tbuckley/cabot-search huggingface dataset:
Biomarker analysis and updated clinical follow-up of preoperative ipilimumab (ipi) plus nivolumab (nivo) in stage III urothelial cancer (NABUCCO).
Authors: Nick Van Dijk, Alberto Gil Jimenez, Karina Silina, Kees Hendricksen, Laura Smit, Jeantine De Feijter, Maurits L van Montfoort, Annegien Broeks, Yoni Lubeck, Karolina Sikorska, Thierry N. Boellaard, Pia Kvistborg, Daniel J Vis, Erik Hooijberg, Ton Schumacher, Maries van den Broek, Lodewyk FA Wessels, Christian U. Blank, Bas W.G. van Rhijn, Michiel Simon Van Der Heijden
Journal: Journal of Clinical Oncology (2020)

5020 Background: Encouraging pathological complete response (pCR) rates were observed in trials testing neoadjuvant pembrolizumab or atezolizumab in urothelial cancer (UC). In cT3-4N0 tumors, pCR to atezolizumab was only 17% and restricted to tumors showing characteristics of preexisting T cell immunity. In NABUCCO, we aimed to increase response to pre-operative checkpoint blockade, particularly in high risk patients (pts), by combining ipi plus nivo in stage III UC. We previously reported pCR in 46% and downstaging to no remaining invasive disease in 58% (ESMO2019). Here, we present biomarker analyses and updated clinical follow-up (FU) data. Methods: Twenty four stage III (cT3-4aN0 or cT2-4aN1-3) UC pts who were unfit to receive cisplatin-based chemotherapy or refused, were treated with ipi 3 mg/kg (day 1), ipi 3 mg/kg + nivo 1 mg/kg (day 22), and nivo 3 mg/kg (day 43), followed by resection. The primary endpoint was feasibility (resection &lt; 12 weeks). Efficacy (pCR), safety and biomarker analysis were secondary endpoints. Whole-exome sequencing (WES) was done on baseline tumor samples and local lymph node (LN) metastases showing no response. RNA-seq and multiplex immunofluorescence (mIF) for immune cell markers were done pre- and post-therapy. Results: After a median FU of 15.6 months, 2 pts relapsed (both non-pCR); 1 of these 2 pts died of metastatic disease. Tumors showing complete response (CR, for biomarker analysis defined as pCR, CIS or pTa) had a significantly higher tumor mutational burden than non-CR tumors. CR to ipi+nivo was independent of baseline CD8 T-cell presence. There was no difference between CR and non-CR tumors in baseline immune gene signatures, such as interferon gamma and T-effector signatures. Surprisingly, exploratory gene expression analysis revealed that non-CR was associated with a baseline B cell immune signature, particularly immunoglobulins and genes involved in B cell receptor signaling. CD20 positive cells (by mIF) and presence of tertiary lymphoid structures (TLS) at baseline were also associated with non-CR. Upon treatment with ipi+nivo, early and mature TLS increased significantly in responding tumors. A subset of pts showed CR in the bladder, but non-CR in a local LN tumor focus. WES revealed that these LN metastases were genetically different from the primary tumor bulk. Conclusions: At 15.6 months follow-up, recurrence after pre-operative ipi+nivo was low. Pathological complete response was not restricted to tumors exhibiting preexisting T cell immunity. Clinical trial information: NCT03387761 .
Treatment patterns among newly diagnosed women with cervical cancer in the United States.
Authors: Anuj Shah, Nehemiah Kebede, Ruchit Shah, Shelby Corman, Chizoba Nwankwo
Journal: Journal of Clinical Oncology (2020)

e18019 Background: To address the gap in US-based real-world data, this analysis described the real-world treatment patterns among newly diagnosed cervical cancer patients. Methods: Women newly diagnosed with cervical cancer between Jan 2015 – June 2018, with a confirmatory diagnosis or treatment within 2 months, and continuous enrollment for 12 months prior and 6 months post diagnosis were identified in the Optum Clinformatics DataMart database. Surgeries (hysterectomy, conization, lymphadenectomy and trachelectomy), radiation (external beam radiotherapy [EBRT]/brachytherapy) and systemic therapies (chemotherapy/immunotherapy) received after diagnosis were described by line of therapy (LOT). The start of the first LOT was the date of the first treatment. All treatments initiated within 90 days of a surgery or the end of radiotherapy, and all systemic treatment started within 28 days of any previous treatment were a part of the same LOT. Most frequently received treatments in LOT1 and 2 and time to treatment initiation were described. Results: Out of 1,004 newly diagnosed women, 655 (65.2%) received at least LOT1 and 162 (16.14%) received LOT2. Median time to first LOT was 1.5 (1.4 – 1.7) months from diagnosis. Surgery was the most common treatment in LOT1 (58.0%). Among patients receiving radiation, the majority received a combination of EBRT and brachytherapy (LOT1: 66.9%, LOT2: 58.0%). The use of chemotherapy increased with subsequent LOTs (LOT1: 53.3%, LOT2: 61.1%). Treatments received in LOT1 and LOT2 are described in the table. Conclusions: This analysis shows that newly diagnosed cervical cancer patients are primarily receiving guideline recommended treatment with surgery or chemoradiation as primary treatment. Radiation therapy includes EBRT and brachytherapy. Counts ≤ 10 are not reported (NR). [Table: see text]
Mismatch repair deficiency testing in colorectal cancer and factors associated with nonadherence to guidelines.
Authors: Phuong Ngo, Rohit Kumar, Adam Rojan
Journal: Journal of Clinical Oncology (2020)

e16069 Background: Mismatch repair (MMR) deficiency is characteristic of Lynch syndrome, which typically affects patients &lt; 50 years old with colorectal cancer (CRC) but can also occur in sporadic CRC. MMR deficiency causes microsatellite instability (MSI) and affects therapy response and prognosis. Guidelines now recommend universal testing of MMR/MSI in all CRC patients, but universal testing has not been achieved. Our study sought to evaluate factors associated with MMR/MSI testing in CRC patients. Methods: The National Cancer Database (NCDB) identified 433,968 patients diagnosed with stages I-IV CRC from 2011-2016. Variables included gender, race, stage, insurance status, education, income, and treatment facility type. Baseline characteristics were compared using Pearson's chi‐square test between patients not tested versus tested for MMR/MSI status. Multivariate logistic regression analysis determined the factors associated with increased probability of MMR/MSI testing. Results: Only 34.7% patients were tested for MMR/MSI and those £ 40 years old were more likely to be tested as were Caucasian patients. Patients with private insurance were more likely to be tested compared to uninsured (OR 1.21; 95% CI 1.1601.27, p &lt; 0.001). Testing also correlated with increasing education, reported as the percentage of adults over 25 years old who did not graduate high school within a zip code. Diagnosis at an academic/research program was also a positive predictor of MMR/MSI testing compared to a community program (OR 1.74; 95% 1.71-1.77, p &lt; 0.001). Testing was dependent on stage with the greatest likelihood of testing in stage II (OR 1.44, 95% CI 1.41-1.46, p &lt; 0.001) and the least in stage IV (OR 0.72; 95% CI 0.71-0.74, p &lt; 0.001) compared to stage I. Still, the trend for testing increased over the years (trend p &lt; 0.001), with that in 2016 being 4 times more likely than in 2011 (OR 4.66; 95% CI 1.53-4.80, p &lt; 0.001). Conclusions: Our study identified established risk factors affecting care such as African American race, treatment at a non-academic facility and being uninsured. It also showed age and stage were factors associated with noncompliance to new guidelines regarding testing for MMR/MSI with testing being less frequent in older patients and those with later stages. An explanation and study limitation is that NCDB only collected diagnoses until 2016 while immunotherapy in MSI-H or dMMR CRC was approved in 2017. With more treatment options available now to these patients, testing rates will hopefully improve with more research needed to capture this.
Noval endoscopic techniques in the diagnosis of Barrett's esophagus
Authors: 贺益萍, 诸琦
Journal: BMJ (2008)

Barrett食管(Barrett esophagus,BE)是指食管下段复层鳞状上皮被化生的柱状上皮所取代的一种病理现象[1]. 由于BE被认为是食管癌的癌前状态之一,与食管腺癌的发生有密切关系,随着BE及其相关的食管腺癌发病率不断增加,对这些患者进行定期的内镜监测非常必要[2].BE通过化生-异型增生-肿瘤的顺序导致食管腺癌的发牛,内镜监测的目的是为了早期诊断和治疗异型增生及早期食管癌,并阻止其向进展期癌发展。
Early response marker during pembrolizumab treatment in metastatic urothelial cancer: Temporal shift in peripheral CD4 T cells expressing chemokine receptors.
Authors: Maud Rijnders, Hayri Emrah Balcioglu, Debbie Robbrecht, Joost L. Boormans, Maureen J.B. Aarts, Paul Hamberg, Jens Voortman, Hans Westgeest, Ronald De Wit, Martijn P. Lolkema, Astrid Aplonia Maria Van Der Veldt, Reno Debets
Journal: Journal of Clinical Oncology (2020)

5033 Background: Approval of PD1 blockade greatly improved treatment possibilities for patients with platinum-resistant metastatic urothelial cancer (mUC), however the current response rate for pembrolizumab is less than 25%. Since PD-L1 expression does not have predictive value in this setting, the aim of this study was to identify new markers to improve patient selection. Methods: Between Sept 2017 and Jan 2020, 84 mUC patients received pembrolizumab in a prospective biomarker discovery study (NCT03263039). Peripheral blood samples (n = 22) taken prior to and at 6 and 12 weeks after start of treatment were analyzed for frequencies of CD4 and CD8 T cells expressing co-inhibitory, co-stimulatory and chemokine receptors using multiplex flow cytometry. Plasma chemokine levels were determined using ELISA (n = 38), and fresh tumor biopsies obtained prior to and during treatment (n = 26) were analyzed for densities and phenotypes of T cells using multiplex immunofluorescence staining. T cell receptor clonality was analyzed in peripheral blood (n = 10) and tumor biopsies (n = 6) using RNA sequencing. Patients were classified as responder (complete or partial response) or non-responder (progressive disease) according to RECIST v1.1 after 12 weeks of treatment. Results: Longitudinal sampling revealed that upon treatment the frequency of CXCR3+ CD4 T cells decreased in responders, whereas the frequency of CXCR3+ CCR1+ CD4 T cells drastically increased in non-responders. Before treatment, the frequency of CD4 T cells co-expressing CXCR3 and CCR1 was already decreased in responders. Notably, in responders, the treatment-related decrease in frequency of CD4 T cells expressing chemokine receptors was accompanied by a decrease in the frequency of CD4 T cells expressing the co-inhibitory receptor PD1, whereas an increase in the frequency of CD4 T cells expressing the co-stimulatory receptor 4-1BB was observed. These findings will be complemented with chemokine levels in plasma, contexture of T cells in tumor biopsies, and T cell receptor clonality analysis. Conclusions: mUC patients responding to pembrolizumab treatment demonstrated an on-treatment decrease in frequency of CD4 T cells expressing chemokine receptors that is accompanied by a changed frequency of co-signaling receptor expressing CD4 T cells. These data show that dynamic immune phenotyping can distinguish effective from less effective immune activation by pembrolizumab, and may provide early markers for benefit from PD1 blockade in mUC patients.
糖尿病患者自主神经病变心脏改变与快速性心律失常的观察
Authors: 朱怀珍, 何东亮, 潘启明, 王伟明, 陈小慈
Journal: BMJ (2007)

采用24 h动态心电图监测82例糖尿病患者的心率和心律,用彩色多谱勒超声仪测定左心室结构和功能参数.结果 伴自主神经病变的患者舒张期二尖瓣口血流频谱E峰与A峰峰值流速比(E/A值)明显减低;室间隔厚度、左心室后壁厚度、左心室重量指数均增加;严重的心律失常如Lown标准≥Ⅲ级的室性心律失常及短阵房性心动过速的发生率也明显增加.提示,合并自主神经病变的糖尿病患者心脏损害严重,并可能合并心动过速性心肌病。
First validation of the supportive care score (SCC) scale: Alert scale for referral of solid cancer patients to supportive oncology team.
Authors: Mathilde Chastenet, Pierre-Antoine Laurain, Typhaine Maupoint, Karine Legeay, Julia Salleron, Florian Baumard, Florian Scotte
Journal: Journal of Clinical Oncology (2020)

e14025 Background: Patients’ needs are still underestimated during cancer course. The development of a simple and accessible screening tool to identify supportive care needs is an innovative approach to improve the cancer care pathway. Supportive Scale sCore (SCC) is a new tool developed to trigger alert in main need of supportive care such as social, nutritional, physical, pain or psychological disorders. This study aimed to develop and validate the SCC tool for detecting supportive care needs. Methods: The SCC, the Edmonton Symptom Assessment System (ESAS), a symptom scale and the EQ-5D (for Quality Of Life) was distributed to cancer patients over a week, in an ambulatory hospital of oncology department. The acceptability was assessed by the fill rate. The validity of alerts generated by the SCC scale was assessed by their consistency with ESAS and EQ-5D scores. Results: Hundred patients were included with an average age of 67,2 years. Acceptability was good with a fill rate of over 90%. For a-priori defined risk groups by SCC with alert or not, ESAS symptom score and QOL differed significantly (p &lt; 0,05) between groups. We observed higher ESAS symptom scores in the alert group [nutritional alert: appetite: 4 (Standard Deviation SD 2,4) vs 0 (SD 1,6), p &lt; 0,001; physical alert: fatigue: 4 (SD 1,7) vs 2 (SD 2,2) p &lt; 0,001; psychological alert: depressed: 3,5 (SD 2,7) vs 0 (SD 1,5), p &lt; 0,001; anxiety: 4 (SD 2,9) vs 0 (SD 1,5), p &lt; 0,001; unwell-being: 4,5 (SD 2,7) vs. 0 (SD 1,5), p &lt; 0,001]. Moreover, the QOL was poorer in each domain of EQ-5D in the alert group. [Social alert, self-care: 9,3% vs 0%, p = 0,02; usual activities: 25% vs 5,4%, p = 0,005. Physical alert, usual activities: 21,3% vs 2,6%, p = 0,008; mobility 29,5% vs 2,6%, p = 0,01. Pain alert, pain: 81,8% vs 11,9%, p &lt; 0,001. Psychological alert, psychological: 56,3% vs 11,9%, p &lt; 0,001]. Conclusions: The SCC seems to be a reliable instrument to detect cancer patients’ supportive care needs.
A pilot study of a wearable monitoring system as an adjunct to geriatric assessment in older adults with cancer.
Authors: Karlton Wong, John Shen, Ramin Ramezani, Wenhao Zhang, Zhuoer Xie, Arash Naeim, David Elashoff
Journal: Journal of Clinical Oncology (2020)

2062 Background: Advances in health technology provide potential tools that can aid in assessing and monitoring the functional status of the growing older adult population diagnosed with cancer. We piloted a novel wearable monitoring platform, Sensing in At-Risk Populations (SARP), which consists of a smartwatch, software application for health monitoring, and a central data processing and analytics engine. Methods: This is a prospective single center, single arm study, utilizing the SARP platform to risk stratify older adults with cancer and determine correlation with treatment-related adverse events and healthcare utilization. Pts age ≥60 undergoing active treatment, were offered participation. Pts were instructed to wear the smartwatch for ≥7 days. We used Kruskal-Wallis to correlate wearable data with clinical outcomes: toxicity, ED visits, hospitalizations, and mortality. We also compared SARP data to independently collected ECOG PS, CARG score, ADLs, and IADLs. Results: From 8/2016 to 8/2017, 54 older adults were consented, and 26 had wearable data available for analysis. The average age was 72 years, with 18 males and 8 females. 12 pts had ECOG PS of 0, 12 with ECOG of 1, and 2 with ECOG of 2. 4 pts had CARG score of low, 17 intermediate, and 3 high. Energy intensity was significantly correlated with ED visits, with an effect size of 0.95 (p = 0.04). Similarly, energy intensity and hospitalizations had an effect size of 0.87 (p = 0.06). The CARG scores were noted to be significantly correlated with dose delay and dose reduction with an effect size 0.45 (p = 0.05) and 0.4 (p = 0.05), respectively. Spearman correlation analysis demonstrated that walking time, active time, and energy intensity positively correlate with ADLs and IADLs, and inversely correlated with ECOG PS and CARG risk. Conclusions: Though this is a limited study due to sample size, the overall trend demonstrated that the SARP platform offers an adjunct tool in assessing and risk stratifying older patients with cancer undergoing active therapy. Additional cohorts are now enrolled with an at-home monitoring system. [Table: see text]
Comprehensive analgesic and nursing intervention for patients with advanced cancer at home
Authors: 马福刚, 王改非, 郭鹏, 母国欣, 王沂娟, 高春玲, 邵换彰
Journal: BMJ (2005)

目的 探讨家庭综合干预治疗对肿瘤晚期患者癌性疼痛的疗效及安全性.方法选取200例经病理确诊的肿瘤晚期患者,随机分为试验组和对照组各100例.试验组按照世界卫生组织(WHO)三阶梯止痛原则,给予家庭镇痛治疗,并进行家庭护理干预.对照组患者按照其自主择医镇痛的意愿,不增加干预.分别于初诊和治疗后4个月对两组患者进行疼痛强度、生活质量、心理功能以及医疗费用的评估并进行比较.结果 试验组患者药物镇痛有效率为93%,对照组为78%,两者差异有统计学意义(P＜0.01).试验组生活质量、心理功能等方面有明显提高和改善(P＜0.01),且优于对照组(P＜0.01),同时总体医疗费用也低于对照组(P＜0.05).结论 对肿瘤晚期患者癌性疼痛进行家庭综合干预治疗安全可靠,切实可行,镇痛效果好,值得推广。
Characterization of first-line use of cyclin dependent kinase 4/6 (CDK4/6) inhibitors in metastatic breast cancer among Florida health care systems.
Authors: Reshma L. Mahtani, Luis E. Raez, Jessica Unzaga, Jorge J García, Krupa Paranjpe, Irene Arias, Aurelio Bartolome Castrellon
Journal: Journal of Clinical Oncology (2020)

e19347 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered standard of care based on the compelling data across all landmark trials. Commission on Cancer (CoC) as well as the Quality Oncology Practice Initiative (QOPI) describe standards for cancer care; some of which include utilizing data for continuous quality improvement as well as using nationally recognized guidelines to drive treatment selection. Reducing unwarranted variations in care through tracking and reporting adherence to nationally-recognized guidelines can be one way to focus on improving quality metrics. We evaluate first-line real-world treatment patterns of HR+/HER2- mBC patients in three health care systems in south Florida and compare with national standards. Methods: A retrospective analysis utilizing pharmacy and medical claims data (commercial and governmental payers) was performed. The data source was the IQVIA anonymized patient longitudinal open claims data for patients treated at the south Florida health systems. Patients age ≥18 years with HR+/HER2- mBC were included. First-line treatment was defined as the first claim for a medication after the mBC diagnosis. Results: Characterization of treatment patterns in three cancer centers in south Florida showed an increased utilization of CDK4/6 inhibitors as compared to the national average across all groups (see table). Conclusions: These data provide a baseline assessment of the utilization of CDK4/6 inhibitors in the first-line treatment of HR+/HER2- mBC. These data are reassuring with respect to the appropriate treatment in south Florida patients. However, we anticipate that treatment patterns may vary in other geographic areas given the national data trends. We would recommend this data be evaluated in other systems to identify potential areas of improvement. Limitations of this evaluation are consistent with any methodology using claims data which include possible coding errors and missing data which may or may not be systematic. [Table: see text]
Recurrent vulvar squamous cell carcinoma: An analysis of clinical outcomes by treatment modality including surgery, chemotherapy, and radiation.
Authors: Trish Dinh, Natalie Andrews Wright, Hari Iyer, Johanne I Weberpals
Journal: Journal of Clinical Oncology (2020)

e18033 Background: Recurrent VSCC carries a poor prognosis, but real-world data on outcomes with standard treatment options are lacking. Specifically, progression free survival (PFS) in recurrent VSCC is ill-defined which is problematic for the design of clinical trials with novel therapies. We aim to address the paucity of outcome data in recurrent VSCC and to compare PFS and overall survival (OS) in patients (pts) undergoing surgery, chemotherapy, radiotherapy or a combination of these treatments. Methods: A retrospective chart review identified 246 pts from 2000-2018 diagnosed with VSCC treated at the Ottawa Hospital Cancer Center and 61 pts with recurrent disease. Data collected included patient demographics, tumour characteristics, recurrence pattern, and treatment modality (surgery only, surgery with chemotherapy, surgery with radiation, surgery with chemoradiation, chemoradiation only, chemotherapy only, or radiation only). Descriptive statistical analysis is reported. Results: Among all study pts, the stage distribution was stage I: 28%, II: 19%, III: 43% and IV: 10%. 61% of pts had one recurrence, 36% had two recurrences, and 3% had three recurrences. The 5-year survival rate was 78% for non-recurrent VSCC vs. 33% for recurrent cases. The median OS for all recurrent and non-recurrent cases was 3.7 years and 13.5 years, respectively. For primary treatment, 87% underwent surgical treatment, of which 60% also had radiation or chemoradiation. The most common treatments for first recurrence were: surgery (25%), radiation (20%), no treatment (16%) and chemotherapy (14%), and for second recurrence: no treatment (50%), radiation (25%), surgery (17%) and chemotherapy (8%). The median PFS after primary treatment and after first and second recurrences were 8.7, 5.3 and 1.4 months (mo), respectively, with no significant difference between treatment regimens. However, when grouped (surgery with or without chemotherapy, radiation or chemoradiation vs. non-surgical management), there was a significant PFS benefit for surgical (15.6 mo) over non-surgical management (0.7 mo) in the treatment of a second recurrence (p = 0.05). Conclusions: At our centre, surgery and radiation have been the mainstay of treatment for recurrent VSCC with particular advantage of surgery in the treatment of a second recurrence. Our study establishes a baseline for VSCC outcomes following standard treatment. Accurate PFS data is an important outcome for the design of future studies in recurrent VSCC with new drug therapies.
Machine learning prediction of survival in diffuse large B-cell lymphoma based on gene-expression profiling.
Authors: Selin Merdan, Kritika Subramanian, Turgay Ayer, Jean Louise Koff, Andres Chang, Johan Van Weyenbergh, Christopher Flowers
Journal: Journal of Clinical Oncology (2020)

8047 Background: The current clinical risk stratification of Diffuse Large B-cell Lymphoma (DLBCL) relies on the International Prognostic Index (IPI) comprising a limited number of clinical variables but is imperfect in the identification of high-risk disease. Our study aimed to: (1) develop a risk prediction model based on the genetic and clinical features; and (2) evaluate the model’s biological implications in association with the estimated profiles of immune infiltration. Methods: Gene-expression profiling was performed on 718 patients with DLBCL for which RNA sequencing data and clinical covariates were available by Reddy et al (2017). Unsupervised and supervised machine learning methods were used to discover and identify the best set of survival-associated gene signatures for prediction. A multivariate model of survival from these signatures was constructed in the training set and validated in an independent test set. The compositions of the tumor-infiltrating immune cells were enumerated using CIBERSORT for deconvolution analysis. Results: A four gene-signature-based score was developed that separated patients into high- and low-risk groups with a significant difference in survival in the training, validation and complete cohorts (p &lt; 0.001), independently of the IPI. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The area-under-the-curve at 2 and 5 years increased from 0.71 and 0.69 to 0.75 and 0.74 in the validation set, respectively. Conclusions: By analyzing the gene-expression data with a systematic approach, we developed and validated a risk prediction model that outperforms existing risk assessment methods. Our study, which integrated the profiles of immune infiltration with prognostic prediction, unraveled important associations that have the potential to identify patients who could benefit from the various therapeutic interventions, as well as highlighting possible targets for new drugs.