tbuckley/cabot-search huggingface dataset:
Targeted next generation sequencing to expand <i>HER2</i> status detection: Implication for newer <i>HER2</i>-directed agents.
Authors: Ning Liao, RongFeng Song, FangQin Xue, Shuirong Zhang, Samuel J Klempner, Lijuan Chen, Kai Wang, Wenjing Wang
Journal: Journal of Clinical Oncology (2020)

1047 Background: Establishment of ERBB2 ( HER2) amplification status in breast carcinoma (BC) and gastric carcinoma (GC) is essential for treatment selection, but no anti- HER2 therapies have been approved for tumors with low level of HER2 expression. The clinical trial ( NCT02564900 ) was initiated to evaluate the safety and efficacy of trastuzumab deruxtecan (DS-8201a) in BC patients with lower HER2 expression by current methods. This study aims to validate NGS-based detection for HER2 low expression. Methods: 275 BC and 425 GC were collected and subjected to NGS for genomic alteration detection. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, Shanghai, China. Protein expression was analyzed by using IHC. FISH was carried out on 108 samples, including 63 BC and 45 GC. To set up NGS cutoff, FISH was performed on additional 34 samples. Sensitivity, specificity and accuracy were evaluated based on FISH as a gold-standard reference. Results: In BC, the expression level of HER2 protein detected by IHC was overall IHC 0 in 28.7%, 1+ in 18.9%, 2+ in 27.3% and 3+ in 25.1%, respectively, while in GC, the expression level was 60.7%, 18.6%, 14.8% and 5.9%, respectively. Log2ratio was used to assess ERBB2 amplification status detected by NGS. According to the FISH results of 34 other samples with high sensitivity (98%) and specificity (100%), the threshold was determined as 0.5. 8 and 10 samples of IHC 1+/2+ met the cutoff in BC and GC, respectively. In 63 BC, there were 17 positive and 46 negative by FISH. According to the threshold, the sensitivity and specificity of NGS detection was 94.1% and 97.8%, respectively. The proportion of samples with IHC 2+ that couldn't determine NGS ERBB2 status was 49.2%. However, except for false positive and false negative, the NGS results were concordant with FISH. In 45 GC, there were 5 positive and 40 negative by FISH. The specificity and sensitivity was 97.5% and 40%, respectively. In 4 samples with IHC 2+, 2 of them were discordant with the results of NGS and FISH. All IHC 1+ didn't meet the cutoff of NGS and was FISH negative in 108 samples. The accuracy of NGS in ERBB2 detection was 96.8% and 91.1% for BC and GC, respectively. Conclusions: Our data indicated that the NGS-based detection of ERBB2 amplification had high sensitivity, specificity and accuracy. In samples with IHC 1+/2+, the results of NGS detection were high concordant with FISH detection.
Sociodemographic factors associated with cancer treatment completion among women with breast cancer at Butaro Cancer Center of Excellence (BCCOE) in Rwanda.
Authors: Abirami Natarajan, Niclas Rudolfson, Daniel O'Neil, Lauren Schleimer, Jean Marie Vianney Dusengimana, Nancy Lynn Keating, Lawrence N. Shulman, Tharcisse Mpunga, Fidel Sebahungu, Cam Nguyen, Aline Umwizerwa, Temidayo Fadelu, Cyprien Shyirambere, Catherine Ndagire Kigonya, John Butonzi, Lydia E. Pace
Journal: Journal of Clinical Oncology (2020)

e19220 Background: Many barriers exist to delivering comprehensive breast cancer care in low-income countries. We examined sociodemographic factors associated with treatment completion among women receiving care for breast cancer at Butaro Cancer Center of Excellence (BCCOE), Rwanda’s first public cancer facility. Methods: We retrospectively measured treatment completion rates in women with early and locally advanced breast cancer diagnosed at BCCOE between July 1, 2012 and December 31, 2016. We defined treatment completion as receipt of surgery, 4 cycles of chemotherapy, and initiation of hormonal therapy for estrogen receptor positive (ER+) breast cancer. We used logistic regression to examine associations between socio-demographic and clinical factors and treatment completion. Travel time was estimated using a geographic information systems model using the WHO tool AccessMod 5.0. Results: Of 212 eligible women, 138 (65%) had surgery and 141 (66%) received 4 cycles of chemotherapy. Among 139 women with ER+ cancer, 59% initiated hormonal therapy. Overall 56% received all indicated treatment including surgery, chemotherapy, and hormonal therapy (if ER positive); 44% did not complete indicated treatment. Women who lived closer to the hospital ( &lt;50 minutes travel time) were more likely than other women to complete treatment (OR 4.2; 95% CI 1.1-15.1). Women with early-stage disease were also more likely than women with locally advanced disease to complete treatment (OR 2.2, 95% CI 1.1-4.4). Among 100 women with available information about ubudehe (Rwandan social categorization used as a proxy for socioeconomic status), rates of treatment completion were higher for women who were eligible for social support (ie: transportation support or insurance subsidy) than women who were not (74% v. 63%), although this difference was not statistically significant (p= 0.51). Conclusions: Significant barriers exist for breast cancer patients receiving treatment in this low resource setting; nevertheless, over half of the patients completed therapy. Interventions are needed to facilitate care for women with long travel times and locally advanced disease to reduce disparities in outcomes for this population of patients. Further research is needed to determine the role of social support in treatment completion.
Health related quality of life (HRQoL) outcomes from the phase III CANDOR study comparing carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients (Pts) with relapsed or refractory multiple myeloma.
Authors: David Samuel DiCapua Siegel, Katja Weisel, Anita Zahlten-Kumeli, Rohan Medhekar, Sandhya Sapra, Bifeng Ding, Xavier Leleu
Journal: Journal of Clinical Oncology (2020)

e20563 Background: In the CANDOR study (N = 466) of pts with relapsed or refractory multiple myeloma (RRMM), a statistically significant improvement in progression-free survival (HR = 0.63; 95% CI, 0.46-0.85; p = 0.0014) was observed in the KdD vs Kd arms. Here, we report a secondary endpoint of CANDOR evaluating HRQoL. Methods: HRQoL was assessed using the Global Health status (GHS)/Quality of Life (QoL) domain of the European Organisation for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30), which was completed on Day 1 of Cycle 1 and every 28±7 days through the first follow-up visit. The GHS/QoL was scored from 0–100, with higher scores indicating better QoL. The scores were compared between the KdD and Kd arms using a restricted maximum likelihood-based mixed effects model for repeated measures under the assumption of missing data at random. A minimally important difference of 5 points between arms was prespecified. An exploratory time-by-time sensitivity analysis by ANCOVA was used to evaluate the treatment effect on the GHS/QoL score among pts who remained on treatment until the specified visit (cycle 3 and every 3 cycles thereafter). Results: GHS/QoL completion rates from baseline through up to cycle 26 (study ongoing) for randomized pts who remained on treatment were &gt; 81% for both the KdD and Kd arms; the median extent of missing GHS/QoL data was 5.3% for the KdD arm and 12.1% for the Kd arm. KdD was associated with higher GHS/QoL scores relative to Kd starting at Cycle 7 and this was maintained until Cycle 26 (by mixed effect model, overall LSME difference [95% CI], 0.06 [–2.39, 2.50]; p = 0.96). At Cycle 18, the mean difference between arms approached the prespecified clinically meaningful difference of 5 points (by ANCOVA, [difference: KdD–Kd (SE), 4.06 (2.45)]). In an exploratory analysis of pts who remained on treatment at each cycle, a higher rate of pts reported an improvement of ≥10 points in GHS/QoL score from baseline in the KdD vs Kd arms, with the greatest differences observed at Cycle 7 (Odds Ratio [OR] for KdD/Kd [95% CI], 2.37 [1.29, 4.34]), Cycle 9 (OR [95% CI], 2.96 [1.46–6.03]), Cycle 13 (OR [95% CI], 2.44 (1.15-5.17), and Cycle 16 (OR [95% CI], 2.77 [1.27–6.07]). Conclusions: In addition to the superior clinical benefit observed with KdD vs Kd, HRQoL was maintained with the KdD triplet. A higher rate of pts treated with KdD reported an improvement of ≥10 points from baseline. Clinical trial information: NCT03158688.
The oncology hospital at home: Health care utilization outcomes from the huntsman at home trial.
Authors: Kathi Mooney, Karen Titchener, Benjamin Haaland, Lorinda Adaire Coombs, Brock O Neil, Richard Nelson, Jordan P. McPherson, Anne C. Kirchhoff, Karen Ameloot, Anna Catherine Beck, John Harris Ward
Journal: Journal of Clinical Oncology (2020)

7000 Background: Unplanned hospitalizations and emergency department (ED) visits are common during cancer care. Providing acute hospital level care at home may add value by decreasing hospital and ED use. We conducted the first evaluation of an oncology Hospital-at-Home program, Huntsman at Home (H@H). Methods: The Huntsman Cancer Institute began H@H services in 2018 and accepts referral of cancer patients for acute-medical or post-surgical care at home. Patients are admitted who require continued acute level medical care after hospitalization or have emergent unstable symptoms related to treatment or disease progression that would otherwise require ED evaluation or hospitalization. Prospectively, patients referred to H@H from 8/2018 through 10/2019 were compared to a usual care comparison group (UC) drawn concurrently from patients living within the Salt Lake City metropolitan area who qualified for admission to H@H, but lived outside the service zip codes. Probability of H@H enrollment propensity scores were constructed via random forest from patient descriptors and health care utilization at admission. We used an intent-to-treat approach for analysis. Primary outcomes were hospitalizations, length of stay (LOS), ED visits and cumulative charges over 30 and 90 days post admission to either group. Comparisons were made by generalized linear models, stratified by tertiles of H@H vs. UC propensity score. Results: 367 patients, 169 H@H and 198 UC, were evaluated. The average age was 62 yrs, 85% were Caucasian, and 77% had stage IV cancer. Propensity score distributions were overlapping, demonstrating group comparability. A variety of cancers were represented; the most common being colon, gynecologic, prostate and lung cancers. Compared to UC, H@H patients were more likely to be female (61% vs 43%) and during the month prior to admission, showed a trend towards longer LOS if hospitalized (6.7 vs 5.5 days). During the first 30 days after admission, propensity stratified comparisons showed H@H patients with lower hospital LOS (mean reduction 1.19 days, p=0.022), 56% lower odds of unplanned hospitalizations (OR 0.44, p=0.001), 45% lower odds of ED visits (OR 0.55, p=0.037) and 50% lower cumulative charges (mean ratio 0.50, p&lt;0.001) compared to UC. Results over 90 days were similarly robust. Conclusions: In the first reported trial of an adult oncology Hospital at Home program, there was strong evidence for reduced hospitalizations, ED visits, and cost. Oncology Hospital at Home programs show promise for increased patient-centered care while simultaneously improving value.
Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys
Authors: Mihalis S. Kariolis, Robert C. Wells, Jennifer A. Getz, Wanda Kwan, Cathal S. Mahon, Raymond Tong, Do Jin Kim, Ankita Srivastava, Catherine Bedard, Kirk R. Henne, Tina Giese, Victoria A. Assimon, Xiaocheng Chen, Yin Zhang, Hilda Solanoy, Katherine Jenkins, Pascal E. Sanchez, Lesley Kane, Takashi Miyamoto, Kylie S. Chew, Michelle E. Pizzo, Nicholas Liang, Meredith E. K. Calvert, Sarah L. DeVos, Sulochanadevi Baskaran, Sejal Hall, Zachary K. Sweeney, Robert G. Thorne, Ryan J. Watts, Mark S. Dennis, Adam P. Silverman, Y. Joy Yu Zuchero
Journal: Science Translational Medicine (2020)

Engineering human IgG1 Fc binding to a brain endothelial cell–enriched receptor allows enhanced brain exposure of biotherapeutics in multiple species.
Comprehensive profiling of genomic in 80 Chinese patients with bladder cancer.
Authors: Zengjin Yuan, Chunhe Yang, Jie Chen, Yanhua Zhu, Xiaohong Xu, Lingyu Wang, Rongbo Lin, Yining Yang
Journal: Journal of Clinical Oncology (2020)

e17024 Background: Bladder cancer (BLCA) is the ninth most common malignant disease and the thirteenth most common cause of cancer death worldwide, To understand the genomic landscape of Chinese BLCA patients, 80 cases were analyzed by comprehensive genomic profiling (CGP) for genomic alterations and genome wide signatures. Methods: Formalin Fixed Paraffin Embedded (FFPE) tumor and matched blood samples of 80 Chinese BLCA patients were obtained for next-generation sequencing (NGS)-based 642 cancer genes panel assay and bladder cancer genomic profiling was evaluated. Results: Collectively, in our Chinese BLCA cohort, multiple histological subtypes, including Non-muscle invasive bladder cancer (NMIBC) (20/80, 25%), muscle invasive bladder cancer (MIBC) (49/80, 61.25%), and other subtypes (11/80, 13.75%). The top ranked somatic gene alterations in Chinese BLCA patients were TP53 (49%), TERT (34%), KMT2D (33%), KMD6A (25%), CDKN2A (23%), FGFR3 (23%), FLG (19%), PIK3CA (19%), CCDN1 (18%), RB1 (18%). Some FGFR2/3 gene fusions were detected such as FGFR2-WDR11 and FGFR3-TACC3. Interestingly, some co-mutations were identified in our cohort, such as ERBB3 was co-mutated with MUC17, FAT1 was co-mutated with RB1 etc. (p &lt; 0.01). Out of 15 most common canonical pathways, potentially targetable genomic alterations were mainly identified in RTK-RAS (74.68%), DNA damage response (53.16%), TP53 (53.16%),chromatin remodeling (51.90%), PI3K (44.30%), NOTCH (41.77%), Cell Cycle(32.91%), Hippo (29.11%) and WNT (29.1%) pathway. Additionally, chromatin remodeling and NOTCH pathways were commonly co-altered with MYC pathway, TP53、Hippo and NOTCH pathways were significantly co-altered with DNA damage response pathway. Across samples, 33 Chinese BLCA patients had high tumor mutational burden (TMB-H) ( &gt; 10 mutations/Mb). Only 2 Chinese patients had high microsatellite instability (MSI-H). Conclusions: Our results displayed the landscape of genomic alterations in 80 Chinese BLCA patients. The genomic alterations identified in our study may provide an opportunity to discover potential strategies for targeted and immunotherapy in BLCA. Future studies should account for these genomic alterations.
电话辅助随访管理2型糖尿病患者五例分析
Authors: 黄萍
Journal: BMJ (2008)

目前由于患者的老龄化和多种原因,有相当多的糖尿病患者不能按时到医疗机构就医,造成治疗达标困难和管理的空白.因此本研究从2007年9月剑2008年4月对5例不同治疗背景的2型糖尿病患者进行电话辅助随访管理[1]9,72,的尝试,取得较好效果。
Impact of Transcatheter Aortic Valve Durability on Life Expectancy in Low-Risk Patients With Severe Aortic Stenosis
Authors: Derrick Y. Tam, Harindra C. Wijeysundera, David Naimark, Mario Gaudino, John G. Webb, David J. Cohen, Stephen E. Fremes
Journal: Circulation (2020)

Recent clinical trial results showed that transcatheter aortic valve replacement (TAVR) is noninferior and may be superior to surgical aortic valve replacement (SAVR) for mortality, stroke, and rehospitalization. However, the impact of transcatheter valve durability remains uncertain.Discrete event simulation was used to model hypothetical scenarios of TAVR versus SAVR durability in which TAVR failure times were varied to determine the impact of TAVR valve durability on life expectancy in a cohort of low-risk patients similar to those in recent trials. Discrete event simulation modeling was used to estimate the tradeoff between a less invasive procedure with unknown valve durability (TAVR) and that of a more invasive procedure with known durability (SAVR). Standardized differences were calculated, and a difference >0.10 was considered clinically significant. In the base-case analysis, patients with structural valve deterioration requiring reoperation were assumed to undergo a valve-in-valve TAVR procedure. A sensitivity analysis was conducted to determine the impact of TAVR valve durability on life expectancy in younger age groups (40, 50, and 60 years).Our cohort consisted of patients with aortic stenosis at low surgical risk with a mean age of 73.4±5.9 years. In the base-case scenario, the standardized difference in life expectancy was <0.10 between TAVR and SAVR until transcatheter valve prosthesis failure time was 70% shorter than that of surgical prostheses. At a transcatheter valve failure time <30% compared with surgical valves, SAVR was the preferred option. In younger patients, life expectancy was reduced when TAVR durability was 30%, 40%, and 50% shorter than that of surgical valves in 40-, 50-, and 60-year-old patients, respectively.According to our simulation models, the durability of TAVR valves must be 70% shorter than that of surgical valves to result in reduced life expectancy in patients with demographics similar to those of recent trials. However, in younger patients, this threshold for TAVR valve durability was substantially higher. These findings suggest that durability concerns should not influence the initial treatment decision concerning TAVR versus SAVR in older low-risk patients on the basis of current evidence supporting TAVR valve durability. However, in younger low-risk patients, valve durability must be weighed against other patient factors such as life expectancy.
Clinical activity and safety of penpulimab (Anti-PD-1) with anlotinib as first-line therapy for advanced hepatocellular carcinoma (HCC).
Authors: Shun Chang Jiao, Li Bai, Jiahong Dong, Chunmei Bai, Chunhong Hu, Liangfang Shen, Qun Qin, Yuxian Bai, Jia Fan, Aimin Zang, Chun Han, Yanyun Zhu, Juan Li, Pengfei Zhang, Sisi Ye, Xindan Kang, Qian Qiao, Weifeng Song, Baiyong Li, Yu Xia
Journal: Journal of Clinical Oncology (2020)

4592 Background: Advanced HCC is a deadly disease with few systemic therapeutic options. VEGF blockade potentiates the effect of PD-1 inhibition by opposing the immunosuppressive effects of VEGF-A (increased DC maturation, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors). A sBLA has been submitted for an anti-PD-L1 + anti-VEGF combination as 1L treatment for advanced HCC. Penpulimab is a novel humanized anti-PD-1 IgG1 antibody with complete removal of Fc receptor mediated effect, and featuring slow antigen binding off-rate and high receptor occupancy. Anlotinib is a multi-targeted tyrosine kinase inhibitor selective for VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit. Methods: In this open-label, multicenter phase Ib/II study, treatment-naive pts with advanced HCC received penpulimab 200mg Q3W in combination with anlotinib 8mg QD (2 weeks on 1 week off) until loss of clinical benefit or unacceptable toxicity. The primary objectives were to assess antitumor activity by ORR (RECIST v1.1). The secondary objectives were to assess antitumor activity by DCR, DoR, TTP, and to assess the safety and tolerability of the combination. Results: As of Jan 14, 2020, 31 pts (median age 56 years [23-74], male 81%, ECOG 0/1 [64%/36%], BCLC B/C [23%/77%], HBV/HCV [61%/7%]) received combined therapy (a median of 6 [1-15] doses). Treatment-related adverse events (TRAEs) occurred in 93.5% of pts (G3 in 9.7% [3/31], no G4, and leading to treatment discontinuation in 6.5% [2/31]). Most frequent TRAEs were increased AST (35.5%), increased ALT (29%), asthenia (22.6%), decreased platelet count (19.4%), increased blood bilirubin (19.4%), increased bilirubin conjugated (19.4%), and rash (16.1%). Of 25 evaluable pts (with the opportunity to be followed-up for ≥2 scans, 12 weeks), confirmed ORR was 24% (6/25) and DCR was 84% (21/25). Five responders remained in response with DoR ranging 1.4+ to 6.9+ months. Median TTP was not reached and 6m-TTP rate was 63% (95% CI: 38%, 81%). Conclusions: Penpulimab in combination with anlotinib had a manageable safety profile and encouraging antitumor activities in patients with advanced HCC. No unexpected AEs were identified beyond the established safety profile for each agent. Evaluation of penpulimab + anlotinib (10 mg QD) in a phase 3 study for 1L HCC is currently underway. Clinical trial information: NCT04172571 .
异位性快速心律失常同步直流电击复律的应用
Authors: 于守华
Journal: BMJ (2004)

同步直流电击复律可用于异位性快速心律失常,现报告4例,摘要如下. 例1 患者女性,46岁,突发心悸1 d入院.心电图示心房扑动、2∶ 1传导,心房率300次/min,患者3个月前接受房间隔缺损心脏修补术治疗,无心动过缓病史.予以胺碘酮治疗2周无效,行食道调搏术500次/min猝发刺激仍无效,决定电击复律治疗.3次静脉注射地西泮共30 mg无效后,用2.5%硫喷妥钠5 ml静脉注射使患者入睡,给予50 J同步直流电击复律1次,患者立即转为窦性心律。
B-TREUH: A single-arm phase II pilot study of euthyroid hypothyroxinemia in metastatic breast carcinoma.
Authors: Shruti Trehan, Suzan S. Cheng, Aleck Hercbergs
Journal: Journal of Clinical Oncology (2020)

TPS1115 Background: It is estimated that there are approximately 155,000 people living with metastatic breast cancer in the US. Studies exploring the connection between hypothyroidism or hyperthyroidism and breast cancer have yielded varying results with up to 33% prevalence of thyroid disease in these patients. L-thyroxine (T4) is the most commonly prescribed agent in the US to manage hypothyroidism. However, there are data suggesting that T4 is a pro-oncogenic agent with proposed mechanisms such as stimulation of mitogenesis, angiogenesis, resistance to apoptosis. In addition, T4 May counter anti-PDL-1 and radiation effects. Triiodothyronine (T3), which is deiodinated form of T4 and also commercially available, is felt to be less oncogenic and less mitogenic. Therefore, exogenous supplementation of T3 would decrease the T4 levels creating the desired state of EUTHYROID HYPOTHYROXINEMIA. The study hypothesizes that replacing L-thyroxine (T4) with Triiodothyronine (T3) in hypothyroid patients with metastatic breast carcinoma, while they simultaneously continue to receive standard systemic therapy, with titrating T3 dose to achieve a state of Euthyroid Hypothyroxinemia would result in improved disease outcomes. Methods: Eligible participants are adults with metastatic breast carcinoma with estimated life expectancy of &gt; 3months, hypothyroidism, and with normal TSH on L-thyroxine (T4). Following consent, participants will discontinue L-thyroixne (T4) and initiate Triiodothyronine (T3) dose based on current T4 dose after an appropriate washout period. Drug titration will be in accordance with thyroid function testing to maintain levels of free T4 at &lt; 50% normal range. The treatment period will continue for 9 months with periodic assessment of disease status, quality of life (FACT-B) and laboratory measures. The primary endpoint is the progression free survival at 12 months while the secondary endpoints are prevalence of hypothyroidism in the cohort, overall survival, quality of life, and duration of time to achieve the Euthyroid Hypothyroxinemia state. Given many uncertainties to calculate power precisely, the sample size is estimated to be approximately 30 patients. Clinical trial information: NCT03787303 .
自发性食管破裂17例临床分析
Authors: 张润起, 王鹏, 张晓燕
Journal: BMJ (2011)

自发性食管破裂是胸外科临床少见而严重的急症之一,其病死率较高.早期诊断和及时采取合理的治疗措施可显著提高治愈率.本科在2001年7月至2010年3月收治17例自发性食管破裂患者,其中大部分患者采取积极手术治疗,效果良好;部分患者因破口较小采用保守治疗,效果比较满意.我们自2010年9月至2011年1月收集此17例患者的临床资料,现将治疗经验回顾分析如下. 关键词：食管穿孔