tbuckley/cabot-search huggingface dataset:
Preliminary dose escalation results from a phase I/II, first-in-human study of MGC018 (anti-B7-H3 antibody-drug conjugate) in patients with advanced solid tumors.
Authors: John D. Powderly, Sekwon Jang, Joanna Lohr, Alexander I. Spira, Gerry C. Bohac, Manish Sharma
Journal: Journal of Clinical Oncology (2020)

3071 Background: Antibody-drug conjugates (ADCs) are cancer agents that have a cytotoxic payload linked to a monoclonal antibody (mAb) that target cancer cells. ADCs offer increased cytotoxic activity while reducing normal tissue exposure. B7-H3 is expressed on multiple solid tumors with limited normal tissue expression. MGC018 is an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 mAb. It is hypothesized that MGC018 has activity against B7-H3 expressing tumors with an acceptable safety profile. Methods: This study evaluates safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) of MGC018 in a dose escalation 3+3+3 design. In addition, pharmacokinetics, immunogenicity, and tumor response using RECIST v1.1 are evaluated. Cohort expansion will enroll at the MTD to assess safety and tumor response. Results: The study is enrolling Cohort 3 (6 total cohorts planned) in dose escalation. 20 patients (pts) were enrolled as of Feb 03, 2020. At least 1 treatment related adverse event (TRAE) occurred in 16 pts (80.0%). The most common TRAEs were neutropenia/decreased neutrophil count (35%); fatigue, lymphopenia/decreased lymphocyte count (30.0%); palmar plantar erythrodysaesthesia (PPE), skin hyperpigmentation (25.0%); pruritis, nausea, chills, infusion related reaction (20.0%); and vomiting, pyrexia, maculopapular rash (15.0%). Eleven pts (55.0%) experienced TRAEs ≥ Grade 3; events were decreased lymphocyte count/lymphopenia (n = 6), decreased neutrophil count/neutropenia (n = 3), PPE (n = 2), and maculopapular rash (n = 2). Three related serious adverse events occurred in 3 unique pts: pneumonitis in a pt with concurrent bacterial pneumonia, non-infectious gastroenteritis, and stasis dermatitis in a pt with chronic venous insufficiency. One DLT has occurred (Grade 4 neutropenia). No febrile neutropenia was observed. Target lesion decrease was noted in 1 pt each with small cell lung cancer (-6.3%), non-small cell lung cancer (-23.8%), and metastatic castrate-resistant prostate cancer (mCRPC) (-29.4%) with PSA change from 82.8 ng/ml to 57.1 ng/ml. One mCRPC pt with bone only disease had substantial improvement on bone scan and PSA decrease from 60 ng/ml to 4.7 ng/ml. Conclusions: Results to date demonstrate a manageable safety profile with early evidence of clinical activity. Continued dose escalation and clinical investigation of MGC018 is ongoing. Clinical trial information: NCT03729596 .
Changes of memory function in the elderly with mild cognitive impairment and their predictive value for dementia
Authors: 肖世富, 薛海波, 李冠军, 李霞, 李春波, 吴文源, 张明园
Journal: BMJ (2006)

目的 观察和评价老年轻度认知功能损害(MCI)患者记忆功能的变化特点及其预测痴呆的价值.方法前瞻性对照研究.对象为患轻度认知功能损害的老年人(MCI组)和认知功能正常的老年人(对照组)两组.主要用韦氏记忆测验(WMS)和简易智力状态检查(MMSE),在基线和3年随访时分别评价轻度认知功能损害的记忆缺损变化.随访对象发展为痴呆的诊断标准为美国精神疾病诊断分类与统计手册第4版(DSM-Ⅳ)标准.结果MCI组共47例,对照组50例.平均随访时间为(34±2)个月,随访期间MCI组13例和对照组1例发展为痴呆,MCI组痴呆的发病率为27.7%,对照组为2.0%,两组差异有统计学意义(P＜0.01).3年间,MCI组的简易智力状态检查总分平均下降了(2.2±3.7)分,对照组下降了(1.0±1.9)分;MCI组的记忆商下降了(12.6±17.3)分,对照组下降了(3.9±8.4)分;MCI组中发展为痴呆的患者的简易智力状态检查和记忆商下降更为明显,分别下降了(5.5±2.8)分和(29.9±18.0)分.logistic回归分析显示,简易智力状态检查和韦氏记忆测验的定向记忆得分对MCI是否发展为痴呆具有显著性预测意义,2个测验预测的总正确率分别为70.3%、78.4%.结论MCI发展为痴呆的主要记忆功能改变有定向、识记、视觉、触觉等短期记忆显著下降,定向记忆的显著下降作为预测痴呆的因素,有助于痴呆的早期识别和预防。
Morphological and biochemical heterogeneity in the tissue of pancreatic ductal adenocarcinoma (PDAC) according to structural and spectrometric MRI data.
Authors: Dmitry Ya. Iozefi, Mikhail A. Vinidchenko, Nikolay S. Demchenko, Oleg I. Kit, Yuriy A. Fomenko, Dmitry S. Petrov
Journal: Journal of Clinical Oncology (2020)

e16727 Background: Comparing the MRI characteristics of pancreatic tissue in normal, solid adenocarcinomas and chronic pancreatitis in a multiparametric study, the radiologist needs tools that reduce the subjective component in making a diagnostic decision. The study is devoted to the assessment of structural heterogeneity, diffusion coefficient, lipid and lactate concentration according to MR spectroscopy in vivo. PDAС cells are proliferating and surviving within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. In this case cells have to show biochemical flexibility (survival phenotype) in order to adapt to unusual conditions. Methods: 20 patients with pancreatic adenocarcinomas (PDAC), 10 patients with chronic pancreatitis and 10 patients with unchanged pancreas were examined MRI using Signa HD 1.5 t General Electric. The results of their multiparametric imaging and NMR spectroscopy were investigated and compared.The heterogeneity coefficients (HC) were measured as ratio standard deviation in small region of interest to signal intensity in T1FS and T2. Lipid concentration was measured by Dixon method as the pancreatic -to-splenic attenuation ratio. Results: In a small sample, we observed a significant increase in HC in chronic pancreatitis, and in solid tissue in adenocarcinomas in comparison with normal tissue, depending on the main source of the MR signal (hydrogen in the macromolecules or hydrogen of water and fat). In adenocarcinomas, an increase in the signal from lipids (lip13a) peak was revealed, with a decrease in the total lipid concentration. A decrease in lipid concentration in the tumor in the presence of diffusion restriction (ADC 0,001-0,0016 мм2/s) and the appearance of a peak of lactate may be a biochemical marker of adenocarcinoma. In chronic pancreatitis, an increase in the mass fraction of lipids was revealed. Conclusions: The results obtained in current and future in-depth studies are promising for creation of a metabolically oriented diagnostic model of pancreatic cancer.
Real-world healthcare resource utilization and costs among relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients receiving ibrutinib or chemoimmunotherapy (CIT).
Authors: Nilanjan Ghosh, Bruno Emond, Marie-Hélène Lafeuille, Aurélie Côté-Sergent, Patrick Lefebvre, Qing Huang
Journal: Journal of Clinical Oncology (2020)

e19408 Background: Ibrutinib is a targeted oral therapy indicated for MCL patients who received ≥1 prior line of therapy (LOT) (conditional approval on 11/13/2013 in the US). This study compared healthcare resource utilization (HRU) and costs of R/R MCL patients treated with ibrutinib ± rituximab (I±R) or CIT in a US-managed care population. Methods: Optum Clinformatics Extended DataMart De-Identified Databases (05/13/2013-6/30/2019) were used to identify adults with MCL receiving I±R or CIT (index date) following ≥1 prior LOT. Patients’ baseline characteristics were balanced using inverse probability of treatment weighting (IPTW). Monthly HRU and costs (plan paid amount) were evaluated during the first Oncology Care Model (OCM) episode (i.e., first 6 months) post-index and during the observed index I±R or CIT LOT (index LOT); and compared using rate ratios (RRs) and mean monthly cost differences (MMCDs), respectively. Results: A total of 146 I±R and 158 CIT patients were identified. Given the small sample size and to ensure outliers were not driving the results, 2 patients with total healthcare costs ≤0.5 th and ≥99.5 th percentile were excluded from each cohort. After IPTW, 149 and 151 patients were included in the weighted I±R and CIT cohorts, respectively (mean length of index LOT: 12.0 vs 11.0 months). During the first OCM episode and during the index LOT, the I±R cohort had significantly fewer monthly days with outpatient services compared to the CIT cohort (OCM: RR= 0.63, P&lt;0.001; index LOT: RR= 0.73, P=0.004). The I±R cohort incurred significantly higher monthly pharmacy costs that were offset by lower monthly medical costs, yielding a monthly total cost reduction of $9,435 (p&lt;0.001) during the first OCM episode and $4,628 (p=0.010) during the index LOT, compared to the CIT cohort (Table). Conclusions: In this study, patients with R/R MCL treated with ibrutinib ± rituximab had significantly fewer days with outpatient services and lower total healthcare costs per month versus those treated with CIT during the first OCM episode and the index LOT. [Table: see text]
外伤性膀胱破裂90例
Authors: 魏民, 丁德武, 侯钦丽, 胡伟, 徐培强, 张正福
Journal: BMJ (2004)

我院1989～2001年收治外伤性膀胱破裂患者90例,报告如下. 1.临床资料:男72例,女18例,9～66岁,平均27岁.损伤类型:腹膜内型45例,腹膜外型20例,混合型25例.闭合性损伤81例,开放性损伤9例.单纯性膀胱破裂20例,合并其他脏器损伤70例,伴创伤性休克32例.90例患者中80例行膀胱修补术并及时对症治疗而治愈,10例保守治疗愈合。
Clinical outcome in terms of survival and treatment response of patients with metastatic urothelial carcinoma harboring FGFR alterations compared to wild-type tumors.
Authors: Elena Sevillano, Juan Francisco Rodriguez-Moreno, Arantzazu Barquin, Monica Yagüe, Sergio Ruiz, Paloma Navarro, Sandra Amarilla, Patricia Polo Ojea, Jesús García-Donas
Journal: Journal of Clinical Oncology (2020)

e17042 Background: FGFR gene alterations are a new target in metastatic urothelial carcinoma (mUC). However, controversial data have been published regarding the outcome of these tumors.In order to assess the prognostic value of this gene, we aimed to compare survival and response to treatment of patients harboring FGFR alterations vs wild type (WT) tumors. Methods: Medical records of patients with advanced urothelial cancer screened for FGFR mutations or fusions at our center were reviewed. Results: Between May 2011 and December 2019 up to 149 patients completed any screening test for FGFR alterations. 30 cases (20,1%) were deemed as positive (mutations: 12, amplifications: 9, rearragements /fusions: 4 and not specified in 5). 30% of the cases were Upper Tract Urothelial carcinoma (UTUC) versus 70% bladder UC. 8% patients had liver metastases and 100% PS ≤ 1 at first line.. 73% (22/30) received chemotherapy (1st line:15, 2nd line; 4, 3rd line: 4) with 1CR, 9 PR, 2SD in first line. 50% (15/30) received a checkpoint inhibitor (1st line:5, 2nd line:5, 3rd line:5). Of these, 2 cases responded, 2 remained stable and 8 progressed. Overall, 40% (12/30) received an FGFR inhibitor (1st line: 7, 2nd line: 4, 3rd line: 1). 54% (6/11) experimented tumor response (complete:1, partial:5). Median overall survival for the whole FGFR population was 24,6 month. Median progresion free survival was:1st line: 4,1 mo, 2nd line: 4,1, 3rd line: 7,1 respectively. Among the 119 cases deemed as FGFR WT. 95% of primary tumors were located at the bladder. 64% had liver metastases and PS ≥2: 34% at first line treatment. 43%(52/119) received chemotherapy: 1 st line:33, 2 nd line:13, 3 rd line: with 4CR, 11PR, 4SD, 9PD. And 40% (48/119 ) CPI: 1 st line: 30, 2 nd line: 15, 3 rd line:3 with 1CR, 3 PR, 4SD, 19PD. The median OS was 9,9 months for patients with wild-type patients. Median progresion free survival was: 1st line: 4,5 mo, 2nd line: 2,3, 3rd line: 0.8 month. Conclusions: FGFR is a relatively common molecular alteration in UC. Patients harboring a FGFR alteration present a better prognosis than wild type tumors. Clinical benefit with chemotherapy and CPIs was similar in both populations.
Pembrolizumab vs paclitaxel as second-line treatment for Asian patients with PD-L1–positive advanced gastric or gastroesophageal cancer (GC) in the phase III KEYNOTE-063 trial.
Authors: Hyun Cheol Chung, Yoon-Koo Kang, Zhendong Chen, Yuxian Bai, Wan Zamaniah Wan Ishak, Byoung Yong Shim, Youngiee Park, Dong-Hoe Koo, Jin Wei LU, Jianming Xu, Pooja Bhagia, Shu Kuang, Chie-Schin Shih, Shukui Qin
Journal: Journal of Clinical Oncology (2020)

e16586 Background: Approximately 75% of GC cases occur in Asian persons. Pembrolizumab has shown antitumor activity in global studies of GC. KEYNOTE-063 (NCT03019588) is a randomized, open-label, phase 3 trial in Asian patients with advanced PD-L1–positive (combined positive score [CPS] ≥1) GC that progressed after platinum + fluoropyrimidine chemotherapy. After the KEYNOTE-063 study began, results of the global KEYNOTE-061 study (NCT02370498) showed that pembrolizumab did not prolong overall survival (OS) vs paclitaxel in patients previously treated for advanced GC (median OS, 9.1 months vs 8.3 months; hazard ratio [HR], 0.82; 95% CI, 0.66-1.03; 1-sided P= 0.0421 [significance threshold for OS was 1-sided P= 0.0135]). Methods: Eligible patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg Q3W for up to 35 cycles (~2 years) or standard-dose paclitaxel. The primary efficacy end points were OS and progression-free survival (PFS). Planned enrollment was ~360 patients. Results: Because pembrolizumab did not significantly prolong OS in KEYNOTE-061, enrollment in KEYNOTE-063 was discontinued after 94 patients were enrolled (47 patients in each treatment group). In these Asian patients, median OS was 8.4 months in the pembrolizumab group and 7.7 months in the paclitaxel group; median PFS was 1.9 months and 4.0 months, respectively (Table). Objective response rate (ORR) and median duration of response (DOR) are shown in the Table. Drug-related adverse events (AEs) occurred in 59.6% of patients receiving pembrolizumab and in 95.5% of patients receiving paclitaxel (Table). Conclusions: In this small sample of Asian patients with PD-L1–positive advanced GC, definitive conclusions are limited; however, second-line pembrolizumab monotherapy seems to be well tolerated in this patient population. Because this study was terminated early, there was insufficient power for comparisons between groups; therefore, these data should be viewed with caution. Clinical trial information: NCT03019588 . [Table: see text]
Absence of optimism bias in industry-sponsored cancer trials.
Authors: Sonal S Noticewala, Roshal R Patel, Ethan B. Ludmir
Journal: Journal of Clinical Oncology (2020)

2020 Background: Randomized controlled trials (RCTs) in oncology power their studies to detect expected effect sizes. Prior studies have shown that there is optimism bias, the a priori overestimation of treatment effect size among cooperative-group-supported RCTs. However, it is unknown whether such bias is present among industry-supported trials. Methods: All published phase 3 clinical oncology RCTs were identified through ClinicalTrials.gov. Only superiority-design RCTs assessing a therapeutic intervention to improve disease-related outcomes were included. We compared the ratio of observed to expected hazard ratio (OEHRR) between trial subgroups using the Mann-Whitney U-test; comparisons of median OEHRR to a hypothetical median of 1 was performed using the Wilcoxon Signed Rank test. Results: We identified 140 phase 3 trials with available hazard ratio (HR) data. Of these, 123 trials (88%) were industry-sponsored, and 38 trials (27%) were cooperative-group-supported. For all trials, the median OEHRR was 1.099 (IQR = 0.855-1.291), demonstrating evidence of optimism bias when compared to a hypothetical median OEHRR of 1 (p = 0.018). In the subgroup analysis, compared to non-industry-sponsored trials (median OEHRR 1.253, IQR 1.061-1.334), industry-supported trials (median OEHRR 1.061, IQR 0.829-1.274) had a significantly lower OEHRR (p = 0.022) and did not demonstrate optimism bias (p = 0.15). Similarly non-cooperative group trials (median OEHRR 1.208, IQR 1.019-1.317) had a significantly lower OEHRR (p = 0.005) and did not demonstrate optimism bias (p = 0.562) compared to cooperative group trials (median OEHRR 1.208, IQR 1.019-1.317), which did demonstrate optimism bias (p &lt; 0.001). Conclusions: Cooperative group trials, which represent a minority of trials, suffer from optimism bias. In contrast, industry-funded trials, which account for the majority of trials, do not demonstrate evidence of optimism bias, and have very close concordance between observed and expected effect size. These findings suggest that the powering and design of industry-funded trials better models the outcomes eventually observed. The reasons for this are likely complex and multifactorial, but may include financial constraint considerations, as industry-supported trials may not be as financially-limited as cooperative group studies. Therefore, industry-supported studies may be able to power trials with sufficient participants to reflect the estimated effect size.
Resilience and cognitive symptoms in cancer: An exploratory study.
Authors: Michael W. Parsons, Lara Traeger, Giselle Katiria Perez, April Hirschberg, Elyse R. Park
Journal: Journal of Clinical Oncology (2020)

e24079 Background: One of the most common concerns of cancer survivors is cancer-related cognitive impairment (CRCI), which affects an individual’s ability to return to work, school, or other life activities. The etiology of CRCI is poorly understood. Numerous studies have demonstrated a relationship between emotional distress and cognitive dysfunction, though the core psychological construct underlying this relationship has been elusive. Resilience, defined as the ability to function well despite adversity, reflects individual capacity to manage stress and reduce allostatic load. We hypothesized that low resilience contributes to stress-related cognitive symptoms in cancer survivors, and that improvement in resilience through the Relaxation Response Resiliency Program (3RP), a psychotherapy group that reduces emotional distress, would reduce cognitive symptoms in cancer survivors. Methods: Consistent with prior protocols, adult cancer survivors participated in the 3RP program, a 9-week resiliency mind-body group treatment led by psychologists and/or psychiatrists. Survivors completed measures of cognitive symptoms (Patient Reported Outcome Measure Information System – Cognitive function; PROMIS-Cog) and resilience (Current Experiences Scale; CES) before and after treatment. Pearson correlations evaluated relationships between resilience and cognition. Results: 46 cancer survivors (mean age = 57, 85% female, 94% White, 4% Asian, 2% Black) completed \ CES and PROMIS-Cog at therapy intake, with 41% of subjects reporting significant cognitive impairment at baseline (defined as scores of &lt; 1.0 SD on PROMIS-Cog). There was a significant correlation between these two scales prior to treatment (r = 0.33; p = 0.025), indicating that subjects with lower resilience reported poorer cognition. Thus far, 13 survivors have completed the 8-week therapy program, with 46% of these patients reporting significant cognitive difficulties. The post-treatment correlation between resilience and cognition was nonsignificant (r = 0.19;p = ns). Treatment effects were operationalized by change scores (follow up – baseline) for CES and PROMIS-Cog. The relationship between CES and PROMIS-Cog change scores was positive but not significant with the small sample size (r = 0.35; p = 0.028). Conclusions: This preliminary study suggests that there is a relationship between resilience and cognition in cancer survivors. Improvements in resilience through the 3RP treatment may reduce cognitive symptoms, though further work is needed to determine the significance of this effect.
Fever of unknown origin and hereditary periodic fever
Authors: 周文静, 杨程德
Journal: BMJ (2007)

发热待查(fever of unknown origin,FUO)病因复杂,是内科鉴别诊断的难题.近年来随临床诊断和治疗水平的提高,FUO的疾病谱亦有所改变,尤其在非感染性炎症性疾病的研究方面进展较快.笔者对该方面作一综述。
食管下段胃近端切除术治疗门静脉高压症断流术后再出血临床观察
Authors: 王伟, 尹家俊, 聂哲群, 韩玉龙
Journal: BMJ (2010)

贲门周围血管断流术是目前国内治疗门静脉高压症上消化道大出血最常用、疗效最佳的术式~([1]),因为其理论上可以有效地预防和治疗食管静脉曲张出血~([2]),同时又不影响门静脉向肝血流,有利于维持肝功能,且手术操作较分流术简单,在我国开展较为普及。
Rapid Emergence of Chronic Lymphocytic Leukemia During JAK2 Inhibitor Therapy in a Patient With Myelofibrosis
Authors: Nikolaos Sousos, Gemma Buck, Alba Rodriguez‐Meira, Ruggiero Norfo, Angela Hamblin, Francesco Pezzella, Jennifer Davies, Philip Hublitz, Bethan Psaila, Adam J. Mead
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
The experience of first-year hematology and oncology fellows after implementing a wellness chief fellow at an academic cancer center.
Authors: Sherise C. Rogers, Alison R. Walker, Gregory Alan Otterson, Janet Dettorre
Journal: Journal of Clinical Oncology (2020)

11017 Background: Hematology &amp; Oncology trainees are high risk for burnout. Risk factors include early stage in career, female gender and isolation. From previous assessment, the program discovered that the feeling of isolation was a problem experienced by our trainees. Our first-year fellows are challenged with multiple acclimations and the intense demands of inpatient service. As a result, we developed the leadership position of Wellness Chief Fellow to address the specific needs of this population during academic year 2019. Methods: The Wellness Chief (WC) is a third-year Hematology and Oncology Fellow with good communication skills and knowledge of resources at the academic cancer center. The WC gave a Wellness lecture during first-year orientation to emphasize the prioritization of personal wellbeing throughout fellowship. The WC developed a list of wellness resources within the hospital system and local community and shared these with the fellows. The WC also provided quarterly one-on-one confidential mentoring to first year fellows. These meetings were informal and semi-structured. Topics included adjusting to the academic center and their new fellowship role, moving to a new city, current support system, clinical and research mentorship, life challenges and self-care. Mid-year, the first-year fellows were surveyed regarding their experience. Results: Eight fellows participated in one-on-one mentoring and 5 completed a mid-year evaluation. 4/5 fellows were new to the city. All trainees felt that mentoring helped them adjust to fellowship. 4/5 stated that they found a clinical mentor and 3/5 have a research mentor and started a research project. 4/5 acknowledged that they have a friend in the fellowship program and 5/5 stated that they do have someone to go to if they were experiencing a challenging life event. All fellows reported gaining something valuable after each mentoring session. 3/5 subjectively experienced burnout within 6 months of the fellowship program. One person stated they experienced burnout once per week and 2 reported monthly burnout. Conclusions: A Wellness Chief Fellow can buffer the effects of isolation within the first-year fellowship experience by providing mentoring and resources during a challenging acclimation period.