tbuckley/cabot-search huggingface dataset:
Markers of a metastatic niche in the omentum in ovarian cancer.
Authors: Tatiana I. Moiseenko, Elena M. Frantsiyants, Irina V. Kaplieva, Valeria A. Bandovkina, Natalia D. Cheryarina, Anna P. Menshenina, Meri L. Adamyan, Ekaterina V. Verenikina, Darya Yakubova, Konstantin P. Boyko, Maria G. Ilchenko, Viktor V. Gurnak, Elena I. Agarkova, Tatiana G. Chalabova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e18081 Background: Ovarian cancer spreads intraperitoneally due to the interaction of tumor cells and the omental mesothelium, creating a metastatic niche and supporting elements of cancer cell expansion such as adhesion, proliferation, migration, and neoangiogenesis. The purpose of the study was to analyze levels of VEGFA, IGF-I, IGF-II and TGFβ1 in omental tissues in ovarian cancer (OC). Methods: The main group included 23 patients with metastatic OC T3-4аN0-3M1; the comparison group – 21 patients with non-metastatic OC T3-4аN0-3M0; the control group – 19 non-cancer patients. Levels of VEGFA, IGF-I, IGF-II and TGFβ1 were measured by standard ELISA methods in tissues of primary tumors and the omentum. Results: Levels of growth factors in the comparison group were not elevated compared to control values. Growth factors in omental tissues in the main group were increased compared to control values: VEGFA – by 2.5 times, IGF-I – by 3.4 times, IGF-II – by 2.5 times, TGFβ1 - by 3.1 times. In the comparison group, the levels in omental tissues were lower than in the main group: VEGFA – by 1.7 times (p &lt; 0.05), IGF-I – by 2.1 times, IGF-II – by 1.6 times (p &lt; 0.05); TGFβ1 did not differ from the levels in the main group. Conclusions: Higher expression of VEGFА in the omentum with metastases can be considered a significant factor in the formation of signaling pathways between metastatic tumor cells and local non-cancer cells. IGF-I and IGF-II trigger the endothelial growth factor. The TGFβ1 activation in the omentum in metastatic ovarian cancer is necessary for the paracrine induction and transition of disseminated tumor and/or stem cells from the "sleeping" to the active state.
Improving the AJCC/TNM staging classification for colorectal cancer: The prognostic impact of tumor deposits.
Authors: Oliver Peacock, Thitithep Limvorapitak, Chung-Yuan Hu, Brian K. Bednarski, Melissa Taggart, Arvind Dasari, Scott Kopetz, Emma B. Holliday, Prajnan Das, Y. Nancy You, George J. Chang
Journal: Journal of Clinical Oncology (2020)

4012 Background: Identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) other than for N1c designation. The aim of this study was to determine the prognostic impact, beyond AJCC N1c designation, of TD among primary CRC patients. Methods: Patients with stage 1 to 3 primary CRC diagnosed between 2010 and 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Cancer specific survival (CSS) stratified by TDs and nodal status was calculated, and Kaplan-Meier method and multivariable COX proportional hazards regression analyses were performed. Results: A total of 74,494 patients with primary CRC were identified. Mean age was 66.4 (SD+/-13.2) years, 36,988 (49.7%) were female and 40,651 (54.6%) were right-sided. TDs were present in 4,481 patients (6.0%) and 26,603 (35.7%) had lymph node metastases. The presence of TDs were significantly associated with adverse tumor characteristics including advanced pathological stage, nodal and metastasis status, higher grade and perineural invasion. Incorporating TDs into each nodal status was independently associated with worse CSS and supported reclassification of nodal status to incorporate TDs following multivariable regression analysis as outlined in the table. Following multivariable regression analysis, the proposed AJCC nodal reclassification incorporating TDs, in combination with tumor stage was a strong predictor of CSS, and also represents a new summary staging. Conclusions: TDs are an independent predictor of worse outcome in CRC. The presence of TDs have distinctly different CSS and these data support modification of the current N classification. This study proposes a reclassification of the AJCC system for CRC to incorporate TDs and informs an updated node and summary stage. [Table: see text]
Covid-19: Doctors need proper mental health support, says BMA
Authors: Ingrid Torjesen
Journal: BMJ (2020)

<sup>211</sup>At is an α-emitter that has similar chemical properties to iodine and is used in targeted α-therapy. In the present study, we added ascorbic acid (AA) to <sup>211</sup>At solution to increase the radiochemical purity of astatide and evaluated its efficacy against differentiated thyroid cancer, which is characterized by the expression of sodium/iodide symporter (NIS). <b>Methods:</b> Crude <sup>211</sup>At solution (AA(−)) and <sup>211</sup>At solution treated with AA (AA(+)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats (<i>n</i> = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(+) and AA(−) conditions. AA(+) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq (<i>n</i> = 6), 0.4 MBq (<i>n</i> = 6), and 0.1 MBq (<i>n</i> = 6), and vehicle was injected into control mice (<i>n</i> = 6). The treatment effects were compared among the 4 groups. <b>Results:</b> Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) as compared with those injected with AA(−). Cellular uptake analysis showed significantly increased uptake of <sup>211</sup>At by the K1-NIS cells under the AA(+) condition as compared with the AA(−) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of <sup>211</sup>At at 3 and 24 h after administration (22.5 ± 10.4 and 12.9 ± 6.8 percentage injected dose, respectively). Tumor growth was immediately inhibited in a dose-dependent manner after administration of <sup>211</sup>At. In the survival analysis, the <sup>211</sup>At groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. <b>Conclusion:</b> Uptake of <sup>211</sup>At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using <sup>211</sup>At solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted α-therapy.
以咽部异物感和声音低哑为表现的脑梗死一例
Authors: 杨建勋
Journal: BMJ (2005)

患者女,50岁,农民.因不明原因声音低哑和咽部异物感1年余来诊.患者1年前无明显诱因突然觉咽部有鸡蛋大小异物阻塞,伴声音低哑、语速减慢,症状持续存在.无发热、咳嗽、咳痰、头痛、恶心、呕吐、意识障碍等,四肢活动正常.曾在外院按咽喉炎、癔病等治疗,无明显疗效.否认高血压病史.检查:体温37.1℃,脉搏68次/min,呼吸20次/min,血压108/74 mm Hg(1 mm Hg=0.133 kPa).步入病房,对答切题,思维连贯、清晰,语速稍显迟缓,双瞳孔等大等圆,对光及调节反射正常,双侧鼻唇沟正常,伸舌无明显偏移,四肢肌力、肌张力正常,浅表反射及腱反射正常,病理反射未引出.咽喉部及声带镜检未见异常.头颅CT扫描示:左侧大脑顶叶陈旧性腔隙性梗死并局限性脑萎缩,硬膜下积液.彩色超声检查示:右侧大脑中动脉痉挛.临床诊断:左侧大脑顶叶腔隙性梗死。
To improve the understanding and reinforce the prevention and treatment of benign prostatic hyperplasia
Authors: 杜林栋, 李炫昊
Journal: BMJ (2010)

良性前列腺增生(benign prostatic llyperplasia,BPH)是老年男性的常见疾病,其发病率随年龄的增长而不断增加.特别近年来,随着社会老龄化人口的不断增加以及饮食等生活方式的改变,BPH在一些国家或者地区已成为老年男性最常见的良性疾病,严重地影响患者的生存质量,增添经济负担。
Phase III trial of metronomic capecitabine maintenance after standard treatment in operable triple-negative breast cancer (SYSUCC-001).
Authors: XI Wang, Shu-Sen Wang, Heng Huang, Li Cai, Rou-Jun Peng, Li Zhao, Ying Lin, Jian Zeng, Le-Hong Zhang, Yong-Li Ke, Xian-Ming Wang, Xin-Mei Liu, Qian-Jun Chen, An-Qin Zhang, Dan-Mei Pang, Fei Xu, Jia Jia Huang, Yanxia Shi, Jun Tang, Zhongyu Yuan
Journal: Journal of Clinical Oncology (2020)

507 Background: Triple-negative breast cancer (TNBC) has a relatively high relapse rate and poor outcome after standard therapy among all subtypes of breast cancer. Effective strategies to reduce risk of relapse and death are unmet medical needs. Methods: In this phase III trial, patients with operable TNBC were randomly assigned to receive metronomic capecitabine (650 mg/m 2 twice daily continuously for one year) as maintenance therapy or observation after standard local and systemic treatment for curative intent. The primary end point was disease-free survival (DFS). Secondary end points included distant disease-free survival (DDFS), overall survival (OS) and safety. Results: A total of 434 patients were randomly assigned to capecitabine group (n = 221) or observation group (n = 213). At a median follow-up of 56.5 months, 5-year DFS was significantly better in capecitabine group than in observation group (83% vs. 73%, HR, 0.63; 95% CI, 0.42 to 0.96; p = 0.027). 5-year DDFS was also significantly better in capecitabine group than in observation group (85% vs. 76%, HR, 0.56; 95% CI, 0.37 to 0.90; p = 0.016). However, 5-year OS was not significantly different between two groups (85% vs. 81%, HR, 0.74; 95% CI, 0.47 to 1.18; p = 0.203). Two hundred and two (91.4%) of patients completed one year of capecitabine therapy as planned. The most common capecitabine-related adverse events were hand-foot syndrome (46%), leukopenia (24%), Hyperbilirubinemia (13%), gastrointestinal pain (7%) and elevated serum transaminases (5%). Conclusions: Maintenance therapy with metronomic capecitabine for one year following standard treatment significantly improved DFS in operable TNBC, which was safe and well tolerated. (SYSUCC-001, Clinical trial information: NCT01112826 .
Building resilient oncologists: A feasibility study of a resiliency curriculum for hematology oncology fellows.
Authors: Monica Sheila Chatwal, Christine Vinci, Richard R. Reich, David C. Boulware, Wenyi Fan, Angela Reagan, Jhanelle Elaine Gray
Journal: Journal of Clinical Oncology (2020)

TPS11043 Background: Rates of burnout and career dissatisfaction have declined slightly, but remain high among oncologists (Berg, AMA 2020). As hematology oncology fellows prepare to join this workforce, the ACGME now mandates wellness be a part of their training curriculum. Yet, there are few, if any, structured and effective programs specifically for these trainees. Based on feedback from our prior mindfulness-based wellness curriculum, we created a more varied and comprehensive resiliency program with the use of our institutional resources to incorporate and evaluate as part of our fellowship curriculum (ASCO, Abstract 10508), and potentially expand to other fellowships. Methods: This is a single-center, non-randomized, pilot project to assess the feasibility, acceptability, and impact of a resiliency training program. All hematology oncology fellows at our institution were eligible for enrollment, and participation was voluntary. A total of seven monthly, 1 hour sessions were conducted through the academic year. Each session focused on a particular topic - alternative forms of wellness through art and music, self care, mindfulness and stretching, reflective writing, and healthy boundaries and work life integration - which have all been studied individually in wellness and burnout with positive results. Sessions were co-led by a peer and “expert” guest speakers from our training institution. Participants completed questionnaires pre and post-program, and feedback evaluations after each session. Questionnaires included the Perceived Stress Scale (PSS), Five Facet Mindfulness Questionnaire (FFMQ), Connor Davidson Resiliency Scale (CDRS-10), and modified Maslach Burnout Inventory (MBI), as well as demographics and open response questions. The primary aim was feasibility (enrollment, completion, and compliance rates), and the secondary aim was acceptability (usefulness of the intervention). Examination of stress, mindfulness, resiliency, and burnout were exploratory. Enrollment and data collection are complete, with 18 of 29 (62%) eligible participants consented. Data analysis is in process.
Evaluation of the inclusion rate in clinical trials of bladder cancer patients evaluated for first time in the oncology department.
Authors: Natalia Vidal, Javier Puente, Fernando Moreno, María del Rosario Alfonso, Lydia Suárez, Mateo Paz Cabezas, Pedro Pérez-Segura
Journal: Journal of Clinical Oncology (2020)

e19219 Background: In the Genitourinary (GU) Cancer Unit of Clínico San Carlos Hospital the inclusion rate in Clinical-Trials (CTs) from January-October 2018 was 39%. However, in bladder cancer patients it was only 24%. We identified improvement areas in order to increase the inclusion rate of these patients up to 30% from November 2018-March 2019. Methods: We used as an instrument the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP). We collected the number of proposals and available CTs, the number of bladder cancer patients evaluated for the first time and the patients enrolled in CTs. We also identified the causes of non-enrollment and elaborated a list of possible solutions. Results: We developed a cause-effect diagram showing that the most relevant causes of non-enrollment in CTs were the eligibility criteria (60%) and the absence of available CTs (35%). We created a list of measures and identified which would have a higher impact. On November 2018 we started a protocolized Supportive-Care evaluation by our Oncology nurses to increase the number of eligible patients. We also initiated the diffusion of CTs in the Investigation Unit and in the GU-board to increase the number of available CTs and recruitment. In January 2019 we implemented a Geriatric evaluation for the elderly, also to increase the number of eligible patients. With these measures the number of accepted trials increased from 5 in January-October 2018 to 12 in November 2018-March 2019. Also, in January-October 2018, 46% of patients were not-enrolled in a CT due to ineligibility, which decreased to 25% from November 2018-March 2019. As a result, the enrollment rate increased to 43, 75% from November 2018-March 2019. We maintained the measures, and achieved an enrollment rate of 54, 83% from May-December 2019. Conclusions: The implementation of a Supportive-Care and a Geriatric evaluation, and the diffusion of CTs helped increase the percentage of eligible patients and the number of available CTs. With these improvements, we were able to increase the enrollment rate in CTs from 24 to 58, 83%.
Time to central nervous system (CNS) metastases (mets) with atezolizumab (A) or placebo (P) combined with cobimetinib (C) + vemurafenib (V) in the phase III IMspire150 study.
Authors: Paolo Antonio Ascierto, Caroline Robert, Karl D. Lewis, Rodrigo Munhoz, Gabriella Liszkay, Luis de la Cruz Merino, Judit Olah, Paola Queirolo, Jacek Mackiewicz, Haocheng Li, Qian Zhu, V. McNally, Edward Francis Mckenna, Ralf Gutzmer, Grant A. McArthur
Journal: Journal of Clinical Oncology (2020)

10023 Background: The phase 3 IMspire150 study (NCT02908672) demonstrated improved progression-free survival with first-line combination treatment with A+C+V vs P+C+V in patients (pts) with previously untreated BRAF V600 mutation–positive advanced melanoma. Here we report incidence and time to development of CNS mets with A+C+V vs P+C+V in the IMspire150 study. Methods: Eligible pts were randomized 1:1 to receive A+C+V or P+C+V. A or P were given on day 1 and 15 of each 28-day cycle after an initial cycle of C+V. Incidence and time to development of CNS mets were evaluated in pts with no history of CNS mets at baseline confirmed by magnetic resonance imaging/computed tomography (MRI/CT). On study MRI/CT assessments were performed as clinically indicated. Time-to-event outcomes were estimated using the Kaplan-Meier method and competing risks analysis. Sensitivity analyses were conducted using landmark analysis at time of initiation of A or P. Results: 514 pts were randomized to receive A+C+V (n = 256) or P+C+V (n = 258); 244 and 247 pts, respectively, had no history of CNS mets at baseline. After a median follow-up of 18.9 months, CNS mets had developed in 52/244 pts (21%) in the A+C+V arm and 62/247 pts (25%) in the P+C+V arm. In both arms, pts with CNS mets were more likely to have other known unfavorable prognostic factors: elevated LDH, presence of liver mets, and/or higher tumor burden. Cumulative incidence of CNS mets as first site of progressive disease with A+C+V vs P+C+V was 8% vs 9%, 16% vs 19%, 20% vs 24%, and 23% vs 26% at 6, 12, 18, and 24 months, respectively (hazard ratio [HR] 0.87; 95% CI 0.60-1.26). Estimated CNS mets-free survival rates for A+C+V vs P+C+V were 91% vs 90%, 81% vs 75%, 74% vs 66%, and 69% vs 62% at 6, 12, 18, and 24 months, respectively, with a trend for improved CNS mets-free survival with A+C+V (HR 0.79; 95% CI 0.55-1.14). Results of landmark analyses for CNS mets-free survival and cumulative incidence of CNS mets were similar to those in the overall analysis. Conclusions: The addition of anti–programmed death-ligand 1 to C+V is associated with numerically lower rates of interval development of CNS mets, consistent with the overall benefit observed for A+C+V in the study. This finding requires further follow-up to fully assess the magnitude of benefit of A+C+V on CNS mets-free survival. Clinical trial information: NCT02908672.
Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.
Authors: Eric J. Rubin
Journal: New England Journal of Medicine (2020)

On May 1, 2020, we published “Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19,”1 a study of the effect of preexisting treatment with angiotensin-converting enzyme (ACE) inhibitors a...
A multicenter real-world study of tumor-derived DNA from pleural effusion supernatant in genomic profiling of advanced lung cancer.
Authors: Renhua Guo, Likun Chen, Chengzhi Zhou, Xinghao Ai, Jun Zhao, Rongrong Chen, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e21584 Background: Pleural effusion (PE) is commonly observed in advanced lung cancer. Researches have suggested molecular profiling of PE represents a minimally invasive approach of detecting tumor driver mutations for clinical decision making. The objective of this study is to investigate the efficacy and precision of detecting gene alterations in PE samples in the real world setting. Methods: 656 metastatic lung cancer patients with pleural effusion were enrolled in this study. Seven hundred and thirty-two samples, including 351 samples of PE supernatant, 224 plasma, 138 tissue, and 25 PE sediments from these patients were collected and subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related genes in a real world setting. The efficacy of pleural effusion in detecting actionable mutations and identifying resistant mechanisms of targeted therapy were analyzed by comparing different samples. Results: Among the 656 NSCLC patients, 413 were in M1a stage and 243 were in M1b/M1c stage, while 272 were newly diagnosed and 384 was previously treated. When comparing different groups of stage and therapeutic history, PE supernatant was preferred as the choice for those patients (46.6% - 48.2% vs 23.3%-34.8% of plasma vs 16.8%-21.2% of tissue and 0.96%-7.3% of PE sediment). While mutant allele frequency (MAFs) of plasma in patients of M1a stage was significantly lower than that of M1b/c stages, MAFs was similar for PE supernatant. EGFR, KRAS, MET, ALK, BRAF, ERBB2, ROS1, and RET actionable mutations were identified in 60, 12, 9, 7, 6, 3, 2, and 1 of the 118 PE supernatant samples at M1a stage taken before treatment. PE-supernatant demonstrated higher sensitivity than plasma of detecting actionable mutations in M1a disease (84.7% of PE-supernatant vs 42.1% of plasma, p &lt; 0.01) but not in M1b/c stages (80.7% of PE-supernatant vs 86.4% of plasma). Seventy-two of the 117 patients who were resistant to 1 st or 2 nd generation of EGFR-TKI, 22 of the 42 patients resistant to osimertinib, and 9 of the 13 patients resistant to crizotinib had known resistant mutations identified. Remarkably, PE supernatant outperformed plasma in identifying resistant mutations to 1 st /2 nd generation EGFR-TKI (75.4% vs 29.8%, p &lt; 0.001). Conclusions: This real world large cohort study verified that genomic profiling of PE-supernatant has higher actionable mutation detection sensitivity than plasma. It offers an alternative approach in assessing tumor genomics in advanced lung cancer when tumor tissue is not available.
Effects of the growing prevalence in oncology: A real-world study on the estimated workload.
Authors: Silvio Ken Garattini, Alessandro Marco Minisini, Francesca Valent, Chiara Riosa, Claudia Andreetta, Giovanni Gerardo Cardellino, Mauro Mansutti, Simona Rizzato, Ciro Rossetto, Cosimo Stanislao Pio Sacco, Alessandro Follador, Gianpiero Fasola
Journal: Journal of Clinical Oncology (2020)

e14148 Background: The increasing prevalence of cancer patients due to new effective treatments is leading to a growing demand in oncology activities, thus requiring a re-modelling towards more sustainable systems. The aim of this study is to estimate the workload generated by each new cancer patient referred to the Oncology Department of the Academic Cancer Center of Udine, Italy, within the two years from first consultation. Methods: We have utilised our electronic “Data Warehouse” accountability system to retrieve anonymous aggregate data of the 2-year oncology workload generated by each new diagnosis, leading to an initial consultation, occurring between 01.01.2012 and 31.12.2017. Initial consultations with no clinical episode in the following 12 months were excluded. Mean value per patient and standard deviations were calculated for the following clinical activities: treatment sessions, unplanned presentations, hospitalisations, re-assessments, follow-up visits and inpatient oncology advices. The total number of patients treated and of episodes were recorded. Follow-up data was collected up to 31.12.2019. Results: During the observation period, 7,454 newly diagnosed patients were referred to our Oncology Unit, resulting in a total of 92,830 clinical activities occurring over an 8-year period. In 1,788 pts (24.0%) only follow-up was needed; 3,152 pts (42.3%) were referred for adjuvant treatment and 2,514 (33.7%) for advanced disease management. Overall, the mean number of clinical activities per patient within the first 2 years was: 6.04 pre-treatment evaluations (52.9%; SD 8.81; 45,003 total episodes), 2.00 follow-up visits (17.5%; SD 1.89; 14,922 total episodes), 0.42 hospitalisations (3.7%; SD 1.21; 3,141 total episodes), 0.36 inpatient oncology advices (3.2%; SD 0.83; 2,705 total episodes), 1.57 re-assessments (13.8%; SD 2.28; 11,723 total episodes) and 1.02 unplanned presentations (8.9%; SD 2.17; 7,601 total episodes). Subgroup analysis in the different tumors and settings are ongoing. Conclusions: The landscape of cancer care is changing due to the growing prevalence of cancer patients that experience longer overall survival. Trying to estimate the amount of clinical activities generated by any new diagnosis is crucial for implementing new models of oncology management and for programming an adequate workforce supply.
罕见成熟畸胎瘤合并高雄激素血症二例
Authors: 孙爱军, 刘春梅, 何方方, 郁琦, 刘海元
Journal: BMJ (2005)

高雄激素血症是妇科内分泌门诊中较为常见的一种疾病,主要为卵巢和肾上腺病变所致.其中卵巢来源的病因最常见,如多囊卵巢综合征、卵巢滤泡膜细胞增生症、卵巢肿瘤等.而临床上有一些少见情况,如无分泌功能的卵巢肿瘤合并有性激素的异常.以下2例即为成熟畸胎瘤合并高雄激素血症。