tbuckley/cabot-search huggingface dataset:
Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma.
Authors: Xinan Sheng, Xieqiao Yan, Zhihong Chi, Lu Si, Chuanliang Cui, Bixia Tang, Siming Li, Lili Mao, BIN LIAN, Xuan Wang, Xue Bai, Li Zhou, Yan Kong, Jie Dai, Keith Flaherty, Jun Guo
Journal: Journal of Clinical Oncology (2020)

10007 Background: Metastatic mucosal melanoma responds poorly to PD-1 blockade therapy in comparison with cutaneous melanoma. Vascular endothelial growth factor (VEGF) is indicated to play an important immunosuppressive role in mucosal melanoma. Combination of VEGF inhibition with PD-1 blockade might provide therapeutic opportunities. Toripalimab was approved as a second-line treatment for metastasis melanoma in Dec 2018. This study is to evaluate the safety and clinical efficacy of toripalimab combined with axitinib for the treatment of metastatic mucosal melanoma. (Clinical trial ID: NCT03086174). Methods: Patients with metastatic melanoma receive 1 or 3 mg/kg toripalimab Q2W in combination with 5 mg axitinib BID until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and gene expression profile (GEP) will be evaluated for correlation with clinical response. Results: From April 2017 to April 2018, 33 patients were enrolled in the study. No DLT or treatment related death was observed. 97% patients experienced treatment related AE (TRAE) and 39.4% patients experienced Grade 3-4 TRAEs. Most common TRAEs include diarrhea, proteinuria, hand and foot syndrome and hypothyroidism. Only one patient discontinued treatment due to TRAE. Among 29 treatment naïve mucosal melanoma patients, 14 PR and 11 SD were observed for an ORR of 48.3% and a DCR of 86.2%. The median DOR was 13.7 months. The median PFS was 7.5 months and the median OS was 20.7 months. PD-L1 expression or TMB had no significant differences in responders versus non-responders. In contrast, GEP scores of eight selected immune-related and four angiogenesis-related genes showed strong correlation with clinical response, whereas previous published immune related signature or angiogenesis signature alone had no correlation. Conclusions: Toripalimab combined with axitinib is a promising treatment option for metastatic mucosal melanoma. GEP scores of selected immune-related and angiogenesis-related genes might predict the response to the combination. A randomized 3-arm Phase 2 trial has been initiated to compare toripalimab plus axitinib with toripalimab or axitinib alone. Clinical trial information: NCT03086174.
高血钾致心源性休克抢救成功一例
Authors: 田野, 黎兰芝
Journal: BMJ (2005)

患者男,41岁.因突发心悸1 h,晕厥10 min由我院急诊科转心内科抢救.既往有慢性肾功能衰竭病史5年,近1年来进入尿毒症期.查体:体温35℃,呼吸30次/min,脉搏180次/min,血压60/40 mm Hg(1 mm Hg=0.133 kPa).神志不清,烦躁,全身冷汗,贫血貌,颜面部轻度浮肿,对光反射迟钝,双肺闻及少量湿啰音,心率170～180次/min,心音低弱,未闻及杂音。
Molecular detection of pancreatic neuroendocrine tumors using methylated DNA markers: Discovery and tissue validation.
Authors: Shounak Majumder, Calise K. Berger, Patrick H. Foote, Xiaoming Cao, Maria McGlinch, Brianna Gysbers, Thorvardur Ragnar Halfdanarson, Rondell P. Graham, Jaime de la Fuente, Mariah J Robran, Karen A Doering, Kelli Burger, Douglas W. Mahoney, William R. Taylor, Gloria M. Petersen, David A. Ahlquist, John B. Kisiel
Journal: Journal of Clinical Oncology (2020)

e16705 Background: The prevalence of pancreatic neuroendocrine tumors (PNETs) has increased in the last decade. Despite being clinically asymptomatic PNETs can be biologically aggressive. There is currently no reliable non-invasive diagnostic biomarker for PNETs. In this study we aimed to identify and validate methylated DNA marker (MDM) candidates that differentiate PNET from normal pancreas. Methods: For discovery, reduced representation bisulfite sequencing (RRBS) was performed on DNA extracted from frozen normal pancreas (n = 13) and PNET (n = 51) tissues. Area under the receiver operator characteristic curve (AUC), fold-change, and p-value criteria selected candidates MDMs for blinded validation in independent FFPE tissues from primary PNET (n = 67; solid = 50, cystic = 17), normal pancreas controls (n = 24), and normal buffy coat (n = 36) using methylation specific PCR. MDM distributions in primary PNETs were compared to primary lung (n = 36) and small bowel (n = 36) NETs and metastatic PNET tissue (n = 25). The discrimination accuracy of candidate markers was summarized as the AUC with corresponding 95% confidence intervals (CI). Results: From the RRBS discovery, 31 candidate MDMs were selected for validation. Four MDMs ( SRRM3, HCN2, SPTBN4 and TMC6) achieved individual AUCs ≥0.95 in the validation set (Table). These MDMs were similarly discriminant in metastatic PNET tissue and in primary lung and small bowel NETs. Three out of these 4 MDMs perfectly differentiated PNET tissue from buffy coat with AUC of 1 and may be ideally suited for further development of a blood-based assay. Conclusions: We identified and validated novel MDMs in tissue that discriminate PNETs from controls with normal pancreas and buffy coat with high accuracy. These MDMs also differentiated metastatic PNETs from normal pancreas tissue. Further exploration of these candidate tissue MDMs in plasma can potentially guide diagnosis and management of PNETs. Funding: P30DK084567. [Table: see text]
Predicting the risk of VISIT emergency department (ED) in lung cancer patients using machine learning.
Authors: Pablo Rodriguez-Brazzarola, Nuria Ribelles, Jose Manuel Jerez, Jose Trigo, Manuel Cobo, Inmaculada Ramos Garcia, M Vanesa Gutierrez Calderon, Jose Luis Subirats, Ana María Galeote Miguel, Hector Mesa, Laura Galvez Carvajal, Leo Franco, Begoña Jimenez Rodriguez, Ana Godoy, Sofía Ruíz, Andres Mesas, Marcos Iglesias Campos, Irene López, Antonio Rueda Dominguez, Emilio Alba
Journal: Journal of Clinical Oncology (2020)

2042 Background: Lung cancer patients commonly need unplanned visits to ED. Many of these visits could be potentially avoidable if it were possible to identify patients at risk when the previous scheduled visit takes place. At that moment, it would be possible to perform elective actions to manage patients at risk to consult the ED in the near future. Methods: Unplanned visits of patients in active cancer therapy (i.e. chemo or immunotherapy) are attended in our own ED facilities. Our Electronic Health Record (EHR) includes specific modules for first visit, scheduled visits and unplanned visits. Lung cancer patients with at least two visits were eligible. The event of interest was patient visit to ED within 21 or 28 days (d) from previous visit. Free text data collected in the three modules were obtained from EHR in order to generate a feature vector composed of the word frequencies for each visit. We evaluate five different machine learning algorithms to predict the event of interest. Area under the ROC curve (AUC), F1 (harmonic mean of precision and recall), True Positive Rate (TPR) and True Negative Rate (TNR) were assessed using 10-fold cross validation. Results: 2,682 lung cancer patients treated between March 2009 and October 2019 were included from which 819 patients were attended at ED. There were 2,237 first visits, 47,465 scheduled visits (per patient: range 1-174; median 12) and 2,125 unplanned visits (per patient: range 1-20; median 2). Mean age at diagnosis was 64 years. The majority of patients had late stage disease (34.24 % III, 51.56 % IV). The Adaptive Boosting Model yields the best results for both 21 d or 28 d prediction. Conclusions: Using unstructured data from real-world EHR enables the possibility to build an accurate predictive model of unplanned visit to an ED within the 21 or 28 following d after a scheduled visit. Such utility would be very useful in order to prevent ED visits related with cancer symptoms and to improve patients care. [Table: see text]
Health-related quality of life (HRQoL) for olaparib versus enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) gene alterations: PROfound.
Authors: Antoine Thiery-Vuillemin, Johann S. De Bono, Fred Saad, Giuseppe Procopio, Neal D. Shore, Karim Fizazi, Guilhem Roubaud, Gabriel dos Anjos, Gwenaelle Gravis, Jae Young Joung, Nobuaki Matsubara, Daniel Castellano, Arnold Degboe, Christopher Gresty, Jinyu Kang, Allison Allen, Joseph E Burgents, Maha H. A. Hussain
Journal: Journal of Clinical Oncology (2020)

5539 Background: In the randomized Phase III PROfound trial (NCT02987543), olaparib significantly prolonged radiographic progression-free survival compared with physician’s choice of new hormonal agent (pcNHA, enzalutamide or abiraterone) in men with mCRPC and HRR gene alterations, whose disease had progressed on prior NHA. Olaparib significantly improved time to pain progression in Cohort A. We report additional patient reported outcome measures of HRQoL in the overall study population (Cohorts A+B). Methods: HRQoL was assessed in the overall study population using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, comprising 5 subscales: physical wellbeing (PWB), functional wellbeing (FWB), emotional wellbeing, social wellbeing, and prostate cancer subscale (PCS). The Trial Outcome Index (TOI; PWB+FWB+PCS) and FACT Advanced Prostate Symptom Index (FAPSI-6: derived from 6 FACT-P items) were also calculated. Adjusted mean change and time to deterioration in scores were statistically analyzed. Results: Baseline FACT-P total score was similar for both treatment arms. FACT-P total and subscale scores during treatment were all higher for olaparib vs pcNHA, with clinically meaningful differences between treatment arms in the adjusted least square (LS) mean changes from baseline in all but FWB and FAPSI-6 (Table). The time to deterioration in FACT-P total and TOI, FAPSI-6, PWB and PCS scores favored olaparib but were not statistically significant, with hazard ratios ranging from 0.68 to 0.94. Further HRQoL results for cohort A will also be presented. Conclusions: Olaparib delayed deterioration in HRQoL scores vs pcNHA and was associated with better HRQoL functioning over time compared with pcNHA in men with mCRPC and HRR gene alterations. Clinical trial information: NCT02987543 . [Table: see text]
SimBioSys TumorScope: Spatio-temporal modeling of the tumor microenvironment to predict chemotherapeutic response.
Authors: John A Cole, Joseph R Peterson, Tyler M Earnest, Micahel J Hallock, John R Pfeiffer, Tushar Pandey, Eduardo Braun
Journal: Journal of Clinical Oncology (2020)

e12650 Background: One of the most important sources of variability affecting each patient’s response to neoadjuvant chemotherapy (NACT) is drug and nutrient perfusion, The SimBioSys TumorScope is a computational decision-support system that is designed to predict the flow of drugs and nutrients throughout the tumor microenvironment, and the subsequent response of the tumor to treatment. By enabling healthcare providers to simulate a range of different standard-of-care treatment regimens in a realistic 3D model of each patient’s tumor, providers can predict which treatments are most effective, and provide the best possible care for their patients. Methods: SimBioSys TumorScope implements a multi-scale simulation technology that couples several biophysical and biochemical models in order to predict how individual patients' tumors respond to NACT. The simulations explicitly track the 3D morphology of the tumor and surrounding tissues (based on MRI images), as well as the concentrations of key nutrients and drugs as they change over time. At each location within the 3D model, these concentrations are used to predict cell growth and death rates. As different regions of the tumor grow or die, its macroscopic shape changes. Results: SimBioSys TumorScope was retrospectively applied to over 300 breast cancer patients that received NACT. Simulations were initialized with pre-treatment MRI data, and run through the entirety of each patient's specified treatment regimen. Predicted changes in tumor volume and longest dimension were then compared against measured values at several time-points after initiation of therapy, yielding Pearson correlations of over 0.93 for both. Work is underway to extend the technology to lung tumors; early results show very different metabolic behaviors from those of breast tumors, and significantly less response to treatment overall. Conclusions: Through accurate spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physico-chemical interactions that arise between tissues, the SimBioSys TumorScope for Breast Cancer can accurately predict the response of patients treated with NACT.
Relative gene copy numbers in various patterns of cervical cancer growth.
Authors: Natalya N. Timoshkina, Natalia A. Petrusenko, Vera P. Nikitina, Diana A. Spiridonova, Ekaterina V. Verenikina, Ivan S. Nikitin, Oksana E. Zhenilo, Liubov Yu Vladimirova, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e18029 Background: Numerous studies on cervical cancer confirm an important role of specific genomic changes in the onset and development of cervical intraepithelial neoplasia and their effect on the progression of cervical cancer. Solid tumors are characterized by genomic changes leading to a change in the DNA sequence copy number. The purpose of the study was to reveal changes in the relative copy number of the ESR1, ESR2, GPER1, STS, SULT1A1, SULT1E1, CYP1A1, CYP1A2 genes responsible for the reception and metabolism of estrogens in cervical tissues in endophytic and exophytic patterns of tumor growth in order to find predictive markers of malignancy. Methods: The study included 40 patients aged 28-65 years with cervical cancer of endophytic (n = 20) and exophytic (n = 20) growth patterns. Eligibility criteria included a morphologically confirmed cervical squamous cell cancer T1b-2aN0M0, stage I-II. The Thermo Scientific GeneJET FFPE DNA Purification Kit was used for the DNA extraction from FFPE blocks of tumor and healthy tissues. DNA concentrations were measured on the Qubit 2.0 fluorimeter (Invitrogen, USA) using the Quant-iT dsDNA High-Sensitivity (HS) Assay Kit (Invitrogen, USA). Results: The relative copy number of the GPER1, SULT1A1, CYP1A1 genes in tumor samples increased (p &lt; 0.05) compared with normal tissues in the total sample of patients diagnosed with cervical cancer. In contrast to the total sample, an increase in the SULT1A1 gene dosage did not reach a statistically significant level in any group (p = 0.242 and p = 0.157); the copy number of the GPER1 locus significantly increased only in the group with the endophytic growth pattern (p = 0.040), as well as the CYP1A2 gene dosage (p = 0.025). Patients of 36-55 years with endophytic tumors showed a statistically significant (p &lt; 0.05) increase in the GPER1 and CYP1A1 gene copy numbers with the rates of 41.7% and 66.7%, respectively, as well as an increased amplification of the CYP1A2 gene in 41.67% of patients. In women of 56-75 years with endophytic tumors, an increase in the copy numbers of the ESR2, GPER1, SULT1A1 genes was observed with a frequency of 50%, 100% and 75%, respectively. Patients aged 20-35 and 36-55 years with exophytic tumors showed a statistically significant (p &lt; 0.05) increase in the CYP1A1 gene copy numbers in 33.33% and 45.45%, respectively. Conclusions: The results suggest the use of the GPER1, SULT1A1 and CYP1A1 gene copy numbers as biomarkers of cervical tumors.
Achieving national cancer governance reform: Lessons from a successful academic, clinical, and community advocacy approach in New Zealand.
Authors: Christopher G. C. A. Jackson, Diana Sarfati
Journal: Journal of Clinical Oncology (2020)

e14131 Background: Cancer survival in New Zealand (NZ) is high in global terms but gains in outcome are less than in comparable countries over recent time cohorts. Outcomes of indigenous Māori New Zealanders are significantly worse for most major cancers. This is potentially due to decentralisation of cancer provision and lack of emphasis on national governance. Methods: In 2017, academics, clinicians and patient advocates embarked on a planned and sustained programme of advocacy with the goal of establishing a national cancer plan, centralised cancer governance, and publicly reportable cancer outcomes and quality indicators by region and ethnicity. Elements central to success were partnerships with politicians and opposition parties, building credible media voices, establishing international academic collaborations, clear problem identification, positive evidence-based policy solutions, sustained and consistent yet varied media messaging, and strong relatable patient stories with direct citizen engagement. Results: As a direct result, in 2019 the Government established a National Cancer Agency, updated the national cancer plan for the first time in 16 years, moved to dissolve regional cancer networks, and appointed a national director of cancer control. New funding specifically for cancer investment was also announced and commitments to additional funding have been made. We review the strategies that were most successful, challenges encountered, and outcomes achieved. Conclusions: Advocacy and collaboration between patients, academics and clinicians remains a powerful stimulus for meaningful policy change. Our approach can be instructive for other countries where national cancer control and governmental leadership are faltering.
Progress on evaluation of frailty in elderly patients with chronic kidney disease
Authors: Xu Wang
Journal: BMJ (2019)

The frailty is a common syndrome in the elderly, with the population aging it has become a hot topic in geriatrics. In the elderly, frailty is closely associated with the existence of comorbidities, such as chronic kidney disease (CKD), which can promote the occurrence and development of frailty. There are many assessment tools for frailty. This article provides a brief review on the weak assessment tools; focuses on the association between CKD and frailty and related interventions in elderly patients.


Key words: 
Aged; Chronic kidney disease; Frailty; Intervention
Clinical analysis of 260 cases of hypopituitarism
Authors: Jun Li, Gui-jun Qin, Ying-hui Zhang, Yu-shan Yan
Journal: BMJ (2012)

Objective To review the clinical features,etiology and differential diagnosis of hypopituitarism.Methods The clinical data of 260 patients with hypopituitarism admitted to our hospital during 2007 to 2011 were retrospectively analyzed.Results In 260 patients 96 were males and 164 were females,the average age of female patients was significantly higher than that of males[ (44 ± 16) vs.(32 ± 20) years; t =3.821,P =0.001 ].Patients under 20 years accounted for the highest proportion in male cases (38/96,39.6％) ; while patients aged 40 - 60 years were the highest proportion for female cases (86/164,52.4％).Pituitary tumor and postoperative damage was the most common cause for hypopituitarism accounting for 36.2％ (94/260),followed by Sheehan syndrome (86/260,33.1％).The most common manifestation of hypopituitarism was anemia (102 eases) ; 26 cases presented all pituitary function failure.The causes leading to hypopituitarism usually showed specific manifestations in imaging examinations.The overall misdiagnosis rate was 40.4％ (105/260)in this series,while that of etiological diagnosis was 25.4％ (66/260).Conclusions This study suggests that hypopituitarism caused by different causes can be diagnosed by disease history,clinical manifestations and pituitary imaging examination.

Key words: 
Hypopituitarism; Clinical feature; Diagnosis
吡拉西坦片致严重过敏反应一例
Authors: 熊修安, 张逸仙, 马朝阳
Journal: BMJ (2007)

患者女,75岁,既往患有高血压、脑梗死、脑萎缩、心律不齐,无糖尿病、肝炎、结核、哮喘,药物过敏史不详.患者因左侧肢体无力在家服用吡拉西坦(脑复康,湖北华中药业有限公司,产品批号20060105)2片,30 min后出现全身皮肤发痒,脸潮红,有发热感,头昏,胸闷,呼吸急促,咽痒,恶心,全身乏力,当时神志尚清楚,立即送往某医院就诊。
Surrogate endpoints for overall survival in anti-programmed death-1 and anti-programmed death ligand 1 trials of advanced melanoma.
Authors: Run-Cong Nie, Shu-Qiang Yuan, Yuanfang Li, Yingbo Chen, Zhiwei Zhou
Journal: Journal of Clinical Oncology (2020)

10030 Background: The mechanisms of action of anti-PD-1/PD-L1 agents are markedly distinct from those of cytotoxic agents, thus a critical issue that is under investigation is what is the optimal endpoint and how should tumor response be evaluated in anti-PD-1/PD-L1 trials for metastatic melanoma. Here, we assessed surrogacy of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) for overall survival (OS) in anti-PD-1/PD-L1 trials of metastatic melanoma through a meta-analysis of randomized controlled trials (RCTs). Methods: PubMed and EMBASE were searched for phase 2/3 RCTs till June 2019 investigating anti-PD-1/PD-L1 agents. Treatment effect (hazard ratio or odds ratio) on potential surrogates (ORR/DCR/PFS) and OS were collected. At trial level, we assessed the correlation between treatment effect on potential surrogates and OS, weighted by sample size, fixed and random effect models, and calculated the surrogate threshold effect (STE). Sensitivity analyses and leave-one-out cross-validation approach were performed to evaluate the robustness of our findings. Results: We included 8 RCTs (4,110 patients; 11 comparisons). We did not identify strong correlations between ORR (coefficient of determination [ R 2 ]: 0.09 to 0.25), DCR (0.41 to 0.57) and OS. However, we noted a strong correlation between PFS and OS, with R 2 of 0.82 in sample size, 0.75 in fixed effect, and 0.72 in random effect model weighting, the robustness of which was further verified by leave-one-out cross-validation approach. Sensitivity analyses with restriction to trials with less than 50% crossover ( R 2 : 0.94-0.94), phase 3 trials ( R 2 : 0.94-0.95), large trials ( R 2 : 0.78-0.86) and first-line trials ( R 2 : 0.83-0.91) strengthened the correlation. The STE for PFS was 0.78. Conclusions: PFS may be the appropriate surrogate for OS in anti-PD-1/PD-L1 trials of metastatic melanoma. A future anti-PD-1/PD-L1 trial would need less than 0.78 for PFS of the upper limit of confidence interval to predict an OS benefit.