tbuckley/cabot-search huggingface dataset:
Racial/ethnicity differences when endorsing influential factors for prostate cancer treatment choice: An analysis of data from the personal patient profile-prostate (P3P) I and II trials.
Authors: Donna Lynn Berry, Fangxin Hong, Barbara Halpenny, Matthew Epstein, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2020)

351 Background: Race and ethnicity impact the type of treatment received for localized prostate cancer in American men. We hypothesized that there may be differences in men’s influential values and preferences related to treatment decisions. Methods: We analyzed samples from two multicenter, randomized trials of the Patient Profile-Prostate (P3P) decision aid, first comparing the trial groups on demographic and decisional variables using Chi-square tests. Stratified (P3P I vs II) logistic regression was then used to assess the univariate association between race/ethnicity and endorsement of moderate-or-strong influence of 14 lifestyle factors, current or future symptoms, or important others on the decision. A multivariable stratified logistic regression with backward variable selection was used to further estimate the association between influential factors and race/ethnicity. Results: Data from 494 and 392 participants in P3PI and P3PII, respectively, were analyzed for 40 Hispanic, 168 non-Hispanic black, 637 non-Hispanic white, 19 others and 6 missing. Age (p=.0001), education (p&lt;.0001), marital status (p&lt;.0001), income (p&lt;.0001), Internet use for information (p&lt;.0001) and decisional control preference were significantly different across racial/ethnic groups. In adjusted analyses, racial/ethnic differences existed for influence of age (Non Hispanic Black (NHB) vs. Non Hispanic White (NHW) OR: 0.56 95%CI 0.38-0.85p=.002), religion/spirituality (NHB vs. NHW OR: 3.2095%CI1.95-5.26, p&lt;.0001), future bladder function (NHB vs. NHW OR: 0.5795%CI0.35-0.90, p=.04), future ability to engage in recreation (NHB vs. NHW OR: 0.5495%CI 0.34-0.86, p=0.02), and a story of a famous person with prostate cancer (NHB vs. NHW OR: 2,11 95%CI1.30-3.43, p=.007). Conclusions: Our results suggest racial/ethnic differences for influences underlying treatment choice. Better understanding these influences may help us present salient information about treatment options to patients and address disparities.
Cost analysis of post-nephrectomy follow-up schedules from three North American clinical practice guidelines for localized renal cell carcinoma (RCC).
Authors: Myuran Thana, Alice Dragomir, Wassim Kassouf, Lori Wood
Journal: Journal of Clinical Oncology (2020)

657 Background: Several guidelines have been developed for follow up of patients after nephrectomy for RCC. The direct financial cost of following recommendations in three North American guidelines were estimated in this analysis. Methods: Recommendations from the American Urological Association (AUA), Canadian Urological Association (CUA), and National Comprehensive Cancer Network (NCCN) for post-radical nephrectomy care were compiled. Data regarding costs of testing and physician visits were obtained from the Ontario Health Insurance Plan Schedule of Benefits. Both the cost per patient completing five years of surveillance (scenario A), and the estimated cost adjusted for attrition from predicted recurrences (scenario B) were calculated. A sensitivity analysis was performed and will be presented. Results: For five years of follow up of a single patient in both scenarios, the costs are summarized in the table. For scenario A, follow up costs ranged from $515-1112 for T1N0, $1639-2746 for T2N0, $1856-2746 for T3/4 and $1918-2746 TxN+. For scenario B, costs were $497-1051 for T1N0, $1259-2198 for T2N0, $1008-1595 for T3/4N0 and $1043-1595 for TxN+. Conclusions: The AUA, CUA, and NCCN guidelines showed considerable differences in their associated costs, particularly when expected recurrences were accounted for. The NCCN recommendations are predicted to be the costliest to implement, irrespective of stage.[Table: see text]
Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non–Small Cell Lung Cancer
Authors: Charu Aggarwal, Jeffrey C. Thompson, Austin L. Chien, Katie J. Quinn, Wei-Ting Hwang, Taylor A. Black, Stephanie S. Yee, Theresa E. Christensen, Michael J. LaRiviere, Benjamin A. Silva, Kimberly C. Banks, Rebecca J. Nagy, Elena Helman, Abigail T. Berman, Christine A. Ciunci, Aditi P. Singh, Jeffrey S. Wasser, Joshua M. Bauml, Corey J. Langer, Roger B. Cohen, Erica L. Carpenter
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non–small cell lung cancer (mNSCLC) has not been explored. Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS). Results: Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range, 1.9–52.5) and was significantly higher for patients achieving DCB compared with no durable benefit (21.3 mut/Mb vs. 12.4 mut/Mb, P = 0.003). For patients with pTMB ≥ 16 mut/Mb, median PFS was 14.1 versus 4.7 months for patients with pTMB &amp;lt; 16 mut/Mb [HR, 0.30 (0.16–0.60); P &amp;lt; 0.001]. Median OS for patients with pTMB ≥ 16 was not reached versus 8.8 months for patients with pTMB &amp;lt; 16 mut/Mb [HR, 0.48 (0.22–1.03); P = 0.061]. Mutations in ERBB2 exon 20, STK11, KEAP1, or PTEN were more common in patients with no DCB. A combination of pTMB ≥ 16 and absence of negative predictor mutations was associated with PFS [HR, 0.24 (0.11–0.49); P &amp;lt; 0.001] and OS [HR, 0.31 (0.13–0.74); P = 0.009]. Conclusions: pTMB ≥ 16 mut/Mb is associated with improved PFS after first-line standard-of-care pembrolizumab-based therapy in mNSCLC. STK11/KEAP1/PTEN and ERBB2 mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies.
Clinical utility of biomarkers 4K score, SelectMDx and ExoDx with MRI for the detection of high-grade prostate cancer.
Authors: Vittorio Fasulo, Claire Marie de la Calle, Janet E. Cowan, Annika Herlemann, Carissa Chu, Adam John Gadzinski, Reuben Au Yeung, Alberto Saita, Matthew R. Cooperberg, Katsuto Shinohara, Peter Carroll, Hao Gia Nguyen
Journal: Journal of Clinical Oncology (2020)

307 Background: Although adoption of new biomarkers and MRI has become widespread, their utility when deciding to biopsy is unclear. We aim to evaluate and compare 4K, SelectMDx, ExoDx and their added value when combined with prostate MRI in the detection of high-grade prostate cancer (HG PC) and avoidance of unnecessary biopsies. Methods: Patients referred for consideration of prostate biopsy at UCSF between 2016-2019 were enrolled and had either 4K, SelectMDx or ExoDx testing with/without MRI. Logistic regression and AUC were used to determine the performance of each biomarker in detecting HG PC (≥Gleason grade (GG) 3+4). In the subgroup of patients that underwent biopsy, with PSA 2.5-10 and negative DRE, we determined the number of avoided unnecessary biopsies (with GG 3+3 cancer or no cancer) and missed HG PC for each biomarker with/without MRI. Results: A total of 896 patients were enrolled, 457 were biopsied. Mean age was 65.5 years, median PSA was 6.32. Logistic regression showed that having an abnormal biomarker score or PI-RADS 4/5 on MRI (P4/5) was strongly associated with finding HG PC: 4K OR 12.9 (CI 4.58-36.1), ExoDx OR 14.7 (CI 3.31-65.3), SelectMDx OR 3.62 (CI 1.44-9.11), P4/5 OR 6.20 (CI 3.93-9.79), TRUS ≥T2a OR 4.33 (CI 2.78-6.75), PSAD &gt;0.15 OR 4.01 (CI 2.59-6.20), p&lt;0.01). Combining biomarker and P4/5 lesion on MRI increased AUC for detecting HG PC. In the biopsy subgroup, a normal 4K or ExoDx test missed only 4-5% HG PC, while an abnormal test resulted in avoiding 14-20% unnecessary biopsies. Combining MRI with ExoDx or 4K missed 0-1.43% HG PC but avoided only 7-9% unnecessary biopsies (Table). Conclusions: 4K and ExoDx outperformed MRI and SelectMDx but combining the biomarkers with MRI resulted in the best predictive ability for detecting HG PC. Negative MRI avoided more biopsies than a normal 4K or ExoDxbut missed more aggressive cancers. Our data suggest that MRI alone is not sensitive enough to detect all HG PC and that 4K or ExoDx testing alone could be sufficient when deciding to proceed with biopsy.[Table: see text]
The Affordable Care Act and Insurance Status, Stage, and Timely Treatment Among Patients With Cancer
Authors: Sue Fu, Liam Rose, Lisa Knowlton
Journal: JAMA Network Open (2020)

Samuel U. Takvorian, MD, MS; Arman Oganisian, MS; Ronac Mamtani, MD, MSCE; Nandita Mitra, PhD; Lawrence N. Shulman, MD; Justin E. Bekelman, MD; Rachel M. Werner, MD, PhD
Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients With Secondary Mitral Regurgitation
Authors: Farnaz Namazi, Pieter van der Bijl, Kensuke Hirasawa, Vasileios Kamperidis, Suzanne E. van Wijngaarden, Bart Mertens, Martin B. Leon, Rebecca T. Hahn, Gregg W. Stone, Jagat Narula, Nina Ajmone Marsan, Victoria Delgado, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2020)
“Real world” use of a highly reliable imaging sign: “T2-FLAIR mismatch” for identification of IDH mutant astrocytomas
Authors: Rajan Jain, Derek R Johnson, Sohil H Patel, Mauricio Castillo, Marion Smits, Martin J van den Bent, Andrew S Chi, Daniel P Cahill
Journal: Neuro-Oncology (2020)

Abstract AbstractThe T2-FLAIR (fluid attenuated inversion recovery) mismatch sign is an easily detectable imaging sign on routine clinical MRI studies that suggests diagnosis of isocitrate dehydrogenase (IDH)–mutant 1p/19q non-codeleted gliomas. Multiple independent studies show that the T2-FLAIR mismatch sign has near-perfect specificity, but low sensitivity for diagnosing IDH-mutant astrocytomas. Thus, the T2-FLAIR mismatch sign represents a non-invasive radiogenomic diagnostic finding with potential clinical impact. Recently, false positive cases have been reported, many related to variable application of the sign’s imaging criteria and differences in image acquisition, as well as to differences in the included patient populations. Here we summarize the imaging criteria for the T2-FLAIR mismatch sign, review similarities and differences between the multiple validation studies, outline strategies to optimize its clinical use, and discuss potential opportunities to refine imaging criteria in order to maximize its impact in glioma diagnostics.
Lisa: inferring transcriptional regulators through integrative modeling of public chromatin accessibility and ChIP-seq data
Authors: Qian Qin, Jingyu Fan, Rongbin Zheng, Changxin Wan, Shenglin Mei, Qiu Wu, Hanfei Sun, Myles Brown, Jing Zhang, Clifford A. Meyer, X. Shirley Liu
Journal: Genome biology (2020)

Abstract We developed Lisa ( http://lisa.cistrome.org/ ) to predict the transcriptional regulators (TRs) of differentially expressed or co-expressed gene sets. Based on the input gene sets, Lisa first uses histone mark ChIP-seq and chromatin accessibility profiles to construct a chromatin model related to the regulation of these genes. Using TR ChIP-seq peaks or imputed TR binding sites, Lisa probes the chromatin models using in silico deletion to find the most relevant TRs. Applied to gene sets derived from targeted TF perturbation experiments, Lisa boosted the performance of imputed TR cistromes and outperformed alternative methods in identifying the perturbed TRs.
Gemcitabine combined with the MTOR Inhibitor Temsirolimus(CCI-779) in Patients with Inoperable or Metastatic Pancreatic Cancer (He 3/07). A Phase I Study by the Hellenic Cooperative Oncology Group
Authors: V. Karavasilis, G. Pentheroudakis, J. Sgouros, S.T. Dimoudis, I. Varthalitis, E. Samantas, G. Fountzilas
Journal: Annals of Oncology (2012)
CD28/4-1BB CD123 CAR T cells in blastic plasmacytoid dendritic cell neoplasm
Authors: Elodie Bôle-Richard, Maxime Fredon, Sabeha Biichlé, François Anna, Jean-Marie Certoux, Florian Renosi, Frédéric Tsé, Chloé Molimard, Séverine Valmary-Degano, Alizée Jenvrin, Walid Warda, Jean-René Pallandre, Francis Bonnefoy, Margaux Poussard, Marina Deschamps, Tony Petrella, Christophe Roumier, Elizabeth Macintyre, Frédéric Féger, Eolia Brissot, Mohamad Mohty, Kiave-Yune HoWangYin, Pierre Langlade-Demoyen, Maria Loustau, Julien Caumartin, Yann Godet, Delphine Binda, Maïder Pagadoy, Eric Deconinck, Etienne Daguindau, Philippe Saas, Christophe Ferrand, Fanny Angelot-Delettre, Olivier Adotévi, Francine Garnache-Ottou
Journal: Leukemia (2020)
Outcomes of urothelial carcinoma patients with central nervous system metastases.
Authors: Erik Andrews, Catherine Curran, Petros Grivas, Leonidas Nikolaos Diamantopoulos, Ravindran Kanesvaran, Jue Wang, Rohit K. Jain, Ankita Tandon, Alexandra Drakaki, Guru Sonpavde
Journal: Journal of Clinical Oncology (2020)

468 Background: Urothelial carcinoma (UC) metastatic to the central nervous system (CNS) is extremely rare. Given the lack of systematic data regarding outcomes in UC metastatic to the CNS, we conducted a retrospective multicenter study to more broadly characterize outcomes. Methods: Patients (pts) diagnosed with metastatic UC to the CNS were identified from collaborating institutions. Data were collected for demographics, clinical and pathological variables. Descriptive statistics were reported to examine tumor regression, time to treatment discontinuation or failure (TTF), and overall survival (OS). Results: 39 pts with UC metastatic to the CNS were evaluable from 6 institutions. The ECOG-PS ranged from 0-4 (median 2), the median age was 67 (range 39-82), and 8 (20.5%) were female. The histology consisted of pure urothelial, mixed predominant urothelial, and mixed predominant non-urothelial in 26 (66.7%), 8 (20.5%), and 5 (12.8%) pts, respectively. The sites of CNS metastases (mets) were the brain, meninges, and a combination of CNS sites in 37 (95%), 1 (2.5%) and 1 (2.5%) pts, respectively. 33 (84.6%) pts received radiation therapy (RT) to their mets and 6 (15.4%) did not. Of 16 pts who received systemic therapy (ST), cisplatin-based chemotherapy, non-cisplatin based chemotherapy, and PD-1/L1 inhibitors were administered in 6 (37.5%), 5 (31.25%), and 5 (31.25%) pts, respectively. The overall median TTF and OS were 90 and 154 days (d). The median OS for pts who had ST compared to those who did not was 193.5 (n=12) versus 71 (n=17) d. The median OS for pts who had RT compared to those who did not was 92 (n=25) versus 15.5 (n=4) d. The median OS for pts who received neither ST nor RT, compared to pts receiving both, was 12 (range 7-19) versus 232 (n=11) d. Best response to systemic therapy PR, CR, SD and PD were seen in 2 (12.5%), 1 (6.25%), 1 (6.25%) and 12 (75%) pts, respectively. For the 5 pts who received RT only, best response PR and PD were seen in 2 (40%) and 3 (60%) pts, respectively. Conclusions: Pts with UC metastatic to the CNS present with a poor performance status and have outcomes that are dismal and appear worse than those with metastases to other organs. A combination of systemic and radiation therapy might achieve improved outcomes in selected pts.
Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy
Authors: Siri Tähtinen, Sara Feola, Cristian Capasso, Netta Laustio, Christianne Groeneveldt, Erkko O. Ylösmäki, Leena Ylösmäki, Beatriz Martins, Manlio Fusciello, Marta Medeot, Maria Tagliamonte, Jacopo Chiaro, Firas Hamdan, Karita Peltonen, Tuuli Ranki, Luigi Buonaguro, Vincenzo Cerullo
Journal: Cancer Research (2020)

Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although CD8+ antitumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4+ T-cell help is also required for an optimal antitumor immune response to occur. Hence, we investigated whether the pathogen-related CD4+ T-cell memory populations could be reengaged to support the CTLs, converting a weak primary antitumor immune response into a stronger secondary one. To this end, we used our PeptiCRAd technology that consists of an oncolytic adenovirus coated with MHC-I-restricted tumor-specific peptides and developed it further by introducing pathogen-specific MHC-II-restricted peptides. Mice preimmunized with tetanus vaccine were challenged with B16.OVA tumors and treated with the newly developed hybrid TT-OVA-PeptiCRAd containing both tetanus toxoid- and tumor-specific peptides. Treatment with the hybrid PeptiCRAd significantly enhanced antitumor efficacy and induced TT-specific, CD40 ligand-expressing CD4+ T helper cells and maturation of antigen-presenting cells. Importantly, this approach could be extended to naturally occurring tumor peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetanus, highlighting the usefulness of this technique to take full advantage of CD4+ memory T-cell repertoires when designing immunotherapeutic treatment regimens. Finally, the antitumor effect was even more prominent when combined with the immune checkpoint inhibitor anti-PD-1, strengthening the rationale behind combination therapy with oncolytic viruses. SIGNIFICANCE: These findings establish a novel technology that enhances oncolytic cancer immunotherapy by capitalizing on pre-acquired immunity to pathogens to convert a weak antitumor immune response into a much stronger one.
Three-Year Safety and Efficacy of Benralizumab for Adolescent Patients with Severe, Uncontrolled Asthma: Results of the BORA Extension Study
Authors: William Busse, Eugene Bleecker, J. Mark FitzGerald, Gary Ferguson, Peter Barker, Laura Brooks, Richard Olsson, Ubaldo Martin, Mitchell Goldman
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 17232: Different Clinical Significance of Prolonged and Fragmented QRS in Hypertrophic Cardiomyopathy
Authors: Takashi Nakamura, Yoshitaka Iwanaga, Yoshinori Kagioka, Takayuki Kawamura, Masakazu Yasuda, Ryobun Yasuoka, Takashi Kurita, Shunichi Miyazaki
Journal: Circulation (2016)

Background: Prolonged QRS duration (pQRS) and fragmented QRS (fQRS) are reported to have associations with severe arrhythmia events or heart failure (HF). However, controversy exists regarding the ...
Corrigendum to Overview of the relevance of PI3K pathway in HR-positive breast cancer
Authors: N. Vasan, E. Toska, M. Scaltriti
Journal: Annals of Oncology (2020)

The authors regret that after publication they discovered two errors in Figure 1:1.The orange bubble "mTORC2" should read "mTORC1". Additionally, "everolimus" and "temsirolimus" should not be indicated as inhibiting mTORC1 and mTORC2, but rather as a separate inhibition for mTORC1 only.2."AZD6363" should be read "AZD5363". The authors would like to apologise for any inconvenience caused. Overview of the relevance of PI3K pathway in HR-positive breast cancerAnnals of OncologyVol. 30PreviewOne of the hallmarks of hormone receptor (HR)-positive breast cancer is its dependence on the phosphatidylinositol-3-kinase (PI3K) pathway. Here, we review the epidemiologic, functional, and pharmacologic interactions between oncogenic PI3K and the estrogen receptor (ER). We discuss the epidemiology of PI3K pathway alterations, mechanisms of resistance to PI3K inhibitors, and the current mechanistic landscape of crosstalk between PI3K and ER, which provide the rationale for dual ER and PI3K inhibition and is now a standard of care in the treatment of ER+ PIK3CA-mutant metastatic breast cancer. Full-Text PDF Open Access
Potential treatment effect of the SQ tree SLIT‐tablet on pollen food syndrome caused by apple
Authors: Stephen J. Till, Brian Sonne Stage, Isabel Skypala, Tilo Biedermann
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Sequential delivery of nanoformulated α-mangostin and triptolide overcomes permeation obstacles and improves therapeutic effects in pancreatic cancer
Authors: Jingxian Feng, Minjun Xu, Jiahao Wang, Songlei Zhou, Yipu Liu, Shanshan Liu, Yukun Huang, Yu Chen, Liang Chen, Qingxiang Song, Jingru Gong, Huiping Lu, Xiaoling Gao, Jun Chen
Journal: Biomaterials (2020)
Correction to: Predictive biomarkers and mechanisms underlying resistance to PD1/PD-L1 blockade cancer immunotherapy
Authors: Daixi Ren, Yuze Hua, Boyao Yu, Xin Ye, Ziheng He, Chunwei Li, Jie Wang, Yongzhen Mo, Xiaoxu Wei, Yunhua Chen, Yujuan Zhou, Qianjin Liao, Hui Wang, Bo Xiang, Ming Zhou, Xiaoling Li, Guiyuan Li, Yong Li, Zhaoyang Zeng, Wei Xiong
Journal: Molecular Cancer (2020)

After publication of the article [1], authors found out that Fig. 1 was inadvertently replaced.
Managing multimorbidity: listening to patients and integrated care
Authors: Charles Coughlan, Mando Watson
Journal: BMJ (2020)

We welcome the call from Whitty and colleagues for a coordinated, cross sectoral response to the challenges posed by multimorbidity.1 The authors, however, overlook two important factors that could help the profession to meet these demands—listening to patients and integrated care.

We agree that leadership and action from medical schools, professional bodies, regulators, and policy makers are essential to tackle this problem. But where are …
TCL1 transgenic mice as a model for CD49d-high chronic lymphocytic leukemia
Authors: Eva Szenes, Andrea Härzschel, Sarah Decker, Erika Tissino, Justine Pischeli, Julia Christine Gutjahr, Sandra Kissel, Sandra Pennisi, Jan Philip Höpner, Alexander Egle, Nadja Zaborsky, Christine Dierks, Marie Follo, Alexandre Chigaev, Antonella Zucchetto, Richard Greil, Valter Gattei, Tanja Nicole Hartmann
Journal: Leukemia (2020)