tbuckley/cabot-search huggingface dataset:
Trial in progress: A multicenter phase Ib/II study of pelcitoclax (APG-1252) in combination with paclitaxel in patients with relapsed/refractory small-cell lung cancer (R/R SCLC).
Authors: Angel Qin, Gregory Peter Kalemkerian, Jyoti D. Patel, Nisha Anjali Mohindra, Jennifer W Carlisle, Jacob Sands, Zhicong He, Robert Winkler, Zhiyan Liang, Vakessa Hammock, Riccardo Bombelli, Ming Lu, Yang Xu, Tommy Fu, Cunlin Wang, Dajun Yang, Yifan Zhai
Journal: Journal of Clinical Oncology (2021)

TPS8589 Background: Increased expression of BCL-2, BCL-xL, and MCL-1 allows certain tumors to evade apoptosis. Pelcitoclax is a novel, dual BCL-2/BCL-xL inhibitor with strong single-agent antitumor activity against tumor cells addicted to BCL-2, BCL-xL, and BCL-w, and exhibits even broader antitumor activity when administered with chemotherapy. Pelcitoclax reduces tumor growth in SCLC and other human cancer xenograft models, with manageable effects on platelet counts. Preliminary findings from the first-in-human study suggested promising antitumor activity and a favorable safety profile. Methods: This open-label study is evaluating the safety and preliminary efficacy of pelcitoclax combined with paclitaxel in adults with R/R SCLC that has progressed on or after initial treatment. Prior treatments may include platinum-based therapy (± thoracic radiation), immunotherapy, or chemotherapeutic agents other than paclitaxel. Eligible patients have an ECOG performance status of 0-2; adequate organ function; no known bleeding diathesis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, serious gastrointestinal bleeding, or concomitant use of most anticoagulants; and no residual grade ≥ 2 adverse events from previous treatment. In the phase Ib study, the pelcitoclax maximum tolerated dose is being determined using a time-to-event continual reassessment method. In this phase, pelcitoclax is administered by IV infusion over 30 minutes on Days 1, 8, and 15 at dose levels of 80, 160, and 240 mg per week, with fixed-dose paclitaxel 80 mg/m 2 on Days 1 and 8 of a 21-day cycle. In addition to a baseline scan within 4 weeks before study entry, computed tomography will be performed every two cycles to evaluate antitumor response. Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, or administrative discontinuation. The primary endpoint of this phase includes dose-limiting toxicity by NCI CTCAE v5.0 over 21 days. After determination of the recommended phase II dose of pelcitoclax in the phase Ib study, the efficacy of pelcitoclax with paclitaxel will be determined in the phase II study using a Simon two-stage design, with overall response rate as the primary endpoint. Other study endpoints in the phase II study include pharmacokinetics of pelcitoclax with paclitaxel, as well as progression-free and overall survival. As of February 8, 2021, 15 of 58 patients had been enrolled. Internal study identifier APG1252SU101. Clinical trial information: NCT04210037.
The Neat-HER virtual registry: Updated results on HER2+ breast cancer patients receiving neratinib as extended adjuvant therapy.
Authors: Gregory A. Vidal, Debu Tripathy, Nina Hill, Deepa Lalla, Gillian Hanson, Daniel R. Drozd, Feng Xu, Hope S. Rugo
Journal: Journal of Clinical Oncology (2021)

e13565 Background: Data from traditional registries are usually limited to patients treated at study sites. Virtual registries can enroll a broader real-world population. Neat-HER is a U.S.-based virtual registry pilot through PicnicHealth that is enrolling patients with HER2+ breast cancer receiving neratinib as extended adjuvant therapy. Methods: Neat-HER evaluates the feasibility of enrolling patients and answering research questions using a novel electronic platform. Eligibility includes receipt of neratinib in the extended adjuvant setting, signed informed consent for medical record retrieval/data abstraction and age &gt; 18 years. Patients who do not complete enrollment procedures, are participating in a clinical trial or have metastatic disease are excluded. Patients are recruited through multiple mechanisms including private social media groups, treating clinicians and patients enrolled in the Puma Texting Program. Patient health records for breast cancer-related treatment are collected from time of diagnosis to 1-year post-enrollment in the registry. Research questions focus on patient and tumor characteristics, receipt of therapy (e.g. radiotherapy, adjuvant therapy), neratinib duration, and diarrhea prophylaxis. Results: 33 patients with HER2+ early-stage breast cancer who received neratinib as extended adjuvant therapy have been enrolled in this registry study since December 2018. Median age was 50 years, with 79% of patients self-identifying as white. 82% of patients had hormone receptor-positive (ER/PR) disease and 73% of patients had node-positive disease. Prior HER2-targeted adjuvant therapy regimens were as follows: trastuzumab with paclitaxel (9%); trastuzumab/pertuzumab in combination with a taxane(s) (91%). 17 patients (52%) completed 12 months of neratinib treatment; 4 patients (12%) discontinued treatment early; 10 patients (30%) were still ongoing at the time of data cutoff. 31 patients (94%) had diarrhea prophylaxis discussed prior to the start of neratinib treatment. Conclusions: Neat-HER provides useful information on patient/tumor characteristics and treatment patterns in a real-world cohort receiving extended adjuvant neratinib and patient recruitment is ongoing. Updated results show that this pilot virtual registry continues to be a feasible and efficient modality to collect important data on descriptive characteristics and treatment patterns for a patient population derived from real-world practice settings. Validation of this method is needed and could be used in other tumor types.
TET2 Deficiency Led to Expansion of Dysfunctional Erythroid Progenitors
Authors: Xiaoli Qu, Lixiang Chen, Yaomei Wang, Yumin Huang, John Hale, Wei Li, Huizhi Zhao, Shijie Zhang, Xinhua Guo, Abdullah Mahmood Ali, Azra Raza, Mohandas Narla, Qiaozhen Kang, Xiuli An
Journal: Blood (2017)
Dasatinib-Induced Lymphocyte Elevation and Imbalance of T Cell Receptor V Beta Gene Expression in Chronic Phase Chronic Myelogenous Leukemia Patients
Authors: Tatsuro Jo, Sadaharu Irie, Kazuhiro Noguchi, Shizuka Hayashi, Risa Hayase, Haruna Shioya, Yohei Kaneko, Kensuke Horio, Jun Taguchi
Journal: Blood (2017)
MLkit: A machine-learning-powered automatic workflow for classification of cancer samples.
Authors: Qingyuan Li, Ji He
Journal: Journal of Clinical Oncology (2021)

e13583 Background: In the era of data explosion, precision classification of cancer samples based on multi-dimensional medical data provides more insights into disease mechanism and useful hints on clinical treatment associated with tissue of origin, recurrence tendency and prognostic of chemotherapy or immunotherapy. We developed an automatic workflow MLkit to select features from large-scale multi-dimensional medical data and conduct classification through various machine learning techniques. Methods: MLkit is an automatic and one-stop workflow for classification of cancer samples with four modules: preprocessing (missing data remove or imputation and feature standardization), feature selection (unsupervised multi-statistics and supervised multiple machine estimators with recursive feature elimination and cross-validation), modeling (hyper-parameter, performance evaluation and probability calibration) and prediction. Most of current machine learning algorithms were implemented in this workflow, including linear model (logistic regression, ridge regression and stochastic gradient descent), ensemble model (gradient boosting, random forest, xgboost, catboost, lightgmb and stacking), support vector kernel (linear and non-linear), naive Bayes, k-nearest neighbors and multi-layer perceptron neural network. To evaluate the performance of this workflow, we utilized it to fit a model used for prediction of tissue of origin based on 450K DNA methylation data of 2,210 samples from lung, kidney and breast cancer patients collected in TCGA. Results: MLkit performed well in the prediction of tissue of origin for independent validation sets of cancer patients with stable feature selection, automatic hyper-parameters and efficient probability calibration, in which the model achieved AUCs ranged from 0.85 to 0.96. In addition, we also utilized this workflow on extensive real world data and most of results showed superior accuracy and stable performance. Conclusions: MLkit facilitates automated and one-stop classification of cancer samples using machine learning algorithms. It can be operated with simple command line, making it accessible to a broad range of users. The well performance of this workflow based on multi-dimensional medical data can help to improve the discovery of tumor biomarker and optimize clinical follow-up and therapeutic treatment for cancer patients.
Detection of azole resistance in Aspergillus fumigatus complex isolates using MALDI-TOF mass spectrometry
Authors: Margarita Estreya Zvezdanova, Manuel J. Arroyo, Gema Méndez, Ana Candela, Luis Mancera, Julio García Rodríguez, Julia Lozano Serra, Rosa Jiménez, Inmaculada Lozano, Carmen Castro, Concepción López, Patricia Muñoz, Jesús Guinea, Pilar Escribano, Belén Rodríguez-Sánchez, Waldo Sánchez-Yebra, Juan Sánchez-Gómez, Inmaculada Lozano, Eduardo Marfil, Montserrat Muñoz de la Rosa, Rocío Tejero García, Fernando Cobo, Carmen Castro, Concepción López, Antonio Rezusta, Teresa Peláez, Cristian Castelló-Abietar, Isabel Costales, Julia Lozano Serra, Rosa Jiménez, Cristina Labayru Echeverría, Cristina Losa Pérez, Gregoria Megías-Lobón, Belén Lorenzo, Ferrán Sánchez-Reus, Josefina Ayats, María Teresa Martín, Inmaculada Vidal, Victoria Sánchez-Hellín, Elisa Ibáñez, Javier Pemán, Miguel Fajardo, Carmen Pazos, María Rodríguez-Mayo, Ana Pérez-Ayala, Elia Gómez, Jesús Guinea, Pilar Escribano, Julia Serrano, Elena Reigadas, Belén Rodríguez, Estreya Zvezdanova, Judith Díaz-García, Ana Gómez-Núñez, José González Leiva, Marina Machado, Patricia Muñoz, Isabel Sánchez-Romero, Julio García-Rodríguez, José Luis del Pozo, Manuel Rubio Vallejo, Carlos Ruiz de Alegría-Puig, Leyre López-Soria, José María Marimón, Diego Vicente, Marina Fernández-Torres, Silvia Hernáez-Crespo
Journal: Clinical Microbiology and Infection (2021)
Tumor acid microenvironment-activated self-targeting &amp; splitting gold nanoassembly for tumor chemo-radiotherapy
Authors: Xiaomin Li, Licheng Yu, Chuangnian Zhang, Xiaoyan Niu, Mengjie Sun, Zichao Yan, Wei Wang, Zhi Yuan
Journal: Bioactive Materials (2021)

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.
Intensity of end-of-life care for gynecologic cancer patients by primary oncologist specialty.
Authors: Katherine Hicks-Courant, Genevieve P. Kanter, Marilyn M. Schapira, Colleen Brensinger, Qing Liu, Emily Meichun Ko
Journal: Journal of Clinical Oncology (2021)

12032 Background: The impact of primary oncologist specialty, medical oncology (MO) versus gynecologic oncology (GO), on intensity of care at the end of life (EOL) in elderly patients with gynecologic cancer is unclear. Methods: This retrospective cohort study used Surveillance, Epidemiology and End Results (SEER) Medicare data. Subjects were fee-for-service Medicare enrollees over 65 years old, who had seen a GO or MO in an outpatient setting in the last year of life and died of a gynecologic cancer between 2006 and 2015. The primary oncologist was defined as the provider with the majority of outpatient visits in the last year of life. The primary outcome was intensity of care at the EOL, a composite score defined by receipt of chemotherapy in the last 14 days of life, death in the hospital, enrollment in hospice for less than three days, more than one ED visit, more than one hospital admission, spending more than 14 days in the hospital, or any ICU admission in the last 30 days of life. Simple and multivariable linear regression analyses were conducted to evaluate for differences in EOL care outcomes by primary oncologist specialty. Linear regressions were repeated after creating a more similar control group through nearest-neighbor propensity score matching, with and without replacement. Results: Of 12,189 subjects, 63% were primarily treated by a MO and only 27% by a GO for EOL care. Most died of ovarian cancer (55.1%), followed by uterine (31.4%), cervical (6.9%), and other cancers (6.7%). Compared to GO patients, MO patients were younger, more likely to be white, married, not dual-eligible, higher stage, and to die of ovarian cancer. Overall, 55.4% (95% CI 54.73-56.49) received intense care at the EOL. Although both specialties engaged in high levels of intense EOL care, the adjusted rates for GO (54.03%; 95% CI 52.28-55.77) were significantly less compared to MO (56.53%; 95% CI 55.36-57.69; p=0.023) in unadjusted and adjusted analyses of the entire and propensity-matched cohorts (Table). Conclusions: Approximately 2/3 of women with gynecologic cancer will receive EOL care from a MO, compared to 1/3 from a GO. Both specialists engage in high levels of intense EOL care in over half of their patients, although GO less so. Future work should focus on identifying approaches to reduce high-intensity EOL care, which may include additional training or incorporation of palliative medicine into cancer care.[Table: see text]
Consistency of O6-methylguanine-DNA methyltransferase in intracranial and extracranial lesions and the therapeutic effect of temozolomide in patients with advanced lung cancer and brain metastasis.
Authors: Ying Fan, Qian Yun Shan, Jia Li Gong, Na Han, Hongyang Lu
Journal: Journal of Clinical Oncology (2021)

e14001 Background: Targeted drugs have made a major breakthrough except small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) of brain metastasis (BM) patients with negative driving gene. Because of the difficulty to obtain pathology of intracranial metastases lesions and the low acceptance of patients, the heterogeneity of O6-methylguanine-DNA methyltransferase (MGMT) between extracranial lesions and intracranial metastatic lesions worth exploring. Methods: 10 patients were administered TMZ after the progression of radiotherapy and chemotherapy and included in one group; the efficacy and safety of TMZ were assessed. Moreover, 15 patients who underwent resection of the lung and brain without neoadjuvant therapy formed another cohort. The promoter methylation status of MGMT was analyzed and compared in the paired primary and BM lesions. Results: The overall response (OS) rate of TMZ was 50% and the disease control rate was 80% in patients with BM lesions. The median progression-free survival was 13.6 months, and the median overall survival was 18.9 months after a median follow-up of 120 months. No grade 3 or higher side effects were reported, but grade 1 or 2 side effects, such as leucopenia, nausea, or vomiting, occurred. However, in another cohort, MGMT promoter methylation was detected in 2 patients (with primary lesions; unmethylation was detected in BM lesions, and the methylation status of MGMT promoter was consistent in paired primary and BM lesions).Conclusions: TMZ was effective against SCLC and NSCLC combined with BM having negative driving genes. Whether primary lesions can replace the MGMT methylation level of BM lesions, as well as the consistency of the promoter methylation status of MGMT in patients with advanced lung cancer, needs exploration.[Table: see text]
The completeness and accuracy of DataDerm: The database of the American Academy of Dermatology
Authors: Marta Van Beek, Robert A. Swerlick, Barbara Mathes, Margo J. Reeder, Toni Kaye, Arik Aninos, Matthew E. Fitzgerald, Caryn D. Etkin, Jeffrey P. Jacobs
Journal: Journal of the American Academy of Dermatology (2021)
Role of adjunct plasma exchange or high cut-off hemodialysis in the management of myeloma cast nephropathy: A systematic review.
Authors: Nazma Hanif, Muhammad Khawar Sana, Basel Abdelazeem, Abdul Rafae, Muhammad Umair Mushtaq, Faiz Anwer
Journal: Journal of Clinical Oncology (2021)

e20032 Background: Renal impairment by cast nephropathy is a common complication in multiple myeloma. Tubulointerstitial injury results from precipitation of filtered free light chains (FLC) with Uromodulin in the distal convoluted tubules. Rapid reduction in serum FLC levels has shown to improve renal function in modeling studies. Extracorporeal light chain removal techniques such as plasma exchange (PEX) and high cut-off hemodialysis (HCO-HD) have been explored as potential adjunct treatment options for cast nephropathy in various clinical trials. Methods: PubMed, Cochrane library, and Clinicaltrials.gov were searched systematically for the use of plasma exchange and/or hemodialysis with chemotherapy in the treatment of myeloma cast nephropathy using their MeSH words and keywords. PRISMA guidelines were followed for screening and 5 out of 866 studies were finalized (N = 342). Results: Zucchelli et al. 1988 (n = 29) reported a dramatic reduction in Bence Jones protein (BJP) levels of 0.81 ± 0.46 g/day (P value &lt; 0.01) and 1-year survival rate of 66% in the PEX group and decrease in BJP of 3.25 +/- 0.21 g/day (P-value &lt; 0.05) with a survival rate of 28% in the control group. Clark et al. 2005 (n = 104) reported a primary composite response (patient alive at 6 months + dialysis independence + serum creatinine improvement of 50% at 6 months) in 57.9% of patients in the PEX group and 69.2% in the control group [95% CI, -8.3% to 29.1%]; P = 0.36. Johnson et al. 1990 (n = 21) reported a mean change of 880 μmol /L ± 260(SD) in serum creatinine in the PEX group and 570 μmol /L +/-240 in the control group. HD independence at 3 months was reported as 41.3% (n = 19) in the HCO-HD group and 33.3% (n = 16) in the conventional HD group (95% CI -12%–27.9%; P = 0.42) in the MYRE trial 2017 (n = 98). The EuLITE trial 2019 (n = 90) compared the efficacy of the high cut-off vs high flux hemodialysis (HF-HD) technique and concluded that there was no clinical benefit of one over the other. Independence from HD was achieved in 56% (n = 24) in the HCO-HD cohort vs 51% (n = 24) in HF-HD cohort (relative risk [RR] 1.09, 95% CI 0.74–1.61; P = 0.81). Conclusions: The use of high cut-off hemodialysis and plasma exchange as adjunct therapy did not show any significant survival benefit or improvement in clinical outcome. The role of routine use of PEX/HCO-HD in the management of cast nephropathy is still unclear and the decision to use these modalities should be made on an individual basis.
Malignant Extrarenal Rhabdoid Tumor of the Vagina on FDG PET/CT
Authors: Guohua Shen, Rang Wang, Lili Pan, Anren Kuang
Journal: Clinical Nuclear Medicine (2021)

Abstract Malignant rhabdoid tumor is an aggressive neoplasm commonly arising from the kidney during infancy and childhood. Extrarenal forms of this tumor are relatively rare and have been reported in several extrarenal sites including central nervous system, liver, bladder, vulva, and head and neck. Hereby, we present FDG PET/CT findings of malignant extrarenal rhabdoid tumor originating from the vagina in an 8-year-old girl.
Dysregulation of soluble immune checkpoint proteins in newly-diagnosed early breast cancer patients.
Authors: Bernardo Leon Rapoport, Helen C Steel, Teresa Smit, Liezl Heyman, Annette J Theron, T Nomsa Hlatswayo, Luyanda LI Kwofie, Carol Benn, Ronald Anderson
Journal: Journal of Clinical Oncology (2021)

556 Background: Checkpoint proteins regulate the immune system. Breast cancer (BC) cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICM) can be measured in human plasma, however their biological and clinical significance remains essentially unknown. The aim of the present analysis was to measure the pre-treatment ICM in newly- diagnosed BC patients (pts) and compare them to healthy controls. Methods: Soluble forms of ICM, as well as cytokines and chemokines, were measured using Multiplex bead array and ELISA technologies. Plasma samples from 98 BC pts and 45 healthy controls were analyzed for each protein. Data was prospectively obtained. Measured levels were compared between BC pts and healthy controls using a non-parametric test (Mann-Whitney). P-values below 0.05 were considered statistically significant. Results: Soluble stimulatory molecules GITR (p &lt; 0,000002), GITRL (p &lt; 0,007), CD27 (p &lt; 0,002), CD28 (p &lt; 0,003), CD40 (p &lt; 0,003), CD80 (p &lt; 0,009), ICOS (p &lt; 0,0006), as well as inhibitory molecules PD-L1 (p &lt; 0.0000001), CTLA-4 (p &lt; 0,005), TIM-3 (p &lt; 0,00006), HVEM (p &lt; 0,00002) TLR-2 (p &lt; 0,05), levels were significantly lower in early BC pts compared to healthy controls. When analyzed according to BC characteristics (TNBC vs. non-TNBC, tumor size, stage, nodal status and age) no significant difference was detected between the soluble levels of these ICM between the different subsets. Additionally, serum CXCL5 (p &lt; 0,000001), CCL23 (p &lt; 0,04), IL-16 (p &lt; 0,00005), interferon-α (p &lt; 0,03) and IL1-RA (p &lt; 0,03) were significantly lower compared to healthy controls. Serum CX3CL1 or fractalkine (p &lt; 0,024465) was significantly higher compared with healthy controls. Serum interferon-γ (p &lt; 0,2), IL-6 (p &lt; 0.6) and IL-2 (p &lt; 0.6) levels were not significantly different between the BC pts and the healthy controls. Conclusions: We identified low levels of both the stimulatory and inhibitory immune checkpoint molecules, in newly-diagnosed, non-metastatic BC pts compared to healthy controls. These results indicate that early BC is associated with a down-regulation of both soluble stimulatory and inhibitory immune-checkpoint pathways. Newly-diagnosed early BC pts have a generalized immune-suppression independent of subtype (TNBC vs non-TNBC) and stage, which, to our knowledge, is the first study to describe soluble immune checkpoints in early BC pts.