tbuckley/cabot-search huggingface dataset:
Impact of race on biomarker testing among HER2- advanced breast cancer (ABC) patients (pts) in the United States: Results from a real-world study.
Authors: Reshma L. Mahtani, Alexander Niyazov, Katie Lewis, Lucy Massey, Alex Rider, Bhakti Arondekar, Michael P Lux
Journal: Journal of Clinical Oncology (2021)

10598 Background: African Americans (AA) have the highest breast cancer (BC) mortality rate. Access to treatment is a known contributing factor. In the past 4 years, several targeted therapies for HER2- BC have become available which require testing for specific biomarkers. This study assessed the impact of race on biomarker testing rates in HER2- ABC pts receiving treatment in the US. Methods: Oncologists were recruited to abstract data from medical charts for the next 8-10 pts receiving treatment with HER2- ABC during Sept 2019-Apr 2020. Pts records were stratified by race and categorized into 3 mutually exclusive cohorts [White/Caucasian (White), AA, Other]. The other race cohort was excluded from this analysis due to small sample size. Differences in pt demographics/clinical characteristics were analyzed via Fisher’s exact tests. Testing rates for actionable biomarkers (i.e. BRCA1/2, PIK3CA, PD-L1) were compared between White and AA pts utilizing logistic regressions controlling for age, known family history of a BRCA-related cancer, hormone receptor (HR) status and practice setting (academic vs. community). Further analyses by age will be presented. Results: This analysis included 378 pts records, provided by 40 oncologists. Mean age was 64 years; 77% had HR+/HER2- ABC; 20% had advanced triple negative breast cancer (TNBC), 3% had ABC with an unknown HR status. Compared to White pts, AA pts were significantly more likely to have advanced TNBC (27% vs. 18%, p&lt;0.05). Compared to White pts, AA pts had significantly lower BRCA1/2 mutation (mut) testing rates (Table). Numerically lower rates of PIK3CAmut and PD-L1 testing were observed among AA pts (Table). BRCA1/2mut positivity rate (germline [g] and/or somatic [s]) was higher among AA vs. White pts (30% vs. 22%). Positivity rate for PIK3CAmut was lower for AA vs. White pts (8% vs. 11%). Conclusions: A higher than expected BRCA1/2mut positivity rate was observed than previously reported in the literature. This is likely because this analysis included s BRCA1/2mut and represented a high risk pt population. Across all biomarkers assessed, AA pts had lower testing rates than White pts. This suggests racial disparities in testing rates of actionable biomarkers. Consistent with guidelines, and with the increased availability of targeted therapies, focused efforts should be developed to increase biomarker testing in AA pts. Funding: Pfizer Biomarker Testing Rates by Race.[Table: see text]
A single-arm, multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.
Authors: Yuxian Bai, Jianming Xu, Huichuan Sun, Chunmei Bai, Ru Jia, Yi Li, Wenjie Zhang, Lei Liu, Cheng Huang, Mei Guan, Jinghong Zhou, Weiguo Su
Journal: Journal of Clinical Oncology (2021)

e16123 Background: Several clinical studies of vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) therapy as second-line treatment for biliary tract cancer (BTC) has demonstrated moderate efficacy. In this study, surufatinib was evaluated as a second-line VEGFR therapy in BTC patients. Methods: This was a single-arm, multi-center, open-label phase 2 study conducted in China. The study enrolled eligible BTC patients who progressed after fist-line chemotherapy. Patients received surufatinib monotherapy as second-line treatment, at doses of 300 mg, once daily, in 28-day cycles. Tumor assessments were performed every 8 weeks ± 7 days according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Results: As of Nov. 30, 2018, a total of 39 BTC patients, including 29 (74.4%) with intrahepatic cholangiocarcinoma, 5 (12.8%) with extrahepatic cholangiocarcinoma, and 5 (12.8%) with gallbladder cancer, were enrolled and treated with surufatinib. Sixteen-week progression-free survival (PFS) rate was 46.33% (95% confidence interval [CI], 24.38‒65.73), with median PFS of 3.7 months and median overall survival (OS) of 6.9 months. In addition, results from subgroup and post-hoc analyses suggested the trends of better clinical efficacy in patients with tumor locations inside the liver, or with lower baseline values of CA19-9 (≤ 1000 IU/mL) and CEA (≤ 3 ng/mL). The top three treatment-related adverse events (TRAEs) with severity of Grade ≥ 3 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%). Conclusions: When applied in the treatment of BTC patients, surufatinib monotherapy has offered moderate clinical efficacy and has demonstrated favorable tolerability and safety profiles. Moreover, surufatinib further boosting the antitumor effects of cancer immunotherapy is desirable. Clinical trial information: NCT02966821.
Effect of antibiotic therapy on immunotherapy outcomes for non-small cell lung cancer: Analysis from the Veterans Health Administration Database.
Authors: William A. Stokes, Madhusmita Behera, Renjian Jiang, David Gutman, Felipe Giuste, Abigail Burns, Nikhil Sebastian, Selvi Ramalingam, Vidula Sukhatme, Michael C. Lowe, Suresh S. Ramalingam, Vikas Sukhatme, Drew Moghanaki
Journal: Journal of Clinical Oncology (2021)

9017 Background: Dysregulation of the gut microbiota induced by antibiotic therapy (Abx) may alter the anticancer immune response. Multiple small studies have associated Abx use with inferior immune checkpoint inhibitor (ICI) efficacy in patients with non-small cell lung cancer (NSCLC). We aimed to study the impact of Abx in a larger population of NSCLC patients treated with ICI within the Veterans Health Administration. Methods: We conducted a nested cohort study of Veterans who were diagnosed with NSCLC between 2010 &amp; 2018 and treated with ICI. Two exposures to Abx were specified and separately analyzed: prior Abx (pAbx) was defined as receipt of an Abx prescription within 30 days prior to initiation of ICI, and concurrent Abx (cAbx) was defined as receipt of an Abx prescription within 60 days following ICI initiation. A landmark analysis of 2 months from ICI start was applied to the cAbx analysis to exclude any Veterans with an OS event before that time point. OS was measured from start of ICI using Cox proportional hazard multivariate analyses (MVA). Results: 3,634 Veterans received ICI, mostly nivolumab (59.3%) or pembrolizumab (35.1%). Their median age was 69, and a plurality had male gender (97.0%), white race (73.0%), comorbidity count ≥1 (60.4%), adenocarcinoma (47.8%), and stage IV disease at diagnosis (40.9%). Of the 762 (21.0%) Veterans prescribed pAbx, beta-lactams, quinolones, and macrolides were the most common classes. These patients had shorter OS than those without pAbx (median 7 versus 10 months). Receipt of pAbx was also associated with lower OS on MVA (HR 1.31, p&lt;0.01). In the propensity-matched cohort analysis, Veterans receiving pAbx had lower OS (HR 1.27, p&lt;0.01) (Table top). For the cAbx analysis, 3,223 Veterans survived to the 2-month landmark, of whom 970 (30.1%) received cAbx. These Veterans had shorter OS than those without cAbx (median 7 versus 10 months). Lower OS with cAbx was also observed both on Cox MVA (HR 1.33, p&lt;0.01) and in the matched cohort (HR 1.32, p&lt;0.01) (Table bottom). Conclusions: In the largest analysis to date of Abx use in NSCLC patients receiving ICI, receipt of Abx within either 30 days before or 60 days after start of ICI was associated with lower OS. These findings suggest Abx therapy may have a detrimental effect on immunotherapy outcomes.[Table: see text]
Investigation Concerning Origin of Q Wave Disappearance in Patients with Myocardial Infarction Using 201Tl+123I-BMIPP Dual SPECT
Authors: Mera Hisaaki, Nishimura Toru, Taniai Siichi, Mitani Kazuhiko, Sakata Konomi, Yotsukura Masayuki, Yoshino Hideaki
Journal: Circulation (2006)
First-line (1L) nivolumab (NIVO) plus chemotherapy (chemo) versus chemo in advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy and safety data from CheckMate 649.
Authors: Markus H. Moehler, Kohei Shitara, Marcelo Garrido, Pamela Salman, Lin Shen, Lucjan Wyrwicz, Kensei Yamaguchi, Tomasz Skoczylas, Arinilda Silva Campos Bragagnoli, Tianshu Liu, Michael Schenker, Patricio Eduardo Yanez, Mustapha Tehfe, Mingshun Li, Dana Cullen, Arteid Memaj, Ming Lei, Hong Xiao, Yelena Y. Janjigian, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2021)

4002 Background: CheckMate 649 is the largest randomized, global phase 3 study of 1L programmed death (PD)-1 inhibitor–based therapy in GC/GEJC/EAC. 1L NIVO + chemo demonstrated superior overall survival (OS) vs chemo, with progression-free survival (PFS) benefit and an acceptable safety profile in pts whose tumors expressed PD-ligand (L)1 at combined positive score (CPS) ≥ 5 and ≥ 1, and in all randomized pts (Moehler et al. Ann Oncol 2020). We report additional data for all randomized pts. Methods: Eligible pts had previously untreated, unresectable advanced or metastatic GC/GEJC/EAC. Known HER2-positive pts were excluded. Pts were randomized to receive NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO + ipilimumab, or chemo. Dual primary endpoints for NIVO + chemo vs chemo were OS and PFS by blinded central review in PD-L1 CPS ≥ 5 pts. Hierarchically tested secondary endpoints were OS in PD-L1 CPS ≥ 1 and all randomized pts. Results: At 12-month minimum follow-up for 1581 randomized pts, NIVO + chemo had a statistically significant OS benefit vs chemo (HR 0.80 [99.3% CI 0.68–0.94; P = 0.0002]) in all randomized pts; PFS benefit was also seen (HR 0.77 [95% CI 0.68–0.87]). OS benefit was observed in multiple prespecified subgroups, consistent with the primary population. Grade 3–4 treatment-related adverse events (TRAEs) were reported in 59% (NIVO + chemo) and 44% (chemo) of pts. TRAEs with potential immunologic etiology (select TRAEs; sTRAEs) are shown in the table. Pts in the NIVO + chemo arm had decreased risk of symptom deterioration on treatment vs those in the chemo arm (HR 0.77 [95% CI 0.63–0.95; P = 0.0129]). Tolerability as measured by the FACT-Ga GP5 item was similar in both treatment groups. Conclusions: The addition of NIVO to chemo demonstrated improved OS and PFS benefit in all randomized pts, along with an acceptable safety profile and maintained tolerability as well as QoL, providing further support for NIVO + chemo as a standard 1L treatment for advanced GC/GEJC/EAC. Clinical trial information: NCT02872116. [Table: see text]
Sex Differences in Subclinical Coronary Atherosclerosis in Psoriasis by Coronary Computed Tomography Angiography
Authors: Meron Teklu, Wunan Zhou, Promita Kapoor, Nidhi Patel, Martin P. Playford, Alexander V. Sorokin, Amit K. Dey, Heather L. Teague, Khaled M. Abdelrahman, Grigory A. Manyak, Julie A. Erb-Alvarez, Sujata M. Shanbhag, Justin A. Rodante, Andrew Keel, Benjamin Lockshin, Marcus Y. Chen, Joel M. Gelfand, David A. Bluemke, Nanette K. Wenger, Nehal N. Mehta
Journal: JACC. Cardiovascular imaging (2021)
A phase 2 study of liposomal irinotecan with 5-fluorouracil and leucovorin in squamous cell carcinoma of head and neck or esophagus after prior platinum-based chemotherapy or chemoradiotherapy.
Authors: Li-Yuan Bai, Muh-Hwa Yang, Nai-Jung Chiang, Shang-Yin Wu, Chen-Yuan Lin, Ming-Yu Lien, Jia-Hong Chen, Mu-Hsin Chang, Ching-Yun Hsieh, Ruey-Long Hong, Hsiang-fong Kao, Ren-Hua Ye, Shang-Hung Chen, Chin-Fu Hsiao, Li-Tzong Chen, Tsang-Wu Liu
Journal: Journal of Clinical Oncology (2021)

6025 Background: Liposomal irinotecan (nal-IRI) + 5-FU/LV has been approved and used in treating patients with metastatic pancreatic cancer after gemcitabine-based therapy through the NAPOLI-1 study result. This phase 2 trial evaluated the activity of NAPOLI-1 regimen in patients with squamous cell carcinoma (SCC) of head and neck (H&amp;N) or esophagus that progressed on or recur after platinum-based chemotherapy or concurrent chemoradiotherapy. Methods: Patients with histologically confirmed SCC of H&amp;N or esophagus whose disease progressed while on or progressed/recurred within 6 months after platinum-based chemotherapy or chemoradiotherapy, and unsuitable for further surgical or radiation intervention were eligible. Prior anti-EGFR or anti-PD1/anti-PDL1 treatment was allowed. The regimen consisted of nal-IRI 70 mg/m 2 (irinotecan free base) followed by LV 400 mg/m 2 and 5-FU 2400 mg/m 2 , every 2 weeks. A Simon’s 2-stage design was used with planned 30 evaluable patients in the first stage and 52 evaluable patients in total. The primary endpoint is objective tumor response. Results: From December 2018 to April 2020, 59 subjects were enrolled, including 16 with esophagus cancer and 43 with H&amp;N cancer. Thirty-seven (63%) patients had metastatic disease at enrollment. The mean of treatment cycles were 5 (range, 1-21). Among the total 59 enrolled subjects, 53 subjects (14 esophagus cancer, 39 H&amp;N cancer) were evaluable for objective tumor response. The disease control rate in esophagus cancer was 50% (7 SD, intent-to-treat (ITT) population 43.8%). For H&amp;N patients, 1 CR, 4 PR, and 23 SD resulted in the response rate 12.8% (11.6% in ITT population) and disease control rate 72% (65% in ITT population). The median progression free survival (N = 59) was 2.5 months (esophagus/H&amp;N: 1.5/2.7 months) and the median overall survival was 5.9 months (esophagus/H&amp;N: 4.2/7.3 months). Seventy-eight percent of patients had ≥grade 3 treatment-related adverse events. The most frequent ≥grade 3 toxicities were decreased lymphocyte count (50.8%), decreased neutrophil count (42.4%), and decreased white blood count (33.9%). Only 3 patients (5%) had grade 3 diarrhea during the treatment period. Conclusions: This study showed the modest efficacy and manageable toxicity profile of nal-IRI+5-FU/LV in platinum-refractory locally advanced or metastatic H&amp;N or esophagus cancer patients. Clinical benefits including complete tumor response were noted in H&amp;N patients. The role of this regimen in selective patients and the efficacy of combination with immunotherapeutic agents warrant further explorations. Clinical trial information: NCT03712397.
A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation
Authors: Kenta Moriwaki, Katsuhisa Noda, Takatoshi Nakagawa, Naoyuki Taniguchi, Eiji Miyoshi
Journal: Cancer Research (2008)

2738  Heatocellular carcinoma (HCC) is one of the most lethal cancers and individuals with HCC show a poor 5-year survival rate. To provide effective treatment for HCC, it is necessary to develop advanced diagnosis and treatment methods by new strategy. Fucosylation critically involves in biological phenotypes of cancer cells. In HCC, fucosylation is increased compared with chronic liver disease and fucosylated α-fetoprotein (AFP-L3) has been clinically used as a specific tumor marker since 1996 in Japan and 2005 in the United States. However, detailed molecular mechanisms that explain the increased fucosylation in HCC remain unknown. Fucosylation is regulated by complicated mechanisms that involve several factors: fucosyltransferases, GDP-fucose, and GDP-fucose transporter (GDP-Fuc Tr). GDP-fucose, which is a donor substrate for fucosyltransferases, is synthesized in cytosol by several kinds of synthetic enzymes, such as GDP-mannose 4, 6-dehydratase (GMD), GDP-4-keto-6-deoxy-mannose-3, 5-epimerase-4-reductase (FX), and GDP-fucose pyrophosphorylase. GDP-fucose is transported by GDP-Fuc Tr from cytosol into Golgi lumen to serve as a substrate for fucosyltransferases.  In this study, the expression of fucosylation-related genes in HCC tissues was comprehensively studied by real-time RT-PCR analysis using 13 human HCC tissues and 2 normal liver tissues and it was found that GDP-Fuc Tr and FX expression were significantly increased in HCC compared with chronic liver disease and normal liver. Western blot analysis of GMD revealed that GMD protein was increased in HCC, which is independent of the levels of GMD mRNA. In vitro cell experiments showed that the level of GDP-Fuc Tr was the most significantly correlated with the level of cellular fucosylation. In Hep3B cells, whereas the extreme elevation of GDP-fucose could not lead to increase of cellular fucosylation, the over-expression of GDP-Fuc Tr dramatically increased it. The importance of GDP-Fuc Tr in the increase of fucosylation observed was also confirmed with immunohistochmical analyses using 59 cases of HCC tissue. To know characters of hepatoma cells with over-expression of GDP-Fuc Tr, cell adhesion and spreading on the ECMs were investigated. Over-expression of GDP-Fuc Tr resulted in the inhibition of cell adhesion and spreading on collagen, fibronectin, and laminin, suggested that the function of β1-integrin, which is a fucosylated glycoprotein, was disrupted by increase of fucosylation.  These findings suggest that the up-regulation of GDP-Fuc Tr plays a pivotal role in increase of fucosylation in HCC and leads to the inhibition of integrin function. Because dysfunction of integrin facilitates cancer metastasis, GDP-Fuc Tr becomes an attractive target for new treatments and diagnosis for HCC.
An international, multicenter, real-world analysis of epithelial ovarian cancer treatment and outcomes.
Authors: Geoff Hall, Sue Cheeseman, Bethany Levick, Eun Ji Nam, Subin Lim, Jean-Marc Classe, Elodie Martin, Paul Kubelac, Patriciu Achimaș-Cadariu, Joana Savva-Bordalo, Marina Borges, Sven Becker, Shabnam Shaid, Nicolas Niklas, Mariana Guergova-Kuras
Journal: Journal of Clinical Oncology (2021)

5531 Background: Few major studies have examined and compared the management and outcomes of patients from diagnosis to death between countries. We have established an international collaboration across Europe and South Korea to compare treatment and outcomes in Epithelial Ovarian Cancer (EOC). Methods: Patients diagnosed with EOC between January 2012 and December 2018 (age ≥18), were included for analysis. Data from medical records from five European and a single South Korean treatment centre were extracted, standardised to a common data model and analysed at each centre using a common script developed in R. Time to each progression/recurrence event (defined as time to next treatment) and overall survival have been estimated using Kaplan Meier methodology and outcomes stratified by categories of interest. Changes in the use of anti-cancer therapies over time and the incidence of BRCA mutations and incidence/timing of second breast cancers have also been examined. Results: A total cohort of 2925 patients was identified with a median age at each centre of 53 to 67 years. Advanced disease (FIGO stage III - IV) (range 57% to 84%) and high-grade serous morphology (38% to 70%) were most common at each centre. The timing of surgery (primary, interval debulking or delayed) and the proportion of patients undergoing surgery varied with stage. Patients with stage I disease where most likely to undergo surgery (range 73% to 100%) and stage IV the least (range 39% to 84%). Median overall survival for high grade serous cancers ranged from 1.9 to 4.9 years, and for the whole cohort from 2.1 to 5.5 years. Median time to next treatment at first relapse for the whole cohort ranged from 14 to 22 months. Second breast cancers were noted in 6 to 17% of patients and the majority of these occurred before the diagnosis of EOC at a median time of 96 to 118 months prior to diagnosis of EOC. Additional data on treatment pathways, BRCA status and outcomes by line of therapy for each centre will be presented. Conclusions: Preliminary analysis of results across this network suggests a variation in patient populations between sites and substantial differences in both treatments and outcomes. The establishment of a common data model and the use of a common analytic script between sites across six different countries allows for detailed exploration of the factors influencing differences in patient management and treatment outcomes in ovarian cancer patients.
Patient-Reported Sleep Quality at Baseline Correlates with 1-Year Survival after Allogeneic Hematopoietic Cell Transplantation in Adults
Authors: Anita D'Souza, Heather R. Millard, Jennifer Knight, Ruta Brazauskas, Jenny Vogel, Deborah Mattila, Kathryn Flynn, Stephanie J Lee, Mary M. Horowitz, J. Douglas Rizzo, Bronwen E. Shaw
Journal: Blood (2017)
Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial
Authors: Renato D Lopes, Pedro Gabriel Melo de Barros e Silva, Remo H M Furtado, Ariane Vieira Scarlatelli Macedo, Bruna Bronhara, Lucas Petri Damiani, Lilian Mazza Barbosa, Júlia de Aveiro Morata, Eduardo Ramacciotti, Priscilla de Aquino Martins, Aryadne Lyrio de Oliveira, Vinicius Santana Nunes, Luiz Eduardo Fonteles Ritt, Ana Thereza Rocha, Lucas Tramujas, Sueli V Santos, Dario Rafael Abregu Diaz, Lorena Souza Viana, Lívia Maria Garcia Melro, Mariana Silveira de Alcântara Chaud, Estêvão Lanna Figueiredo, Fernando Carvalho Neuenschwander, Marianna Deway Andrade Dracoulakis, Rodolfo Godinho Souza Dourado Lima, Vicente Cés de Souza Dantas, Anne Cristine Silva Fernandes, Otávio Celso Eluf Gebara, Mauro Esteves Hernandes, Diego Aparecido Rios Queiroz, Viviane C Veiga, Manoel Fernandes Canesin, Leonardo Meira de Faria, Gilson Soares Feitosa-Filho, Marcelo Basso Gazzana, Idelzuíta Leandro Liporace, Aline de Oliveira Twardowsky, Lilia Nigro Maia, Flávia Ribeiro Machado, Alexandre de Matos Soeiro, Germano Emílio Conceição-Souza, Luciana Armaganijan, Patrícia O Guimarães, Regis G Rosa, Luciano C P Azevedo, John H Alexander, Alvaro Avezum, Alexandre B Cavalcanti, Otavio Berwanger
Journal: The Lancet (2021)