tbuckley/cabot-search huggingface dataset:
Amount of cancer stem cells in tumors of patients with ovarian cancer with different responses to platinum-containing chemotherapy.
Authors: Aleksandr B. Sagakyants, Elena S. Bondarenko, Darya Yu. Yakubova, Elena P. Ulianova, Galina V. Zhukova, Anna P. Menshenina, Inna A. Novikova, Ekaterina V. Verenikina, Meri L. Adamyan, Anna A. Cherkasova
Journal: Journal of Clinical Oncology (2021)

e17527 Background: Resistance to chemotherapy is a complex problem in the treatment of patients with ovarian cancer (OC), and this phenomenon is associated, among other things, with the presence of cancer stem cells (CSCs). The purpose of the study was to determine the amount of CSCs in tumors of OC patients with different responses to chemotherapy they receive. Methods: Samples of ovarian tumors were obtained from 100 patients (aged 29-79 years) with advanced ovarian cancer stage IIIC-IV with/without ascites. All patients recruited in 2016-2020 received standard combination treatment with surgery and platinum-containing polychemotherapy (Pt CT). Based on the results of neoadjuvant Pt CT, patients were divided into groups: patients with stabilization or progression–group 1 “without effect”; patients with complete/partial regression–group 2 with positive effect. All patients gave their informed consent for the study. Cell suspension obtained from the tumor fragments was processed using monoclonal antibodies labeled with various fluorochromes: CD45-APC-Cy7, CD44-FITС, CD133–РЕ according to the manufacturer's instructions (BD, USA). The percentage of CSCs was determined using the FACS Canto II flow cytometer (BD, USA). The amount of cells with CSC markers (CD44 + , CD133 + , CD44 + CD133 + ) was calculated as a percentage from the total amount of CD45 - -cells. Statistics: STATISTICA 13 (StatSoftInc., USA). Results were presented as Me (LQ; UQ). The significance of differences was assessed using the Mann-Whitney test (the differences were considered significant at p&lt;0.05). Results: The amount of CD45 - _ cells, as well as CD45 - CD44 + cells, in OC tumors did not differ between patients of groups 1 and 2: 79.0 (72.1; 85.9) vs. 82.8 (76.7; 89.0), and 6.2 (3.3; 9.1) vs. 6.6 (3.5; 9.8), respectively. The percentage of cancer cells with the CD45 - CD133 + phenotype in group 2 was significantly lower than in group 1: by 52% (p≤0.05), 3.2 (2.4; 3.9) vs. 6.7 (3.8; 9.6), respectively. The amount of CD45 - CD44 + CD133 - CSCs in tumors in group 1 was lower than in group 2: by 82% (p≤0.05), 0.6 (0.3; 0.7) vs. 3.3 (1.8; 4.7), respectively. Conclusions: The results demonstrated certain differences in the distribution of CSCs in tumors of OC patients with different sensitivity to chemotherapy, which may be one of the factors determining the treatment outcomes.
Cost-effectiveness analysis of platinum-based chemotherapy treatment options for germline BRCA-mutated locally advanced/borderline resectable pancreatic cancer.
Authors: Myles Ingram, Yoanna S Pumpalova, Jiheum Park, Francesca Lim, Gulam Abbas Manji, Chung Yin Kong, Chin Hur
Journal: Journal of Clinical Oncology (2021)

e16246 Background: Patients with germline BRCA1/2 mutations (gBRCAm) have an increased risk for pancreatic ductal adenocarcinoma (PDAC). The NCCN 2020 guidelines recommend platinum-based chemotherapy (FOLFIRINOX or gemcitabine plus cisplatin) in patients with gBRCAm diagnosed with borderline resectable or locally advanced (BR/LA) PDAC; for patients without progression on chemotherapy, maintenance therapy with a PAPR inhibitor (PARPi) can be considered. FOLFIRINOX and gemcitabine plus cisplatin (GemCis), with or without maintenance PARPi, have not been directly compared in this patient population. The purpose of our study was to compare treatment outcomes, toxicity, costs, and quality-of-life of the two recommended platinum-based regimens, with or without maintenance PARPi (olaparib or veliparib), in patients with gBRCAm and BR/LA PDAC. Methods: We developed a decision-analytic mathematical model comparing the total cost and health outcomes of FOLFIRINOX, FOLFIRINOX + olaparib (FOLFIRNOX-O), GemCis, and GemCis + veliparib (GCV) over twelve years. The inputs for the model were estimated using clinical trial data and published literature. Natural history was used as a comparator. The primary endpoint was incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted-life-year (QALY). Secondary endpoints included overall survival (OS), progression-free survival (PFS), life-years (LYs) and total cost of care (USD). Results: Both FOLFIRINOX strategies were dominated by the GemCis strategies and thus eliminated from the efficiency frontier. GCV was the strategy that yielded the most life-years (2.05 LYs) but the ICER of $629,697.46 for this regimen far exceeded the WTP threshold. Therefore, GemCis was the cost-effective strategy, totaling incremental QALYs of 1.31 at a cost of $61,228.40 per QALY when compared to natural history. A one-way sensitivity analysis found that the GCV becomes the cost-effective strategy when the cost of maintenance PARPi is lowered to 4% of the base case. Conclusions: Our model found that GemCis is the cost-effective option for patients with gBRCAm and BR/LA PDAC. Neither of the strategies with maintenance PARPi were cost-effective. Additional clinical trial data with adequate follow-up are needed to confirm our findings.[Table: see text]
Abstract AP03: DISTINCT CELL/TISSUE SOURCES OF HIGH-GRADE SEROUS OVARIAN CANCER
Authors: Shuang Zhang, Benjamin G. Neel
Journal: Clinical Cancer Research (2019)

Abstract The cell-of-origin of high grade serous ovarian carcinoma (HGSC) has been a focus of debate. Here, by using genetic mouse models as well as cognate organoid systems, we assessed the tumor forming capacity and properties of the fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) bearing the same oncogenic abnormalities. Combined RB family inactivation (via T121 expression) and Tp53 mutation in Pax8+ fallopian tube secretory cells causes transformation and characteristics of Serous Tubal Intraepithelial Carcinoma (STIC). This genetically engineered mouse HGSC model is faithfully recapitulated in fallopian organoids, from which serous ovarian cancer with broad abdominal metastasis is generated upon orthotropic injection. The same genetic events in Lgr5+ OSE cells organdies derived from these cells also result in an apparent neoplastic process, expressing markers of early serous carcinoma (but not Pax8), which subsequently develop into serous-like tumors. Hence, both Pax8+ fallopian tube epithelial cells and Lgr5+ ovarian surface epithelial cells can undergo similar neoplastic transformation, suggesting that HGSC might derive from distinct cell and tissue sources. Similar organoid systems can be used to rapidly model other gene combinations associated with HGSC. Citation Format: Shuang Zhang, Benjamin G. Neel. DISTINCT CELL/TISSUE SOURCES OF HIGH-GRADE SEROUS OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP03.
Predicting disease progression and mortality in metastatic colorectal cancer patients (mCRC) through an artificial intelligence-based analytical tool.
Authors: Carlos Maria Galmarini, Maximiliano Lucius
Journal: Journal of Clinical Oncology (2021)

1549 Background: Predicting the clinical course of metastatic disease remains a key challenge in CRC. Estimating prognosis of these late-stage patients can avoid undertreatment or overtreatment and also guide the follow-up intensity. This study has investigated the ability of an artificial intelligence-based analytical tool to identify those mCRC patients with high risk of disease progression and mortality based on their clinical parameters. Methods: Through www.projectdatasphere.org we accessed datasets of two randomised phase III trials including chemo-naïve (NCT00364013, n = 1183 patients) and chemo-refractory (NCT00113763, N = 483) mCRC patients. We generated synthetic fingerprints (SF) for each patient through the integration of 44 clinical features (demographics, anthropometrics, medical history, blood tests and treatment characteristics) collected, respectively, during the screening phase and the first month of inclusion in each trial. These SF were then input into a deep learning framework (DLF) to identify subgroup of patients based on their similarities. The resultant clusters were correlated with progression-free survival (PFS) and overall survival (OS). Results: After discarding missing data, 861 chemo-naïve and 341 chemo-resistant mCRC patients were eligible for the study. In the chemo-naïve cohort, the SF/DLF system was able to detect two different clusters: C0 (n = 31) and C1 (n = 830). Patients in C0 had a higher risk of progression (median PFS 6.2 months vs. 9.1 months; hazard ratio 1.83, 95% CI 1.16-2.88; p = 0.008) and death (median OS 13.2 months vs. 20.1 months; hazard ratio 2.84, 95% CI 1.68-4.80; p &lt; 0.001) compared to patients in C1. When applied to the chemo-resistant cohort, the SF/DLF system was again able to identify two different clusters: P0 (n = 159) and P1 (n = 182). Patients in P0 had a higher risk of progression (median PFS 1.7 months vs. 1.8 months; hazard ratio 1.32, 95% CI 1.05-1.67; p &lt; 0.001) and death (median OS 6.1 months vs. 6.8 months; hazard ratio 1.34, 95% CI 1.07-1.68; p = 0.01) compared to patients in P1. In both cases, feature contribution analysis showed that major differences between clusters were related to clinical status, anthropometrics and haematological and biochemistry tests. Conclusions: Our SF/DLF system can identify mCRC subtypes based on distinct clinical features that correlate with higher risk of progression and death. Further work is required to validate this approach as a novel prognostic biomarker tool for monitoring mCRC patients.
18F-FET PET/CT as a Diagnostic Tool for Brain Abscess
Authors: Seo Young Kang, Yunejeong Jang, Min-Sun Cho, Soo Jeong Park, Byung Seok Moon, Hye Ok Kim, Hai-Jeon Yoon, Bom Sahn Kim
Journal: Clinical Nuclear Medicine (2021)

A 49-year-old man presented with sudden right-sided weakness and seizure. Brain MRI identified a lobulated mass with diffusion restriction and irregular wall enhancement in the left parietal lobe. 18F-FET (O-(2-[18F]fluoroethyl)-l-tyrosine) PET/CT was performed, which identified a cystic mass in the left parietal lobe accompanied by FET uptake. Compartmentalized uptake was also confirmed throughout the left parietal lobe. Considering the relatively low target-to-background ratio and uptake observed in the entire left parietal lobe, the lesion was more likely to be a brain abscess than a tumor. The pathologic diagnosis after mass removal was acute and chronic inflammation with abscess.
Parsimonious Gene Correlation Network Analysis in DLBCL Allows Refined Linkage to Mutation State and Treatment Response
Authors: Matthew A Care, Sharon Barrans, Michael A Bentley, Ming Wang, Alexandra Clipson, Ming-Qing Du, Cathy H Burton, Josh Caddy, Andrew J Davies, Peter Johnson, David R Westhead, Reuben M Tooze
Journal: Blood (2017)
A contemporary practical approach to the multidisciplinary management of unclassifiable interstitial lung disease
Authors: Christopher J. Ryerson, Tamera J. Corte, Jeffrey L. Myers, Simon L.F. Walsh, Sabina A. Guler
Journal: European Respiratory Journal (2021)

Fibrotic interstitial lung diseases (ILDs) frequently have nonspecific and overlapping clinical and radiological features, resulting in ∼10–20% of patients with ILD lacking a clear diagnosis and thus being labelled with unclassifiable ILD. The objective of this review is to describe how patients with unclassifiable ILD should be evaluated, and what impact specific clinical, radiological and histopathological features may have on management decisions, focusing on patients with a predominantly fibrotic phenotype. We highlight recent data that have suggested an increasing role for antifibrotic medications in a variety of fibrotic ILDs, but justify the ongoing importance of making an accurate ILD diagnosis given the benefit of immunomodulatory therapies in many patient populations. We provide a practical approach to support management decisions that can be used by clinicians and tested by clinical researchers, and further identify the need for additional research to support a rational and standardised approach to the management of patients with unclassifiable ILD.
T follicular helper cells: linking cancer immunotherapy and immune-related adverse events
Authors: Dirk Baumjohann, Peter Brossart
Journal: Journal for ImmunoTherapy of Cancer (2021)

Cancer immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of numerous cancer types. As the underlying mechanism of these treatments lies in the interference with inhibitory signals that usually impair potent antitumor immunity, for example, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein 1 (PD-1):programmed death-ligand 1/2 (PD-L1/2) pathway, it is not surprising that this could also promote exaggerated adaptive immune responses to unrelated antigen specificities. One of the side effects of ICI-based cancer immunotherapy that is increasingly observed in the clinic is immune-related adverse events (irAEs), including various types of autoimmunity. However, the precise etiology is incompletely understood. T follicular helper (Tfh) cells provide essential help to B cells for potent antibody responses and their tumor tissue presence is often correlated with a better outcome in several solid tumor entities. Importantly, these CD4+ T cells express very high amounts of PD-1 and other co-stimulatory and inhibitory receptors. Here, we address the hypothesis that targeting CTLA-4 or PD-1 and its ligand PD-L1 critically impacts the function of Tfh cells in patients that receive these ICIs, thereby providing a link between ICI treatment and the development of secondary autoimmunity.
Long-term quality of life of cancer survivors: A case-control study.
Authors: Joaquin Ponce-Zepeda, Tuyen Hoang
Journal: Journal of Clinical Oncology (2021)

12077 Background: There were extensive reports in literature about the debilitating health experienced by cancer patients during treatment. This study examined how the quality of life of cancer survivors changed over time. Methods: The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the U.S. This study involved participants in NHANES from 2000-2020. Participants who reported having had a cancer diagnosis were matched one to one with participants who reported no cancer diagnosis by age, gender, race, year of recruitment into NHANES, and comorbidities. Quality of life measures including self-reported general/physical/mental health, examinations, and laboratory tests were compared between cancer cases and matched controls using paired t tests. Results: This study included 5,166 pairs of cancer cases and matched controls. Mean age was 66 (±15 years). Male 47% and female 53%. White 69%, Black 14%, Hispanic 12%, others 5%. Most common comorbidities were hypertension (56%), arthritis (50%), diabetes (19%), and thyroid (18%). About 38% of cancer cases had survived in 1-5 years; 22% in 6-10 years; 39% in 10+ years. Most prevalent cancers were skin (28%), breast (15%), and prostate (15%). Compared to controls, cancer cases who had survived in 1-5 years reported higher rates of poor general health (38% vs. 27%, p &lt;.0001), hospitalizations (31% vs. 17%, p &lt;.0001), mental health visits (9% vs. 7%, p =.0204). There were no significant differences in general health and healthcare utilization between cancer cases who survived &gt; 5 years and controls. There were no clinically meaningful differences in laboratory tests and examinations between cancer cases and controls regardless of survival time. Conclusions: During the first 5 years after cancer diagnosis, survivors reported worse health than controls. As survival time extended, there was no difference between cancer cases and controls. The debilitating health reported during the first 5 years could not be explained by examinations and laboratory tests alone. Future research should explore neurochemical and hormonal markers to investigate adverse effects of cancer treatment on long-term quality of life.
OMIC-11. SINGLE CELL RNA SEQUENCING FROM THE CSF OF SUBJECTS WITH H3K27M+ DIPG/DMG TREATED WITH GD2 CAR T-CELLULAR THERAPY
Authors: Aaron Mochizuki, Sneha Ramakrishna, Zina Good, Shabnum Patel, Harshini Chinnasamy, Kristen Yeom, Liora Schultz, Rebecca Richards, Cynthia Campen, Agnes Reschke, Jasia Mahdi, Angus Toland, Christina Baggot, Sharon Mavroukakis, Emily Egeler, Jennifer Moon, Kayla Landrum, Courtney Erickson, Lindsey Rasmussen, Valentin Barsan, John Tamaresis, Anne Marcy, Michael Kunicki, Michelle Celones, Zach Ehlinger, Sreevidya Kurra, Timothy Cornell, Sonia Partap, Paul Fisher, Gerald Grant, Hannes Vogel, Kara Davis, Steven Feldman, Bita Sahaf, Robbie Majzner, Crystal Mackall, Michelle Monje
Journal: Neuro-Oncology (2021)

Abstract Introduction We are conducting a Phase I clinical trial utilizing chimeric antigen receptor (CAR) T-cells targeting GD2 (NCT04196413) for H3K27M-mutant diffuse intrinsic pontine glioma (DIPG) and spinal cord diffuse midline glioma (DMG). Cerebrospinal fluid (CSF) is collected for correlative studies at the time of routine intracranial pressure monitoring via Ommaya catheter. Here we present single cell RNA-sequencing results from the first 3 subjects. Methods Single cell RNA-sequencing was performed utilizing 10X Genomics on cells isolated from CSF at various time points before and after CAR T-cell administration and on the CAR T-cell product. Output was aligned with Cell Ranger and analyzed in R. Results As detailed in the Majzner et al. abstract presented at this meeting, three of four subjects treated at dose-level one exhibited clear radiographic and/or clinical benefit. We have to date completed single cell RNA-sequencing for three of these four subjects (two with benefit, one without). After filtering out low-quality signals and doublets, 89,604 cells across 3 subjects were analyzed. Of these, 4,122 cells represent cells isolated from CSF and 85,482 cells represent CAR T-cell product. Two subjects who demonstrated clear clinical and radiographic improvement exhibited fewer S100A8+S100A9+ myeloid suppressor-cells and CD25+FOXP3+ regulatory T-cells in the CSF pre-infusion compared to the subject who did not derive a therapeutic response. In one subject with DIPG who demonstrated improvement, polyclonal CAR T-cells detectable in CSF at Day +14 demonstrated enrichment of CD8A, GZMA, GNLY and PDCD1 compared to the pre-infusion CAR T-cells by trajectory analysis, suggesting differentiation toward a cytotoxic phenotype; the same subject exhibited increasing numbers of S100A8+S100A9+ myeloid cells and CX3CR1+P2RY12+ microglia over time. Further analyses will be presented as data become available. Conclusions The presence of immunosuppressive myeloid populations, detectable in CSF, may correlate to clinical response in CAR T cell therapy for DIPG/DMG.
Upfront thoracic radiotherapy to primary lession improve outcomes in patients with stage IV non-small cell lung cancer harboring EGFR mutations.
Authors: Ayse Kotek Sedef, Ahmet Taner Sümbül, Berna Akkus Yildrim, Erkan Topkan
Journal: Journal of Clinical Oncology (2021)

e21167 Background: The role of thoracic radiotherapy in the treatment of metastatic EGFR mutant non-small cell lung cancer patients in literature datas are insufficient.The aim of this study was to examine the effectiveness of upfront thoracic radiotherapy in metastatic EGFR mutant NSCLC patients treated with chemotherapy or TKI. Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 141 patients with metastatic EGFR mutant non-small cell lung cancer who has followed in two different oncology centers at Turkey between 2014 and 2020. have been included to this study. Results: The median age of the patients was 63 (range 35-91) years. EGFR mutation results of exon 19 deletion, exon 21 mutation and exon 18 mutation were found in 82 (58.2%), 56 (39.7%) and 3 (2.1%) patients, respectively. The median follow-up time was 22 months and 94 (33.3%) patients died during follow-up. Median overall survival (OS) was 26 months and progression free survival (for first line treatment) (PFS) was 10 months for whole patients, respectively. Radiotherapy was given to the primary tumor site in 32 (22,6%) patients. Patients receiving radiotherapy to primary tumor site had better overall survival than those not (31 versus 23 months respectively and p = 0,02) The survival advantage was also seen for patients group taking TKI at upfront setting (33 versus 23 months respectively and p = 0.05). Conclusions: In this study, we have showed that upfront thoracic radiotherapy to primary lession as combination with EGFR-TKI treatment may improve the outcome in advanced stage IV NSCLC patients harboring EGFR mutations.
Comparative assessment of the eighth and seventh AJCC staging edition prognostic performance of patients with p16 positive oropharynx cancer.
Authors: Felippe Lazar Neto, Luana Guimarães Sousa, Faye M. Johnson, J. Jack Lee, Steven J. Frank, Amy Catherine Moreno, Kristina Dahlstrom, Renata Ferrarotto
Journal: Journal of Clinical Oncology (2021)

6067 Background: The American Joint Committee on Cancer (AJCC) TNM staging system defines the anatomical extent of disease and serves as a guide for treatment and prognosis. The favorable prognosis of p16+ oropharyngeal squamous cell carcinoma (OPSCC) compared to p16 negative counterpart led to major updates in the AJCC 8th edition. Its prognostic performance, however, warrants further validation. Methods: We included patients diagnosed with p16+ OPSCC enrolled in a prospective registry ( Stiefel) at The University of Texas MD Anderson Cancer Center between March 2015 and December 2018. Patients’ stage at diagnosis was classified according to the AJCC 7th (AJCC-7) and 8th (AJCC-8) editions. Overall survival (OS) and progression-free survival (PFS) was defined as time from diagnosis to death or to progression or death, respectively. The Kaplan-Meier method was used to calculate 1- and 3-year survival probabilities. Differences between groups were compared using the log-rank test. Prognostic discriminative performance of each staging system was evaluated using Harrel’s C-statistic. Survival differences between heavy (&gt; 10 pack-years [PY]) vs. light/never smokers (≤ 10 PY) by AJCC-8 staging groups was assessed with the log-rank test. Results: Of 463 patients, the median follow-up was 34.7 months (2.3-169.74). Nearly 90% (N=413) of patients were down-staged from AJCC-7 to AJCC-8 with 69% of patients with IVA disease based on AJCC-7 (N=319) re-staged as stage I (N=196 [42%]), II (N=79 [17%]) or III (44 [10%]) according to AJCC-8. Over 60% (N=279) of patients were staged as I with AJCC-8. Compared to AJCC-7, AJCC-8 had improved prognostic ability (C-statistic, 0.58 for AJCC-7 vs. 0.63 for AJCC-8) and provided better discriminative survival probabilities at 1 and 3-year follow-up (Table). Similar results were observed for PFS. Smoking status did not impact OS when stratified by AJCC-8 staging groups: I, p=0.347; II, p=0.310; and III, p=0.532 for &gt; 10 vs. ≤ 10 PY. Conclusions: Our cohort validates that the AJCC-8 provides better prognostic discriminative performance when compared to AJCC-7, however, a disproportionate number of patients were classified as stage I. Smoking was not associated with survival within each staging group.[Table: see text]