tbuckley/cabot-search huggingface dataset:
心筋症ハムスターに対するL型およびT型Ca 2+ チャンネルブロカー,エホニジピンの有効な作用
Authors: Suzuki Shinsuke, Ohkusa Tomoko, Ono Katsushige, Sato Takashi, Yoshida Masa-aki, Yano Masafumi, Takebayashi Satoshi, Matsuzaki Masunori
Journal: Circulation (2007)
Decreased enrollment of patients with advanced lobular breast cancer compared to ductal breast cancer in interventional clinical trials.
Authors: Mary Kathryn Abel, Michelle E. Melisko, Hope S. Rugo, Amy Jo Chien, Italia Diaz, Julia K. Levine, Ann Griffin, Joseph McGuire, Laura Esserman, Hala Borno, Rita A. Mukhtar
Journal: Journal of Clinical Oncology (2021)

1092 Background: Response Evaluation Criteria in Solid Tumors (RECIST) criteria are often used to measure tumor response in cancer trials, especially in the stage IV setting. However, RECIST requires measurable disease, which is less common in invasive lobular breast carcinoma (ILC) of the breast, a diffusely growing tumor type, compared to invasive ductal carcinoma (IDC). We examined the prevalence of RECIST in breast cancer clinical trials, and whether there are differential trial enrollment rates by histology and stage. Methods: We analyzed the clinicaltrials.gov database to evaluate the proportion of interventional, stage IV clinical trials that require measurable disease as inclusion criteria or outcome measures. We then performed an institutional cohort study comparing the proportion of patients in the University of California, San Francisco (UCSF) OnCore clinical trials management system (CTMS) to the UCSF Cancer Registry between 2000-2018, stratified by histology and stage. We hypothesized that the proportion of patients with ILC in the CTMS would be significantly lower than in the cancer registry. Results: There were 146 actively-recruiting, interventional clinical trials for stage IV breast cancer that were identified in our search on clinicaltrials.gov. Overall, 108 (74%) required measurable disease for study participation. The UCSF Cancer Registry included 8,679 patients, while the UCSF OnCore CTMS included 1,511 patients (Table). In those with early stage disease, where RECIST is not typically used, there was no difference in the proportion of ILC patients enrolled in clinical trials versus in the cancer registry. However, among those with stage IV disease, there was a significantly lower proportion of patients with ILC in the CTMS than in the cancer registry (9.2% versus 17.9%, p = 0.005). In contrast, patients with stage IV IDC were overrepresented in the clinical trials database compared to the cancer registry. Conclusions: Patients with metastatic ILC were significantly less likely to be enrolled in clinical trials than those with metastatic IDC. This decreased enrollment may be due to the widespread use of RECIST, and further investigation is needed to ensure equity in access to clinical trials.[Table: see text]
Pulmonary sarcomatoid carcinoma: Retrospective analysis from a single center.
Authors: Suresh Kumar Kumar, Ravindra Nandhana, Aditya Dhanawat, Vanita Noronha, Vijay Maruti Patil, Nandini Menon, Rajiv Kumar, Amit Joshi, Anil Tibdewal, Sabita S. Jiwnani, Anuradha Choughule, Abhishek Mahajan, Amit Janu, Shripad Dinanath Banavali, Kumar Prabhash
Journal: Journal of Clinical Oncology (2021)

e21188 Background: Pulmonary sarcomatoid carcinoma (PSC) constitutes a heterogeneous group of poorly differentiated non-small cell lung cancer (NSCLC). Since these are rare tumors, no definitive randomized trials or clinical guidelines are available for management. This is the largest single centre study of patients with pulmonary sarcomatoid carcinoma. Methods: We retrospectively evaluated all patients with pulmonary sarcomatoid carcinoma between January 2013 to September 2020 at the Tata Memorial Hospital, Mumbai, India. Cases were identified from the pathology database. Baseline demographic, treatment data and outcomes were obtained from a prospectively maintained database in the Department of Medical Oncology. Results: A total of 151 patients with PSC were diagnosed during this period. Among these, 129 patients were included for survival analysis. The median age at diagnosis was 61 years (range, 18-87) with a majority of them being males (81.5%) and smokers (73%). A significant percentage of patients presented with poor performance status (PS was 2-4 in 48%). A majority of patients had T4 (73%) or N3 nodal status (44%). The clinical stage was stage I in 2%, stage II in 2.7%, stage III in 25.9%, and stage IV in 69.4%. The initial treatment modalities include surgery (10.9%), radical chemoradiotherapy (CRT, 3.9%), palliative chemotherapy (46.5%), palliative radiotherapy (7%), and best supportive care (31.8%). The median follow-up duration for the entire cohort was 32 months (95% CI 15.0 to 48.9). The median OS for the entire patient cohort was 5 months (95% CI 3.4 to 6.5). The median OS of patients who received curative surgery was 18 months (95% CI: 2.59 to 33.4) and the corresponding 1- and 5-year survival rates for patients who underwent surgery were 64% and 33% respectively. The median OS for patients who received CRT was 11 months (95% CI: 2.99 to 19). The median OS for the patients who received palliative radiotherapy alone was 4 months (95% CI: 1.91 to 6.08), for palliative chemotherapy was 8 months (95% CI: 5.24 to 10.75) and for patients who received only best supportive care was 1 month (95% CI: 0.43 to 1.57, p = 0.001). The median PFS and ORR for first, second- and third-line palliative chemotherapies were 4 months (95% CI: 2.95 to 5.04) and 15.1%, 4 months (95% CI: 0.33 to 7.67) and 13.3%, and 1 month (95% CI 0.21 to 1.78) and 0%. In a multivariate analysis, independent prognostic factors included the presence of brain metastasis (p 0.018, HR, 2.47, 95% CI 1.34-4.49) and administration of palliative chemotherapy (p = 0.037, HR2.2, 95% CI 1.04-4.94). Conclusions: PSC usually presents in advanced stages and carries a poor prognosis. Effective therapeutic options are required to improve the outcomes.
Single cell multiomic analysis and immune cell type profiling of multiple myeloma with t(4;14).
Authors: Sanjay deMel, Jonathan Scolnick, Xiaojing Huo, Cinnie Soekojo, Fangfang Song, Melissa Ooi, Wee Joo Chng
Journal: Journal of Clinical Oncology (2021)

e20013 Background: Multiple Myeloma (MM) is an incurable plasma cell (PC) malignancy and high risk (HR) MM remains an unmet clinical need. Translocation 4;14 occurs in 15% of MM and is associated with an adverse prognosis. A deeper understanding of the biology and immune micro-environment of t(4;14) MM is necessary for the development of effective targeted therapies. Single Cell multi-omics provides a new tool for phenotypic characterization of MM. Here we used Proteona’s ESCAPE™ single cell multi-omics platform to study a cohort of patients with t(4;14) MM. Methods: Diagnostic bone marrow (BM) samples from 14 patients with t(4;14) MM were analysed using the ESCAPE platform from Proteona which simultaneously measures gene and cell surface protein expression in single cells. Cryopreserved BM samples were stained with 65 DNA barcoded antibodies and subsequently sorted on CD138 expression. The CD138 positive and negative fractions were recombined at a known ratio for analysis using the 10x Genomics 3’ RNAseq kit. Resulting data were analyzed with Seurat and MapCell. Results: The patients had a median age of 63 years. All received novel agent based induction. Median progression free and overall survival (PFS and OS) were 22 and 34 months respectively. MMSET was overexpressed in all PCs while FGFR3 expression could be categorized into zero cells expressing FGFR3, low expression (&lt; 10% of cells expressing FGFR3) or high expression (&gt; 80% of cells expressing FGFR3). We also found heterogeneity in the expression of cancer testis antigens (CTA) such as FA133A and CTAG2 between PC clusters across samples. Variation in the immune microenvironment of the BM was seen across all patient samples with no correlation between cell types and PFS or OS. However, an analysis of BM samples at diagnosis and relapse in one patient showed a shift in the ratio of T cells to CD14 monocytes with a ratio of 5.7 at diagnosis compared to 0.6 at relapse. Further analysis of PCs in this patient found 8 PC populations, each containing variable numbers of cells from both the diagnostic and relapse samples. This suggests that all populations present at relapse were also present at diagnosis, although at variable proportions. Increased expression of RCAN3 (associated with cereblon depletion) was detected at relapse. Conclusions: We present the first application of single cell multi-omics immune profiling in high risk MM. The heterogeneity in expression of CTA has implications for the application of immunotherapies, while the upregulation of RCAN3 may explain failure of immunomodulatory therapy. Our small sample size may explain the lack of correlation between gene or protein expression with clinical outcomes. We propose that t(4;14) MM is a genomically and immunologically heterogeneous disease. Single cell analysis of larger cohorts is required to build on our findings.
Improving the diagnostic yield of biliary stricture biopsies using a directional atherectomy device.
Authors: Glynn Weldon Gilcrease, Preston Eiswirth, Hannah Beth Suchy, Benjamin L Witt, Rulon L Hardman, Ziga Cizman
Journal: Journal of Clinical Oncology (2021)

e16167 Background: Diagnosing the pathologic etiology of biliary strictures presents challenges that have been well-documented. Accuracy of traditional brushing and fine needle aspirate techniques range from 44% to 73%. 2 Over the last 2 decades the use of atherectomy catheter biliary biopsy has demonstrated high sensitivity and positive predictive values with a low complication rate. This endoluminal approach allows for larger volume histologic samples, allowing for the potential to obtain adequate tissue for next generation sequencing (NGS). The aim of this retrospective review of a single-center’s experience was to define the accuracy, ease of evaluation, and the ability to obtain NGS for personalized treatment. Methods: A retrospective review was performed under a waiver from the Institutional Review Board. A search of medical records from 1/2016 to 2/2021 yielded 20 biopsies in 19 patients. The 20 biopsies were completed by 4 interventional radiologists with between 2-11 years of experience. All available samples were analysed by a pathologist with greater than 10 years of experience and graded for adequacy and feasibility of NGS. Results: The patient population was 53% female with average age of 65.1 years. 12/19 (63%) patients had prior non-atherectomy biopsy attempts. The average ease of evaluation score for the 19 biopsies was 7.8/9, compared to 6.2/9 for the brushing specimens obtained from a subset of the same patients. Seven biopsies were positive for malignancy, ten were benign and three were non-diagnostic. The 7 biopsies that rendered a definitive diagnosis of malignancy had an average ease of evaluation score 8.7/9. The overall accuracy rate was 78.9%, and 71% of malignant samples were deemed adequate for NGS. There were two biopsy related complications; one pseudoaneurysm treated with embolization and one biliary drain dislodgement. Conclusions: Biliary biopsy using an atherectomy device has similar accuracy to traditional techniques; however, it allows for improved diagnostic yield and increased tissue specimen with 71% of samples adequate for NGS testing.
Health-related quality of life (HRQOL) in patients (pts) with advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC) or esophageal adenocarcinoma (EAC): Interim results of nivolumab plus chemotherapy (N+C) versus (C) from CheckMate 649.
Authors: Lucjan Wyrwicz, Elena Elimova, Steven I. Blum, Hong Xiao, Eric Davenport, Jinyi Wang, Shannon Hunter, Mingshun Li, Kaoru Kondo, Markus H. Moehler
Journal: Journal of Clinical Oncology (2021)

4066 Background: CheckMate 649 (NCT02872116) is a randomized, open label phase 3 study in first line (1L) GC/GEJC/EAC. Prespecified interim results showed statistically significant improvement in overall survival (OS) and progression-free survival (PFS) for N+C vs C in all randomized pts and pts whose tumors expressed programmed death-ligand 1 combined positive score (CPS) ≥ 5. We present interim HRQOL results for CPS ≥ 5 pts, included as exploratory in the study. Methods: HRQOL was assessed using EQ-5D-3L (EQ-5D) and Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga). Assessments were performed at baseline (BL), every 6 weeks during treatment, and during follow-up. Change from BL EQ-5D Visual Analog Scale (VAS), Utility Index (UI) and FACT-Ga scores were analyzed using mixed models. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated with Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds. Results: 1,581 pts were randomized to N+C (n = 789) and C (n = 792); of those, 955 pts had CPS ≥ 5 (N+C [n = 473] and C [n = 482]). Among 821 pts with BL and post BL PROs (N+C [n = 421] and C [n = 400]), BL scores for FACT-Ga total were similar for N+C and C. Least-squares mean differences from BL favored N+C at most visits for EQ-5D and FACT-Ga total and GaCS, and were comparable for other FACT subscales (data not shown). TTI largely favored N+C (most hazard ratios (HR) &gt; 1) but was not significantly different between treatments. For TTSD, pts treated with N+C had decreased risk of deterioration (HR &lt; 1) in EQ-5D UI, FACT-Ga total, and GaCS. TuDD showed statistically significant delays in deterioration (HR with confidence intervals [CI] &lt; 1) for all scores. Conclusions: Pts with 1L GC/GEJC/EAC experienced better HRQOL with N+C compared with C alone. Change from BL in EQ-5D and FACT-Ga total and GaCS favored N+C at most visits. N+C decreased deterioration risk compared to C with OS and PFS improvement, suggesting favorable benefits in 1L GC/GEJC/EAC pts with CPS ≥ 5. Clinical trial information: NCT02872116. [Table: see text]
Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium
Authors: Irene Sarosiek, Mark Van Natta, Henry P. Parkman, Thomas Abell, Kenneth L. Koch, Braden Kuo, Robert J. Shulman, Gianrico Farrugia, Madhusudan Grover, Frank A. Hamilton, Pankaj J. Pasricha, Katherine P. Yates, Laura Miriel, Laura Wilson, Goro Yamada, James Tonascia, Richard W. McCallum
Journal: Clinical Gastroenterology and Hepatology (2021)
The microbial characteristics of patients with esophageal squamous cell carcinoma before and after immunotherapy.
Authors: Jing Zuo, Wenjing Lv, Yudong Wang, Zhisong Fan, Li Feng, Long Wang, Xue Zhang, Jing Han, Da Jiang
Journal: Journal of Clinical Oncology (2021)

e16016 Background: Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. Immune checkpoint–oriented immunotherapies have shown considerable promise and the advent of esophageal microbiome provides researchers with new ideas. Methods: DNA was extracted from blood, oral mucosal, saliva, urine, fecal samples from 20 ESCC patients before and after immunotherapy. Total microbial genomic DNA samples were extracted using an OMEGA Soil DNA Kit (D5625-01). The V3–V4 regions of bacterial 16S rRNA genes were amplified by PCR using the forward primer and the reverse primer and were sequenced with Illumina MiSeq platform. In order to comprehensively evaluate the α diversity of microbial communities, we used Chao1 and Observed Species indices to characterize the richness, Shannon and Simpson indices to characterize the diversity. PCoA were used to analyze differences in β diversity. Functions of 16S rRNA sequences were predicted using the PICRUSt2 and KEGG databases. Results: A comparison of blood, oral mucosal, saliva, urine, fecal samples of ESCC patients before and after immunotherapy showed that α diversity was not statistically significant. In terms of β diversity, no statistically significant differences were detected within blood, oral mucosal, saliva, urine, fecal samples of ESCC patients before and after immunotherapy. In ESCC patients treated before immunotherapy, the α diversity and β diversity of blood, oral mucosal, saliva, urine, fecal samples were different, and in ESCC patients treated after immunotherapy had the same rule. At the phylum level, the top 5 microbes in ESCC patients before and after immunotherapy were Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria. At the genus level, the top 5 microbes in ESCC patients before immunotherapy were Aquabacterium, Streptococcus, Prevotella, Veillonella, Bacteroides, and in ESCC patients after immunotherapy were Aquabacterium, Streptococcus, Prevotella, Faecalibacterium, Veillonella. In terms of the microbial functions in ESCC patients before and after immunotherapy, the metabolic pathways accounted for the most. Conclusions: This study is conducive to exploring new mechanisms for tumor cells to evade host immune surveillance, providing new ideas and new strategies for the microecology-based immunotherapy of ESCC.
Efficacy of regional nodal ultrasound surveillance for metastatic detection in sentinel- and complete lymph node dissection-eligible melanoma patients.
Authors: Susan M. Swetter, Lucy Y. Liu, Samvel Gyurdzhyan, Lisa C. Zaba
Journal: Journal of Clinical Oncology (2021)

e21568 Background: Nodal ultrasound (US) is the preferred method for regional surveillance of clinically node-negative (cN0) primary cutaneous melanoma (CM) when sentinel lymph node biopsy (SLNB) is not performed or unsuccessful, and for pathologically node-positive (pN+) disease without completion lymph node dissection (CLND). Methods: Retrospective review was performed of nodal US surveillance from 2011-2021 in SLNB-eligible cN0 CM patients when SLNB was deferred or technically not feasible ( i.e., from failure of lymphoscintigraphic dye migration) or those with pN+ disease on SLNB, without subsequent CLND. Patients were followed for at least 2 years or until recurrence. The primary endpoints were US detection of regional nodal recurrence and comparison to clinical exam or cross-sectional imaging (PET-CT and/or CT). Results: In total, 67 patients met inclusion criteria and underwent a median of 4 nodal US exams (interquartile range, IQR 3-5) over 2-3 years of follow-up. Thirty-two (47.8%) patients declined or had unsuccessful SLNB, and 35 (52.2%) deferred CLND in favor of nodal US surveillance. Sixteen (23.9%) patients had clinical stage IA/IB (cIA/IB) CM, 15 (22.3%) had clinical stage II (cII) disease, and 36 (53.7%) had pathologic stage III (pIII) disease. Three (4.5%) patients developed satellite/in-transit metastasis, 6 (8.9%) had regional nodal recurrence, 4 (6.0%) had both local and regional recurrence, and 7 (10.4%) developed distant metastasis. Eighteen (26.9%) patients underwent tissue sampling, with 10 positive for melanoma. Nodal recurrence was observed in patients with initial cIB (1), cIIA (1), cIIB (1), cIIC (2), pIIIA (1), and pIIIC (4) disease. Three patients (cIIA, cIIB, and pIIIC due to microsatellites) had abnormal clinical exams with concurrent palpable regional adenopathy and in-transit metastasis. One patient (pIIIC) developed local satellite metastasis followed by palpable regional adenopathy. The most common surveillance method for metastatic detection was US (6/10), followed by clinical exam (3/10) and PET-CT (1/10). All metastatic nodes on US were metabolically active on subsequent PET-CT. One patient in whom PET-CT was the initial method of detection had no confirmatory US. Conclusions: Nodal US for CM requires specific radiologic expertise and is gaining traction as a cost-effective imaging modality in the United States. Our findings support the effectiveness of nodal US surveillance in cN0 or pN+ CM patients in whom SLNB or CLND is not performed.[Table: see text]
Assessment of vitamin D deficiency and COVID-19 diagnosis in patients with breast or prostate cancer using electronic medical records.
Authors: Aaron Galaznik, Emelly Rusli, Vicki Wing, Rahul Jain, Sheila Diamond, David Fajgenbaum
Journal: Journal of Clinical Oncology (2021)

6589 Background: While patients with cancer are known to be at increased risk of infection in part due to the immunocompromising nature of cancer treatments, recent data indicate a particularly high risk for COVID-19 infection and poor outcomes (Wang et al., 2020). A recent study (Meltzer et al., 2020) demonstrated Vitamin D deficiency may increase risk of COVID-19 infection, and a small randomized controlled trial in Spain reported significant improvement in mortality among hospitalized patients treated with calcifediol. Vitamin D deficiency has been reported in two leading causes of cancer deaths: breast and prostate. In this study, we performed a retrospective cohort analysis on nationally representative electronic medical records (EMR) to assess whether Vitamin D deficiency affects risk of COVID-19 among these patients. Methods: Patients with breast (female) or prostate (male) cancer were identified between 3/1/2018 and 3/1/2020 from EMR data provided pro-bono by the COVID-19 Research Database ( covid19researchdatabase.org ). Patients with an ICD-10 code for Vitamin D deficiency or &lt; 20ng/mL 20(OH)D laboratory result within 12 months prior to 3/1/2020 were classified as Vitamin D deficient. COVID-19 diagnosis was defined using ICD-10 codes and laboratory results for COVID-19 at any time after 3/1/2020. Logistic regressions, adjusting for baseline demographic and clinical characteristics, were conducted to estimate the effect of Vitamin D deficiency on COVID-19 incidence in each cancer cohort. Results: A total of 16,287 breast cancer and 14,919 prostate cancer patients were included in the study. The average age was 68.9 years in the breast cancer cohort and 73.6 years in the prostate cancer cohort. The breast cancer cohort consisted of 85% Whites, 13% Black or African Americans, and less than 5% of other races. A similar race distribution was observed in the prostate cancer cohort. Unadjusted analysis showed the risk of COVID-19 was higher among Vitamin D deficient patients compared to non-deficient patients in both cohorts (breast: OR = 1.60 [95% C.I.: 1.15, 2.20]; prostate: OR = 1.59 [95% C.I.: 1.08, 2.33]). Similar findings were observed when assessed in subgroups of patients with newly diagnosed cancer in the dataset, as well as after adjusting for baseline characteristics. Conclusions: Our study suggests breast and prostate cancer patients may have an elevated risk of COVID-19 infection if Vitamin D deficient. These results support findings by Meltzer et al., 2020 demonstrating a relationship between Vitamin D deficiency and COVID-19 infection. While a randomized clinical trial is warranted to confirm the role for Vitamin D supplementation in preventing COVID-19, our study underscores the importance of monitoring Vitamin D levels across and within cancer populations, particularly in the midst of the global COVID-19 pandemic.