tbuckley/cabot-search huggingface dataset:
Abstract PL2: The role of radiotherapy combined with immunotherapy in oligometastatic cancer
Authors: RR Weichselbaum, S Hellman
Journal: Cancer Research (2020)

Abstract In 1995 Samuel Hellman and I advanced the hypothesis that many cancers represent a spectrum of disease from purely localized to widespread, highlighting a disease state we termed “oligometastasis.” We proposed that oligometastasis represented an intermediary state between localized and widespread disease that was amenable to cure by metastasis-directed therapies. We also hypothesized that tumor clones that escape systemic therapies, now termed “oligoprogressors,” might be targets for ablation by focal treatments. I will present data supporting the basis and classification of (oligo)metastatic disease, as well as clinical trial results from patients, including those with breast cancer, that informs us regarding future clinical strategies. A decade ago our group noted that large radiation doses used in stereotactic radiotherapy employed in clinical trials of oligometastatic tumors induced immunogenic cell death, which has led us to investigations into the potential interaction between radiotherapy and immunotherapy. I will also present basic and clinical data from investigations into combined radio-immunotherapy treatment and suggest how these investigations might improve treatment of patients. Citation Format: RR Weichselbaum, S Hellman. The role of radiotherapy combined with immunotherapy in oligometastatic cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PL2.
Abstract P2-11-13: Specific aspect of utilization of the prognostic multigene assay for invasive lobular carcinoma at early stage: Oncotype Dx in the prospective French cohort PONDx
Authors: Gaëlle Douchet, Elsa Curtit, Hugues Bourgeois, Sandrine Richard, Sonia Zilberman, Younes Mahi, Joseph Gligorov
Journal: Cancer Research (2020)

Abstract Introduction: Invasive lobular carcinoma (ILC) differs from invasive ductal carcinoma (IDC) in a number of biological features with possible implication in treatment choice particularly for adjuvant chemotherapy. Multigene assay are being used increasingly to guide therapy for endocrine responsive breast cancer without HER2 overexpression or amplification at early stage. But if their interest is well defined for IDC, there are few data for ILC. Our study examine the impact of a multigene assay, Oncotype Dx (ODx), for the population of lobular breast cancer. Patients and methods: It was a retrospectively analysis of a French prospective cohort of patients (PONDx), with use of ODx (n= 882 patients). We studied and compared the specifics aspects of the use and the results of ODx for the ILC ( n= 125 (14,2%)) and IDC patients (n= 691 (78.3%)). We took account of the clinicopathological features, the Recurrence Score (RS), resulting of ODx and its impact on decision making. Results: In our cohort ILC were more frequently grade 2 tumours, had a significantly larger size, and lower Ki67 than IDC. RS distribution was lower for ILC (p&amp;lt;0,007): 66,4% of ILC had RS&amp;lt;18, 28,8% had RS from 18 to 30 and 4,8% had RS&amp;gt;30 ; whereas for IDC RS&amp;lt;18 for 52,2%, RS 18-30 for 36,8% and RS&amp;gt;30 for 11%. But there was a similar overall rate of change in treatment decision for ILC (46,4%) and IDC (43%) and a de-escalation of treatment (for no adjuvant chemotherapy) for 67,7% of ILC and 57,1% of IDC with initial indication of adjuvant chemotherapy. On the other hand, about 10% of patients with no initial indication of chemotherapy had an escalation of treatment after ODx for adjuvant chemotherapy. The analysis of the whole population shows a correlation of the lobular histologic type with low RS in univariate or multivariate analysis. Conclusion: RS is clearly prognostic for ILC and IDC. The predictive value of chemotherapy benefit was prospectively demonstrated for IDC, but not so clearly for ILC. In the PONDx cohort, despite a larger size of tumors, the RS of ILC was lower showing different biological features among the gene studied by ODx. The impact on decision making of ODx was similar for ILC and IDC, showing the interest of genomic assay in decision making independently from histologic subtypes (between ILC and IDC). Citation Format: Gaëlle Douchet, Elsa Curtit, Hugues Bourgeois, Sandrine Richard, Sonia Zilberman, Younes Mahi, Joseph Gligorov. Specific aspect of utilization of the prognostic multigene assay for invasive lobular carcinoma at early stage: Oncotype Dx in the prospective French cohort PONDx [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-13.
Covid-19: Contact tracing requires ending the hostile environment
Authors: Greg Dropkin
Journal: BMJ (2020)

<h3>Objective</h3> To determine whether brief interventions promoting physical activity are cost-effective in primary care or community settings. <h3>Design</h3> Systematic review of economic evaluations. <h3>Methods and data sources</h3> We searched MEDLINE, EMBASE, PsycINFO, CINAHL, EconLit, SPORTDiscus, PEDro, the Cochrane library, National Health Service Economic Evaluation Database and the Cost-Effectiveness Analysis Registry up to 20 August 2014. Web of Knowledge was used for cross-reference search. We included studies investigating the cost-effectiveness of brief interventions, as defined by National Institute for Health and Care Excellence, promoting physical activity in primary care or the community. Methodological quality was assessed using Drummond9s checklist for economic evaluations. Data were extracted from individual studies fulfilling selection criteria using a standardised pro forma. Comparisons of cost-effectiveness and cost-utility ratios were made between studies. <h3>Results</h3> Of 1840 identified publications, 13 studies fulfilled the inclusion criteria describing 14 brief interventions. Studies varied widely in the methods used, such as the perspective of economic analysis, intervention effects and outcome measures. The incremental cost of moving an inactive person to an active state, estimated for eight studies, ranged from £96 to £986. The cost-utility was estimated in nine studies compared with usual care and varied from £57 to £14 002 per quality-adjusted life year; dominant to £6500 per disability-adjusted life year; and £15 873 per life years gained. <h3>Conclusions</h3> Brief interventions promoting physical activity in primary care and the community are likely to be inexpensive compared with usual care. Given the commonly accepted thresholds, they appear to be cost-effective on the whole, although there is notable variation between studies.
Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma
Authors: Matthew Kyle Labriola, Jason Zhu, Rajan Gupta, Shannon McCall, Jennifer Jackson, Eric F Kong, James R White, Gustavo Cerqueira, Kelly Gerding, John K Simmons, Daniel George, Tian Zhang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint inhibitors (ICIs) have expanded treatment options for metastatic renal cell carcinoma (mRCC); however, there are limited predictive biomarkers for response to ICIs in this indication, with programmed death-ligand 1 (PD-L1) status demonstrating little predictive utility in mRCC. While predictive of ICI response in other tumor types, the utility of tumor mutation burden (TMB) in mRCC is unclear. Here, we assess TMB, loss of antigen presentation genes and PD-L1 status correlated with outcomes to ICI treatment in mRCC. Methods Tumor samples from 34 patients with mRCC treated with ICI therapy at Duke Cancer Institute were retrospectively evaluated using Personal Genome Diagnostics elio tissue complete (RUO version), a tumor genomic profiling assay for somatic variants, TMB, microsatellite status and genomic status of antigen presentation genes. Tumor samples were also analyzed with the Dako 28-8 PD-L1 immunohistochemistry assay. Deidentified clinical information was extracted from the medical record, and tumor response was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1 criteria. Results Patients were stratified by overall response following ICI therapy and designated as progressive disease (PD; n=18) or disease control groups (DC; n=16). TMB scores ranged from 0.36 to 12.24 mutations/Mb (mean 2.83 mutations/Mb) with no significant difference between the PD and DC groups (3.01 vs 2.63 mutations/Mb, respectively; p=0.7682). Interestingly, 33% of PD patients displayed loss of heterozygosity of major histocompatibility complex class I genes (LOH-MHC) vs 6% of DC patients. Nine of 34 samples were PD-L1-positive (4 in the PD group; 5 in the DC group), suggesting no correlation between PD-L1 expression and response to ICI therapy. Notably, the DC group displayed an enrichment of mutations in DNA repair genes (p=0.04), with 68.8% exhibiting at least one mutated homologous recombination repair (HRR)-related gene compared with only 38.9% of the PD group (p=0.03). Conclusions Overall, neither TMB nor PD-L1 correlated with ICI response and TMB was not significantly associated with PD-L1 expression. The higher incidence of LOH-MHC in PD group suggests that loss of antigen presentation may restrict response to ICIs. Separately, enrichment of HRR gene mutations in the DC group suggests potential utility in predicting ICI response and a potential therapeutic target, warranting future studies.
Corrigendum to “Tumor-selective lipopolyplex encapsulated small active RNA hampers colorectal cancer growth in vitro and in orthotopic murine” [Biomaterials 141 (2017) 13–28]
Authors: Lu-Lu Wang, Chen-Lin Feng, Wen-Sheng Zheng, Shuai Huang, Wen-Xuan Zhang, Hong-Na Wu, Yun Zhan, Yan-Xing Han, Song Wu, Jian-Dong Jiang
Journal: Biomaterials (2020)
Abstract 16668: Incidental Pulmonary Nodules in Emergent Coronary CT Angiography for Suspected Acute Coronary Syndrome: Impact of Revised 2017 Fleischner Society Guidelines
Authors: Jan-Erik Scholtz, Michael T Lu, Sandeep Hedgire, Nina Meyersohn, George R Oliveira, Anand M Prabhakar, Rajiv Gupta, Mannudeep K Kalra, Jo-Anne O Shepard, Udo Hoffmann, Brian B Ghoshhajra
Journal: Circulation (2017)

Introduction: Pulmonary nodules (PN) are frequently detected incidentally during coronary computed tomography angiography (CTA). Hypothesis: We evaluated whether the 2017 Fleischner Society Guideli...
Abstract 10656: Ventricular Abnormal Automaticity Involves Mitochondrial Ca2+ Flux
Authors: An Xie, Anyu Zhou, Hong Liu, Guangbin Shi, Man Liu, Feng Feng, Kenneth R Boheler, Samuel C Dudley
Journal: Circulation (2018)

Introduction: Ca2+ release from sarcoplasmic reticulum (SR) is known to contribute to automaticity via the cytoplasmic Na+-Ca2+ exchanger (NCX). Mitochondria participate in Ca2+ cycling. Hypothesis...
Abstract P2-12-11: Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial
Authors: Robert CF Leonard, Janine Mansi, Ann Yellowlees, Lesley Fallowfield, Valerie Jenkins
Journal: Cancer Research (2020)

Abstract The OPTION trial examined whether or not premenopausal women with early breast cancer receiving chemotherapy benefited from ovarian function protection with goserelin. This trial showed some preservation of ovarian function and fertility in women aged 40 years or less*. Additionally the OPTION trial examined the immediate and late impact of treatments on patients’ Quality of Life (QoL) over a 5 year period. Patients and Methods: In the OPTION trial 227 pre-menopausal patients with early stage breast cancer were randomly assigned to chemotherapy with or without goserelin. Patients were stratified by age into ≤40 years and &amp;gt; 40 years of age. QoL was assessed with the Functional Assessment of Cancer Therapy - Breast (FACT-B) and Endocrine Symptom checklist(ES) at baseline (pre- treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Results:-Two hundred and thirteen patients were available for analysis of QoL results. There was a temporary increase in endocrine symptoms of menopause in the goserelin group that was statistically higher than in the controls (P = 0.02) and was associated with a decrease in the main outcome measure of global QoL, TOI. This contrasted with a longer term outcome favouring the intervention in terms of QoL and fewer adverse endocrine symptoms, though these later findings were not statistically significant. Conclusions: Cytotoxic chemotherapy with or without goserelin causes a short term decrement in QoL for up to 6 months in otherwise well women.* Ann Onc 2017 28 1811-1816. Citation Format: Robert CF Leonard, Janine Mansi, Ann Yellowlees, Lesley Fallowfield, Valerie Jenkins. Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-11.
The blood–brain barrier in health and disease: Important unanswered questions
Authors: Caterina P. Profaci, Roeben N. Munji, Robert S. Pulido, Richard Daneman
Journal: The Journal of Experimental Medicine (2020)

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.
Cutaneous absorption of tretinoin in 0.05% cream and 5% chemical peel formulas
Authors: Ana Claudia Pompeu Raminelli, Andre Felipe Rodrigues-Oliveira, Rodrigo Yokota, Juliana Mayumi Sumita, Diogo Oliveira-Silva, Carlos Gustavo Wambier, Edileia Bagatin, Gislaine Ricci Leonardi
Journal: Journal of the American Academy of Dermatology (2020)
Abstract P4-13-09: Oncoplastic breast conserving surgery (OBCS): A meta-analysis of real-world data
Authors: Sebastian Kosasih, Salim Tayeh, Kefah Mokbel, Abdul Kasem
Journal: Cancer Research (2020)

Abstract Background: The role of oncoplastic breast conserving surgery (OBCS) is that of a middle ground between standard breast conserving surgery (SBCS) and mastectomy - it allows adequate resection margins of tumours unsuitable for traditional breast conserving surgery whilst allowing for a better cosmetic outcome and a reduced morbidity rate when compared to a traditional mastectomy. However, due to this being a relatively new type of procedure, there is limited evidence on its oncological safety, which is the ultimate goal of any breast cancer surgery. Methods: This study aims to compare oncological safety of OBCS with SBCS and mastectomy by examining the relative risk of cancer recurrence and re-operation rates through meta-analysis. Literature search of Pubmed and Web of Science databases was conducted looking for studies up until February 2019. Meta-Analysis was performed using R Statistical Software (www.r-project.org). Results: Initial finding of 645 studies was narrowed down to a pool of 19 studies including 18,163 patients. For the primary outcome measure of recurrence there was found to be no significant difference between the OBCS and SBCS or mastectomy (RR 0.861; 95% CI 0.640-1.160; p&amp;lt;0.296). The secondary outcome measure of re-operation was initially found to be significant in favour of OBCS (RR 0.64; 95% CI 0.46-0.89; p&amp;lt;0.01), however after adjustment for publication bias this was attenuated to an insignificant difference between the two study groups (RR 0.86; 95% CI 0.56-1.31; p&amp;gt;0.05). Conclusions: For both recurrence of cancer and re-operation rate, there was not found to be a significant difference between OBCS and more traditional techniques. This would suggest that OBCS is of comparable oncological safety to more established operations and a useful option in suitable patients. Citation Format: Sebastian Kosasih, Salim Tayeh, Kefah Mokbel, Abdul Kasem. Oncoplastic breast conserving surgery (OBCS): A meta-analysis of real-world data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-09.
Practical and low-cost strategies to increase the adenoma detection rate
Authors: Sergio Cadoni
Journal: Endoscopy (2020)

The quality of colonoscopy is measured predominantly by the adenoma detection rate (ADR), defined as the proportion of procedures with at least one adenoma removed. Despite the fact that the ADR rewards the same credit to an endoscopist who finds one adenoma as another who consistently finds more than one adenoma, an increase in the ADR is an important proxy for an increase in quality and efficacy of colonoscopy, especially in screening. In fact, both retrospective and prospective studies have shown that ADR is inversely associated with the risk of interval colorectal cancer (CRC) and CRC death [1] [2].
Tocilizumab, an anti-IL-6 receptor antibody, to treat COVID-19-related respiratory failure: a case report
Authors: J.-M. Michot, L. Albiges, N. Chaput, V. Saada, F. Pommeret, F. Griscelli, C. Balleyguier, B. Besse, A. Marabelle, F. Netzer, M. Merad, C. Robert, F. Barlesi, B. Gachot, A. Stoclin
Journal: Annals of Oncology (2020)
Treatment of PD-1/PD-L1 Inhibitor–Induced Dermatitis Resolves Concomitant Eruptive Keratoacanthomas
Authors: Lauren D. Crow, Ifeoma Perkins, Amanda R. Twigg, Marlys S. Fassett, Philip E. LeBoit, Timothy G. Berger, Rita Khodosh
Journal: JAMA Dermatology (2020)

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Abstract P5-11-16: The efficacy and safety of selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC): A systematic review and meta-analysis
Authors: Li Jing, Fu Fangmeng, Yu Liuwen, Huang Meng, Lin Yuxiang, Mei Qian, Lv Jinxing, Wang Chuan
Journal: Cancer Research (2020)

Abstract Background Breakthrough progress has been made in Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors when combined with endocrine therapy (ET) for hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Surprisingly, the overall survival (OS) advantage of ribociclib was reported in the MONALEESE-7 trial. This study was conducted to further evaluate the efficacy and safety of CDK4/6 inhibitors for HR+/HER2- ABC. MethodWe searched PUBMUD, MEDLINE, EMBASE et al to identify relevant randomized controlled trials that compared CDK4/6 inhibitors plus ET to ET alone in HR+/HER2- ABC. We extracted the hazard ratios (HRs) for progression-free survival (PFS) and OS, and risk ratios (RRs) for objective response rate (ORR), clinical benefit rate (CBR), adverse events (AEs). Statistical analysis was performed with random-effects model. Heterogeneity was assessed by I2 statistic. Result Eight trials and 4,580 patients were included in this meta-analysis. Both PFS (HR=0.54, 95% confidence interval [CI]: 0.50-0.59, p&amp;lt;0.00001) and OS (HR=0.79, 95% CI: 0.67-0.93, p=0.004) were significantly improved with CDK4/6 inhibitors for HR+/HER2- ABC. Similarly, the benefit was also manifested in ORR (RR=1.47, 95%CI: 1.30-1.67, p&amp;lt;0.00001) and CBR (RR=1.20, 95%CI: 1.12-1.30, p&amp;lt;0.00001). The improvement of PFS were observed in the combined treatment group, as both first-line (HR=0.56) and second-line therapy (HR=0.53), and irrespective of menopausal statue, the presence of visceral metastasis, previous treatment with chemotherapy, their race or age. Nevertheless, more toxicity profiles were observed with CDK4/6 inhibitors. The most common Grade 3-4 AEs is neutropenia (RR 31.95). Conclusion Substantial advantages of PFS and OS was observed for CDK4/6 inhibitors in HR+/HER2- ABC. Furthermore, the benefit of PFS was across all subgroups. Though associated with an increasing occurrence of AEs, most of which are reversable, manageable and acceptable. Therefore, CDK4/6 inhibitors could be recommended as the preferred options for HR+/HER2- ABC. Citation Format: Li Jing, Fu Fangmeng, Yu Liuwen, Huang Meng, Lin Yuxiang, Mei Qian, Lv Jinxing, Wang Chuan. The efficacy and safety of selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in hormone receptor-positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC): A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-16.