tbuckley/cabot-search huggingface dataset:
Racial diversity of genomic alterations in lung adenocarcinomas.
Authors: Huashan Shi, Fei Heng, Kexun Zhou, Ruqin Chen, Rami Manochakian, Yujie Zhao, Yanyan Lou
Journal: Journal of Clinical Oncology (2020)

9543 Background: Lung cancer is the leading cause of cancer related death in the United States in all racial groups. However, the overall death rate from lung cancer is different among white, black and Asian. Although differences in socioeconomic status and treatments received might be the contributing factors, the biology, particularly genomic alteration of cancer might also have an important impact. To date, the differences of genomic alterations among all racial patients are poorly understood. Methods: The American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE, version 7.0) database was analyzed. A total of 8908 patients with lung adenocarcinoma (LUAD) were identified. Among them, 5652 patients who had comprehensive sequencing results (gene panel ≥ 275) were selected for further analysis. Patients with unknown race, undefined and Pacific Island (only 3 patients) were excluded. Finally, 5360 patients were included in the study. The prevalence and distribution of genomic alteration cross all racial groups were analyzed. Results: Overall 5951 samples from 5360 patients were collected (85.7% white, 7.9% Asian, 4.7% black, 0.2% Native American and 1.4% other). Most patients have only one sample. The median mutation counts in white, black, Asian, Native American and others are 7, 6, 5, 5, 7 respectively (Kruskal–Wallis test, P&lt; 0.001). Asian have significantly higher rates of insertion and deletions than other races (14.8% of Asian versus 9.8% of white, 10.7% of black, 10.4% of Native American, 11.1% of other; Pearson’s chi-square test, &lt; 0.001). TP53, EGFR, KRAS and STK11 are the most frequent alterations in white, black and other. EGFR, TP53, KRAS and APC are the most frequent alterations in Asian. STK11 mutations are rare in both Asian and Native American. Native Americans have more alterations of LRP1B, ARID2 and ATM, although the patients’ number remains small. ATM and KEAP1 mutations are also common in white and black. EGFR is the highest discrepancy gene in racial distribution. 78.9% Asian, 47.7% black, 36.4% of native American had EGFR alteration in comparison to 29.6% in white (Fisher's exact test, P &lt; 0.001). KRAS is the second highest discrepancy gene in racial distribution. 11.6% Asian, 26.3% black, 27.3% of Native American had KRAS alteration in comparison to 36.1% in white (Fisher's exact test, P&lt; 0.001). Conclusions: Our study demonstrated the potential diversity of genomic alterations across all racial groups with potential impact on therapeutic decisions.
Percutaneous transluminal angioplasty and stenting for symptomatic vertebral arterial stenosis
Authors: Xiong-fei Zhao, Wei Zhang, Zhi-ru Zhao, Jia-ping Xu, Feng-long Ren, Rui-juan Zhang
Journal: BMJ (2009)

From April 2006 through June 2008, the percutaneous transluminal angioplasty and stenting (PTAS) was performed in 14 patients with symptomatic vertebral arterial stenosis. The successful rate of stent implantation was 100% without any serious complication. Fourteen patients underwent PTAS with a mean preprocedural vertebrobasilar stenosis of 71.3%. The residual stenosis was less than 10%. Over a mean 6-month follow-up in 9 patients, the Malek' s scale 1 was observed in 7 patients, the scale 2 in 2 patients and no restenosis was found in 3 patients according to cerebral angiography. Preliminary results show that PTAS in the management of the vertebrobasilar arterial stenosis is a safe and effective method.

Key words: 
Vertebrobasilar insufficiency;  Therapy
Hospice use at end of life in children with cancer: The effect of insurance.
Authors: Emily E. Johnston, Elizabeth Davis, Smita Bhatia, Kelly Kenzik
Journal: Journal of Clinical Oncology (2020)

10558 Background: The National Quality Forum has endorsed hospice care as a metric of high quality end-of-life (EOL) care for adults with cancer. Specific hospice-related quality metrics include hospice enrollment, hospice enrollment for ≥3d, and death outside of the acute care setting. These metrics have been examined extensively in adults and disparities related to a number of clinical and sociodemographic factors, including insurance, have been identified. However, for children with cancer, hospice utilization data is lacking. We addressed this gap by examining location of death and hospice utilization at EOL for children with cancer and determining whether these metrics varied with insurance status. Methods: We used national insurance claims data (Truven) to conduct a population-based analysis of patients with cancer who died between 2011 and 2017 at age 0-21y. The dataset was queried for hospice claims, inpatient claims, and location of death. The association between insurance (private vs. Medicaid) and 1) location of death, 2) hospice enrollment, and 3) days between first hospice claim and death was examined using multivariable regression analysis, adjusting for age at death, gender, and cancer diagnosis (hematologic malignancies vs. solid tumor). Results: A total of 1,492 children died at a mean age of 11y (SD: 6y); 56% were privately-insured, 56% were male, and 30% had hematologic malignancies. Overall, 58% died in the hospital (privately-insured: 54% vs. Medicaid: 63%). Forty-five percent enrolled in hospice (privately-insured: 46% vs. Medicaid: 43%) with 2% returning to the hospital to die after enrolling in hospice. The average time between first hospice claim and death was 3d (privately-insured: 10d vs. Medicaid: 2d, p = &lt; 0.001). When compared to privately-insured children, children on Medicaid had similar likelihood of hospice enrollment (RR = 1.0, 95%Cl = 0.6-1.8). However, children on Medicaid were more likely to die in the hospital (RR = 1.3, 95%CI = 1.1-1.4) and have fewer days between hospice enrollment and death if enrolled in hospice (IRR: 0.5, 95%CI = 0.3-0.8). Conclusions: In this first study to examine national hospice utilization in children with cancer, care varies significantly with insurance status. Children on Medicaid are more likely to die in the hospital and have shorter hospice enrollment duration than children with private insurance. Whether this variation represents EOL care preferences, provider biases, differences in quality and availability of hospice or home care to different insurers, or other barriers needs to be examined.
NOMINATOR: Feasibility of genomic testing of rare cancers to match cancer to treatment.
Authors: Damien Kee, Olga Kondrashova, Sumitra Ananda, Michael Paul Brown, Paul Andrew Cohen, Andrew Dean, Jayesh Desai, Andrew Fellowes, Stephen B. Fox, Alison Hadley, Dianne Lindsay, Linda R. Mileshkin, Kenneth John O'Byrne, Owen W.J. Prall, Hamish Scott, David Morgan Thomas, Richard Vines, Nic Waddell, Anthony Papenfuss, Clare L. Scott
Journal: Journal of Clinical Oncology (2020)

103 Background: Rare cancers (RCs) often lack proven treatments and consequently have poorer outcomes. Identification of molecular biomarkers can facilitate treatment selection and trials access for RC patients (pts) where histology-based trials are not feasible. We assessed the potential for next-generation sequencing (NGS) to impact RC care. Methods: Pts with a rare histology, poor-prognosis solid-tumor and no standard of care therapy underwent NGS genomic profiling of paired FFPE tumor and blood (PMCC comprehensive cancer panel; 391 genes). A virtual molecular tumour board (MTB) reviewed curated results regarding diagnosis, actionability (OncoKB) and treatment recommendations. Results: Between July 2017 and Nov 2019, 121 pt were prospectively enrolled across 4 Australian sites. 109 (91%) pts had a tumour with an incidence of &lt; 1/100,000 person/years with 83 diverse RC histologies represented. 100 (83%) cases were successfully sequenced. The most commonly aberrant genes ( &gt; 10%) were: TP53 (45%), CDKN2A/B, RB1, PTEN and NF1. 51 (51%) had at least one potentially actionable finding, with 27 matched to a clinically validated drug (OncoKB level 3 or better) [Table]. In 6 cases NGS resulted in a revised diagnosis (includes 4 with FDA approved therapy). Actionable germline mutations were detected in 3 individuals of which 2 were previously known. The majority of pts remain in follow-up, however, 8 died prior to or within 28 days of NGS result availability. Drug access remains a limitation with only 12 receiving therapy based on NGS/MTB guidance. Clinical trial information: ACTRN12616001000493 . Conclusions: NGS in RCs is feasible with potential impact in half of cases. Earlier testing and improved off-label/trial drug access is necessary to increase the likelihood that RC patients may benefit from molecularly guided therapy. [Table: see text]
Present situation of pain management for advanced cancer patients in community
Authors: Yan-hui Zhai, Zhan-hong Guan, Min Wei, Ying Li
Journal: BMJ (2009)

Data were collected from 236 patients with advanced ClllllCerB through questionnaire survey,home visit,oncology clinics and counseling service.The data were evaluated and classified according to VAS and NCCN aduh cancer pain practice guidelines.Two hundred and eleven in 236 advancad cancer patients(89.4%)Suffered from Cancer pain,with mild pain in 31,moderate in 83 and severe in 97.One hundred and seventeen patients(49.6%)received therapy for pain relief,among whom 78(66.7%)had complete remission(CR),26(22.2%)partial remission(PR)and 13 cages(11.1%)noremission.The main reason for declining pain relief wag being scared of morphine addiction.

Key words: 
Neoplasms; Pain measurement
Correlation of clinical activity of NEO201 mAb with the expression of NK activation markers and levels of soluble factors.
Authors: M. Pia Morelli, Massimo Fantini, Nicole D. Houston, Jung-min Lee, Alexandra Dos Santos Zimmer, Stanley Lipkowitz, Kathryn Trewhitt, Philip M. Arlen, Kwong Y. Tsang, Christina M. Annunziata
Journal: Journal of Clinical Oncology (2020)

e15002 Background: NEO-201 is a humanized IgG1 mAb that targets tumor-associated variants of CEACAM-5/6. NEO201 exerts anti-tumor activity by (NK)-mediated ADCC, CDC, and by enhancing NK cell cytotoxicity through blockade of CEACAM5-CEACAM1 interaction. The first in human phase I clinical trial is ongoing. Neutropenia caused DLT and was observed at 2mg/kg (DL 2). At DL2, 2/6 patients with colorectal cancers had stable disease. In the present study we evaluated the correlation between response, NK status, and profiles of soluble factors. Methods: This is a classic 3+3 dose escalation. NEO-201 is administered intravenously every 2 weeks, with 4 dose levels planned (DL1 = 1mg/kg, DL2 = 2mg/kg, DL3 = 4mg/kg and DL4 = 6mg/kg). So far, 3 patients received DL1 and 6 patients DL2. Safety is evaluated according to CTCAEv5.0, and response according to RECISTv1.1. Biological samples are collected at baseline, at 4, 24 and 72 hours after the first dose, and before C1D15 dose to understand NEO-201 pharmacokinetics (PK), effects on immune profile and correlation with treatment toxicity and response. CD56 + /CD16 + NK cells were evaluated for modulation of NKG2D, CD107a, NKp46 (activation markers), and CEACAM1 (inhibitory marker) by flow cytometry. Soluble factors (cytokines, sMICA and sCEACAM5) were evaluated by ELISA. Results: Among the 3 patients achieving radiological SD, one (DL1) had clinical progression (PD) without radiological progression after 2 cycles due to mucous producing disease, a second patient (DL2) went off study after 2 cycles for drug unrelated issues, and the third patient (DL2) has stable disease (SD) for 6 months without significant toxicity. All other patients had radiologic PD after 2 cycles. Interestingly, baseline CD56 + /CD16 + NK cells from the two patients with SD showed an increase in NKG2D, CD107a and NKp46, and a low expression of CEACAM1. They also had low serum levels of sMICA, sCEACAM5 and IL-6. On contrary, CD56 + /CD16 + NK cells from patients with PD had low expression of NKG2D and CD107a, high expression of CEACAM1, and high levels of sMICA. Conclusions: High expression of activating markers and low expression of CEACAM1 on CD56 + /CD16 + NK cells, as well as low levels of sMICA and sCEACAM5 correlate with clinical response to NEO-201. Thus, the activity of NK cells may serve as predictors for efficacy of tumor-targeting antibody therapy. Further correlation of these biomarkers with PK and CEACAM1/5/6 expression in patients’ tissue samples will provide further support for optimizing the use of NEO201. Clinical trial information: NCT03476681 .
Four-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer in neoadjuvant setting.
Authors: Xavier Pivot, Mark D. Pegram, Javier Cortes, Diana Lüftner, Hope S. Rugo, Gary H. Lyman, Giuseppe Curigliano, Igor Bondarenko, Mikhail Dvorkin, Ye Chan Yoon, Younsoo Kim, Chul Kim
Journal: Journal of Clinical Oncology (2020)

578 Background: SB3 was approved in the US and EU as a biosimilar of reference trastuzumab (TRZ). Here, we report 4-year cardiac safety and survival outcomes. Methods: After completing neoadjuvant-adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study of a phase III trial (Pivot et al. Eur J Cancer 2019). The aim was to observe long-term cardiac safety and survival. EFS and OS were analyzed in subgroups by ADCC status within TRZ in ad-hoc analyses. Results: Of 875 patients randomized in the phase III trial, 367 patients (SB3, N=186; TRZ, N=181) were enrolled in the follow-up study. The median follow-up was 53 months. During the follow-up, the incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease was low (SB3, n=1; TRZ, n=2), with all patients recovering with LVEF ≥ 50%. No cases of symptomatic congestive heart failure, cardiac death, or other significant cardiac condition were reported. 4-year EFS rates were 83.4% for SB3 and 80.7% for TRZ with a HR of 0.77 [95% CI 0.47, 1.27]. 4-year OS rates were 94.3% for SB3 and 89.6% for TRZ with a HR of 0.53 [95% CI 0.24, 1.16]. From ad-hoc analysis, a difference in EFS and OS was seen between Non-drifted TRZ and Drifted TRZ; Difference between SB3 and Non-drifted TRZ was not statistically significant. Conclusions: In a subset of patients from the phase III trial, comparable long-term cardiac safety and survival at 4-year supports biosimilarity between SB3 and TRZ. Ad-hoc analysis results by ADCC status suggest a possible correlation between ADCC and clinical efficacy. Further follow-up is needed. Clinical trial information: NCT02771795 . [Table: see text]
Disparities in cancer survival in patients with multiple myeloma: A community-based cancer center experience.
Authors: Jessica M. Stempel, Vinicius Machado Jorge, Djeneba Audrey Djibo, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2020)

e20530 Background: Multiple myeloma (MM) accounts for nearly 17% of all hematological malignancies and 2% of all cancer-related deaths in 2018. Despite new treatment options, survival disparities among African Americans (AA) and other ethnic minorities still exist. Although cytogenetics and advanced age are high-risk features, equal healthcare access may also impact outcomes. We aim to investigate the social and biological factors which affect overall survival in patients with MM in a community setting with a predominantly AA population. Methods: We retrospectively identified MM cases diagnosed from January 1, 2013 and March 30, 2019, from our tumor registry. We collected demographic, clinical, histopathologic and treatment variables. Our primary endpoint was overall survival (OS). Overall and median survival with 95% confidence intervals were obtained using Kaplan Meier estimates. Results: We identified 73 patients with MM. Median age was 70 years (range, 42-88 years), 31 were female (42%) and 58 were AA (79%). Median household income in the AA group was $37,832 and $50,810 in the non-AA group ( p&lt; 0.05). AA had a median overall survival (OS) of 15.9 months (95% CI, 8.2-23.7) compared to non-AA, 21.9 months (95% CI, 2.1-41.7). After a median follow-up of 20 months, the HR for death in AA was 1.32 (95% CI, 0.71-2.5); p= 0.37. None of the variables investigated were independently associated with an increased risk of mortality. Conclusions: Social determinants of health play a major role in community-based cancer centers, including access to care, income and social support. A difference in household income was found between both groups but was not independently associated with a survival advantage. Although, our results show AA patients with MM have a shorter OS compared to non-AA, this failed to reach statistical significance. The size of our sample limited the discovery of potential discrepancies in social determinants of health between both groups and their effect on outcomes. Larger-scale community-based studies are indispensable to investigate these differences further. [Table: see text]
性传播性疾病病原体与阴道炎
Authors: 郝敏, 王伟
Journal: BMJ (2006)

性传播疾病(sexually transmitted diseases,STD)由于其传播速度快,影响范围广,并能引起并发症和后遗症,已成为困扰人类的重大公共卫生和社会问题之一.引起STD的病原体种类繁多,其中包括病毒、衣原体、支原体、细菌、真菌、螺旋体、原虫和寄生虫等.本文将重点介绍与阴道炎关系密切的几种STD的诊断与治疗进展。
A prospective study of prognostic role of plasma circulating tumor DNA (ctDNA) in patients (pts) with early-stage malignancies.
Authors: Mikhail Fedyanin, Uljana Boyarskikh, Elizaveta Polyanskaya, Vechaslav Aliev, Zaman Mamedli, Andrey Kechin, Igor Oscorbin, Darya Shamovskaya, Anna Popova, Alexandr Polyakov, Nikolay Kudashkin, Alla L. Arzumanyan, Arkadiy Trigolosov, Maxim P. Nikulin, Sergey N. Nered, Ivan Stilidi, Ekaterina Moroz, Antonio Chekini, Maxim Filipenko, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2020)

3559 Background: Recently, conflicting evidence has emerged showing the association of ctDNA level and cancer progression. The aim of our study was the development of a method for detecting ctDNA in plasma and the investigation of the prognostic value of ctDNA retention after surgery in the prospective way. Methods: This prospective, single-center, sample collection study; pts with early-stage malignancies of the different origin were included. Tumor somatic mutations were determined by target sequencing of DNA from FFPE tumor blocks. Sequencing was performed using the custom NGS panel covering regions of frequent somatic mutations in 50 genes. Tumor-specific mutations were monitored in plasma samples taken before and after surgery. The median time between surgery and plasma collection was 7 days (5-15). Mutations of plasma ctDNA were determined by ddPCR. The plasma sample was considered "positive" if the content of ctDNA was more than 0.5 copies of mutant DNA in ml plasma. We needed 265 pts for improving 1-year disease free survival (DFS) from 60% to 80% with α=0.01, β=0.1, 10% loss of f.-up and duration of the study for 2 years. Results: The study comprised 271 pts with various cancers including colorectal – 91 (33,6%), pancreatic – 37 (13,7%), breast – 66 (24,4%), lung – 35 (12,9%) and gastric cancer – 42 (15,5%). Pts with stage I was 50 (18,5%), stage II – 118 (43,5%) and stage III – 103 (38%). The median time of the f.-up was 9 mos. (1-37). No significant association was found between the level of ctDNA before surgery and DFS either in the general group or in groups stratified by tumor sites (HR 2.4, 95%CI 0.8-7.1, р=0.12 and HR 1.5, 95%CI 0.4-6.3, р=0.5, correspondingly). ctDNA was detected in the plasma after surgery in 57 (10%) pts: 9 (9.9%) cases of colorectal, 10 (27%) - pancreatic, 9 (13.6%) - breast, 19 (54.3%) - lung, and 10 (23.8%) - gastric cancer. Progression of the disease was detected in 28/57 (49%) pts with ctDNA(+) and 17/214 (8%) - in ctDNA(-) pts (p&lt;0.001). One-year DFS in ctDNA(+) and ctDNA(-) pts were 57% and 87%, respectively (HR 6.1, 95%CI 3.3-11.2, p&lt;0,001). ctDNA positivity after surgery was an independent negative prognostic factor according to Cox regression model fitted to T, N, and adjuvant chemotherapy (HR 5.7, 95%CI 3.1-10.8, p &lt;0.001). Conclusions: These results demonstrate the prognostic significance of ctDNA persisting after surgery in pts with the early stage of the different malignancies. Further clinical validation of this approach is required in trails with modifications of the adjuvant treatment, according to the content of ctDNA.
The prognostic value of HRD mutations in liver cancer.
Authors: Jinzhang Chen, Tanxiao Huang, Ming Liu, Wenting Liao, Mimi Fu, Bo Yang, Jingxian Duan, Shifu Chen, Yabing Guo
Journal: Journal of Clinical Oncology (2020)

e13546 Background: Liver cancer is the sixth most common cancer in the world and the fourth most common cause of cancer mortality. Genomic alterations including homologous recombination deficiency (HRD) mutations often lead to aberrant regulations of signaling pathways, which play an important role in tumorigenesis. The prognostic value of HRD mutation and its correlation with overall survival in liver cancer is unclear. Methods: We used cBioPortal platform to analyze a cohort of 978 liver cancer samples. Mutations in 13 genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, CHEK1, CHEK2, ABRAXAS1, MRE11, NBN, PALB2, RAD51C, RAD51D) were screened due to the fact that they are the most common indication of deficiency in the homologous recombination (HR) DNA repair pathway. We define overall survival (OS) as the time between the sample collection (surgical) date and the date of death or the last follow-up visit. We conducted Kaplan-Meier survival analysis, and the statistical differences were compared by log-rank tests. Results: 228 of the cases harbored at least one mutation of the HRD-indicator genes. Based on the result, patients were divided into the HRD and non-HRD group. The median OS of the HRD group was 45.47, which is significantly shorter than the OS of the non-HRD group (log-rank test p = 1.6196e-4, Table). Conclusions: HRD mutations are significantly associated with a shorter OS in liver cancer patients. HRD mutation was a negative prognostic factor for overall survival in liver cancer, but the underlying mechanisms remain to be explored. [Table: see text]