tbuckley/cabot-search huggingface dataset:
Lymph node metastases of gastric cancer and blood cell circuit.
Authors: Oleg Kshivets
Journal: Journal of Clinical Oncology (2021)

e16024 Background: Significance of blood cell circuit in terms of detection of gastric cancer (GC) patients (GCP) with lymph node metastases was investigated. Methods: We analyzed data of 793 consecutive GCP (age = 57±9.4 years; tumor size = 5.4±3.1 cm) radically operated (R0) and monitored in 1975-2021 (m = 555, f = 238; distal gastrectomies = 460, proximal gastrectomies = 163, total gastrectomies = 170, combined gastrectomies with resection of pancreas, liver, diaphragm, colon transversum, esophagus, duodenum, splenectomy, small intestine, kidney, adrenal gland = 244; D2-lymphadenectomy = 513, D3-4 = 280; T1 = 235, T2 = 220, T3 = 182, T4 = 156; N0 = 433, N1 = 109, N2 = 251; G1 = 222, G2 = 162, G3 = 409; early GC = 162, invasive = 631; only surgery = 621, adjuvant chemoimmunotherapy-AT = 172 (5-FU+thymalin/taktivin). Variables selected for study were input levels of blood cell circuit, sex, age, TNMG. Differences between groups were evaluated using discriminant analysis, clustering, nonlinear estimation, structural equation modeling, Monte Carlo, bootstrap simulation and neural networks computing. Results: It was revealed that separation of GCP with lymph node metastases (n = 360) from GCP without metastases (n = 433) significantly depended on: eosinophils (%, abs, total), thrombocytes (abs, total), ESS, Hb, erythrocytes (abs), residual nitrogen, protein, cell ratio factors (CRF) (ratio between cancer cells- CC and blood cells subpopulations), T, G, tumor size, histology, tumor growth, blood group, procedures type (P = 0.043-0.000). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships of lymph node metastases and CRF: thrombocytes/CC (rank = 1), healthy cells/CC (2), erythrocytes/CC (3), monocytes/CC (4), segmented neutrophils/CC (5), lymphocytes/CC (6), leucocytes/CC (7), eosinophils/CC (8), stick neutrophils/CC (9). Correct classification N0—N12 was 99.9% by neural networks computing (area under ROC curve = 1.0; error = 0.0). Conclusions: Lymph node metastases of gastric cancer significantly depended on blood cell circuit.
Cholesterol Granuloma
Authors: Haifa Bahri, Catherine Chassagne-Clement, Anne-Sophie Michallet, Thomas Mognetti, Emmanuelle Nicolas-Virelizier
Journal: Clinical Nuclear Medicine (2021)

Abstract Cholesterol granuloma (CG) is a foreign body–type granuloma that forms in response to cholesterol crystals. Its etiology and pathogenesis are unclear. 18 F-FDG is not a tumor-specific agent. Fibroblasts, macrophages, and multinucleated giant cells also take up 18 F-FDG. Like sarcoid granulomas or fibrous dysplasia, CG avidly takes up 18 F-FDG and can mimic tumor involvement. We present 2 cases of histologically proven CG, which has been misinterpreted as active residual Hodgkin lymphoma lesion.
Eribulin and gemcitabine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A multicenter, single-arm, phase 2-trial.
Authors: Chang Gon Kim, Jin-Hee Ahn, Jeong Eun Kim, Jee Hung Kim, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
Journal: Journal of Clinical Oncology (2021)

11516 Background: Eribulin and gemcitabine have shown encouraging efficacy in soft-tissue sarcoma (STS) as a monotherapy. Here, we evaluated the activity and safety of combined use of eribulin and gemcitabine in two most common histologic types of STS, liposarcoma and leiomyosarcoma. Methods: In this non-randomized, multi-center phase 2 study, patients were included if they had progressive disease after one or two prior chemotherapy including doxorubicin. Patient were given eribulin 1.4 mg/m 2 and gemcitabine 1,000 mg/m 2 on day1 and day 8 every 3 weeks. The primary endpoint was progression-free survival rate at 12 weeks (PFSR 12wks ) with null and alternative hypothesis of PFSR 12wks ≤20.0% and ≥40.0%, respectively. Results: Of 37 patients included, 22 had leiomyosarcoma, and 15 had liposarcoma. At 12-weeks after treatment, 16 and (72.7%) 11 (73.3%) patients in leiomyosarcoma and liposarcoma were progression-free. Overall PFSR 12wks was 73.0%, satisfying the primary endpoint. Objective response rate, disease control rate, median progression-free survival, and median overall survival were 16.2%, 78.4%, 23.9 weeks, and 88.9 weeks, without any statistical differences according to histologic subtypes. No new safety signals and treatment-related death were observed. Conclusions: Eribulin and gemcitabine showed promising activity and manageable safety profile in patients with STS of liposarcoma and leiomyosarcoma histology. Updated outcomes for ongoing patients will be presented. Clinical trial information: NCT03810976.
Abstract 10336: Smoking Patterns and High-risk Behavior Among Lesbian, Gay, and Bisexual Adults: The Behavioral Risk Factor Surveillance System (brfss) Survey
Authors: Mahmoud Al Rifai, Mohammadhassan Mirbolouk, Xiaoming Jia, Khurram Nasir, Vijay Nambi, Christie M Ballantyne, Anwar T Merchant, Michael J Blaha, Salim S Virani
Journal: Circulation (2019)

Introduction: The prevalence of smoking and high-risk behaviors among lesbian, gay and bisexual (LGB) adults is not well studied. Hypothesis: We hypothesized that there are differences in smoking p...
The impact of advance care planning on hope among patients with advanced cancer.
Authors: Michael Cohen, Andrew Althouse, Edward Chu, Robert M. Arnold, Douglas B. White, Margaret Q. Rosenzweig, Hailey W. Bulls, Kenneth Smith, Yael Schenker
Journal: Journal of Clinical Oncology (2021)

12029 Background: Providers often cite a fear of “giving up hope” as a reason they defer advance care planning (ACP) among patients with advanced cancer. We sought to determine whether engagement in ACP impacts patient’s hope. Methods: This is a secondary analysis of a randomized controlled trial of primary palliative care in advanced cancer. Patients who had not completed ACP at baseline were included in the analysis. ACP was assessed in the forms of an end of life conversation with one’s oncologist (EOL conversation) and completion of a living will/advance directive (AD). Measurements were obtained at baseline and 3 months. Hope was measured using the Herth Hope Index (HHI, range 12-48, higher scores indicate higher hope). ACP was measured with patient responses to a validated ACP questionnaire that queried (1) if they had had an EOL conversation with their provider and (2) if they had completed a living will or advance directive. Multivariate regression was performed to control for baseline HHI score, study randomization and age, religious importance, education, marital status, socioeconomic status, time since cancer diagnosis, pain/symptom burden (ESAS), and anxiety/depression score (HADS)—all variables known to be associated with ACP and/or hope. Results: A total of 672 patients with advanced cancer were enrolled in the overall study. The mean age was 69±10, and the most common cancer types were lung (36%), GI (20%) and breast/GYN (16%). In this group, 378 (56%) had not had an EOL conversation at baseline, of whom 29% (111/378) reported having an EOL conversation by 3 months. Hope was not different between patients who had or did not have an EOL conversation over the study period (ΔHHI 0.20 ± 5.32 vs -0.53 ± 3.80, p=0.136). After multivariable adjustment, hope was significantly increased in patients who had engaged in an EOL conversation (adjusted mean difference in ΔHHI 0.95 (95%CI 0.08-1.82), p=0.032). Similarly, of 216 (32%) patients without an AD at baseline, 31% (67/216) patients had subsequently completed one. Unadjusted hope was not different between those who had and had not completed an AD (ΔHHI 0.20 ± 3.89 vs -0.91 ± 4.50, p=0.085). After adjustment, hope was significantly higher in those who completed an AD (adjusted mean difference in ΔHHI 1.31 (95%CI 0.13-2.49), p=0.030), (Table). Conclusions: Our results demonstrate that hope is not decreased after engagement in ACP and may, in fact, be increased. These findings may provide reassurance to providers who are apprehensive about having these important and difficult conversations. Unadjusted and adjusted change in hope for those patients who had and had not had completed an EOL conversation or AD.[Table: see text]
A unique molecular identifier-based and clonal hematopoiesis-aware approach for accurate mutation calling in cell-free DNA assays.
Authors: Hongyu Xie, Yaxi Zhang, Pei Zhihua, Jianing Yu, Yiqian Liu, Shiqi Zheng, Geng Chen, Weizhi Chen, Ji He
Journal: Journal of Clinical Oncology (2021)

e22515 Background: Given peripheral blood cells (PBCs) matched cell-free DNA (cfDNA), accurate mutation calling in next generation sequencing (NGS)-based assays relies on discriminating artifacts and clonal hematopoiesis mutations from tissue originated somatic mutations. Although clonal hematopoiesis has been considered in previous overall error modeling, it has not been adapted to PBCs without using unique molecular identifiers (UMIs). Moreover, previous studies on background error profiling were mainly based on healthy controls without matched PBC gDNA, which may lead to potential overestimation of the error rates on those sites with clonal hematopoiesis mutations. Additionally, the fraction of tissue cells is also an important influencing factor but is usually ignored. Methods: We performed UMI-assisted capture-based DNA assays on cfDNA samples, matched PBCs, and oral epithelium cells from 150 healthy donors. A site-specific and subtype-specific background error model was first built for PBCs using the SNVs called from PBCs with matched oral epithelium cells to exclude potential clonal hematopoiesis mutations. Then a similar background model was established for cfDNA with the SNVs inferred from cfDNA to exclude clonal hematopoiesis. The SNVs identified in cfDNA and matched PBCs were separately filtered with the cfDNA and PBC background error models. In this study, we used the ultrasensitive liquid biopsy approach to evaluate paired with tissue and blood samples from 56 early-stage NSCLC patients. All samples are sequenced using NGS target-capture panels covering 29 genes. Results: The mutations were detected in 91.1% of tissue and 67.9% were discovered in plasma. The coincidence rate between tissue and plasma of the 56 early-stage NSCLC patients was 66.1%. Conclusions: We have developed a novel method tailored for UMI-assisted capture-based targeted DNA assays, which outperforms currently available methods in terms of modeling background errors and filtering clonal hematopoietic mutations.
Multiple primary melanoma in association with other personal and family history of cancers.
Authors: Xi Yang, Lilit Karapetyan, Na Bo, Hong Wang, Cindy Sander, John M. Kirkwood
Journal: Journal of Clinical Oncology (2021)

e21559 Background: Patients (PTs) with cutaneous melanoma are at increased risk of developing second primary melanoma and non-melanoma skin cancers. The primary aim of this study was to define the association between MPM and personal history of non-melanoma skin cancers and other non-skin cancers. The secondary aim was to evaluate the association between MPM and the presence of other cancers among first-degree relatives (FDRs). Methods: We performed a retrospective case-control study including cases with MPM and controls with single primary melanoma (SPM) from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank. The proportions and percentages of non-melanoma skin cancer, other non-skin cancer, 1st degree family history of melanoma, and 1st degree family history of other non-melanoma cancers were calculated separately for MPM and SPM groups. Fisher’s exact tests were performed to test whether MPM was associated with these variables. For each significant variable, a multivariable logistic regression model was used to test its association with MPM after adjusting for age, gender, melanoma staging, and smoking status. Results: In total, 311 PTs (39.2% men; median age at initial diagnosis 51years) were enrolled, including 194 with SPM (38.6%; 51) and 117 with MPM (39.8%; 48). 28 (9%) of PTs had squamous cell carcinoma (SCC), and 63 (20%) had basal cell carcinoma (BCC). The most common non-skin cancers in the whole cohort were prostate (4.8%), breast (3.8%), hematological (1.9%), colorectal (1.3%), and cervical cancers (1.3%). FDR history of melanoma, non-melanoma skin cancer, and other cancers were positive in 15.4%, 7.1% and 46.3% PTs, respectively. The most common non-skin cancers in FDRs were breast, prostate, lung, colorectal and hematological malignancies. In comparison to PTs with SPM, PTs with MPM were more likely to have SCC (14.5% vs 5.7%, p=0.013) but not BCC and other non-skin cancers. FDRs of PTs with MPM had higher prevalence of melanoma (23.1% vs 10.8%, p=0.005), prostate cancer (31.9% vs 5.3%, p=0.0002) but not other non-melanoma skin and non-skin cancers. In multivariate analysis the association remained significant between MPM and SCC (OR 2.7, 95% CI 1.1-6.6, p=0.032), FDR history of melanoma (OR 2.0, 95% CI 1.03-4.1, p=0.042), and FDR history of prostate cancer (OR 5.6, 95% CI 1.6-20.3, p=0.008). Conclusions: MPM is associated with higher prevalence of SCC and FDR history of melanoma and prostate cancer, but not BCC and other non-melanoma cancers in comparison to SPM.
HGG-28. ONCOGENIC TYROSINE KINASE GENE FUSIONS IN SUPRATENTORIAL HIGH GRADE GLIOMAS OF YOUNG CHILDREN - COMPARISON OF RNA- AND DNA-BASED METHODS FOR THEIR RELIABLE DETECTION
Authors: Torsten Pietsch, Gerrit Gielen, Andreas Waha, Evelyn Doerner, Andre O von Bueren, Christian Vokuhl, Glen Kristiansen, Christof Kramm
Journal: Neuro-Oncology (2021)

Abstract High-grade diffuse gliomas in early childhood are characterized by a more favorable outcome compared to older children. We have shown in previous studies that these tumors are characterized by stable genomes. The occurrence of tyrosine kinase gene fusions in high-grade gliomas of infancy may represent therapeutic targets. 50 glioblastomas (GBM) with supratentorial location occurring in children younger than four years were retrieved from the archives of the Brain Tumor Reference Center, Institute of Neuropathology, Bonn University. DNA and RNA were extracted from FFPE tumor samples. Gene fusions were identified on the DNA level by FISH using break-apart probes for ALK, NTRK1, -2, -3, ROS1 and MET and Molecular Inversion Probe (MIP) methodology. On the RNA level, fusion transcripts were detected by targeted RNA sequencing as well as Nanostring assay with fusion-specific probes. 37 supratentorial GBM occurred in the first year of life, 13 GBM between one and four years. 18 cases showed fusions of ALK to different partners; all occurred in the first year of life (18/37, 48.6%). Fusions of ROS1 were found in 5, MET in 3, NTRK1, -2, -3 in 10 cases. 12 cases showed no and two cases novel fusions. The different methods led to comparable results. Only recurrent fusions with known fusion partners were detectable with fusion sequence-specific Nanostring probes and library construction for targeted RNA sequencing failed in a fraction of cases. Break-apart FISH led to reliable results on the next day, and MIP technology represented the most sensitive method for analysis of FFPE samples. Gene fusions involving the tyrosine kinase genes ALK, MET, ROS1 and NTRK1, -2, -3 occurred in 72% of glioblastomas of young children; most frequent were ALK fusions occurring in infant GBM. DNA-based MIP technology represented the most robust and sensitive assay. A combination of RNA- and DNA-based methods to detect these fusions with high reliability is recommended.
Interim Results from the Phase 1a/1b Dose-Finding Study of CWP232291 (CWP291) in Relapsed or Refractory Myeloma (RRMM) Alone or in Combination with Lenalidomide and Dexamethasone
Authors: Elisabet E. Manasanch, Sung-Soo Yoon, Chang-Ki Min, Jin Seok Kim, Kenneth H Shain, Robert Hauptschein, Jeongeun E Choi, Kyoung-June Lee
Journal: Blood (2017)
Does fertility preservation affect the start of the oncological treatment and the response to neoadjuvant chemotherapy in breast cancer.
Authors: Sonia Baulies, Maxim Izquierdo, Marta Devesa, Ignacio Rodriguez, Fransec Tresserra, Rafael Fabregas
Journal: Journal of Clinical Oncology (2021)

e12613 Background: Study in breast cancer patients to assess whether fertility preservation (FP) can affect the onset of the oncological treatment and the pathological response in those patients who underwent neoadjuvant chemotherapy (NAC). Methods: Patients with breast cancer who underwent fertility preservation and NAC are matched 1:2.45 to non-FP controls by age and date al diagnosis and are studied: -Timing between the diagnosis of breast cancer and the onset of oncological treatment was performed. The following variables were chosen: 1.- Confirmation (pathologic result), 2.- FP visit, 3.- Onset FP, 4.- Final FP, 5. – Onset oncological treatment. The periods analyzed (median in days) were: 1.- Period of FP visit (AP result-FP visit), 2.- Period of FP (FP beginning –FP ending), 3.- Period of onset of oncological treatment (FP ending-onset of oncological treatment), 4.- Overall period (AP result-onset of oncological treatment). -Studying the pathological complete response (Miller Payne scale) among patients with FP compare to non-FP control group was also performed. Results: 20 patients with FP and NAC are studied between 2010-2019 and were compared to 49 non-FP patients. The median age at diagnosis was 36 years (28-39). The oncological characteristics of the patients are shown in Table 1. The time analysis in FP group was: 1.- Period of FP visit was 4 days (1-26), 2.- the period of FP (start of the stimulation treatment until the recovery of the oocytes) 12 days (7-20), 3.- the Period of onset of oncological treatment 7 days (1-27). The overall period took 26 days (18-51) compared to 17.5 days (1-60) in non-FP group (NS). Pathological complete response (Miller Payne 5): The pathological complete response was 80% (16/20) in FP group versus 40.8% (20/49) in non-FP group. Analyzed by tumor subtype in FP group, a MP5 was achieved in 72.7% luminal tumor (8/11), 75% positive-HER2 (3/4), 100% triple negative (5/5) versus 19% luminal tumor (4/21), 41.6% (5/12) positive-HER2 and 68.7% triple negative (11/16) in non-FP group. Conclusions: FP does not delay the onset of oncological treatment and our data do not suggest an adverse impact of FP on pathological complete response to NAC. [Table: see text]
Resetting the tumor microenvironment to favor anti-tumor immunity after local ablation.
Authors: Corrine A. Nief, Júlia Sroda Agudogo, Alana Gonzales, Rebecca A. Previs, Smita K Nair, Nimmi Ramanujam
Journal: Journal of Clinical Oncology (2021)

2561 Background: Percutaneous tumor ablation is a non-surgical method of tumor destruction that leaves necrotic tumor debris in situ. Tumor associated antigens released after ablation have the potential to initiate a systemic anti-tumor immune response, however the hostile tumor microenvironment hinders antigen presentation and T cell activity. We hypothesized that resetting the tumor microenvironment with oral sodium bicarbonate to decrease tumor acidity and low-dose cyclophosphamide to deplete pro-tumor immune cells would improve the ability of ablation to initiate anti-tumor immunity. Methods: Tumor growth, overall survival, and metastatic burden was assessed in orthotopic tumor models of triple-negative breast cancer (67NR, 4T1, and E0771). Tumor ablation was performed on palpable tumors using percutaneous ethanol injection (PEI) with 6% ethylcellulose to improve retention in the tumor. Surgical excision was used as a negative control to test the role of in situ tumor debris. Before ablation mice were placed on 200 mM of sodium bicarbonate (SB) in their drinking water and received a single intraperitoneal injection of 200 mg/kg of cyclophosphamide (CP). Mice surviving to 60 days after tumor implant without a primary tumor or signs of metastases were considered "cured" and re-challenged with 50e5 tumor cells in the contralateral mammary pad. T cell dependance was assessed with in vivo CD8 depletions. Results: The combination of PEI+SB+CP produced a potent anti-tumor response, curing a majority of mice (5/7 of E0771, 8/12 of 67NR, 7/12 of 4T1). No mice were cured using PEI alone, SB alone, CP alone, or any combination of two therapies (0/51 of E0771, 0/73 of 67NR, 0/75 of 4T1,). Re-challenge tumor growth was hindered in mice cured with PEI+SB+CP. Mice receiving PEI+SB+CP had significantly less metastases and lived longer than mice receiving surgical excision alone or surgical excision with SB+CP. Additionally the anti-metastatic response of PEI+SB+CP was undone when CD8+ T cells were depleted. Conclusions: Here the anti-tumor response of local ablation produced by PEI was enhanced by priming the tumor with low-dose CP and oral SB in metastatic breast cancer. These results suggest that tumor ablation with CP and SB can create a T cell dependent, personalized immune response to a tumor using only low-cost, easily accessible supplies, and the host’s own tumor.
CHEK1 and circCHEK1_246aa evoke chromosomal instability and induce bone lesion formation in multiple myeloma
Authors: Chunyan Gu, Wang Wang, Xiaozhu Tang, Tingting Xu, Yanxin Zhang, Mengjie Guo, Rongfang Wei, Yajun Wang, Artur Jurczyszyn, Siegfried Janz, Meral Beksac, Fenghuang Zhan, Anja Seckinger, Dirk Hose, Jingxuan Pan, Ye Yang
Journal: Molecular Cancer (2021)

Abstract Background Multiple myeloma (MM) is still incurable and characterized by clonal expansion of plasma cells in the bone marrow (BM). Therefore, effective therapeutic interventions must target both myeloma cells and the BM niche. Methods Cell proliferation, drug resistance, and chromosomal instability (CIN) induced by CHEK1 were confirmed by Giemsa staining, exon sequencing, immunofluorescence and xenograft model in vivo. Bone lesion was evaluated by Tartrate-resistant acid phosphatase (TRAP) staining. The existence of circCHEK1_246aa was evaluated by qPCR, Sanger sequencing and Mass Spectrometer. Results We demonstrated that CHEK1 expression was significantly increased in human MM samples relative to normal plasma cells, and that in MM patients, high CHEK1 expression was associated with poor outcomes. Increased CHEK1 expression induced MM cellular proliferation and evoked drug-resistance in vitro and in vivo. CHEK1-mediated increases in cell proliferation and drug resistance were due in part to CHEK1-induced CIN. CHEK1 activated CIN, partly by phosphorylating CEP170. Interestingly, CHEK1 promoted osteoclast differentiation by upregulating NFATc1 expression. Intriguingly, we discovered that MM cells expressed circCHEK1_246aa, a circular CHEK1 RNA, which encoded and was translated to the CHEK1 kinase catalytic center. Transfection of circCHEK1_246aa increased MM CIN and osteoclast differentiation similarly to CHEK1 overexpression, suggesting that MM cells could secrete circCHEK1_246aa in the BM niche to increase the invasive potential of MM cells and promote osteoclast differentiation. Conclusions Our findings suggest that targeting the enzymatic catalytic center encoded by CHEK1 mRNA and circCHEK1_246aa is a promising therapeutic modality to target both MM cells and BM niche.
Comparing real-time and intermittently scanned continuous glucose monitoring in adults with type 1 diabetes (ALERTT1): a 6-month, prospective, multicentre, randomised controlled trial
Authors: Margaretha M Visser, Sara Charleer, Steffen Fieuws, Christophe De Block, Robert Hilbrands, Liesbeth Van Huffel, Toon Maes, Gerd Vanhaverbeke, Eveline Dirinck, Nele Myngheer, Chris Vercammen, Frank Nobels, Bart Keymeulen, Chantal Mathieu, Pieter Gillard
Journal: The Lancet (2021)