tbuckley/cabot-search huggingface dataset:
P24 Access to Oncological Care in Patients with Lung Cancer Treated in Public and Private Hospitals in Buenos Aires, Argentina
Authors: G. Recondo, C. Cosacow, H. Cutuli, L. Cermignani, S. Straminsky, A. Naveira, M. Pitzzu, G. De Ronato, G. Nacuzzi, G. Taetti, S. Corsico, G. Colucci, M. Berrueta, L. Gibbons, L. Gutierrez, E. García Elorrio
Journal: Journal of Thoracic Oncology (2018)
Treatment deintensification to surgery only for stage I human papillomavirus-associated oropharyngeal cancer.
Authors: John David Cramer, Robert L. Ferris, Umamaheswar Duvvuri
Journal: Journal of Clinical Oncology (2018)

6003 Background: Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) is an emerging entity with improved prognosis and distinct staging system. We assessed if deintensificaiton to surgery only decreased survival for stage I patients at low or intermittent risk compared with surgery with adjuvant radiation (RT) or chemoradiation (CRT). Methods: From the National Cancer Data Base (2010-2014), we identified patients with stage I HPV+ OPC (after restaging with eighth edition guidelines) treated with surgery only or with adjuvant RT or CRT. We compared survival for low risk patients (≤1 metastatic lymph nodes with no adverse features) and intermediate risk patients (2-4 metastatic lymph nodes, microscopic extranodal extension (ENE) or lymphovascular invasion). We excluded high risk patients with positive margins or macroscopic ENE. Results: We identified 2,463 patients with median follow-up of 44.3 months. In the low risk group 4-year overall survival was 93.0% with surgery only versus 95.6% with surgery + RT and 93.0% with surgery + CRT. In the intermediate risk group, 4-year overall survival was 92.2% with surgery only versus 93.3% with surgery + RT and 93.2% with surgery + CRT. On multivariate analysis, we observed no difference in survival with treatment between surgery only versus surgery + RT or surgery + CRT for both the low risk group (hazard ratio (HR) 0.75; CI 0.32-1.79 and HR 1.03; CI 0.42-2.51 respectively) or the intermediate risk group (HR 0.78; CI 0.42-1.46 and HR 0.85; CI 0.47-1.53 respectively). Conclusions: This offers retrospective evidence that surgery only for stage I patients at both low and intermediate risk provides equivalent survival to surgery and adjuvant therapy. This offers clinical equipoise for randomization to surgery only for stage I patients in future deintensification trials. Overall survival based on treatment and risk level. Group 1-y 2-y 3-y 4-y Log Rank Low Risk Surgery Only (n = 308) 96.7% 95.0% 94.2% 93.0% 0.59 Surgery + RT (n = 167) 99.4% 97.0% 95.6% 95.6% Surgery + CRT (n = 171) 99.4% 96.9% 94.9% 93.0% Intermediate Risk Surgery Only (n = 228) 97.8% 96.8% 94.1% 92.2% 0.77 Surgery + RT (n = 589) 99.3% 97.6% 96.2% 93.3% Surgery + CRT (n = 1,000) 99.0% 97.6% 95.8% 93.2%
Melapred: first susceptibility test to sporadic melanoma in daily dermatological practice.
Authors: Nadem Soufir, Meriem Benfodda, Steven Gazal, Vincent Descamps, Nika Madjlessi, Celeste Lebbe, Nicole Basset-Seguin, Alain Archimbaud, Kristina Opletalova, Valerie Vuong, Caroline Nicaise Bergere, Sandrine Massart-Manil, Bruno Machuel, Philippe Saiag, Yacine Merrouche, Armand Bensussan, Eduardo Nagore, Rajiv Kumar, Florent Grange
Journal: Journal of Clinical Oncology (2016)

e21056 Background: Melanoma (MM) has a dramatically poor prognosis in case of late diagnosis, emphasizing the critical role of early detection and prevention. We have developed a predictive algorithm calculating an individualized mm risk by combining clinical and genetic factors (test Melapred). We evaluated the acceptability of this test in a pilot study of patients seen in dermatology at hospital or in liberal exercise. Methods: The Melapred test allows the custom calculation of a personnalized mm risk score using an algorithm incorporating clinical risk factors and genetic mm risk factors. From April to October 2014, 261 patients were proposed to have the Melapred test, and results were given during a second clinical consultation, with explanations provided on the impact of the test result on clinical management and behaviour towards UV exposure. A survey was given to the patients, evaluating the service and potential impact of the Melapred test result. A questionnaire to physicians was also performed evaluating the usefulness of Melapred for high-risk mm patients in their daily exercise. An agreement of the local ethic committee has been obtained. Clinical data were collected on data sheet, and salivary DNA was collected by Oragene kit after information, signature and informed consent. Results: The Melapred test classified 64% of patients at high risk, 26% of patients at intermediate risk and 10% at low risk. The survey for the first 163 patients showed a positive evaluation with perception of its usefulness (90%), a clear desire to follow the recommendations of the physicians and to adapte their UV exposition to their mm score, a lack of anxiety generated by pending the result of the test. The physicians also had a very good evaluation of the test in terms of easy logistic, and help to survey and monitoring their patients. Therefore, the Melapred test is very well received and considered useful by patients and physicians, and is not cause of concern. Conclusions: Melapred test is well accepted and perceived by patients and physicians. Indications are the identification of high-risk patients and improved screening. Melapred is commercialized since july 2015 (www.melapred.com) under dermatogical prescription.
Ian Gilmore quits as government alcohol adviser in opposition to industry deal
Authors: Gareth Iacobucci
Journal: BMJ (2018)

A senior adviser to the UK government on alcohol policy has quit after voicing concern at Public Health England’s relations with the industry.

Ian Gilmore has stepped down from his role advising PHE after the agency entered into a partnership with the drinks industry that he argued would undermine efforts to protect public health.1

In a letter to the Times Gilmore and John Britton, who advises PHE on tobacco policy, criticised the agency’s decision to partner with Drinkaware, an alcohol education charity that receives funding from the industry, for a …
Aligning goals of care with aggressiveness at end of life (EOL).
Authors: Sara L Douglas, Barbara J Daly, Neal J. Meropol, Amy R Lipson
Journal: Journal of Clinical Oncology (2018)

10026 Background: Aggressiveness of care at EOL should be aligned with the patient’s (Pt) goals of care that ideally are established in collaboration with the oncologist (MD). This is particularly important for Pts with advanced disease. Methods: A longitudinal study was conducted. Adult Pts with Stage IV gastrointestinal (GI) or lung cancer were eligible. Each Pt and MD were surveyed at study enrollment and every 3 months for 15 months or until the Pt died. The primary variables of interest were the Pt and MD identified goals of care using a visual analog scale (VAS). Scores on the VAS ranged from 0 (comfort, quality of life) to 100 (survival, length of life). Individual scores > = 70 indicated a strong preference for prolonging survival and presumably a willingness to undergo aggressive interventions. Scores < = 30 indicated a strong preference for comfort care and presumably a willingness to forgo aggressive interventions. Aggressiveness of care was assessed using standard indicators (e.g. > 1 hospitalization in last 30 days of life, hospice stay < 3 days, etc.). Results: Between January 2015 and July 2017, 378 Pts were enrolled. Refusal rate was 27.5%; attrition rate 8.1%. 168 Pts (44%) died and their results are presented. Mean age was 64 years (range = 36-88 years); 66% had GI and 34% had lung cancer. Mean time from enrollment to death was 6.5 months (range = 3-15 months). As seen in Table 1, when there was strong agreement between Pt and MD on goals (either survival or comfort) the patient received levels of aggressiveness of care that were reflective of the goals. For example, when Pt and MD agreed on the goal of survival, 90% received at least 1 indicator of aggressive treatment. Conclusions: These data confirm the importance of aligning Pt and MD goals of care. When there are differences in goals, regardless of whether the Pt or MD identified comfort as the priority, Pts are at risk for receiving care that is not congruent with their preferences and goals of care. Survival Pt > MD Survival MD > Pt Survival Agreement Comfort Pt > MD Comfort MD > Pt Comfort Agreement % of Subjects (n = 168) 17.3% 11.3% 5.95% 19.6% 23.8% 12.5% Hospice LOS: Md 12.5 15 2 12 13 20.5 No Aggressive Tx (%) 75% 63% 10% 66% 64% 81%
Efficacy of liver resection for colorectal liver metastases up to mid-10s nodules as a substite of chemotherapy.
Authors: Takeshi Takamoto, Takuya Hashimoto, Shingo Miyamoto, Masatoshi Makuuchi
Journal: Journal of Clinical Oncology (2016)

e15044 Background: Improved technique and safety of liver resection(LR) expanded its indication for colorectal liver metastases (CRLM), irrespective of its size and number. However, as tumor number increases, possibility of disease recurrence and induction of systemic chemotherapy after LR becomes earlier. In this study, the time from LR to disease recurrence beyond further surgical treatment was defined as chemotherapy sparing period (CSP) and the expanded indication for CRLM was reevaluated, not from the point of view of cure but from long CSP. Methods: From 2007 to 2015, a total of 431 patient underwent LR for CRLM in our institution. Among them, 384 patients who did not received adjuvant chemotherapy postoperatively were analyzed. For disease recurrence, surgical treatment was initially applied except for patients with unresectable extrahepatic lesions or hepatic recurrence which was assessed to have no sufficient remnant liver volume after repeat LR. These patients' characteristics, long-term outcome, and the relationship between tumor number and CSP were investigated. Multivariate analysis was performed to identify risk factors for shorter CSP than 10 months, which is currently expectable progression-free survival time of first-line systemic chemotherapy. Results: The number of removed tumors was 3 (1-97) in median (range) and 7.2 in average. There was no surgery-related mortality. Median follow-up period was 32.0 months and 169 patients (54%) had CSP < 10 months. An approximate straight line between tumor number and median CSP showed intersection point 10 months of CSP and tumor number 18.2. Multivariate analysis showed positive primary nodal status, existence of extrahepatic lesions, and interval from last LR shorter than 6 months were independent risk factors for CSP < 10 months, in addition to tumor number and size. Conclusions: A median CSP > 10 months can be expected for patients having up to mid-10s number of CRLM. For these patients, LR can be suggested as a substitute of chemotherapy with consideration of the status of primary lymph node metastases, extrahepatic lesions, and interval from previous liver resection.
Abstract 11846: Cardiac Mitofusin1 Level Predicts the Response to the Treatment of Heart Failure Among Patients With Idiopathic Dilated Cardiomyopathy
Authors: Tohru Watanabe, Ippei Shimizu, Shuang Jiao, Takeshi Kashimura, Yohko Yoshida, Haruo Hanawa, Kazuyuki Ozaki, Tohru Minamino
Journal: Circulation (2016)

Medications targeting cardiac remodeling have become first-line therapy for heart failure. Some patients do not respond to the established treatment and described as non-responders. The prognosis of non-responders is poor and it is our urgent task to understand the underlying mechanism and find new therapeutic targets for this critical condition. In this context, it is essential to find biological markers of non-responding patients. Here we show that mitochondrial size and number in cardiomyocytes is significantly reduced, and this condition associates with a low mitochondrial fusion marker in the cardiac tissue of non-responders with idiopathic dilated cardiomyopathy (IDCM). We examined IDCM patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction and LV end-diastolic dimension did not show more than 10% improvement by the follow-up echocardiogram performed in 7-15months after the biopsy. No differences in the medications and age were observed between the groups. Transmission electron microscopy showed a significant reduction in both the size and number of mitochondria in the cardiomyocytes of non-responders (n=5) compared to responders (n=6) (0.2077±0.025 vs 0.2785±0.022μm 2 ; p&lt;0.05, 250±32 vs 344±48 mitochondria/field; p&lt;0.01). Quantitative PCR and immunofluorescence studies showed a significant reduction in mitofusin1, a critical regulator of mitochondrial fusion, but molecules involved in mitofission ( DNM1L and FIS1 ) and mitophagy ( BNIP3 and MAP1LC3A ) did not show difference between the groups. Studies with neonatal rat ventricular myocytes suggested that beta-1 adrenergic receptor mediated signaling pathway is critically involved in the regulation of Mfn1 , and the suppression of Mfn1 led to the significant reduction in mitochondrial respiration. We also found that cardiac ADRB1 is markedly reduced in non-responders. These results indicate that cardiac mitofusin1 would become a biomarker for non-responders in IDCM patients. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for heart failure patients.
Analysis of mutational burden and adaptive immune response in desmoplastic melanomas treated with PD-1/L1 inhibitors.
Authors: Siwen Hu-Lieskovan, Zeynep Eroglu, Jesse Meir Zaretsky, Dae Won Kim, Alain Patrick Algazi, Douglas Buckner Johnson, Elizabeth Liniker, Ben Kong, Rodrigo Munhoz, Suthee Rapisuwon, Bartosz Chmielowski, Jeffrey Alan Sosman, Richard A. Scolyer, Richard Wayne Joseph, Michael Andrew Postow, Matteo S. Carlino, Wen-Jen Hwu, Georgina V. Long, Antoni Ribas
Journal: Journal of Clinical Oncology (2017)

9558 Background: Desmoplastic melanoma (DM) is a rare subtype of melanoma characterized by a dense fibrous stroma, resistance to chemotherapy and no actionable driver mutation for targeted therapy. We investigated the efficacy of PD-1/L1 inhibitors and correlation with genetic landscape and tumor immune microenvironment in DM. Methods: Retrospective analysis of 1054 pts with melanoma treated with anti-PD-1/L1, resulting in 57 pts with unresectable or metastatic DM. Available baseline biopsies were analysed by digital quantitative immunohistochemistry (IHC) for CD8 and PD-L1 and by whole exome sequencing (WES), compared to available tissue from non-DM pts treated with anti-PD1/L1 at UCLA. Results: At a median follow up of 20 mo, 40 pts (70%, 95% CI 57-82) had an objective response by RECIST 1.1 criteria, including 18 (45%) CRs with no relapse observed to date. Responses were similar in DM subsets (23 pure, 29 mixed and 5 indeterminate). Kaplan-Meier estimated 1-year and 2-year overall survival were 85% (95% CI 78-98) and 74% (95% CI 64-89). WES revealed a median of 1282 (interquartile range 517-1692) non-synonymous somatic mutations per tumor in DM tumors (n = 17), significantly higher (p = 0.02) than the median of 462 (interquartile range 230-1150) in non-DM (n = 23). Mutations in NF-1 were the most common (13/17) followed by loss-of-function TP53 and ARID2, and &gt; 82% of single nucleotide mutations were UV damage signatures. IHC analysis from 19 DM and 13 non-DM revealed a strikingly higher percentage of PD-L1 positive cells in the tumor parenchyma in DM (p = 0.04), highly associated with CD8 density and PD-L1 expression in the tumor invasive margins, indicating an active adaptive immune response. No genetic mechanisms known to cause constitutive PD-L1 expression were detected in these samples. Conclusions: Patients with advanced DM derive significant clinical benefit from PD-1/L1 inhibitors, likely related to the high mutational burden and a highly active adaptive immune response as the main mechanism of immune escape prior to therapy. Our results challenge the general conception that dense fibrous stroma around the malignant cells interferes with immune cell infiltration and efficacy of immunotherapy.
Abstract MP77: Glucose Peaks and Risk of Dementia Among Persons with Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Andreea Rawlings, A. Richey Sharrett, Thomas Mosley, Shoshana Ballew, Jennifer Deal, Michael Steffes, Elizabeth Selvin
Journal: Circulation (2016)

Introduction: The risk of dementia increases with increasing levels of hemoglobin A1c (HbA1c), a measure of average blood glucose. However the association between glucose peaks and dementia in persons with diabetes is unclear. 1,5-anhydroglucitol (1,5-AG) is a novel biomarker of glucose peaks, with low levels reflecting blood glucose concentrations that exceed the renal filtration threshold (~180 mg/dl) over the prior 7-10 days. Hypothesis: Glucose peaks, indicated by low levels of 1,5-AG, will be associated with higher risk of dementia, independent of HbA1c and other dementia risk factors. Methods: We conducted a prospective analysis of 1568 participants with diabetes from visit 2 (1990-1992) of the ARIC Study. Diabetes was defined based on self-reported physician diagnosis, diabetes medication use, or HbA1c ≥ 6.5%. Community surveillance of hospitalizations was used to identify incident dementia. Cases were defined as the first occurrence of a hospitalization with an ICD-9 code for dementia appearing in any position in the hospital discharge record. We used Cox regression to examine the association between 1,5-AG (modeled linearly) and incident dementia, adjusted for demographic and clinical risk factors, including HbA1c. Results: At baseline, the mean age was 58 years, 58% were female, 54% were white, and mean HbA1c was 8.1%. Over a median follow-up of 18 years, 158 participants had a hospitalization with an ICD-9 code of dementia. Each unit decrease in 1,5-AG increased the risk of dementia by 4% (HR=1.04, p-value=0.03, Figure). Associations were similar when 1,5-AG was modeled using linear splines. Conclusions: Short-term glucose peaks were associated with higher risk of dementia among adults with diabetes, independent of HbA1c and other dementia risk factors. More studies are needed to determine if targeting glucose peaks, in addition to average glucose, among persons with diabetes can reduce the risk of dementia.
Are physicians social networks linked to breast cancer screening recommendations for older adults?
Authors: Craig Evan Pollack, Archana Radhakrishnan, Andrew M Parker, Kala Visvanathan, Sarah A Nowak
Journal: Journal of Clinical Oncology (2017)

6550 Background: Physicians’ prior experiences caring for patients with breast cancer along with experiences in their social networks including family members and friends may be a key and understudied driver of recommendations for cancer screening. Methods: The Breast Cancer Social Networks study (CanSNET) is a national, mailed survey of 2,000 primary care providers (PCPs) randomly selected from the American Medical Association Masterfile. PCPs were asked to provide detailed characteristics on up to 2 women they know who have been diagnosed with breast cancer and “whose cancer, broadly speaking, had the greatest impact” on them, including friends, family members and patients. Each woman was categorized as being diagnosed (a) through screening with a good prognosis, (b) not through screening with a good prognosis, (c) through screening with a poor prognosis or (d) not through screening with a poor prognosis. We used a logistic regression model to assess the association between the network member and recommendations for routine screening mammograms to average-risk women ages 75+, adjusting for provider and practice characteristics. Results: Overall 871 physicians responded to the survey yielding an adjusted response rate of 52.3% (out of 1665 eligible). We found that 67% of physicians recommended screening for women 75+. The sample reported on 762 patients, 378 family members and 476 other network members who had been diagnosed with breast cancer. Ten percent of patients and 25.1% of family members reported on died of their disease. In adjusted models, we found that physicians who reported on family members who did not receive a mammogram and had a poor prognosis were significantly more likely to recommend screening compared to those who did not (Odds Ratio 1.22, 95% Confidence Interval 1.03, 1.43). Conclusions: Physicians’ experiences with their social networks was linked to their breast cancer screening recommendations, underscoring the potential for information that is learned from social networks to differ from clinical guidelines and highlighting the need to address a broad array of influences in trying to reduce potential over-screening in cancer.
Reassessing the role of internalin B in Listeria monocytogenes virulence using the epidemic strain F2365
Authors: J.J. Quereda, I.M. Rodríguez-Gómez, J. Meza-Torres, J. Gómez-Laguna, M.A. Nahori, O. Dussurget, L. Carrasco, P. Cossart, J. Pizarro-Cerdá
Journal: Clinical Microbiology and Infection (2018)

ObjectivesTo investigate the contribution to virulence of the surface protein internalin B (InlB) in the Listeria monocytogenes lineage I strain F2365, which caused a deadly listeriosis outbreak in California in 1985.MethodsThe F2365 strain displays a point mutation that hampers expression of InlB. We rescued the expression of InlB in the L. monocytogenes lineage I strain F2365 by introducing a point mutation in the codon 34 (TAA to CAA). We investigated its importance for bacterial virulence using in vitro cell infection systems and a murine intravenous infection model.ResultsIn HeLa and JEG-3 cells, the F2365 InlB+ strain expressing InlB was ≈9-fold and ≈1.5-fold more invasive than F2365, respectively. In livers and spleens of infected mice at 72 hours after infection, bacterial counts for F2365 InlB+ were significantly higher compared to the F2365 strain (≈1 log more), and histopathologic assessment showed that the F2365 strain displayed a reduced number of necrotic foci compared to the F2365 InlB+ strain (Mann-Whitney test).ConclusionsInlB plays a critical role during infection of nonpregnant animals by a L. monocytogenes strain from lineage I. A spontaneous mutation in InlB could have prevented more severe human morbidity and mortality during the 1985 California listeriosis outbreak.