tbuckley/cabot-search huggingface dataset:
P14.57 WHO grade II and III meningioma: a large mono-institutional retrospective series
Authors: G Simonetti, P Gaviani, M Farinotti, F Legnani, B Pollo, V Pinzi, A Botturi, V Redaelli, A Silvani
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningiomas are usually considered benign lesions, however a part of them can show very aggressive behavior with tendency to metastasize. This subgroup is known as high-grade meningiomas (HGM). Due to the rarity of the disease, effective medical treatments are lacking, especially at the time of recurrence. We aim to describe the clinical, radiological and molecular features of a large population of HGM diagnosed between 2010 and 2018. The secondary aim was to evaluate survival (PFS) and overall survival (OS). MATERIAL AND METHODS We collected clinical and survival data from primitive WHO grade II and III meningioma patients treated at Fondazione IRCCS Istituto Neurologico Carlo Besta from January 2010 to December 2018. Records were collected on a web-based platform (Microsoft Excel) that was customized for this study. The database, contained epidemiological, diagnostic (radiological and histological/molecular), surgical, therapeutic and recurrence information, as well as survival data. RESULTS 183 patients (105 females and 78 males), with median age of 58 years (25–88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p=0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00–1.12, p=0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT/SRS while a difference on PFS was seen (4.1 years vs 5.2 years p=0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. CONCLUSION Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT/SRS remains controversial, with no statistically significant impact on OS but a possible role on PFS. At relapse, no chemotherapies are able to achieve disease control and recurrent HGM remains the real challenge for future research, focusing on biological/molecular predictors in order to achieve a patient-tailored treatment.This retrospective study allowed to analyzed the largest national recent series of aggressive meningiomas with the purpose of identify relevant outcome measures for future prospective studies. Our findings could be important to give a snapshot of the current attitude to treat aggressive meningiomas but also to inspire national and international collaboration in order to provide evidence-based management strategies trying to obtain a standard of care.
Implementing a patient navigation program to improve adherence with cancer treatment for community health center patients newly diagnosed with cancer.
Authors: Sanja Percac-Lima, Kelly Irwin, Emma Whited, Carmen Benjamin, Ausubel Pichardo, Mira Oravcova-Mejia, Solomon Thompson, James Morrill, Colleen Ford, Amy Wheeler, Beverly Moy
Journal: Journal of Clinical Oncology (2021)

103 Background: Community health centers’ (CHCs) patients newly diagnosed with cancer often experience barriers to accessing timely treatment. Patient navigation decreases barriers to cancer screening and diagnostic care, but the exact impact on cancer treatment is unclear. We implemented patient navigation to provide underserved patients with support to access and adhere to cancer treatment. The goal of our study is to determine the effect of patient navigation on missed appointment rates, treatment adherence, and health outcomes among an underserved patient population. Here, we present preliminary data about program implementation. Methods: Utilizing a population health registry, TopCare, and referrals from CHCs physician champions, newly diagnosed cancer patients from Massachusetts General Hospital CHCs were referred to the Cancer Center, identified and verbally consented to participate in the study’s intervention. Patients are randomized either to receive in-person patient navigation or enhanced usual care, which consists of two reminder phone calls prior to each oncology appointment. Adherence to treatment, healthcare utilization, patient satisfaction with cancer care and patient navigation, patient engagement, financial burden, symptom burden, health-related quality of life, and psychosocial care are longitudinally assessed. Our primary outcome is missed appointment rate to oncology appointments. Results: The trial started in November 2017 and as of April 2021, we have identified 349 eligible patients and enrolled 261 (82% consent rate for reached patients). Of 261 enrolled patients, 50% were women, 38% identified as non-White, 25% identified as Hispanic or Latino, and 28% did not speak English. The most frequent cancer types enrolled include genitourinary (n=67), thoracic (n=47), gastrointestinal (n=47), and breast (n=46). Patients had 6257 visits and 195 were missed (3.1%). Navigators performed 4553 interventions. There were 152 emergency department visits and 127 unplanned hospital admissions. Of 120 referrals to supportive care, 54 were to social work, 38 to palliative care and 28 to Psychiatric Oncology or behavioral health. Conclusions: Patient navigation is feasible for underserved CHC patients newly diagnosed with cancer. Our current missed appointment rate is 3.1%, including the time period of the COVID-19 pandemic. After trial completion in July 2021, we will compare the outcomes in patients who received in-person patient navigation to patients who were randomized to enhanced usual care. Clinical trial information: NCT03226405.
P14.81 Brain metastases of lung adenocarcinoma - Clinicopathological profile and outcomes of a single-centre
Authors: M J Sousa, R Basto, J C Magalhães, C Costa, R Garcia, I Domingues, E Jesus, G Sousa
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) are considered a major determinant of overall survival (OS). Historically, surgical resection (SR), stereotactic radiosurgery (SRS), or/and whole-brain radiation therapy (WBRT) followed by chemotherapy has been the treatment modalities for BM from lung adenocarcinoma. Recent insights into the biology of adenocarcinoma have led to a wealth of novel therapies, including tyrosine kinase inhibitors (TKIs). Here, we review the pattern of brain metastasis in lung adenocarcinoma patients and management strategies in our centre. MATERIAL AND METHODS We performed a single-centre retrospective analysis of patients with lung adenocarcinoma and BM between 2017–2020. Data were collected from electronic medical records, including clinical and histopathological features and outcomes. Survival curves were estimated with the Kaplan-Meier method and compared using the log-rank test. RESULTS We identified 29 patients, 65% male, median age 65 years (range 38–84); 55% ECOG PS 0–1; 59% smokers; 55% had extracranial metastases (ECM) and 66% were symptomatic, 24% were EGFR mutated, the frequency of ALK rearrangement was 14%, in 14% the molecular testing was not performed. We treated 59% with WBRT, 12% with SRS, 11% with SR+WBRT and 4% with SR+SRS; 14% were referred for palliative care. Clinical deterioration during local therapy was observed in 32% of the patients and, consequently, they haven’t undergone systemic treatment. After local treatment, 26% received chemotherapy (CT) and 28% received TKIs therapy. Median OS (mOS) was 11.3 months (95% CI 2.4–20.3) for the CT subgroup; mOS for the TKIs subgroup was not reached, but the 1-year survival rate was 67%. CONCLUSION BM confers a worse prognosis in lung adenocarcinoma patients. Currently, targeted systemic treatments in patients with driver mutations improve survival and have demonstrated efficacy in lung adenocarcinoma metastatic to the brain. Further research is needed to find better treatments for BM in NSCLC patients with no driver mutations.
A novel β-glucan–oligonucleotide complex selectively delivers siRNA to APCs via Dectin-1
Authors: Atsushi Uno, Kenji Arima, Masako Shimazaki, Maki Ushida, Kanako Amano, Reiko Namikawa, Kazuo Sakurai
Journal: Journal of Controlled Release (2021)

Delivering therapeutic nucleic acids to targeted cells and organs has been a challenge for decades. A novel technology to deliver oligonucleotide therapeutics to immune cells is here described. In this approach, a macromolecular complex of oligonucleotides and the β-1,3-glucan schizophyllan (SPG) is selectively delivered to cells expressing a lectin receptor, Dectin-1, via SPG-Dectin-1 interaction. Detailed investigation of Dectin-1-expressing cells revealed that Dectin-1 is expressed in all subsets of monocytes as well as dendritic cell (DC) populations, including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), in humans. The expression patterns in mice and humans are comparable, except for the expression in pDCs. The results indicate that Dectin-1 is expressed on cells capable of professional antigen presentation, except for B cells. We chose CD40 as a target gene for small interfering RNA (siRNA) as CD40 expression in antigen-presenting cells (APCs), particularly in DCs, plays critical roles in regulating immune responses. Dose-dependent cellular uptake of siCD40-SPG complexes was confirmed in cells expressing Dectin-1. Gene silencing activity was confirmed in vitro by the reduction of CD40 mRNA and by the site-specific cleavage of CD40 mRNA as determined by the 5' RNA ligase-mediated rapid amplification of cDNA ends (5'RLM-RACE) technique. In vivo activity of siCD40-SPG complexes was demonstrated as the reduced CD40 protein expression in monocytes and DCs in mice. Furthermore, the in vivo activity of siCD40-SPG targeting human CD40 was confirmed in cynomolgus monkeys by the 5'RLM-RACE technique. In conclusion, we have demonstrated the receptor-ligand binding-mediated delivery of siRNA targeting immune-regulating monocytes and DCs via the interaction of SPG and its receptor, Dectin-1. As monocytes and DCs play central roles in inducing and controlling immune responses, Dectin-1-targeted delivery of nucleic acids should provide a useful tool for developing drugs to treat a wide range of diseases, including autoimmune diseases, allergy, and cancer, as well as transplantation.
Coronary Artery Disease in Young Women After Radiation Therapy for Breast Cancer
Authors: Lauren E. Carlson, Gordon P. Watt, Emily S. Tonorezos, Eric J. Chow, Anthony F. Yu, Meghan Woods, Charles F. Lynch, Esther M. John, Lene Mellemkjӕr, Jennifer D. Brooks, Julia A. Knight, Anne S. Reiner, Xiaolin Liang, Susan A. Smith, Leslie Bernstein, Lawrence T. Dauer, Laura I. Cerviño, Rebecca M. Howell, Roy E. Shore, John D. Boice, Jonine L. Bernstein, Jonine L. Bernstein, Marinela Capanu, Irene Orlow, Mark Robson, Jørgen H. Olsen, Kathleen E. Malone, Marilyn Stovall, Kristina Blackmore, Irene Harris, Rikke Langballe, Cecilia O’Brien, Rita Weathers, Michele West, Lisa Hunter, Judy Goldstein, Elaine Ramos
Journal: JACC CardioOncology (2021)

Radiation therapy (RT) for breast cancer increases risk of coronary artery disease (CAD). Women treated for left- vs right-sided breast cancer receive greater heart radiation exposure, which may further increase this risk. The risk of radiation-associated CAD specifically among younger breast cancer survivors is not well defined.The purpose of this study was to report CAD risk among participants in the Women's Environmental Cancer and Radiation Epidemiology Study.A total of 1,583 women who were <55 years of age when diagnosed with breast cancer between 1985 and 2008 completed a cardiovascular health questionnaire. Risk of radiation-associated CAD was evaluated by comparing women treated with left-sided RT with women treated with right-sided RT using multivariable Cox proportional hazards models. Effect modification by treatment and cardiovascular risk factors was examined.In total, 517 women who did not receive RT and 94 women who had a pre-existing cardiovascular disease diagnosis were excluded, leaving 972 women eligible for analysis. Their median follow-up time was 14 years (range 1-29 years). The 27.5-year cumulative incidences of CAD for women receiving left- vs right-sided RT were 10.5% and 5.8%, respectively (P = 0.010). The corresponding HR of CAD for left- vs right-sided RT in the multivariable Cox model was 2.5 (95% CI: 1.3-4.7). There was no statistically significant effect modification by any factor evaluated.Young women treated with RT for left-sided breast cancer had over twice the risk of CAD compared with women treated with RT for right-sided breast cancer. Laterality of RT is independently associated with an increased risk of CAD and should be considered in survivorship care of younger breast cancer patients.
OS10.7.A Localization patterns of language errors during direct electrical brain stimulation: a systematic review
Authors: E Collée, A Vincent, C Dirven, D Satoer
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Awake craniotomy with direct electrical stimulation (DES) is the standard treatment for patients with eloquent area gliomas. Language errors (paraphasias) are detected with DES and they indicate functional boundaries that need to be maintained to preserve quality of life. However, it is not fully clear in which brain locations paraphasias at different linguistic modalities and levels (production, comprehension, reading, writing, phonology, semantics, syntax) occur. MATERIALS AND METHODS A systematic review was conducted. We included 102 studies reporting on specific paraphasias and the corresponding brain locations during awake craniotomy with DES in adult glioma patients. RESULTS First, a wide distribution of brain locations for all paraphasias (n=930) was found, but patterns were observed. Cortically, paraphasias occurred most often in the precentral gyrus (22%), while subcortically, they occurred mainly at the inferior fronto-occipital fascicle (IFOF: 10%). Localization patterns for different paraphasia types and the corresponding language functions were also found: production/articulation (n=393)-precentral gyrus (41%), inferior frontal gyrus (9%), frontal aslant/striatal tract (4%), postcentral gyrus (3%); semantics (n=128)-IFOF (57%), superior temporal gyrus (9%); phonology (n=115)-arcuate fascicle (52%), superior longitudinal fascicle (10%), uncinate fascicle (3%); reading (n=25)-temporal lobe (48%), inferior longitudinal fascicle (32%); syntax (n=15)-inferior frontal gyrus (27%); speech initiation (n=9)-supplementary motor area (33%), frontal aslant tract (22%), frontal striatal tract (22%); writing (n=7)-superior parietal gyrus (71%). Second, 59% of all paraphasias occurred cortically, 40% subcortically and 1% at both levels. CONCLUSION The localization of most paraphasias are consistent with the assumed functionality of those brain locations as presented in the Dutch Linguistic Intraoperative Protocol model. However, new locations for production/articulation, phonology, reading and writing were found. This needs to be taken into consideration for future selection of pre, intra and postoperative language tasks at different language modalities and levels. Additionally, DES should always be applied at the subcortical level as a standard addition to the routine cortical mapping during awake craniotomy. In conclusion, this is the first systematic review on the localization of specific paraphasias during awake craniotomy. Based on the identified language localization patterns, language tasks could be selected more accurately. This could guide, and perhaps improve, pre, intra and postoperative language testing and monitoring, which in turn, may pave the way to a better postoperative language outcome. The possible relation between different intraoperative paraphasias and language outcome has yet to be determined.
Cachexia is Prevalent in Patients With Hepatocellular Carcinoma and Associated With Worse Prognosis
Authors: Nicole E. Rich, Samuel Phen, Nirali Desai, Sukul Mittal, Adam C. Yopp, Ju Dong Yang, Jorge A. Marrero, Puneeth Iyengar, Rodney E. Infante, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2021)
Prevalence and incidence of young onset dementia and associations with comorbidities: A study of data from the French national health data system
Authors: Laure Carcaillon-Bentata, Cécile Quintin, Marjorie Boussac-Zarebska, Alexis Elbaz
Journal: PLoS Medicine (2021)

Background Dementia onset in those aged &lt;65 years (young onset dementia, YOD) has dramatic individual and societal consequences. In the context of population aging, data on YOD are of major importance to anticipate needs for planning and allocation of health and social resources. Few studies have provided precise frequency estimates of YOD. The aim of this study is to provide YOD prevalence and incidence estimates in France and to study the contribution of comorbidities to YOD incidence. Methods and findings Using data from the French national health data system (Système National des Données de Santé, SNDS) for 76% of the French population aged 40 to 64 years in 2016 ( n = 16,665,795), we identified all persons with dementia based on at least 1 of 3 criteria: anti-Alzheimer drugs claims, hospitalization with the International Classification of Diseases-10th Revision (ICD-10) dementia codes (F00 to F03, G30, G31.0, G31.1, or F05.1), or registration for free healthcare for dementia. We estimated prevalence rate (PR) and incidence rate (IR) and estimated the association of comorbidities with incident YOD. Sex differences were investigated. We identified 18,466 (PR standardized = 109.7/100,000) and 4,074 incident (IR standardized = 24.4/100,000 person-years) persons with prevalent and incident YOD, respectively. PR and IR sharply increased with age. Age-adjusted PR and IR were 33% (95% confidence interval (CI) = 29 to 37) and 39% (95% CI = 31 to 48) higher in men than women ( p &lt; 0.001 both for PR and IR). Cardio- and cerebrovascular, neurological, psychiatric diseases, and traumatic brain injury prevalence were associated with incident YOD (age- and sex-adjusted p -values &lt;0.001 for all comorbidities examined, except p = 0.109 for antihypertensive drug therapy). Adjustment for all comorbidities explained more than 55% of the sex difference in YOD incidence. The lack of information regarding dementia subtypes is the main limitation of this study. Conclusions We estimated that there were approximately 24,000 and approximately 5,300 persons with prevalent and incident YOD, respectively, in France in 2016. The higher YOD frequency in men may be partly explained by higher prevalence of cardiovascular and neurovascular diseases, substance abuse disorders, and traumatic brain injury and warrants further investigation.
Assessment of Survival Model Performance Following Inclusion of Epstein-Barr Virus DNA Status in Conventional TNM Staging Groups in Epstein-Barr Virus–Related Nasopharyngeal Carcinoma
Authors: Wang-Zhong Li, Hai-Jun Wu, Shu-Hui Lv, Xue-Feng Hu, Hu Liang, Guo-Ying Liu, Nian Lu, Wei-Xin Bei, Xing Lv, Xiang Guo, Wei-Xiong Xia, Yan-Qun Xiang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Nonanatomic prognostic factors complement the traditional anatomic staging system and could be incorporated into the tumor-node-metastasis (TNM) framework. Several diseases have incorporated nonanatomic prognostic factors into the determination of TNM staging groups. <h3>Objective</h3> To refine TNM staging groups for Epstein-Barr virus (EBV)–related nonmetastatic nasopharyngeal carcinoma (NPC) by incorporating EBV DNA status. <h3>Design, Setting, and Participants</h3> This multicenter prognostic study included patients with NPC treated with radiotherapy at 2 hospitals in China from January 2008 to December 2016. Progression-free survival and overall survival according to EBV DNA status and the TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings, and then a refined RPA staging schema was developed, validated, and compared with existing staging schemes. Statistical analyses were conducted from October 1, 2020, to June 15, 2021. <h3>Exposures</h3> Curative intensity-modulated radiotherapy with or without platinum-based chemotherapy. <h3>Main Outcomes and Measures</h3> The primary end point was progression-free survival. The performance of the staging system was assessed using the time-dependent area under the receiver operating characteristic curves and the TNM stage system's evaluation methodology. <h3>Results</h3> A total of 2354 patients (1709 men [72.6%]; median [interquartile range] age, 45 [38-53] years) were split into training (1372 [58.3%]), internal validation (672 [28.5%]), and external validation (310 [13.2%]) cohorts. Pretreatment EBV DNA was detected in 1338 (56.8%) patients. EBV DNA status was an independent prognostic factor: lower survival probability by higher TNM stage was evident in EBV DNA–positive patients but not in those with EBV DNA–negative disease. After integrating EBV DNA status and TNM stage, nonmetastatic NPC cases were categorized into RPA-I (T1-3N0 or EBV DNA–negative T1-3N1 cancers), RPA-II (EBV DNA–positive T1-3N1-2 or EBV DNA–negative T1-3N2-3/T4N0-3 cancers), and RPA-III (EBV DNA–positive T4N0-3/T1-3N3 cancers) groups, each with distinctly different prognosis. This system of RPA staging outperformed the current TNM stage system and 2 reported RPA staging schemes. These results were internally and externally validated. <h3>Conclusions and Relevance</h3> An RPA-based staging system for EBV-related NPC cases was associated with improved outcomes. This staging system may facilitate prognostic stratification and clinical trial designs.
Tenofovir Is Superior to Entecavir on Tertiary Prevention for BCLC Stage 0/A Hepatocellular Carcinoma after Curative Resection
Authors: Ming-Chao Tsai, Chih-Chi Wang, Wei-Chen Lee, Chih-Che Lin, Kuo-Chin Chang, Chien-Hung Chen, Chao-Hung Hung, Ming-Tsung Lin, Chang-Chun Hsiao, Chao-Long Chen, Rong-Nan Chien, Tsung-Hui Hu
Journal: Liver Cancer (2021)

It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for hepatitis B virus (HBV)-related HCC.The aim of this study was to compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival (OS) of patients after curative hepatectomy.From January 2010 to December 2019, 20,572 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 219 consecutive patients treated with ETV (n = 146) or TDF (n = 73) after curative hepatectomy for HBV-related HCC of Barcelona Clinic Liver Cancer stage 0 or A were analyzed by propensity score matching (PSM) (2:1) analysis and competing risk analysis. HCC recurrence and OS of patients were compared between ETV and TDF groups.After a median follow-up of 52.2 months, 81 patients (37.0%) had HCC recurrence, 33 (15.1%) died, and 5 (2.3%) received liver transplantation. TDF therapy was an independent protective factor for HCC recurrence compared with ETV therapy (HR, 1.687; 95% CI, 1.027-2.770, p = 0.039); however, no difference in the risk of death or liver transplantation. Results were similar in competing risk analysis. We further found that TDF therapy was significantly associated with a lower risk of late recurrence (HR, 4.705; 95% CI, 1.763-12.558, p = 0.002), but not in early recurrence.TDF therapy is associated with a significantly lower risk of HCC recurrence, especially of late recurrence, than ETV therapy among patients who undergo curative hepatectomy for HBV-related early-stage HCC.