tbuckley/cabot-search huggingface dataset:
Demographics, outcomes, and risk factors for patients (Pts) with sarcoma and COVID-19: A multi-institutional cohort analysis.
Authors: Michael J Wagner, Matthew Ingham, Corrie Painter, Rashmi Chugh, Jonathan C. Trent, Vivek Subbiah, Ali Raza Khaki, Lisa May Ling Tachiki, Elizabeth Trice Loggers, Chris Labaki, Rana R. McKay, Elizabeth A. Griffiths, Katherine Anne Thornton, Anup Kasi, Clara Hwang, James Lin Chen, Thorvardur Ragnar Halfdanarson, Daniel Y. Reuben, Cathleen Park, Elizabeth J. Davis
Journal: Journal of Clinical Oncology (2021)

11523 Background: Sarcoma pts often receive aggressive, highly immunosuppressive therapy and may be at high risk for severe COVID-19. Demographics, outcomes and risk factors for pts with sarcoma and COVID-19 are unknown. We aimed to describe the course of COVID-19 in sarcoma pts and to identify factors associated with adverse outcomes. Methods: The COVID-19 and Cancer Consortium (NCT04354701) is an international registry of pts with cancer and COVID-19. Adult pts (≥18 years old) with a diagnosis of sarcoma and laboratory confirmed SARS-CoV-2 were included from 50 participating institutions. Data including demographics, sarcoma diagnosis and treatment, and course of COVID-19 infection were analyzed. Primary outcome was the composite rate of hospitalization or death at 30 days from COVID-19 diagnosis. Secondary outcomes were 30 day all-cause mortality, rate of hospitalization, O2 need, and ICU admission. Descriptive statistics and univariate Fisher tests are reported. Results: From March 17, 2020 to February 6, 2021, N=204 pts were included. Median follow up was 42 days. Median age was 58 years (IQR 43-67). 97 (48%) were male. 30 (15%) had ECOG performance status ≥2. 104 (51%) received cancer treatment, including surgery or radiation, within 3 months of COVID-19 diagnosis. 153 (75%) had active cancer, of whom 34 (22%) had lung metastases. 100 (49%) pts met the composite primary endpoint; 96 (47%) were hospitalized and 18 (9%) died within 30 days from COVID-19 diagnosis. 64 (31%) required oxygen, and 16 (8%) required ICU admission. Primary endpoint rates were similar for pts who received cytotoxic chemotherapy (38/58, 66%) or targeted therapy (16/28, 57%). Pts with higher rates of the primary endpoint included patients ≥60 years old (59% vs 40%, OR 2.04, 95% CI 1.12-3.74, p=0.016), pts with ECOG PS ≥2 vs 0-1 (90% vs 41%, OR 12.2, 95% CI 3.44-66.8, p&lt;0.001), pts receiving any systemic therapy within 3 months of COVID-19 diagnosis (62% vs 39%, OR 2.65, 95% CI 1.43-4.97, p=0.001), and pts with lung metastases (68% vs 42%, OR 2.77, 95% CI 1.19-6.79, p=0.013). Primary endpoint rates were similar across sarcoma subtypes (Table). Conclusions: This is the largest cohort study of pts with sarcoma and COVID-19 to date. Sarcoma pts have high rates of complications from COVID-19. Older patients, those with poor performance status, those recently receiving systemic cancer therapy, and those with lung metastases appear to have worse outcomes.[Table: see text]
Abstract 815: Bilirubin Level as a Protective Factor for Diabetes Mellitus
Authors: Pramil Cheriyath, Nadine Srouji, Venkata Subhash Gorrepati, Ian Peters, Megan E Murphy, Vinod Nookala, Daniel Fischman
Journal: Circulation (2009)

Introduction: Diabetes Mellitus(DM) is a rampantly growing epidemic in the United States, affecting nearly 10% of the adult population. Studies have shown that higher levels of Total Bilirubin (TBi...
Creation of a primary breast cancer culture repository from patients with a BMI &gt;30 kg/m2: A Mexican endeavor.
Authors: Daniela Shveid Gerson, Alejandro Zentella - Dehesa, Raquel Gerson Cwilich, Benigno Rodriguez, Omar Serrano Villamayor, Diana Alejandra Villegas Osorno, Ervin Saúl Enciso López, Efrain Isaias Camarin Sanchez, Alejandro Noguez-Ramos, Lorena López Zepeda, Alberto Villalobos, Guillermo Olivares, José Fabián Martínez-Herrera
Journal: Journal of Clinical Oncology (2021)

e12574 Background: Currently there are no primary cultures or cell lines derived from patients with breast cancer and obesity. It has been postulated that breast cancer in obese women behaves differently as it does in non-obese women, as is composed of distinct biological features, as was generated in a different metabolic environment, as well as pertains to a different prognosis and different response to chemotherapy, lower rates of overall survival and a greater probability of recurrence. By creating a primary breast cancer culture bank of breast cancer tumors from women with obesity (BMI &gt; 30kg/m 2 ), we will establish a cell line exclusive to obese women in Mexico, where targeted therapy may be tested and treatment may be individualized depending on the characteristics of the patient. Methods: This study recruited 32 women with breast cancer and a BMI &gt; 30 kg/m 2 , matched by 6 controls with are non-obese women with breast cancer. Elegibility criteria was determined by women with breast cancer confirmed by pathology, who had not been subjected to prior treatment regarding the neoplasm. The breast cancer removing surgeries and the patients were selected from the ABC Medical Center in Mexico City and all procedures were approved by the research and ethics committee of the hospital in question. Results: Through extensive communication a cooperative protocol was established between the departments of surgery, oncology, pathology and nursing to coordinate efforts and be able to take a 2 – 5 mm sample of the breast tumor removed from the patient. To be able to distinguish cancer cells from non-cancer cells (epithelial cells, fibroblasts, adipocytes) the Hayflick limit was be utilized. Once a primary breast cancer culture was established, 12 million cells will be injected into the subscapular area of athymic, nu-nu mice to be able to monitor tumoral growth in vivo and conduct a subsequent cellular analysis, determining it still pertains to the same characteristics of the tumor from which it was obtained. Conclusions: A primary breast cancer culture repository from patients with a BMI &gt; 30 kg/m2 was established. This is the first primary breast cancer culture for both Mexican and obese women with breast cancer, the first in vitro method of analysis of specific characteristics typical of the Mexican population. Translational research may now be conducted on these new tumoral cultures to create individualized therapy for women with the distinct, aforementioned characteristics.
Reduction in prostate cancer hospitalizations in the COVID-19 pandemic epicenter of Latin America.
Authors: Isabella Batista Martins Portugal, Fernando Adami, Jean Henri Schoueri, Leandro Fórnias Machado Rezende, Fernando Luiz Affonso Fonseca, Gerson Ferrari, Luiz Carlos de Abreu, Luis Eduardo Werneck De Carvalho
Journal: Journal of Clinical Oncology (2021)

e18814 Background: The novel SARS-CoV-2 coronavirus disease 2019 (COVID-19) has disrupted health care systems worldwide since December 2019 causing atypical pneumonia and affecting multiple body organs. In Latin America, COVID-19 had its first case in the megacity of São Paulo, Brazil, thus being the starting point and epicenter of this disease. In this context, prostate cancer (PC) is the most common non-skin cancer among men and its preventive healthcare is substantial to public health surveillance. Additionally, PC raises particular interest during COVID-19 outbreak as PC androgen-deprivation therapies have shown to mitigate SARS-CoV-2 infection, which suggests an association between SARS-CoV-2 and PC cells. Thus, the consequences of the COVID-19 outbreak on male genital cancers care remain inconclusive and will probably be felt for decades. This study aimed to determine the impact of pandemic on the incidence of hospital admissions (HA) due to malignant neoplasms of male genital organs in the city of São Paulo, Brazil. Methods: This is a cross-sectional study of the HAs due to malignant neoplasms of male genital organs in the city of São Paulo comparing the outbreak period (January-June 2020) and a pre-pandemic corresponding period of the years 2017-2019. Data were obtained from the Brazilian Unified Health System - Hospital Information System database according to the chapter II of the International Classification of Diseases - 10th revision (ICD-10). Linear regression was used to analyze the relationship between the incidence of HAs and time (months). Results: A significant reduction in HAs due to malignant neoplasms of male genital organs was observed in PC, but not other malignant neoplasms of male genital organs during the outbreak period (January-June 2020). PC (-19, CI -36 to -1) showed to be remarkably affected while other male genital cancers (-1, CI -5 to 3) did not (Table). Conclusions: Our findings seem to be associated to delayed oncological care delivery to PC during the lockdown and health system disruption. Further studies are required to evaluate the impact of the ongoing pandemic in malignant neoplasm of male genital organs, particularly PC, in order to strategically corroborate public health actions for implications of COVID-19 pandemic. Linear regression of hospital admissions for the years 2017-2020 (January until June) due to malignant neoplasms of male genital organs (chapter II of the ICD-10). Municipality of São Paulo, São Paulo, Brazil.[Table: see text]
Treatment patterns for patients with metastatic or recurrent head and neck cancer in a large integrated health-care system.
Authors: Tiffany Seto, Navendu D. Samant, Nina Shah, Aida Shirazi, A. Dimitrios Colevas, Jed Abraham Katzel
Journal: Journal of Clinical Oncology (2021)

e18015 Background: Since publication of the landmark KEYNOTE-048 Trial, pembrolizumab alone or with platinum-based chemotherapy and 5-fluorouracil (5FU) was established as a standard of care for the frontline treatment of patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC), replacing the EXTREME regimen of Cetuximab with platinum and 5FU. In clinical practice, some clinicians modify the KEYNOTE-048 regimen by substituting a taxane for 5FU (i.e., Paclitaxel + Carboplatin + Pembrolizumab, PCT). Within the Kaiser Permanente Northern California (KPNCAL) network, we identified a cohort of 123 patients who received palliative first-line therapy for metastatic HNSCC to identify practice patterns in a real-world setting within a large health care delivery system. Methods: This is a data-only cohort study of all adult KPNCAL members diagnosed with metastatic HNSCC treated with palliative combination chemotherapy and/or immunotherapy between January 1, 2018 and July 31, 2020. Results: Among a cohort of 123 patients, 28 patients received the EXTREME regimen (platinum + 5FU + cetuximab), 10 received modified EXTREME (platinum + taxane + cetuximab), 14 received platinum + 5FU + pembrolizumab, 9 received platinum + taxane + pembrolizumab and 62 received single agent immunotherapy. From 2018 through mid-2020, there was an apparent shift away from cetuximab based regimens and a concurrent rise in immunotherapy-based regimens. By mid-2020, the majority of patients received an immunotherapy-based regimen (28 patients), while only 5 patients received a cetuximab based regimen (Table). Conclusions: Data from our cohort reported clinical practice patterns within a large multispecialty integrated health-care system in Northern California. Our findings highlight the marked variability in practice patterns within a single health care system for first-line metastatic therapy. While we identified trends away from cetuximab based therapy and toward immunotherapy-based therapy in clinical practice there remained wide practice variations among clinical oncologist treating patients with newly diagnosed metastatic HNSCC. This further emphasizes the need for prospective clinical trials to identify the optimal regimen or to confirm clinical equipoise between regimens among patients with metastatic or recurrent head and neck cancer. [Table: see text]
Variant reclassification and its impact on clinical care in an Asian cancer center.
Authors: Jianbang Chiang, Tze Hao Chia, Sock Hoai Chan, Joanne YY Ngeow
Journal: Journal of Clinical Oncology (2021)

10583 Background: Genetic testing has demonstrated clinical utility in the identification and subsequent surveillance of patients with cancer predisposition syndromes. However, the increased likelihood of encountering a variant of uncertain significance (VUS) in individuals of non-European descent such as Asians may be challenging to both clinicians and patients in interpretation and management. VUS can be reclassified as more data becomes available. VUS reclassification is important, as it may have implications for surveillance and treatment. This study aims to evaluate the prevalence and patterns of variant reclassification in an Asian country and its impact on patient management. Methods: A prospective cohort of patients seen at the Cancer Genetics Service at the National Cancer Center Singapore between February 2014 to March 2020 was evaluated. The frequency, direction and time to variant reclassification was assessed by comparing the reclassified report against the original report. Results: A total of 1412 VUS were reported in 49.9% (845/1695) of patients. Over six-years, 6.7% (94/1412) of variants were reclassified. Most VUS (94.1%; 80/85) were downgraded to benign/likely benign variant, with a smaller proportion of VUS (5.9%; 5/85) upgraded to pathogenic/likely pathogenic variant. Actionable VUS upgrades and pathogenic/likely pathogenic variant downgrades, that resulted in management changes, happened in 31.0% (39/126) of patients. The median and mean time taken for reclassification were 1 and 1.62 year(s) respectively. Conclusions: Clinicians need to put in place a system for review of variants, as variant reclassification can lead to changes in management in nearly 1/3 of patients. Management should be based on the patient’s personal history, family history and variant interpretation. We propose a clinical guideline to standardize management of patients with VUS. For clinically relevant or suspicious VUS, follow-up is recommended every two years, as actionable reclassifications may happen during this period.
A deep learning survival model for triple-negative breast cancer patients.
Authors: Yiyue Xu, Bing Zou, Bingjie Fan, Wanlong Li, Shijiang Wang, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e12594 Background: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis. There is no reliable model for survival prediction of TNBC patients. The traditional Cox regression analysis with poor prediction power cannot satisfy the clinical needs. The purpose was to establish a deep learning model and develop a new prognostic system for TNBC patients. Methods: This study collected data of TNBC patients from the Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2016. 70% were used to develop the deep learning model, 15% were used as the validation set, and 15% as the independent testing set. Then the concordance-index (c-index) and Brier score (IBS) were calculated and compared with the Cox regression analysis and random forest. Finally, according to the classification of the deep survival model, an individualized prognosis system was established. Results: A total of 37,818 patients were enrolled in this study. In the validation set, the c-index of the deep learning was 0.799, which was better than the traditional Cox regression model (0.774) and random forest (0.763). The independent testing set further proved the robustness of the deep survival model (c-index 0.788). The new prognosis system based on the deep survival model reached an area under the curve (AUC) of 0.805, which was better than the Tumor, Node, Metastases (TNM) staging system (0.771). Conclusions: Deep learning model had better prediction power than the Cox regression analysis and the random forest. The established prognosis system can better predict prognosis and aid individual risk stratification for TNBC patients patients.
Clinical features, treatments and survival of HER2 positive gastric cancer with elevated alpha-fetoprotein: An analysis of 16 cases.
Authors: Shaohua Ge, Yi Ba, Ting Deng, Yuchong Yang, Tao Ning, Hongli Li, Ming Bai, Le Zhang, Jingjing Duan, Rui Liu, Xia Wang, Zhi Ji
Journal: Journal of Clinical Oncology (2021)

e16000 Background: Gastric cancer with elevated alpha-fetoprotein (AFP) is a special type of gastric cancer with elevated serum AFP. It is often misdiagnosed as primary hepatic cancer due to abnormal AFP and liver metastasis. The AFP level is related to the prognosis of these patients in whom there is prone to high HER2 positive rate. Therefore, anti-HER2 treatment is optional, as well as the emerging immunotherapy with immune checkpoint inhibitors. Methods: Gastric cancer patients with HER2 and serum AFP examination were collected in our hospital from May 2017 till now. Serum AFP level over 7 ng/ml was defined as elevated AFP. The clinical characteristics, treatments and survival of the patients with HER2 positive and elevated AFP were picked and analyzed. Results: Among 135 gastric cancer patients with elevated AFP, 16 (11.9%) were HER-2 positive (12 with HER2 3+, 3 with HER2 2+/FISH+ and 1 with HER2 gene amplification in NGS). The mean serum AFP is 201.4± 476.7ng/ml (range: 7.74 -1335). There were 9 males and 7 females. The mean age was 55 years (range: 38-90). The tumors were located in stomach cardia and fundus in 5 cases, body in 5 cases, antrum in 4 cases, body and antrum in 1 case and whole stomach in 1 case. There were 2 patients in stage III and 14 patients in stage IV with metastasis to lymph node metastasis in 15, liver in 9, abdominal cavity in 3 and peritoneum in 3. As for the treatments, three patients underwent surgery, one of whom with exploratory laparotomy (no antitumor treatment after surgery, died from infection). In 13 advanced patients, 12 patients received systemic antitumor therapies (8 with chemotherapy+Trastuzumab+ immunotherapy, 2 with chemotherapy+Trastuzumab, 1 with chemotherapy+ immunotherapy and 1 with chemotherapy). The chemotherapy regimens were XELOX in 5 cases, SOX in 4 cases and FLOT in 2 cases. The response rate was 50% (6 in 12 patients) and the disease control rate was 100%. The median PFS was 7.5 months in first line therapy with six patients without progression disease yet. The longest PFS with PR lasted for 16.5 months with chemotherapy, trastuzumab and immune checkpoint inhibitor. Conclusions: Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics. Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors. This combination is expected to become a new regimen to improve survival of such special patients.
Integrated genomic analyses of cutaneous T-cell lymphomas reveal the molecular bases for disease heterogeneity
Authors: Joonhee Park, Jay Daniels, Tim Wartewig, Kimberly G. Ringbloom, Maria Estela Martinez-Escala, Sara Choi, Jane J. Thomas, Peter G. Doukas, Jingyi Yang, Caroline Snowden, Calvin Law, Yujin Lee, Katie Lee, Yancong Zhang, Carly Conran, Kyle Tegtmeyer, Samuel H. Mo, David R. Pease, Balaji Jothishankar, Pui-Yan Kwok, Farah R. Abdulla, Barbara Pro, Abner Louissaint, Titus J. Boggon, Jeffrey Sosman, Joan Guitart, Deepak Rao, Jürgen Ruland, Jaehyuk Choi
Journal: Blood (2021)
Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center
Authors: Xue Chen, Fang Wang, Yang Zhang, Xiaoli Ma, Panxiang Cao, Lili Yuan, Lan Wang, Jiaqi Chen, Xiaosu Zhou, Qisheng Wu, Ming Liu, David Jin, Hongxing Liu
Journal: Blood Cancer Journal (2021)

Abstract Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.
Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer
Authors: Robert J. Harris, Anthony Cheung, Joseph C.F. Ng, Roman Laddach, Alicia M. Chenoweth, Silvia Crescioli, Matthew Fittall, Diana Dominguez-Rodriguez, James Roberts, Dina Levi, Fangfang Liu, Elena Alberts, Jelmar Quist, Aida Santaolalla, Sarah E. Pinder, Cheryl Gillett, Niklas Hammar, Sheeba Irshad, Mieke Van Hemelrijck, Deborah K. Dunn-Walters, Franca Fraternali, James F. Spicer, Katie E. Lacy, Sophia Tsoka, Anita Grigoriadis, Andrew N.J. Tutt, Sophia N. Karagiannis
Journal: Cancer Research (2021)

Abstract In breast cancer, humoral immune responses may contribute to clinical outcomes, especially in more immunogenic subtypes. Here, we investigated B lymphocyte subsets, immunoglobulin expression, and clonal features in breast tumors, focusing on aggressive triple-negative breast cancers (TNBC). In samples from patients with TNBC and healthy volunteers, circulating and tumor-infiltrating B lymphocytes (TIL-B) were evaluated. CD20+CD27+IgD− isotype-switched B lymphocytes were increased in tumors, compared with matched blood. TIL-B frequently formed stromal clusters with T lymphocytes and engaged in bidirectional functional cross-talk, consistent with gene signatures associated with lymphoid assembly, costimulation, cytokine–cytokine receptor interactions, cytotoxic T-cell activation, and T-cell–dependent B-cell activation. TIL-B–upregulated B-cell receptor (BCR) pathway molecules FOS and JUN, germinal center chemokine regulator RGS1, activation marker CD69, and TNFα signal transduction via NFκB, suggesting BCR–immune complex formation. Expression of genes associated with B lymphocyte recruitment and lymphoid assembly, including CXCL13, CXCR4, and DC-LAMP, was elevated in TNBC compared with other subtypes and normal breast. TIL-B–rich tumors showed expansion of IgG but not IgA isotypes, and IgG isotype switching positively associated with survival outcomes in TNBC. Clonal expansion was biased toward IgG, showing expansive clonal families with specific variable region gene combinations and narrow repertoires. Stronger positive selection pressure was present in the complementarity determining regions of IgG compared with their clonally related IgA in tumor samples. Overall, class-switched B lymphocyte lineage traits were conspicuous in TNBC, associated with improved clinical outcomes, and conferred IgG-biased, clonally expanded, and likely antigen-driven humoral responses. Significance: Tumor-infiltrating B lymphocytes assemble in clusters, undergoing B-cell receptor–driven activation, proliferation, and isotype switching. Clonally expanded, IgG isotype-biased humoral immunity associates with favorable prognosis primarily in triple-negative breast cancers.