tbuckley/cabot-search huggingface dataset:
Characteristics of patients with lymphoma presenting initially as a neck mass referral to otolaryngology.
Authors: Andrew Lynch, Meredith Anderson, Rijul Kshirsagar, David M. Baer, Joan C. Lo, Jason Glide, Kevin H. Wang
Journal: Journal of Clinical Oncology (2021)

e18054 Background: Lymphomas that present initially as a neck mass can be challenging to diagnose as their onset is often insidious, frequently without classic symptoms, and fine-needle aspiration has limited utility for diagnosis. Understanding their clinical presentation may facilitate recognition and diagnosis, essential for timely treatment of aggressive lymphoma subtypes. Methods: Using data from a large integrated healthcare delivery system, adults aged 18-89 years without known previous cancer who were referred to Head and Neck Surgery for evaluation of a “neck mass” in 2017 were identified. Among the subset of 205 patients found to have malignancy, 76 had lymphoma (N = 69) or leukemia (N = 7) and 129 had a non-lymphoma/leukemia malignancy. The demographic characteristics of patients with and without lymphoma/leukemia were compared. Among the 69 with lymphoma, tumor histology and stage were examined. Differences between subgroups were compared using Chi-squared, Fisher’s exact, Student’s t-test, F-tests, and Tukey’s range tests for pairwise comparison. Results: Among 205 patients identified with a malignant neck mass, 76 (37%) were diagnosed with lymphoma/leukemia. Patients with lymphoma/leukemia were more likely to be female (47% vs. 27%, p = 0.003) and under age 50 years (36% vs. 13%, p = 0.001). There were no statistically significant differences in race, smoking status, or BMI between the two groups. Among the lymphoma/leukemia subset, 18 (24%) had Diffuse Large B-Cell Lymphoma (DLBCL), 13 (17%) had Follicular Lymphoma (FL), and 25 (33%) had Hodgkin’s Lymphoma (HL). The HL subset was significantly younger than both the FL and DLBCL subsets (mean age 41.6 years vs. 62.2 and 66.6, p &lt; 0.001). A range of findings was seen when examining sex (72%, 44% and 46% male), race/ethnicity (60%, 72% and 69% non-Hispanic White), smoking status (36%, 33% and 62% current/former) and tumor stage at presentation (52%, 50% and 69% late stage (III-IV)) for HL, DLBCL and FL subtypes, respectively, but the differences were not statistically significant in these smaller subsets. Conclusions: Significant differences in baseline characteristics exist between lymphoma and non-lymphoma patients presenting with a malignant neck mass. Notably, the lymphoma subset was younger and, except for those with HL, did not demonstrate a male predominance. Within the lymphoma subset, HL patients were significantly younger than patients with other lymphoma subtypes. Further studies in a larger population identifying demographic differences by cancer subtype may inform efforts to prevent diagnostic delays in head and neck lymphoma. Characterizing the diagnostic pathway is also needed to quantify room for improvement in the treatment approach of patients with neck mass considered at higher risk for lymphoma.
Meaningful Reduction of Annual Bleeding Rate with Lower Dose Prophylaxis in Minimally Treated Children with Hemophilia in India
Authors: Aby Abraham, Shashikant Apte, Abraham Sunder Singh, Kannan Subramaniam, Anu Korula, Aditi Joshi, Dipti Khedekar, Kavitha M Lakshmi, Biju George, Vikram Mathews, Alok Srivastava
Journal: Blood (2017)
Global line-1 hypomethylation as novel biomarker for cervical cancer in Nigerian women living with HIV.
Authors: Yinan Zheng, Jonah Musa, Brian Thomas Joyce, Jun Wang, Demirkan Gursel, Olugbenga A. Silas, Fatimah Biade Abdulkareem, Godwin Imade, Alani Akanmu, Jian-Jun Wei, Masha Kocherginsky, Kwnag-Youn Kim, Firas Hazem Wehbe, Chad Achenbach, Rose Anorlu, Melissa A. Simon, Atiene Sagay, Folasade Ogunsola, Robert Murphy, Lifang Hou
Journal: Journal of Clinical Oncology (2021)

e17513 Background: Nigeria faces a high health burden of cervical cancer (CC), which is worsened by high prevalence of human immunodeficiency virus (HIV) infection. Repetitive elements (RE) are DNA sequences that occur in multiple copies throughout the human genome. HIV infection can lead to RE hypomethylation that causes genome instability, an event often seen in the early phase of tumorigenesis. We aim to examine global RE hypomethylation as a novel epigenetic biomarker for CC among HIV-positive women in Nigeria. Methods: This study involved three groups of women: a) HIV-positive with CC (n=39); b) HIV-positive and cancer-free (n=52); and c) HIV-negative with CC (n=23). We estimated three types of global RE methylation in cervical tissue using genome-wide methylation data: long interspersed nuclear elements (LINE-1), Alu, and human endogenous retrovirus (HERV). We used multiple linear regression adjusting for age, education, parity, employment, cancer stage, body mass index, and sample batch to compare the biomarkers across the HIV/ICC groups and paired t-test to compare 26 pairs of tumor vs. surrounding normal tissues, stratified by HIV status. Receiver operating characteristic curve (ROC) and area under the ROC (AUC) were used to examine the diagnostic value. Results: Among HIV-positive women, all 3 global RE methylation biomarkers were hypomethylated in CC compared to cancer-free (LINE-1: mean difference [MD]=-0.049, p-value=2.9e-8; Alu: MD=-0.011, p-value=2.0e-4; HERV: MD=-0.013, p-value=1.7e-6). Paired analyses showed a larger, more significant MD in HIV-positive stratum than HIV-negative, especially LINE-1 (MD=-0.048 vs. -0.020, p-value=0.004 vs. 0.254). LINE-1 achieved the highest AUC (0.85, 95% CI: 0.76-0.95) in distinguishing tumor tissue from normal tissue among HIV-positive women, followed by HERV (0.82, 95% CI: 0.73-0.92) and Alu (0.60, 95% CI: 0.47-0.72). Conclusions: Global LINE-1 hypomethylation may serve as a novel biomarker for CC screening and early detection for women living with HIV in low- and middle-income countries.
Ki67 and PR to predict sensitivity of palbociclib: A real-world study.
Authors: Xi-Ying Shao, Xia-Bo Shen, Guang-Liang Li, Ya-Bing Zheng, Wen-Ming Cao, Zhan-Hong Chen, Xiao-Jia Wang
Journal: Journal of Clinical Oncology (2021)

e13032 Background: Palbociclib combined with endocrine therapy are approved as a front-line treatment for hormone receptor (HR)-positive, HER2-negative advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment. Methods: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR), detected by immunohistochemistry, in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS). Results: In total population, women with Ki67≥14% had marginal significant shorter PFS than those with Ki67&lt;14%. Patients with Ki67≥30% had significant shorter PFS than those with Ki67&lt;30% ( P=0.048). While PR≥ 20% was associated with longer PFS. And what’s more, the change trend of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. In regard with hormone therapy subgroup, there were significant association between Ki67 and PR levels and PFS in aromatase inhibitors (AIs) subgroup. Patients with Ki67≥14% or Ki67≥ 30% had shorter PFS than those with Ki67&lt;14% or Ki67&lt;30%, respectively ( P=0.024, P &lt;0.001). Additionally, the change trend of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. When both Ki67 and PR are considered, there were significant differences between different cohort. Compared with those with Ki67≥14% and PR &lt;20%, patients with Ki67&lt;14% and PR≥20% had significant longer PFS. In addition, patients with Ki67&lt;30% and PR≥20% had significant longer PFS than those with Ki67≥30% and PR&lt;20%. Besides, in AIs cohort, patients with Ki67&lt;14% and PR≥20% had significant longer PFS than those with Ki67≥14% and PR &lt;20%. Women with Ki67&lt;30% and PR≥20% had significant longer PFS than those with Ki67≥30% and PR&lt;20%. Conclusions: The present study indicates that both Ki67 and PR have a greater impact on palbociclib and hormone therapy and may help selecting a more effective partner of palbociclib.
Outcomes and predictors of hospital mortality of patients with Philadelphia-negative myeloproliferative neoplasms and sepsis: A Nationwide Inpatient Sample Database analysis.
Authors: Luis F. Gonzalez Mosquera, Pool Tobar, Diana D. Cardenas Maldonado, Bernard Moscoso, Alida I. Podrumar, John A. Cuenca
Journal: Journal of Clinical Oncology (2021)

e19038 Background: Sepsis is associated with increased mortality in patients with hematologic malignancies, especially in those receiving cytotoxic chemotherapy. The development of new therapies also increases the risk of infections in Philadelphia negative myeloproliferative neoplasms (MPN). However, the clinical implications and costs of sepsis in patients with polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF) have not been reported at a national level. Therefore, we aimed to determine the outcomes, hospitalization costs, and predictors of mortality in patients with MPN and sepsis. Methods: We retrieved adult patients with MPN from the Nationwide Inpatient Sample database from 2016-2018. We used the ICD-10 codes to identify and compare patients with and without sepsis. The main outcomes were hospital mortality and predictors of mortality. We computed the chi-squared test and the Mann-Whitney U-test. Mortality predictors are estimated using multivariate logistic regression and logistic fixed-effect methods to control for admission cohort and hospital time invariant characteristics. All analyses were performed using Stata Statistical Software version 14 (StataCorp, College Station, TX). Results: A total of 86,723 patients with MPN were identified. The majority of them were white (66.9%), female (54.3%), with a median age of 62 (IQR 47-76). The most common MPN was ET (84.3%), followed by PV (14.2%). Sepsis was diagnosed in 16,146 (18.6%) of the MPN patients. There was a significantly higher mortality in the sepsis group vs. the non-sepsis group (7.4% vs. 1.8%; p &lt; 0.001), longer LOS (8 vs. 4 days; p &lt; 0.001), and higher median hospitalization cost (US$74,128 vs. US$39,987; p &lt; 0.001). In the multivariable analysis, sepsis was associated with higher mortality (OR: 4.74; CI 95%: 4.33-5.18; p &lt; 0.001). Among the MPN, those with PMF and sepsis had a higher risk of death (OR: 2.21; CI 95%: 1.72-2.82; p &lt; 0.001). Other significant variables associated with mortality were age &gt; 65 (OR: 2.51; CI 95%: 2.14-2.95; p &lt; 0.001), concomitant chronic heart failure (CHF) (OR: 1.57; CI 95%: 1.39-1.77; p &lt; 0.001), chronic kidney disease (CKD) (OR: 1.22; CI 95%: 1.10-1.35; p &lt; 0.001), and weight loss (OR: 2.12; CI 95%: 1.79-2.51; p &lt; 0.001). There was no significant association with sex and race/ethinicity. Conclusions: On patients with MPN, sepsis was associated with higher mortality, hospitalization costs, and LOS. Additionally, those with increased age, CHF, CKD, weight loss, and PMF were also at increased risk of death. There should be more emphasis on assessing the risk of sepsis on MPN to prevent worse outcomes and higher costs. Further studies should focus on identifying the specific causes of sepsis in MPN and promoting early recognition.
The PLATON pilot-study “Platform for analyzing targetable tumor mutations”: A PLATON network study.
Authors: Arndt Vogel, Bianca Zäpf, Thorsten Oliver Goetze, Benedikt Westphalen, Lothar Müller, Sebastian Broeckling, Jean-Charles Moulin, Jochem Potenberg, Michael Sohm, Thomas Gabrysiak, Vera Heuer, Bodo Klump, Jack Chater, Matthias Zeth, Anna Saborowski, Facher Quader, Felicia Michael, Claudia Pauligk, Leonie Amstein, Salah-Eddin Al-Batran
Journal: Journal of Clinical Oncology (2021)

TPS6598 Background: PLATON Network is designed as a platform to improve personalized therapy based on genomic profiles in gastrointestinal cancer patients. PLATON’s study-design focuses on patient’s molecular profiling and will provide a network web application for interlinking PLATON investigators which integrates information of the participating centers, their patients, the molecular profiles and available clinical trials at PLATON`s study-sites. Methods: The PLATON Network is designed as a permanent open, multicenter, prospective, cohort study with biobanking, with a shared platform infrastructure for associated sub-studies. In a first approach the PLATON Network enrolls within its pilot-study 200 patients in Germany of both sexes and ages over 18 at 40 study sites (NCT04484636) with signed informed consent. All patients of the pilot-study are diagnosed with hepatocellular cancer (HCC), intra- and extrahepatic cholangiocellular carcinoma (CCA), gallbladder carcinoma (GBCA), pancreatic cancer (PDCA) or esophagogastric cancer (EC/GC). At the time of enrolment, patients are within their first-line therapy and no local curative therapy is available. Molecular profiling will be performed with the Foundation Medicine Assays FoundationOne CDx and FoundationOne Liquid CDx. Investigators may use the platform for searching clinical trials matching the individual molecular profile of their patients or may identify a patient, who may be eligible for a study or other treatment options available at the corresponding centers of the PLATON network. The interactive network web application will comprise a dashboard and a moderated chat room to interact for example in a virtual Molecular Tumor Board. The first patient was included on the 25 th of November 2020. Up to 12 th of February 2021, a total of 36 patients HCC (N = 1), CCA (N = 6), PDCA (N = 12), GBCA (N = 0) and EC/GC (N = 16) were enrolled at 11 study-sites and the results of 29 genetic analyses were completed. All cohorts of the pilot-study are open for recruitments up to a maximum of 40 individuals per diagnostic group. Clinical trial information: NCT04484636.
Does multilobularity of left atrial appendage represent an additional Risk for thrombus formation in Atrial fibrillation
Authors: D. Galzerano, B. Tuccillo, D. Lama, G. Mirra, M. Giasi, M. Varricchio, J. Yao, N.G. Masani, N.G. Pandian
Journal: Journal of the American College of Cardiology (1997)
HGG-31. HISTONE H3.3 G34R/V MUTATIONS STIMULATE PEDIATRIC HIGH-GRADE GLIOMA FORMATION THROUGH THE INDUCTION OF CHROMOSOMAL INSTABILITY
Authors: Florina Grigore, James Robinson, Alyssa Langfald, Edward Hinchcliffe, Charles Day
Journal: Neuro-Oncology (2021)

Abstract The histone H3.3 G34R/V mutations are known drivers of high-grade pediatric glioma (pHGG). However, the mechanism(s) for H3.3 G34R/V induced tumor formation are unclear. Chk1 phosphorylates H3.3 S31 at the pericentromere during early mitosis, suggesting a novel mitotic function. We observed that H3.3 G34 mutant pHGG cells have reduced mitotic H3.3 S31 phosphorylation compare to WT H3.3 cell lines. The H3.3 G34R mutation reduced Chk1 phosphorylation at S31 by &amp;gt;90% in an in vitro kinase assay. Overexpression of either H3.3 G34R or non-phosphorylatable S31A in H3.3 WT, diploid cells led to a significant increase in chromosome mis-segregations. Likewise, H3.3 G34 mutant pHGG cells have significantly elevated rates of mis-segregation as compare to H3.3 WT pHGG cells. During normal cell division, phospho-S31 is lost in late anaphase. However, when chromosome missegregation occurs, phospho-S31 spreads and stimulates p53 accumulation in G1 – thus suppressing aneuploid cell proliferation. Here we show that cells expressing mutant G34 fail to arrest following mis-segregation, despite having WT p53. These studies demonstrate that the H3.3 G34R/V mutations are sufficient to transform normal, diploid cells into proliferative, chromosomally instable cells. To determine if this process contributes to tumorigenesis, we used the RCAS/TVA mouse model to overexpress H3.3 WT, G34R, or S31A in the glial precursor cells of mice pups. Over 100 days, S31A and G34R mice had drastically reduced survival (averaging 77, 81, and 100 days for S31A, G34R, and WT mice). Furthermore, most G34R and S31A mice developed HGG, while H3.3 WT mice remained tumor-free and did not develop high-grade tumors. Our work strongly indicates that a major factor in H3.3 G34R pHGG formation is the induction of chromosomal instability – which occurs directly through the suppression of H3.3 S31 phosphorylation.
HER2CLIMB-04: Phase 2 open label trial of tucatinib plus trastuzumab deruxtecan in patients with HER2+ unresectable locally advanced or metastatic breast cancer with and without brain metastases (trial in progress).
Authors: Ian E. Krop, Jorge Ramos, Chiyu Zhang, Erika P. Hamilton
Journal: Journal of Clinical Oncology (2021)

TPS1097 Background: Tucatinib (TUC) is an oral, reversible, small molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2) with minimal inhibition of human epidermal growth factor receptor (EGFR). In the pivotal, randomized HER2CLIMB trial (NCT02614794), the combination of TUC + trastuzumab (T) + capecitabine (C) demonstrated statistically significant and clinically meaningful improvements in progression free survival (PFS), overall survival (OS), and PFS in patients (pts) with brain metastases (BM), compared to T + C alone. These data supported regulatory approvals in the US and internationally for TUC in combination with T + C in pts with HER2+ metastatic breast cancer (MBC). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate of trastuzumab and a topoisomerase I inhibitor payload approved in the US for treatment of HER2+ MBC in pts who have received 2 or more prior anti-HER2 regimens in the metastatic setting. Approval was based on data from the single arm Destiny-Breast01 trial (NCT03248492) where treatment with T-DXd resulted in a confirmed objective response rate (cORR) of 61.4% (95% CI: 54.0, 68.5) in pts with HER2+ MBC who had prior ado-trastuzumab emtansine treatment. Despite these advances, HER2+ MBC remains incurable, and pts will eventually progress on currently available therapies. Combining TUC and T-DXd may result in further improvement on the efficacy seen with either agent alone. Methods: HER2CLIMB-04 (NCT04539938) is a single arm, open-label phase 2 trial evaluating safety and antitumor activity of TUC + T-DXd in pts with HER2+ unresectable locally-advanced or MBC who have received 2 or more prior HER2-based regimens in the metastatic setting. Pts with BM, including active BM, may be enrolled. Ten pts will be enrolled in the safety lead-in portion of the trial and followed for at least 1 cycle. If safety of the combination is acceptable, the trial will continue until approximately 60 response-evaluable pts have been enrolled, approximately evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are PFS, duration of response (DOR), and disease control rate (DCR) by INV per RECIST v1.1, OS, and safety. Exploratory endpoints will include cORR, PFS, DOR, DCR by independent central review per RECIST v1.1, pharmacokinetic analyses, biomarker analyses, and changes in patient-reported outcomes using the European Quality of Life 5-Dimension 5-Level instrument. Enrollment began in late 2020 in the United States. Clinical trial information: NCT04539938 .
Awareness and utilization of tumor mutation burden (TMB) as a biomarker for administration of immuno-oncology (I-O) therapeutics by practicing community oncologists in the United States (U.S.).
Authors: Kristin M. Zimmerman Savill, Marjorie E. Zettler, Bruce A. Feinberg, Yolaine Jeune-Smith, Ajeet Gajra
Journal: Journal of Clinical Oncology (2021)

2608 Background: TMB, a measurement of the number of mutations carried by tumor cells, is emerging as a biomarker for the identification of patients who may benefit from certain I-O-based therapies. TMB-high (TMB-H) tumors, defined by the detection of ≥10 mutations/megabase (mut/Mb) in tumor cells using a tissue-based assay such as the FoundationOneCDx (F1CDx) assay (Foundation Medicine, Inc.), may be more likely to respond to some I-O therapies. Higher neoantigen loads of TMB-H tumors have been proposed to contribute to increased responsiveness of TMB-H tumors to certain I-O therapeutics. Pembrolizumab was approved by the FDA on June 16, 2020 for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H tumors, as determined by F1CDx, based on results from the KEYNOTE-158 trial (NCT02628067), which demonstrated that 50% of patients with TMB-H tumors had response durations of ≥24 months, with objective response rates in TMB-H vs. non-TMB-H patients of 29% and 6%, respectively (Marabelle et al, The Lancet Oncology, 2020). This survey-based study aimed to evaluate awareness and utilization of TMB as a biomarker for I-O therapeutics among practicing community oncologists in the U.S. Methods: Questions related to awareness and utilization of TMB as a biomarker for I-O therapeutics were developed by two medical oncologists (AG and BF) and presented to community oncologists in a web-based survey prior to virtual meetings held between October and November 2020. Descriptive statistics were used to analyze the results. Results: Of the 193 participating providers geographically distributed across the U.S., 15% reported being unaware of either the concept of TMB in I-O therapy or how to use the information clinically. 39% of these providers reported testing ≤25% of patients with advanced cancer for TMB, including 8% who do not test for TMB at all. Misconceptions regarding TMB identified among participating providers included the belief that high TMB is considered to be &gt; 5 mut/Mb among 20% of providers, that TMB is essentially the same as MSI-high among 8% of providers, and that there are no therapies with FDA approval based on TMB among 15% of providers. Further, 37% of the participants did not identify pembrolizumab as an agent approved for the treatment of solid tumors based on TMB-H status. Conclusions: These findings demonstrate that there is a knowledge gap regarding the definition of TMB, testing for TMB, as well as implementation of TMB status in clinical decision making. Education directed towards community oncology providers regarding TMB and its use as a predictive biomarker for I-O therapy may improve its utilization and adoption in solid tumors to improve patient outcomes.
Umbralisib/TGR-1202 As a Novel Dual PI3K/CK1 Inhibitor Has a Unique Therapeutic Role in Silencing Oncogenes in Aggressive Lymphomas
Authors: Ipsita Pal, Yu Ri Kim, Luigi Scotto, Mark R Lipstein, Abdullah Mahmood Ali, Siddhartha Mukherjee, Susan E. Bates, Owen A. O'Connor, Changchun Deng
Journal: Blood (2017)
Dose-intensified Versus Conventional-dose Salvage Radiotherapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: The SAKK 09/10 Randomized Phase 3 Trial
Authors: Pirus Ghadjar, Stefanie Hayoz, Jürg Bernhard, Daniel R Zwahlen, Tobias Hölscher, Philipp Gut, Bülent Polat, Guido Hildebrandt, Arndt-Christian Müller, Ludwig Plasswilm, Alexandros Papachristofilou, Corinne Schär, Marcin Sumila, Kathrin Zaugg, Matthias Guckenberger, Piet Ost, Christiane Reuter, Davide G Bosetti, Kaouthar Khanfir, Silvia Gomez, Peter Wust, George N Thalmann, Daniel M Aebersold
Journal: European Urology (2021)