centres français.
Utility of Genomic Analysis In Circulating Tumor DNA from Patients with Carcinoma of Unknown Primary
Authors: Shumei Kato, Nithya Krishnamurthy, Kimberly C. Banks, Pradip De, Kirstin Williams, Casey Williams, Brian Leyland-Jones, Scott M. Lippman, Richard B. Lanman, Razelle Kurzrock
Journal: Cancer Research (2017)

Carcinoma of unknown primary (CUP) is a rare and difficult-to-treat malignancy, the management of which might be improved by the identification of actionable driver mutations. We interrogated 54 to 70 genes in 442 patients with CUP using targeted clinical-grade, next-generation sequencing of circulating tumor DNA (ctDNA). Overall, 80% of patients exhibited ctDNA alterations; 66% (290/442) ≥1 characterized alteration(s), excluding variants of unknown significance. TP53-associated genes were most commonly altered [37.8% (167/442)], followed by genes involved in the MAPK pathway [31.2% (138/442)], PI3K signaling [18.1% (80/442)], and the cell-cycle machinery [10.4% (46/442)]. Among 290 patients harboring characterized alterations, distinct genomic profiles were observed in 87.9% (255/290) of CUP cases, with 99.7% (289/290) exhibiting potentially targetable alterations. An illustrative patient with dynamic changes in ctDNA content during therapy and a responder given a checkpoint inhibitor-based regimen because of a mismatch repair gene anomaly are presented. Our results demonstrate that ctDNA evaluation is feasible in CUP and that most patients harbor a unique somatic profile with pharmacologically actionable alterations, justifying the inclusion of noninvasive liquid biopsies in next-generation clinical trials. Cancer Res; 77(16); 4238-46. ©2017 AACR.
Hartmann's Procedure – An analysis of 72 consecutive cases
Authors: S Dalmia, K Marimuthu, K Nagpal, G Matthew
Journal: Endoscopy (2005)

Methods: We retrospectively analysed 72 consecutive Hartmann's Procedure performed in our Hospital from 1 st January 2000 to 31 st December 2003 i.e., in a 4 year period. We analysed indications, age, postoperative deaths, emergency or elective operations, complications, reversal rate and complications of reversal.