tbuckley/cabot-search huggingface dataset:
Node marking techniques and targeted axillary dissection in patients with cN1 disease undergoing neoadjuvant chemotherapy: Analysis of initial 500 participants in the ATNEC trial.
Authors: Amit Goyal, Nada Elbeltagi, Andrea Marshall, Sophie Nicholls, Natalie Hammonds, Beatrix Elsberger, Duncan Wheatley, Abeer Shaaban, Janice Rose, Helen Teresa Edwards, Zohal Nabi, Tara Homer, Samreen Ahmed, Janet Dunn
Journal: Journal of Clinical Oncology (2024)

609 Background: In the ongoing neoadjuvant ATNEC breast cancer trial (NCT04109079), cT1-3N1M0 patients receive neoadjuvant chemotherapy (NACT) followed by sentinel node biopsy (SNB) or targeted axillary dissection (TAD). If the sentinel nodes (SNs) convert to benign (ypN0), patients are randomized to receive Axillary Treatment vs. no Axillary Treatment. Standardized node marking procedures are promoted in this study. This study evaluates node marking techniques, rates of marked node identification, and concordance of the marked node with the sentinel node in the initial 500 participants. Methods: Data from 587 patients registered from December 2021 to January 1, 2024, across 77 UK centers were analyzed. These patients presented with cT1-3N1M0 breast cancer and received or planned to receive NACT. Results: The median age was 54 years (range 28-81), with a median of 4 nodes [interquartile range, 3-5] removed during SNB/TAD. Among 470 patients with node marking data, 72% (339) had the involved node marked. Sentinel node biopsy was performed using a combination of radioisotope and blue dye in 51%, blue dye only in 13%, radioisotope only in 10%, and Magtrace only in 9%. The marked node was successfully removed in 90% (305/339) of these patients, with the marked node being the sentinel node in 80% (243/305) of cases. In patients with complete pathological nodal response, the marked node did not show signs of downstaging (e.g. fibrosis) in 15% (46). Common techniques used for node marking included clip/coil only before NACT (29%), clip/coil before NACT with another wireless marker after NACT (26%), Magseed only before NACT (16%), and black dye only before NACT (15%). Conclusions: Notably, 72% of patients underwent node marking, with an intra-operative identification rate of 90%, demonstrating the successful implementation of node marking in the UK through the ATNEC trial. Clinical trial information: NCT04109079 .
Human Case of Leptospirosis During a Canine Disease Outbreak — Wyoming, 2023
Authors: Brittney Waranius, Courtney Tillman, Clay Van Houten, Alexia Harrist, Rose Digianantonio, Hallie Hasel, Christine Atherstone, Emily Curren
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Leptospirosis is a zoonotic bacterial disease spread through the urine of infected animals; the typical incubation period is 5-14 days.In approximately 90% of human cases, illness is asymptomatic or mild, characterized by fever, chills, myalgia, nausea, vomiting, diarrhea, headache, calf pain, and conjunctival suffusion, but severe illness can progress to multiorgan dysfunction and death.Although Wyoming is considered a low-risk area for leptospirosis because of its cold and semiarid climate, the Wyoming Department of Health was notified of a probable human case in August 2023, the first reported in the state since 1983.The patient had occupational exposure to dogs but did not report other risk factors.The same week that the human patient's illness began, public health authorities received notification of an increase in canine leptospirosis cases.Public health authorities investigated to determine potential sources of infection, identify additional cases, and recommend control measures.After public health outreach activities were implemented, canine vaccination practices changed substantially in the affected city: a survey conducted after the outbreak revealed that all responding veterinary clinics in the affected city were recommending the vaccine more frequently to dog owners and reporting higher levels of owner compliance with vaccination recommendations.Increased vaccination coverage offers protection from leptospirosis for both dogs and persons exposed to them.Leptospirosis should be considered in the differential diagnosis of persons with occupational exposure to animals and clinically compatible signs and symptoms, including fever, chills, myalgia, nausea, vomiting, diarrhea, headache, calf pain, and conjunctival suffusion, irrespective of geographic location.
Exploration of microRNA biomarker panel as a predictor of evolution of pancreatitis to pancreatic ductal adenocarcinoma.
Authors: Mira Nuthakki
Journal: Journal of Clinical Oncology (2024)

e16343 Background: PDAC (pancreatic ductal adenocarcinoma) is 3rd most common cause of cancer deaths, and is projected to become the 2nd leading cause of cancer death by 2030 even as it comprises only 3.2% of all cancer cases. The most important predictor of survival is resection of early stage cancer. Currently, screening for early detection of PDAC via annual MRI or endoscopic ultrasound (EUS) is recommended only in the 10% of total cases, that have hereditary/ genetic associations. PDAC risk is doubled even 5 years after acute pancreatitis and is 15-16 fold for chronic pancreatitis. Biomarkers such as CA19-9, peptide panels, tumor-associated autoantibodies and microRNAs have been studied for early diagnosis of PDAC. However, biomarkers that can predict risk of PDAC following pancreatitis have not been well studied. This study aims to identify, compare, and extract a differentially expressed microRNA (DEM) panel in serum, that could predict risk of progression to PDAC from pancreatitis. Methods: Two microarray Genomic Spatial Event (GSE) datasets containing pancreatitis (n = 75), PDAC (90), and control samples (164) were used to extract DEM (n = 22), common to both pancreatitis and PDAC. 8 smaller subgroups of DEM (for cost benefit) were derived from bioinformatics methods such as ROC/AUC of expression values, up and downregulated clustering, correlation analysis, miRNA interaction networks, target gene prediction tools, target gene interaction and functional enrichment analysis for all target genes and top modules, as well as decision tree/cross-validated random forest machine learning models. Results: The DEM main group (n = 22) and the smaller subgroups were trained on the original datasets, and were used to predict the risk of pancreatic cancer vs control in a validation set consisting of six other GSE datasets. The main 22miRNA panel had the highest accuracy (0.928), F1(0.976), precision and recall, followed by subgroup 6 (accuracy 0.910, F1 0.968) derived from the target hub genes with the highest interaction (hsa-miR-28-3p, 320b, 320c, 320d, 532-5p, and 423-5p). The associated main pathways were ubi-conjugation and ubiquitin pathway, mRNA splicing/processing/binding, and endocytosis. Conclusions: A new serum 22 microRNA biomarker panel predicting evolution of pancreatitis to pancreatic ductal adenocarcinoma, and it’s associated pathways, has been identified, that also performed very well in distinguishing pancreatic cancer (with or without pancreatitis risk factor) from control. A smaller subpanel of 6 microRNA may have a cost benefit. Further studies with larger samples, specifically differentiating PDAC vs all pancreatic cancer, and acute vs chronic pancreatitis among the samples are needed.
Germline ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition
Authors: Jiarna R. Zerella, Claire C. Homan, Peer Arts, Xuzhu Lin, Sam J. Spinelli, Parvathy Venugopal, Milena Babic, Peter J. Brautigan, Lynda Truong, Luis Arriola-Martinez, Sarah Moore, Rachel Hollins, Wendy T. Parker, Hung Nguyen, Karin S. Kassahn, Susan Branford, Simone Feurstein, Lise Larcher, Flore Sicre de Fontbrune, Serwet Demirdas, Sonja de Munnik, Hélène Antoine-Poirel, Benedicte Brichard, Sahar Mansour, Kristiana Gordon, Marcin W. Wlodarski, Ashwin Koppayi, Sara Dobbins, Pim G. N. J. Mutsaers, Kim E. Nichols, Ninad Oak, Desiree DeMille, Rong Mao, Ali Crawford, Julie McCarrier, Donald Basel, Josue Flores-Daboub, Michael W. Drazer, Kerry Phillips, Nicola K. Poplawski, Graeme M. Birdsey, Daniela Pirri, Pia Ostergaard, Annet Simons, Lucy A. Godley, David M. Ross, Devendra K. Hiwase, Jean Soulier, Anna L. Brown, Catherine L. Carmichael, Hamish S. Scott, Christopher N. Hahn
Journal: Blood (2024)

Abstract The genomics era has facilitated the discovery of new genes that predispose individuals to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ETS-related gene (ERG), a novel, autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor that is critical for definitive hematopoiesis, stem cell function, and platelet maintenance. ERG colocalizes with other transcription factors, including RUNX family transcription factor 1 (RUNX1) and GATA binding protein 2 (GATA2), on promoters or enhancers of genes that orchestrate hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 individuals with thrombocytopenia from 1 family and 14 additional ERG variants in unrelated individuals with BMF/HM, including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germ line ERG variants included cytopenias (thrombocytopenia, neutropenia, and pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense and 1 truncating), including 3 missense population variants, were functionally characterized. Thirteen potentially pathogenic erythroblast transformation specific (ETS) domain missense variants displayed loss-of-function (LOF) characteristics, thereby disrupting transcriptional transactivation, DNA binding, and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture and to promote acute erythroleukemia when transplanted into mice, concordant with these being LOF variants. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germ line ERG variants has clinical implications for patient and family diagnoses, counseling, surveillance, and treatment strategies, including selection of bone marrow donors and cell or gene therapy.
Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): Primary analysis of a prospective, multicenter, response-adapted study.
Authors: Fei Wang, Yongjiu Wang, Bin Xiong, Zhenlin Yang, Jingfen Wang, Yumin Yao, Lixiang Yu, Qinye Fu, Liang Li, Qiang Zhang, Chao Zheng, Shuya Huang, Liyuan Liu, Chun Liu, Huaibo Sun, Beibei Mao, Zhigang Yu
Journal: Journal of Clinical Oncology (2024)

603 Background: The contribution of biological characteristics and treatment patterns to the survival difference between male and female breast cancer patients is understudied, which is controversial but fundamental in determining strategies for cancer treatment and survivorship care. To evaluate the efficacy and safety of additional pyrotinib in patients with HER2-positive breast cancer who had no early response to neoadjuvant trastuzumab in combination with chemotherapy. Methods: A prospective, multicenter, response-adapted study including patients diagnosed with HER2-positive breast cancer from 2020 to 2022 were conducted. A total of 129 female patients from 5 hospitals participated in this neoadjuvant setting study. The primary endpoint was pathological complete response ( pCR), defined as the absence of invasive cancer in both the breast and axilla as determined by a local pathologist after surgery (ypT0ypN0). Results: Among 129 enrolled participants, 62 (48.1%) were identified as MRI-responders (Cohort A), 26 non-responders received 4 more cycles of TCbH (Cohort B), while 41 received additional pyrotinib (Cohort C). The pCR rates were 30.6% (95%CI: 20.6%-43.0%) in Cohort A, 15.4% (95%CI: 6.2%-33.5%) in Cohort B and 29.3% (95%CI: 17.6%-44.5%) in Cohort C. Similar difference patterns of breast pCR rates across 3 cohorts were observed. Multivariable logistic regression analyses showed that, in comparison to those in Cohort A, patients in Cohort C had comparable probability of pCR (OR=1.03, 95%CI: 0.40 to 2.67). The most common adverse events among patients who received pyrotinib were diarrhoea, anaemia, and erythropenia, and no cardiovascular event was observed. Participants with low TMB and no RTK-RAS mutation had a quite low pCR rate of 4%. Conclusions: The addition of pyrotinib to trastuzumab increases the pCR rates among patients who had no early response to neoadjuvant trastuzumab. Further studies are warranted to identify biomarkers predicting those who may benefit from pyrotinib in addition to trastuzumab. Clinical trial information: NCT03847818 .
Are Oral Selective Estrogen Receptor Degraders Beneficial for Patients With <i>ESR1</i>-Mutated Estrogen Receptor–Positive Human Epidermal Growth Factor 2–Negative Breast Cancer?
Authors: Aoba Okeya, Akihiko Shimomura, Dai Kitagawa, Chikako Shimizu
Journal: Journal of Clinical Oncology (2024)
Systematic therapy for metastatic solid pseudopapillary neoplasm of the pancreas: A single-center experience.
Authors: Yuting Sun, Huijing Tan, Yihebali Chi
Journal: Journal of Clinical Oncology (2024)

e16341 Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare tumor with low-grade malignancy. However, a small proportion of cases still exhibit more aggressive behavior and emerge as distant metastases. Limited data exist on systemic therapy for these entities. Methods: A retrospective analysis was performed on patients diagnosed with SPN of the pancreas who underwent medical treatment in our hospital between January 2020 and December 2023. The clinicopathological characteristics and therapeutic regimens of the patients were collected. The primary outcomes were disease control rate (DCR) and progression free survival (PFS). SPSS software V27.0 was used for data analysis. Results: Five patients were identified and 60.0% of patients were female . The median age was 34 years (range 16-53). All patients first underwent surgical resection. Four individuals had metachronous distant metastasis and one had synchronous distant metastasis. The most common metastatic site was peritoneum (3/5) and liver (3/5), followed by the distant lymph node (2/5). Progesterone receptor positive expression was found in four cases. Four patients received targeted therapy as first-line treatment (3 receiving anlotinib 12mg once daily on days 1-14 every 3 weeks and 1 receiving everolimus 10mg per day). All patients receiving targeted therapy had stable disease, with a DCR of 100%. The median PFS in the targeted therapy group was 8.1 months (95% CI, 6.7-9.5). Only one patient underwent first-line chemotherapy (gemcitabine plus S-1) and experienced disease progression at the initial efficacy evaluation. Data for second-line treatment was available for three patients. One patient got progressive disease (PD) after etoposide administration. Two individuals received everolimus 10mg daily, one of whom showed PD and the other achieved a partial response (PR). All treatment-related adverse events (AEs) were manageable. Conclusions: Metastatic SPN of the pancreas may be not chemosensitive. Targeted therapy, such as anlotinib and everolimus, appears to be a potential therapeutic option.
Automated prediction of response to neoadjuvant chemotherapy from digitized H&amp;E slides of pre-treatment core needle biopsies in germline BRCA carriers with HER2-negative breast cancer (TBCRC 031).
Authors: Nadine M. Tung, Stuart J. Schnitt, Judy Ellen Garber, Satabhisa Mukhopadhyay, Tathagata Dasgupta, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2024)

605 Background: The INFORM trial, a phase II study of neoadjuvant cisplatin (C) vs doxorubicin-cyclophosphamide (AC) in germline BRCA carriers with HER2-negative breast cancer, demonstrated no difference in response rates between the two arms. The aim of the current study was to determine if quantification of features related to the immune response, proliferative status, and key cell cycle deregulation extracted from digital images of H&amp;E-stained pre-treatment core needle biopsies (CNB) could distinguish patients with a good response to neoadjuvant chemotherapy (NAC) (RCB 0,1) from those with a poor response (RCB 2,3). Methods: CNBs (n=92 with RCB scores available) scanned at 40x on a Hamamatsu Nanozoomer scanner were evaluated using the 4D QPOR platform to generate digital biomarkers as continuous indices measuring immune, proliferation, and key cell cycle deregulation signatures. 96% (88/92) could be analyzed successfully. All biomarkers generated were based on an algorithm that combines statistical physics and tumor biology features to quantify cell cycle aberrations, from H&amp;E whole slide images alone, and were evaluated at their median cut-off to determine if they could identify responders to NAC. Other QPOR indices were analyzed using AUC-ROC to further reduce false positive (FP) and false negative (FN) rates. Pathology review was done on FP and FN cases to determine if they were associated with any specific features. Results: The QPOR Immune Heterogeneity Index (IHI), measuring intra-slide spatial heterogeneity of stromal tumor infiltrating lymphocytes (sTIL), was predictive of RCB 0,1 with greater heterogeneity associated with worse response. IHI identified patients with RCB 0,1 with overall accuracy = 65%, sensitivity = 63%, specificity = 66%, PPV = 62%, NPV = 67%. IHI performed better in predicting RCB 0,1 than pathologist-identified sTIL in the full cohort, TNBC, and BRCA1 sub-cohorts (two sample Wilcoxon test p-value = 0.013, 0.047 and 0.013 respectively, with nonsignificant p-values for sTIL). IHI combined with a proliferative index and a G1S phase deregulation index (CmbI) was predictive of RCB 0,1 with improved accuracy over that of any of these features alone (overall accuracy = 80%, sensitivity = 71%, specificity = 87%, PPV = 83%, NPV = 77%, OR = 16.51 95% CI: 10.05-1.14, kappa = 0.59 (p&lt;0.00001), AUC=0.80 95% CI: 0.71-0.89). CmbI better predicted RCB 0,1 for both AC and C arms (AUC=0.83 95% CI: 0.71-0.96 and 0.77 95% CI: 0.63-0.91, OR = 23.22 95% CI: 148.88-5.10 and 6.47 95% CI: 28.08-1.72, respectively) than IHI alone. Conclusions: QPOR-generated immune, proliferative, and key cell cycle signature indices individually, and more strongly in combination, appear predictive of NAC response in germline BRCA carriers with HER2-negative breast cancers.
Pancreatoblastoma: A study of demographic and socioeconomic factors.
Authors: Gabriel Anthony Bitar, Yanick Tade, Nikhita Tandon, Assal Sadighian, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e16345 Background: Pancreatoblastoma (PB) is a rare tumor originating from pancreatic epithelial exocrine cells with a very poor prognosis. At diagnosis, it often presents with large lesions encompassing overlapping regions and may involve the entire pancreas. PB is frequently associated with distant metastasis and often occurs in children under the age of 10. An optimal treatment strategy has yet to be established. Analyzing trends in diagnoses may yield valuable information about its epidemiology. The National Cancer Database (NCDB) was utilized to uncover the demographic factors in patients diagnosed with PB. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 82 patients were found with a histologically confirmed diagnosis of PB (ICD-8971-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics. Trends in incidence were interpreted using regression analysis. Results: A total of 82 individuals in the NCDB were confirmed to be diagnosed with pancreatoblastoma between 2004-2020. The incidence rate of patients diagnosed per year is steady (R² =0.0). The average age of diagnosis was 55.3 years (SD = 15.4, range = 19-90) with women (89%) being more likely to be diagnosed compared to men (11%). None of the observed patients utilized palliative care, and from this population, 87% received surgery, and 28% received chemotherapy as their primary treatment. The majority of the patients were non-Hispanic (89%) and White (87%). Most patients were privately insured (52%) and lived in metropolitan areas with a population greater than 1 million (51%). More patients were in the highest quartile of income earners (33%), compared to those in the second, third, or fourth quartiles. Fewer patients were treated at a comprehensive community cancer program (28%) than in an academic/research program (37%). Most patients (79%) had a Charlson/Deyo comorbidity scores of 0 and were applicable to Stage I group (49%). Conclusions: This represents the first analysis of pancreatoblastoma within the NCDB to our knowledge, addressing a notable knowledge gap. Pancreatoblastoma is predominantly treated by surgery, consistent with previous case reports. Notably, our study pioneers the exploration of socioeconomic aspects among pancreatoblastoma patients. Findings reveal a higher likelihood of these patients belonging to the highest income quartile, residing in densely populated metropolitan areas, and receiving treatment within academic/research programs. Further investigation is warranted to comprehend the influence of demographic and socioeconomic variables on the diagnosis, treatment approaches, and overall survival of individuals with pancreatoblastoma.