tbuckley/cabot-search huggingface dataset:
Long‐term survivors of early breast cancer treated with chemotherapy are characterized by a pro‐inflammatory biomarker profile compared to matched controls
Authors: Jasper Tromp, Liselotte M. Boerman, Iziah E. Sama, Saskia W.M.C. Maass, John H. Maduro, Yoran M. Hummel, Marjolein Y. Berger, Geertruida H. de Bock, Jourik A. Gietema, Annette J. Berendsen, Peter van der Meer
Journal: European Journal of Heart Failure (2020)

Abstract Background Chemo‐ and radiotherapy for breast cancer (BC) can lead to cardiotoxicity even years after the initial treatment. The pathophysiology behind these late cardiac effects is poorly understood. Therefore, we studied a large panel of biomarkers from different pathophysiological domains in long‐term BC survivors, and compared these to matched controls. Methods and results In total 91 biomarkers were measured in 688 subjects: 342 BC survivors stratified either to treatment with chemotherapy ± radiotherapy ( n = 170) or radiotherapy alone ( n = 172) and matched controls. Mean age was 59 ± 9 years and 65 ± 8 years for women treated with chemotherapy ± radiotherapy and radiotherapy alone, respectively, with a mean time since treatment of 11 ± 5.5 years. No biomarkers were differentially expressed in survivors treated with radiotherapy alone vs. controls ( P for all &gt;0.1). In sharp contrast, a total of 19 biomarkers were elevated, relative to controls, in BC survivors treated with chemotherapy ± radiotherapy after correction for multiple comparisons ( P &lt;0.05 for all). Network analysis revealed upregulation of pathways relating to collagen degradation and activation of matrix metalloproteinases. Furthermore, several inflammatory biomarkers including growth differentiation factor 15, monocyte chemoattractant protein 1, chemokine (C‐X‐C motif) ligand 16, tumour necrosis factor super family member 13b and proprotein convertase subtilisin/kexin type 9, elevated in survivors treated with chemotherapy, showed an independent association with lower left ventricular ejection fraction. Conclusion Breast cancer survivors treated with chemotherapy ± radiotherapy show a distinct biomarker profile associated with mild cardiac dysfunction even 10 years after treatment. These results suggest that an ongoing pro‐inflammatory state and activation of matrix metalloproteinases following initial treatment with chemotherapy might play a role in the observed cardiac dysfunction in late BC survivors.
Association of Indoor Tanning Regulations With Health and Economic Outcomes in North America and Europe
Authors: Louisa G. Gordon, Astrid J. Rodriguez-Acevedo, Brian Køster, Gery P. Guy, Craig Sinclair, Emilie Van Deventer, Adèle C. Green
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> UV radiation emissions from indoor tanning devices are carcinogenic. Regulatory actions may be associated with reduced exposure of UV radiation at a population level. <h3>Objective</h3> To estimate the long-term health and economic consequences of banning indoor tanning devices or prohibiting their use by minors only in North America and Europe compared with ongoing current levels of use. <h3>Design, Setting, and Participants</h3> This economic analysis modeled data for individuals 12 to 35 years old in North America and Europe, who commonly engage in indoor tanning. A Markov cohort model was used with outcomes projected during the cohort's remaining life-years. Models were populated by extracting data from high-quality systematic reviews and meta-analyses, epidemiologic reports, and cancer registrations. <h3>Main Outcomes and Measures</h3> Main outcomes were numbers of melanomas and deaths from melanoma, numbers of keratinocyte carcinomas, life-years, and health care and productivity costs. Extensive sensitivity analyses were performed to assess the stability of results. <h3>Results</h3> In an estimated population of 110 932 523 in the United States and Canada and 141 970 492 in Europe, for the next generation of youths and young adults during their remaining lifespans, regulatory actions that ban indoor tanning devices could be expected to gain 423 000 life-years, avert 240 000 melanomas (−8.2%), and avert 7.3 million keratinocyte carcinomas (−7.8%) in North America and gain 460 000 life-years, avert 204 000 melanomas (−4.9%), and avert 2.4 million keratinocyte carcinomas (−4.4%) in Europe compared with ongoing current levels of use. Economic cost savings of US $31.1 billion in North America and €21.1 billion (US $15.9 billion) in Europe could occur. Skin cancers averted and cost savings after prohibiting indoor tanning by minors may be associated with one-third of the corresponding benefits of a total ban. <h3>Conclusions and Relevance</h3> Banning indoor tanning may be associated with reduced skin cancer burden and health care costs. Corresponding gains from prohibiting indoor tanning by minors only may be smaller.
Association of black race with improved outcomes following definitive radiotherapy with androgen deprivation therapy for high-risk prostate cancer: A meta-analysis of eight randomized trials.
Authors: Amar Upadhyaya Kishan, Tahmineh Romero, Matthew Rettig, Isla Garraway, Mack Roach, Thomas Michael Pisansky, Jeff M. Michalski, W. Robert Lee, Christopher U. Jones, Seth A. Rosenthal, Felix Y Feng, Paul Christopher Boutros, Nicholas George Nickols, Brandon Arvin Virgil Mahal, Robert Timothy Dess, Phuoc T. Tran, Michael L. Steinberg, David Elashoff, Howard M. Sandler, Daniel Eidelberg Spratt
Journal: Journal of Clinical Oncology (2020)

327 Background: Though Black men with prostate cancer are more likely to have aggressive disease features than White men, race-specific differences in initial treatment responses in localized disease remains unknown. Methods: Individual patient data were obtained for 9259 patients (including 1674 [18.1%] Black men and 7585 [81.9%] White men) enrolled on eight randomized controlled trials evaluating definitive radiotherapy (RT) ± short-term or long-term androgen deprivation therapy (STADT and LTADT). The primary endpoints were biochemical recurrence (BCR), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Fine-Gray subdistribution HR (sHR) models were developed to evaluate the cumulative incidences of all endpoints after stratification by National Comprehensive Cancer Network risk grouping. A meta-analysis was done to estimate pair-wise comparisons of treatments within and between Black and White men, after adjusting for age, Gleason score, clinical T stage, and initial PSA. Results: Black men were more likely to have NCCN high-risk disease at enrollment (656/1674 [39.2%] vs 2506/7585 [33%], p&lt;0.001). However, within the high-risk stratum Black men had lower 10-year rates of BCR (46.1% vs. 50.4%, p=0.02), DM (14% vs. 21.6%, p&lt;0.001), and PCSM (4.9% vs. 9.8%, p&lt;0.001). After adjusting for age and disease characteristics, Black men with high-risk prostate receiving RT+STADT had lower rates of BCR (sHR 0.73, 95% CI 0.62-0.86, p&lt;0.001), DM (sHR 0.64, 95% CI 0.49-0.84, p=0.001) and PCSM (sHR 0.49, 95% CI 0.25-0.95, p=0.04). There were no differences in BCR, DM, or PCSM among men receiving RT+LTADT. The interaction between race and the impact of adding STADT to RT alone on BCR was statistically significant (p=0.003). Conclusions: Black men enrolled on randomized trials with long-term follow-up have higher risk disease at enrollment, but have better BCR, DM, and PCSM outcomes with RT-based therapy compared with White men, particularly with the addition of STADT.
Patient commentary: Incarceration is dehumanising, but good healthcare can restore dignity
Journal: BMJ (2020)

I arrived in prison a cocaine addict with a £2000 (€2390; $2580) a week habit. My daily consumption was so extreme that I supplemented it with copious amounts of Xanax to “take the edge off.” The reception prison doctor’s eyes bulged in disbelief, telling me that I could die from a seizure if I wasn’t properly detoxed.

Like many others, I was oblivious to the physical danger I’d been in, having neglected my health for years in addiction. I was grateful for the little cupful of benzodiazepine liquid handed though the “meds hatch” each day. It barely took the edge off the nightmare I was living, but at least I didn’t die.

That was …
Abstract 13310: Anti-Inflammatory HDL Function and Incident Cardiovascular/Death Events: A Secondary Analysis of the JUPITER Trial
Authors: Oluremi N Ajala, Olga Demler, Zareen Farukhi, Yanyan Liu, Steven Adelman, Heidi Collins, Robert Glynn, Paul Ridker, Amit Khera, Dan Rader, Samia Mora
Journal: Circulation (2018)

Background: HDL cholesterol (HDLC) is an established marker of cardiovascular risk that possesses anti-inflammatory properties in vitro. It is unclear whether the anti-inflammatory quality of HDL i...
TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma
Authors: Brenda De Keersmaecker, Sofie Claerhout, Javier Carrasco, Isabelle Bar, Jurgen Corthals, Sofie Wilgenhof, Bart Neyns, Kris Thielemans
Journal: Journal for ImmunoTherapy of Cancer (2020)

We previously reported that dendritic cell-based mRNA vaccination plus ipilimumab (TriMixDC-MEL IPI) results in an encouraging rate of tumor responses in patients with pretreated advanced melanoma. Here, we report the TriMixDC-MEL IPI-induced T-cell responses detected in the peripheral blood.Monocyte-derived dendritic cells electroporated with mRNA encoding CD70, CD40 ligand, and constitutively active TLR4 (TriMix) as well as the tumor-associated antigens tyrosinase, gp100, MAGE-A3, or MAGE-C2 were administered together with IPI for four cycles. For 18/39 patients, an additional vaccine was administered before the first IPI administration. We evaluated tumor-associated antigen specific T-cell responses in previously collected peripheral blood mononuclear cells, available from 15 patients.Vaccine-induced enzyme-linked immunospot assay responses detected after in vitro T-cell stimulation were shown in 12/15 patients. Immune responses detected in patients with a complete or partial response were significantly stronger and broader, and exhibited a higher degree of multifunctionality compared with responses in patients with stable or progressive disease. CD8+ T-cell responses from patients with an ongoing clinical response, either elicited by TriMixDC-MEL IPI or on subsequent pembrolizumab treatment, exhibited the highest degree of multifunctionality.TriMixDC-MEL IPI treatment results in robust CD8+ T-cell responses in a meaningful portion of stage III or IV melanoma patients, and obviously in patients with a clinical response. The levels of polyfunctional and multiantigen T-cell responses measured in patients with a complete response, particularly in patients evidently cured after 5+ years of follow-up, may provide a benchmark for the level of immune stimulation needed to achieve a durable clinical remission.NCT01302496.
Integrating comprehensive genomic profiling into the clinical management of prostate cancer patients: A single institution community practice experience.
Authors: Neal D. Shore, James Haberberger, Eric Allan Severson, Brian Michael Alexander, Pratheesh Sathyan, Prasanth Reddy, Shakti H. Ramkissoon
Journal: Journal of Clinical Oncology (2020)

281 Background: Prostate cancer is a leading cause of cancer-related mortality with a 5-year survival rate of 69%. In this study, we examine the role of integrating CGP, including tissue and liquid biopsy testing, into the clinical management of prostate cancer patients. Methods: We analyzed 140 cases of advanced prostate carcinoma with tissue and ctDNA based Comprehensive Genomic Profiling (CGP). CGP analysis revealed genomic alterations (GAs), TMB and MSI status. Germline testing, using multiple commercially assays was also obtained. Results: The median age of patients tested by tissue-based and liquid-based CGP was 65 years (46 to 85 yrs) and 69 years (51 to &gt; 89 years), respectively. CGP analysis of tissue samples revealed the most commonly altered genes to be TP53 (34.6%), TMPRSS2- ERG (25.9%), PTEN (23.5%), NBN (14.8%), MYC (13.6%), BRCA2 (14.3%) and CDKN2A (13.3%). TMB analysis determined in 77 tissue samples showed a median (mean) value of 2.61 (5.00) mutations/Mb. 3.9% cases (3/77) were found to be hypermutated. MSI status was determined in 74 cases of which 2.7% (2/74) were found to be MSI-High. Of the tissue-based samples tested, 30.9% (25/81) were derived from metastatic sites. Analysis of commonly altered genes between primary vs metastatic tissue samples revealed TP53 mutations were significantly enriched in metastatic tumors. CGP analysis of the 59 liquid biopsy samples revealed the most commonly altered genes to be TP53 (37.3%), NF1 (10.2%), ATM (10.2%), CHEK2 (8.5%) and GNAS (8.5%). Germline testing was performed as described above on a clinically indicated subset of patients, which revealed alterations in BRCA, ATM, CHEK2, BRIP1 and TP53, among others. We are evaluating additional patient samples as part of the data set, which will be added to the final abstract presentation with a cutoff date of 12-31-2019. Conclusions: Genomic testing for high risk and advanced prostate cancer patients per the NCCN recommendations, with somatic testing, using tissue and liquid biopsy testing, as well as germline testing in selected cases, identifies DNA alterations which have potential clinical utility for clinical trial enrollment.
Dose-Response of the Pro-Inflammatory Potential Induced by Indoor Settled Dust from Homes with Different Levels of Water-Damage during Hurricane Maria in San Juan, Puerto Rico
Authors: Felix Rivera-Mariani, Summer Pellechio, Hayat Srour, Ruslan Fomenko, Benjamin Bolanos, Filipa Godoy-Vitorino, Kerry Kinney, Juan Maestre, Humberto Cavallin
Journal: Journal of Allergy and Clinical Immunology (2020)
Laparoscopic Gastrectomy After Neoadjuvant Chemotherapy
Authors: Fausto Rosa, Sergio Alfieri
Journal: JAMA Surgery (2020)

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Risk of Offspring Birth Defects in Women After Bariatric Surgery
Authors: Nathalie Auger, Marianne Bilodeau-Bertrand, Laura Arbour
Journal: JAMA (2020)

To the Editor In a Research Letter, Dr Neovius and colleagues investigated the association between gastric bypass surgery and risk of birth defects in offspring.1 The authors found that bariatric surgery was protective against birth defects.
Erratum: Corrigendum: Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness
Authors: Nicholas M Morton, Jasmina Beltram, Roderick N Carter, Zoi Michailidou, Gregor Gorjanc, Clare McFadden, Martin E Barrios-Llerena, Sergio Rodriguez-Cuenca, Matthew T G Gibbins, Rhona E Aird, José Maria Moreno-Navarrete, Steven C Munger, Karen L Svenson, Annalisa Gastaldello, Lynne Ramage, Gregorio Naredo, Maximilian Zeyda, Zhao V Wang, Alexander F Howie, Aila Saari, Petra Sipilä, Thomas M Stulnig, Vilmundur Gudnason, Christopher J Kenyon, Jonathan R Seckl, Brian R Walker, Scott P Webster, Donald R Dunbar, Gary A Churchill, Antonio Vidal-Puig, José Manuel Fernandez-Real, Valur Emilsson, Simon Horvat
Journal: Nature Medicine (2018)
Personalized Models of Psychopathology
Authors: Aidan G.C. Wright, William C. Woods
Journal: Annual Review of Clinical Psychology (2020)

The personalized approach to psychopathology conceptualizes mental disorder as a complex system of contextualized dynamic processes that is nontrivially specific to each individual, and it seeks to develop formal idiographic statistical models to represent these individual processes. Although the personalized approach draws on long-standing influences in clinical psychology, there has been an explosion of research in recent years following the development of intensive longitudinal data capture and statistical techniques that facilitate modeling of the dynamic processes of each individual's pathology. Advances are also making idiographic analyses scalable and generalizable. We review emerging research using the personalized approach in descriptive psychopathology, precision assessment, and treatment selection and tailoring, and we identify future challenges and areas in need of additional research. The personalized approach to psychopathology holds promise to resolve thorny diagnostic issues, generate novel insights, and improve the timing and efficacy of interventions.
Blinatumomab versus historical standard therapy in pediatric patients with relapsed/refractory Ph-negative B-cell precursor acute lymphoblastic leukemia
Authors: Franco Locatelli, James A. Whitlock, Christina Peters, Christiane Chen-Santel, Victoria Chia, Robyn M. Dennis, Kenneth M. Heym, Aaron J. Katz, Michael A. Kelsh, Richard Sposto, Huakang Tu, Catherine A. Tuglus, Anupam Verma, Luciana Vinti, Jennifer J. Wilkes, Nathalya Zubarovskaja, Gerhard Zugmaier, Arend von Stackelberg, Weili Sun
Journal: Leukemia (2020)

Relapse and, less frequently, refractoriness to front-line therapy are the main causes of treatment failure in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), occurring in 15-20% of patients [1,2].Prognosis after relapse depends primarily on the time elapsing between diagnosis and relapse, site of relapse, and disease immunophenotypes [2]; unfortunately, many of these patients further relapse despite receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) [3].Blinatumomab, a bispecific T-cell engager antibody construct, directs CD3-positive effector-memory T lymphocytes towards CD19-positive cells, triggering cell death of the latter [4].Efficacy of blinatumomab in pediatric patients with relapsed/refractory (R/R) BCP-ALL has been demonstrated in an international phase 1/2, single-arm study (NCT01471782) [4].R/R pediatric ALL is rare; consequently, most studies are single-arm and limited by small population sizes.Complete remission (CR) rates for pediatric patients in first or more advanced relapse vary from 8 to 75% [2,[5][6][7][8][9].This variation can be attributed to differences among patient characteristics, sample sizes, and definition of CR used [2,[5][6][7][8][9].For rare diseases, one approach to estimate treatment efficacy is to identify appropriate control populations with similar characteristics [9,10].Such a comparison has been undertaken for adult patients with Ph-negative R/R BCP-ALL from a single-arm study of blinatumomab with a historical dataset [11], but not for children.
Depth of response (DepOR) analysis and correlation with clinical outcomes from JAVELIN Renal 101.
Authors: Martin H Voss, Robert J. Motzer, Laurence Albiges, Brian I. Rini, Manuela Schmidinger, James M. G. Larkin, John B. A. G. Haanen, Christian K. Kollmannsberger, Matthew T. Campbell, Marc-Oliver Grimm, Sumanta K. Pal, Gwenaelle Gravis, Michael B. Atkins, Bo Huang, Aleksander Chudnovsky, Alessandra di Pietro, Despina Thomaidou, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2020)

690 Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), avelumab + axitinib (A+Ax) significantly improved progression-free survival (PFS) in patients (pts) with advanced renal cell carcinoma (aRCC) compared with sunitinib (S); median PFS (mPFS) in the A+Ax arm was 13.8 mo (95% CI, 11.1 mo, not estimable [NE]) vs 8.4 mo (95% CI, 6.9, 11.1) in the S arm (HR, 0.69; 95% CI, 0.56, 0.84; P &lt; 0.001) (Motzer NEJM 2019). Here, we report on the correlation of PFS with DepOR at early imaging timepoints. Methods: Data from pts in both arms were analyzed based on blinded independent central review (BICR) per RECIST 1.1. Tumor shrinkage or growth was categorized by best percent change in target lesions on imaging obtained up to 13 wk: shrinkage ≥0% to &lt; 30%, ≥30% to &lt; 60%, and ≥60% and growth &gt; 0% to &lt; 20%. Pts without progressive disease and who had not died at or prior to 13 wk after randomization were included in the landmark analysis. PFS data were analyzed for each category. A Cox multivariate landmark analysis was conducted for PFS for pts in the A+Ax arm, with DepOR as a continuous variable. Results: Results are reported on the basis of the first interim analysis, with a minimum follow-up of 6.0 mo in all pts. The table shows the proportion of pts in each shrinkage category and PFS outcomes according to best percent change in target lesions at the 13-wk landmark. After adjusting for prognostic covariates, Cox multivariate analyses showed a meaningful association between DepOR and PFS for pts in the A+Ax arm, consistent with the results observed in each shrinkage category. Conclusions: Greater tumor shrinkage at early imaging timepoints was associated with longer PFS in JAVELIN Renal 101. Clinical trial information: NCT02684006 .[Table: see text]
Relationship between Geriatric 8 screening score and treatment selection in patients with prostate cancer.
Authors: Shingo Hatakeyama, Masaki Momota, Itsuto Hamano, Teppei Okamoto, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto, Chikara Ohyama
Journal: Journal of Clinical Oncology (2020)

206 Background: This study aimed to evaluate the geriatric 8 (G8) screening tool for detecting frailty in patients with prostate cancer. Methods: Between January 2017 and June 2019, we prospectively evaluated the G8 in 540 prostate cancer patients, 444 with localized stage M0 and 96 with metastatic stage M1 disease. The primary endpoint was the comparison of G8 scores in patients treated with robot-assisted radical prostatectomy (RARP), radiotherapy, androgen deprivation therapy alone (ADT-alone) for localized disease, and standard care for the M1 disease. Secondary endpoint included the cutoff estimation of G8 score and the influence of G8 on prognosis. Results: The median age was 75 years. G8 scores ≤14 indicating frailty were seen in 36% of RARP (n = 214), 57% of RT (n = 209), 91% of ADT-alone (n = 21), and 70% of M1 disease (n=96). The median G8 score in M0 patients was significantly higher than that in M1 patients (14.5 vs 12.8, respectively). The median G8 score in patients treated with RARP, RT and ADT-alone was 15, 14, and 12, respectively. The patients with RARP had significantly higher G8 score than that of RT or ADT-alone. The optimal G8 cutoff score for patients with M0 and M1 disease was 13.0 (AUC: 0.681). The overall survival was significantly shorter in patients with G8 &lt;13 than that of ≥13. Conclusions: The G8 score of patients with localized and metastatic PC was significantly different. Frailty was significantly associated with treatment selection and prognosis in patients with PC.