tbuckley/cabot-search huggingface dataset:
Treatment-related side effects and views about dosage assessment to sustain quality of life: Results of an advocate-led survey of patients with metastatic breast cancer (MBC).
Authors: Anne L Loeser, Jeffrey M. Peppercorn, Mark E. Burkard, Kevin Kalinsky, Hope S. Rugo, Aditya Bardia
Journal: Journal of Clinical Oncology (2021)

1005 Background: Metastatic breast cancer (MBC) is generally incurable and the majority of patients with MBC will remain on treatment indefinitely. Patients usually begin each new treatment at the Recommended Starting Dose (RSD) on the FDA-approved label based on results from clinical trials. However, patients’ ability to tolerate the RSD in the real-world may differ from the clinical trial setting. While the importance of patient reported outcomes is recognized, understanding tolerability from the patient’s perspective is lacking and patients’ willingness to discuss individualized doses for MBC therapy has not been evaluated. Methods: Patient advocates from the Patient-Centered Dosing Initiative distributed a confidential online survey to patients with MBC via social media groups, organizational newsletters, and online support forums. The survey was developed by patients and medical oncologists to ascertain the prevalence and impact of patients’ treatment-related side effects, quality of patient-physician communication, management of side effects, and interest in alternative approaches to the RSD when a new treatment is initiated or adverse side effects are experienced. Results: 1,221 patients with MBC completed the survey within 15 days. The median number of lines of MBC therapy was 2.5 (range 1 - ≥5) and 46% (n = 564) of patients received their MBC diagnosis within two years of taking the survey. 86% (n = 1,051) reported experiencing at least one significant treatment-related side effect, and of these, 20% (n = 213) visited the Emergency Room/hospital and 43% (n = 454) missed at least one treatment. 98% (n = 1,026) of patients with side effects discussed them with their doctors and 82% (n = 838) were helped by their physicians. The most common (non-exclusive) mitigation strategies were dosage reductions (66%, n = 556) and prescription medications (59%, n = 494). Of the 556 patients given a dosage reduction, 83% (n = 459) reported feeling better. Notably, 92% (n = 1,127) of patients expressed willingness to discuss alternative dosing options with their physicians based upon their personal characteristics and individual preferences. Conclusions: Given that 86% of patients with MBC experienced at least one significant treatment-related side effect and 83% improved after dosage reduction, innovative dosage-related strategies are warranted to sustain Quality of Life. Patient-physician discussions in which the patient’s physical attributes and circumstances are periodically assessed may determine the right dose for the patient upon treatment initiation and afterwards, and the vast majority of patients would be receptive to such discussions.
The Effect of Sorafenib Therapy on the Outcome of Acute Myeloid Leukemia with FLT3-ITD Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Li Xuan, Yu Wang, Fen Huang, Bingyi Wu, Zhiping Fan, Na Xu, Jieyu Ye, Jing Sun, Xiaojun Huang, Qifa Liu
Journal: Blood (2017)
Maternity care: CQC imposes sanctions on Sheffield unit over concerns about safety and quality
Authors: Gareth Iacobucci
Journal: BMJ (2021)

England’s healthcare regulator has imposed sanctions on a maternity unit in Sheffield after an unannounced inspection.

In March the Care Quality Commission (CQC) inspected maternity services at the Jessop Wing run by Sheffield Teaching Hospitals NHS Foundation Trust after concerns about the safety and quality of services provided to women and babies.

In a report published on 9 June,1 CQC inspectors said that the trust lacked effective systems for ensuring that staff had the skills, competence, knowledge, and experience to safely care for women and their babies.

They also observed that the unit lacked effective systems …
Combination of sintilimab, anlotinib and pegaspargase "sandwich" with radiotherapy in localized natural killer/T cell lymphoma: A multicenter, phase 2 study.
Authors: Zhiming Li, Peng Sun, Yu Wang, Hang Yang, Yajun Li, Hui Zhou, Haiyan Yang, Liqun Zou
Journal: Journal of Clinical Oncology (2021)

7537 Background: NK/T-cell lymphoma (NKTL) is a rare and distinct subtype NHL. Most newly diagnosed NKTL cases were localized-stage. For localized NKTL, RT alone is inadequate due to high systemic failure rate. Chemoradiation has been increasingly applied. However, current chemotherapy (CT) regimens have severe toxicity and infection, which reduce the completion of RT and patients’ medical compliance. Therefore, novel regimens with mild toxicity are needed. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has showed encouraging antitumor efficacy in pts with r/r NKTL. Anlotinib, a multiple-targeted TKI that mainly blocks VEGF/VEGFR pathway, has been approved for several solid tumor types in china. Anti-angiogenesis therapy could improve efficacy of ICI in multiple tumor types. This multicenter, single-arm, phase 2 study aims to evaluate the efficacy and safety of sandwich chemoradiotion of sintilimab combined with anlotinib and pegaspargase (PEG-ASP) in newly diagnosed localized NKTL pts. Methods: Patients with pathologically confirmed previously untreated stage NKTL were enrolled. All enrolled patients received 3 cycles of sintilimab (200mg D1 ivdrip) combined with anlotinib (12mg po D1-14) and PEG-ASP (2500U/m 2 D1) every 3 weeks followed by RT, then received additional 3 cycles of combination therapy as described above. The primary endpoint was overall response rate (ORR) by LUGANO 2014 criteria. Results: A total of 39 pts were enrolled, and 24 pts eligible for response evaluation (70.8% men; median age, 46 y [range 20-64]; 58.3% stage). According to PINK-E system, 8 pts (33.3%) were identified as intermediate risk group and 16 patients were low risk group. 23 of 24 patients completed protocol-specified therapeutic schemes, one patient discontinued the study after the second cycle due to disease progression. ORR was 95.8% (23/24, 95%CI: 76.9%-84.1%). Surprisingly, all the responded patients achieved CR, while 66.7% (16/24, 95%CI: 44.7%-83.6%) patients achieved CR after the second cycle. Median PFS and OS have not been reached. 1-year OS and PFS was 100% and 95.8%, respectively. All grade TRAEs occurred in 84.6% of all enrolled patients and 92.1% were grade 1-2. The most common TRAE was lymphocytopenia (9.9%). Of note, grade 3-4 hematological toxicity was reported in only one patient (4.2%). All AEs were resolved after symptomatic treatment, without systematic corticosteroid intervention. Conclusions: Sintilimab combined with anlotinib and PEG-ASP upfront and after radiotherapy was effective and could be well tolerated in localized NKTL, achieving promising CRR and rapid and long-term remission with mild toxicity. Further investigation of survival outcome is warranted. Clinical trial information: NCT03936452.
Ninjurin1 Is a Novel Factor to Regulate Angiogenesis Through the Function of Pericytes
Authors: 考樹 松木, 真樹 鹿原, 幸裕 齊藤, 浩平 島村, 暁帆 簑島, 正人 西村, 達也 青沼, 有史 竹原, 直幸 長谷部, 淳一 川辺
Journal: Circulation (2015)
Guidelines of care for the management of actinic keratosis: Executive summary
Authors: Daniel B. Eisen, Maryam M. Asgari, Daniel D. Bennett, Suzanne M. Connolly, Robert P. Dellavalle, Esther E. Freeman, Gary Goldenberg, David J. Leffell, Sue Peschin, James E. Sligh, Peggy A. Wu, Lindsy Frazer-Green, Sameer Malik, Todd E. Schlesinger
Journal: Journal of the American Academy of Dermatology (2021)
Neoadjuvant chemotherapy and disease recurrence after curative-intent surgery in patients with pancreatic adenocarcinoma: A single-center retrospective review.
Authors: Khaled Alhamad, Nada Alrifai, Abraham Attah Attah, Karthik Shankar, Lynna Alnimer, Yazan Samhouri, Thejus Thayyil Jayakrishnan, Srividya Srinivasamaharaj, Dulabh K. Monga
Journal: Journal of Clinical Oncology (2021)

e18610 Background: Early stage pancreatic ductal adenocarcinoma (PDAC) account for up to 30% of newly diagnosed patients. Until recently, the mainstay of treatment remained curative-intent surgery followed by adjuvant chemotherapy. More recently, the incorporation of neoadjuvant therapy (NAT) has demonstrated clinical benefit. The two commonly used regimens are 5-Fluorouracil, Leucovorin, Oxaliplatin and Irinotecan (FOLFIRINOX), or Gemcitabine and nab-Paclitaxel. Limited data is available to differentiate outcomes between the 2 common NAT regimens. We conducted a retrospective review to assess the rates of disease recurrence and progression after neoadjuvant chemotherapy and to identify any associations that may predict early recurrence. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Disease recurrence or progression was assessed radiologically, and time to progression was calculated as time (months) since diagnosis to evidence of radiological progression. Results: Out of 171 patients reviewed, 56 were deemed resectable or borderline resectable and underwent curative-intent surgery and were included in the analysis. Median age was 68, and 12 (41%) were male. Majority of the patients were white (90%). 29 (52%) patients received neoadjuvant chemotherapy: 16 (55%) received FOLFIRINOX, 12 (41%) received Gemcitabine with nab-Paclitaxel, and 1 received another regimen. 9 patients out of 16 (56%) that received FOLFIRINOX progressed, and 5 out of 12 patients (42%) who received Gemcitabine with nab-Paclitaxel progressed. Patterns of progression in those that received FOLFIRINOX: 1 (11%) within 6 months, 4 (44%) between 6-12 months, and 4 (44%) after 12 months. Of those that received Gemcitabine with nab-Paclitaxel, 2 (40%) progressed within 6 months, 1 (20%) progressed between 6-12 months, and 2 (40%) progressed after 12 months. On multivariate analysis, no association was identified to predict progression. Conclusions: There was no significant difference in disease progression rates among patients that received neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel (42% vs. 56%; p = 0.46). No predictive associations were identified in patients with disease recurrence. Study limitations include a low sample size and retrospective analysis. Further, larger scale studies are warranted to better assess the difference in rates of progression after neoadjuvant FOLFIRINOX versus Gemcitabine and nab-Paclitaxel.[Table: see text]
Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma
Authors: Jeff M. Michalski, Anna J. Janss, L. Gilbert Vezina, Kyle S. Smith, Catherine A. Billups, Peter C. Burger, Leanne M. Embry, Patricia L. Cullen, Kristina K. Hardy, Scott L. Pomeroy, Johnnie K. Bass, Stephanie M. Perkins, Thomas E. Merchant, Paul D. Colte, Thomas J. Fitzgerald, Timothy N. Booth, Joel M. Cherlow, Karin M. Muraszko, Jennifer Hadley, Rahul Kumar, Yuanyuan Han, Nancy J. Tarbell, Maryam Fouladi, Ian F. Pollack, Roger J. Packer, Yimei Li, Amar Gajjar, Paul A. Northcott
Journal: Journal of Clinical Oncology (2021)

Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment. Efforts to mitigate these effects include deintensification of craniospinal irradiation (CSI) dose and volume.ACNS0331 (ClinicalTrials.gov identifier: NCT00085735) randomly assigned patients age 3-21 years with average-risk MB to receive posterior fossa radiation therapy (PFRT) or involved field radiation therapy (IFRT) following CSI. Young children (3-7 years) were also randomly assigned to receive standard-dose CSI (SDCSI; 23.4 Gy) or low-dose CSI (LDCSI; 18 Gy). Post hoc molecular classification and mutational analysis contextualized outcomes according to known biologic subgroups (Wingless, Sonic Hedgehog, group 3, and group 4) and genetic biomarkers. Neurocognitive changes and ototoxicity were monitored over time.Five hundred forty-nine patients were enrolled on study, of which 464 were eligible and evaluable to compare PFRT versus IFRT and 226 for SDCSI versus LDCSI. The five-year event-free survival (EFS) was 82.5% (95% CI, 77.2 to 87.8) and 80.5% (95% CI, 75.2 to 85.8) for the IFRT and PFRT regimens, respectively, and 71.4% (95% CI, 62.8 to 80) and 82.9% (95% CI, 75.6 to 90.2) for the LDCSI and SDCSI regimens, respectively. IFRT was not inferior to PFRT (hazard ratio, 0.97; 94% upper CI, 1.32). LDCSI was inferior to SDCSI (hazard ratio, 1.67%; 80% upper CI, 2.10). Improved EFS was observed in patients with Sonic Hedgehog MB who were randomly assigned to the IFRT arm (P = .018). Patients with group 4 MB receiving LDCSI exhibited inferior EFS (P = .047). Children receiving SDCSI exhibited greater late declines in IQ (estimate = 5.87; P = .021).Reducing the radiation boost volume in average-risk MB is safe and does not compromise survival. Reducing CSI dose in young children with average-risk MB results in inferior outcomes, possibly in a subgroup-dependent manner, but is associated with better neurocognitive outcome. Molecularly informed patient selection warrants further exploration for children with MB to be considered for late-effect sparing approaches.
Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.
Authors: Kihyun Kim, Chang Ki Min, Youngil Koh, Kenichi Ishizawa, Sung-Hyun Kim, Shigeki Ito, Tanaka Junji, Michihiro Uchiyama, Yawara Kawano, Jin Seok Kim, Philippe Moreau, Thomas G. Martin, Yvonne Dong, Marie-Laure Risse, Kenshi Suzuki
Journal: Journal of Clinical Oncology (2021)

e20015 Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m 2 days 1-2, 56 mg/m 2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]
Increase in Prevalence of Diabetic Ketoacidosis at Diagnosis Among Youth With Type 1 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: Elizabeth T. Jensen, Jeanette M. Stafford, Sharon Saydah, Ralph B. D’Agostino, Lawrence M. Dolan, Jean M. Lawrence, Santica Marcovina, Elizabeth J. Mayer-Davis, Catherine Pihoker, Arleta Rewers, Dana Dabelea
Journal: Diabetes Care (2021)

We previously reported a high (˜30%) but stable prevalence of diabetic ketoacidosis (DKA) at youth-onset diagnosis of type 1 diabetes (2002 and 2010). Given the changing demographics of youth-onset type 1 diabetes, we sought to evaluate temporal trends in the prevalence of DKA at diagnosis of type 1 diabetes from 2010 to 2016 among youth <20 years of age and evaluate whether any change observed was associated with changes in sociodemographic distribution of those recently diagnosed.We calculated prevalence of DKA within 1 month of type 1 diabetes diagnosis by year and evaluated trends over time (2010-2016) (n = 7,612 incident diabetes cases; mean [SD] age 10.1 [4.5] at diagnosis). To assess whether trends observed were attributable to the changing distribution of sociodemographic factors among youth with incident type 1 diabetes, we estimated an adjusted relative risk (RR) of DKA in relation to calendar year, adjusting for age, sex, race/ethnicity, income, education, health insurance status, language, season of diagnosis, and SEARCH for Diabetes in Youth Study site.DKA prevalence increased from 35.3% (95% CI 32.2, 38.4) in 2010 to 40.6% (95% CI 37.8, 43.4) in 2016 (Ptrend = 0.01). Adjustment for sociodemographic factors did not substantively change the observed trends. We observed a 2% annual increase in prevalence of DKA at or near diagnosis of type 1 diabetes (crude RR 1.02 [95% CI 1.01, 1.04] and adjusted RR 1.02 [95% CI 1.01, 1.04]; P = 0.01 for both).Prevalence of DKA at or near type 1 diabetes diagnosis has increased from 2010 to 2016, following the high but stable prevalence observed from 2002 to 2010. This increase does not seem to be attributable to the changes in distribution of sociodemographic factors over time.
What Is the Optimal Method on Myocardial Suppression in FDG PET/CT Evaluation of Cardiac Sarcoidosis?
Authors: Yang Lu, Nadera J. Sweiss, Homer A. Macapinlac
Journal: Clinical Nuclear Medicine (2021)

Abstract Based on the recent publications, including large cohort retrospective study and prospective clinical trial data, we are commenting on the optimal methods on myocardial suppression in FDG PET/CT evaluation of patients with suspected cardiac sarcoidosis.
MDNA11 is a long-acting IL-2 superkine that potentiates durable immune response in mouse tumor models and non-human primates.
Authors: Minh D. To, Fahar Merchant, Nina Merchant
Journal: Journal of Clinical Oncology (2021)

e14546 Background: The efficacy and safety of recombinant human IL-2 (rhIL-2; Proleukin) to treat certain cancers is limited by a short half-life, marked toxicity and selective high affinity binding to IL2Ra over IL2Rb, resulting in preferential activation of suppressive Tregs. In contrast, MDNA11 has been engineered as a long-acting IL-2 superkine with high affinity IL2Rb receptor selectivity, resulting in preferential anti-cancer effector immune cell activation. Methods: MDNA11 was characterized in both in vitro and in vivo studies including assessment of receptor binding kinetics using BLI/Octet, receptor-mediated signaling in human PMBCs, efficacy in syngeneic mouse tumor models including memory response, as well as safety and PK/PD assessments in non-human primates (NHP). Results: Unlike rhIL-2, MDNA11 does not bind to human IL2Ra but demonstrates a 30-fold higher affinity binding to human IL2Rb. This selectivity resulted in enhanced in vitro STAT5 signaling in human NK and resting CD8 T cells with diminished signaling in Tregs; validation studies in humanized mice are ongoing. In CT26 and MC38 syngeneic tumor models, MDNA11 demonstrates potent and durable efficacy as monotherapy following a Q1W dose schedule for 2 weeks. Synergy with anti-PD1 and anti-CTLA4 immune checkpoint inhibitors (ICIs) was observed and a robust immune memory response developed in all mice with complete tumor clearance. These mice were protected against relapse and tumor re-challenges for up to 8 months without any further treatment, and showed the presence of antigen-specific CD8 T cells. In binding studies with IL-2 receptors of different species, MDNA11 showed highly similar affinity towards human and cynomolgus IL2Rb, confirming the latter as a highly relevant model for toxicology study. MDNA11 was well tolerated in cynomolgus monkeys up to 0.6 mg/kg, while inducing durable (≥10 days) proliferation and expansion of NK and CD8 T cells. Effects on Tregs were minimal and there was no eosinophilia and hypotension (associated with vascular leak syndrome). At high doses of MDNA11, the most common clinical observations were transient loss of appetite and diarrhea. There was modest increase in levels of IFNg and TNFa, but no sign of cytokine release syndrome. Dosing did not trigger development of anti-drug antibodies or histopathologic evidence of pulmonary edema (a major IL-2 induced toxicity). Conclusions: MDNA11 is a long-acting IL-2 superkine that exhibits robust efficacy in mouse tumor models as a single agent and was synergistic in combination with ICIs (anti-CTLA4 and anti-PD1). In NHP, MDNA11 demonstrates selective immune effector cell activation and a favorable safety profile. These data constitute a strong framework for the design of a pivotal GLP toxicology study to further support the planned clinical study of MDNA11 either as a single agent or in combination with ICIs.
A Single Gene-Mediated Perturbation of the Human Genome Leads to Malignant Transformation in a Murine Transgenic Model
Authors: Jianhong Lin, Chun Yang, Li Xue, Zhenkui Wang, Yan Xu, Mehmet Kemal Samur, Jianjun Zhao, Ariel Kwart, Masood A. Shammas, Xiaofeng Jiang, Wong Kwok-Kin, Ruben D. Carrasco, Kenneth C Anderson, Nikhil Munshi
Journal: Blood (2017)
QuickStats: Rates* of Firearm-Related Deaths† Among Persons Aged ≥15 Years, by Selected Intent§ and Age Group — National Vital Statistics System, United States, 2019
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

All intentsSuicide Intent Homicide 15-24 yrs 25-44 yrs 45-64 yrs ≥65 yrs Deaths per 100,000 population * Crude death rate per 100,000 population; 95% confidence intervals indicated with error bars.† Deaths caused by firearm-related injuries were identified using the following International Classification of Diseases, Tenth Revision underlying cause-of-death codes: U01.4; W32-W34; X72-X74; X93-X95; Y22-Y24; and Y35.0.§ In addition to suicide and homicide, all intents include other intent categories (unintentional, legal intervention, and undetermined intent), which are not shown separately and accounted for 3.3% of all firearm-related deaths (all intents) in 2019.Among persons aged ≥15 years, for all firearm-related deaths (all intents), rates were highest among those aged 15-24 years (17.4 per 100,000).For deaths involving firearm-related suicides, rates increased with age, from 6.6 among persons aged 15-24 years to 11.8 among those aged ≥65 years.A different pattern was found for firearm-related homicides, in which rates decreased with age, from 10.2 among those aged 15-24 years to 0.9 among those aged ≥65 years.