tbuckley/cabot-search huggingface dataset:
Retrospective study on the management of patients admitted for febrile neutropenia and considered to be at low risk at the Centre Hospitalier Universitaire de Québec.
Authors: Tommy Jean, Julie Lemieux, Geneviève Soucy, Francis Caron, Dominique Leblanc
Journal: Journal of Clinical Oncology (2021)

e18762 Background: Febrile neutropenia is a serious complication of chemotherapy leading to hospitalization in cancer patients. According to a practice guidelines published by ASCO (American Society of clinical Oncology) and IDSA (Infectious Diseases Society of American) in 2018, patients meeting the criteria for low-risk neutropenia according to the MASCC score (Multinational Association for Supportive Care in Cancer Score) could be treated as outpatient and thus avoid hospitalization. The objective of the study was to assess the number and proportion of patients who were hospitalized for febrile neutropenia in university hospital that would have met the low risk criteria of febrile neutropenia. We also wanted to know if these patients had experienced a favorable outcome during hospitalization. Methods: We performed a retrospective study including all patients admitted for febrile neutropenia in 3 hospitals in Quebec City during the period from January 1, 2018 to December 31, 2019. We excluded patients with leukemia, as well as stem cell transplant patients. The chart review retrospectively established the MASCC score for each patient. We also established according to predefined criteria whether the clinical course was favorable or unfavorable. Results: A total of 177 hospitalizations met our inclusion criteria. We found that 101/177 (57.1%) of hospitalized patients met the criteria for low-risk neutropenia according to the MASCC score (score of 21 and above). Of this number 74/177 (41.8%) presented all the criteria suggested for receiving outpatient treatment. In these patients 70/177 (39.5%) presented a favorable evolution during hospitalization and thus 4/177 (2.3%) presented an unfavorable evolution. Among these, 2 patients presented with infections considered major (2 bacteremia), 1 patient developed acute renal failure, and 1 other patient developed delirium. There was no death or admission to the intensive care unit in these 4 patients. Conclusions: According to this retrospective study, about 40% of patients admitted for febrile neutropenia filled the criteria of low risk febrile neutropenia and could be treated as outpatient. Given this represents a significant proportion of patients, a protocol for systematic follow-up of outpatient treatment with low-risk febrile neutropenia should be put in place.
Evaluation and comparison of accurate automated spinal curvature estimation algorithms with spinal anterior-posterior X-Ray images: The AASCE2019 challenge
Authors: Liansheng Wang, Cong Xie, Yi Lin, Hong-Yu Zhou, Kailin Chen, Dalong Cheng, Florian Dubost, Benjamin Collery, Bidur Khanal, Bishesh Khanal, Rong Tao, Shangliang Xu, Upasana Upadhyay Bharadwaj, Zhusi Zhong, Jie Li, Shuxin Wang, Shuo Li
Journal: Medical Image Analysis (2021)
Interactive online skin cancer training game “Whack-a-Mole” assesses training strategies and real-time feedback on melanoma identification among U.S. adults.
Authors: Margaret Sanchez, Nicholas Carcioppolo, Soyoon Kim, Di Lun, Kate Malova, Bingjing Mao, Ashley Renee Reynolds, Clay Ewing, Shasa Hu
Journal: Journal of Clinical Oncology (2021)

10564 Background: Cutaneous melanoma is a deadly form of skin cancer. Several studies have shown that early melanoma detection is associated with decreased mortality through self-examination and dermatology full-body skin exams. ABCD rule and the ugly duckling sign (UDS) are used to identify melanomas, but little research has explored the comparative efficacy of these approaches. This investigation compares the effectiveness of different mole identification training strategies and explores the effect of real-time feedback on decision-making. Methods: We developed an online melanoma identification game that tests differences between training types and expert feedback on mole identification. This online RCT tests a 4 (training: ABCD, UDS, both, control) X 3 (feedback: standard, motivational, control) factorial design on melanoma identification, skin cancer beliefs (perceived susceptibility and self-efficacy), and skin cancer prevention intentions. Standard feedback included expert evaluations of moles, whereas motivational feedback added statements grounded in fear appeals theory to encourage skin self-examination. An online research panel service was used to recruit 1025 US adults. Participants were randomly assigned to condition, completed a pretest, participated in the game intervention, and completed a posttest. Gameplay incorporates the same mechanics as Tinder (swipe left on benign moles and swipe right on malignant moles). Results: In total, participants reviewed 48 moles, 12 of which were melanomas. We used two-way ANCOVA for the analysis. ABCD training resulted in significantly higher melanoma identification than the control ( p =.011). Every training type resulted in significantly higher self-efficacy than the control ( p =.007). Additionally, there was a significant main effect of feedback on self-efficacy ( p =.001), where both standard and motivational feedback elicited significantly higher levels of self-efficacy than the control condition. Around 88% of participants intend to conduct skin self-exams and wear sunscreen. Conclusions: Our data suggests that “Whack a Mole” is an efficacious tool for melanoma training. ABCD and UDS training with interactive feedback are important to improve accuracy and ability for melanoma identification.
Gender disparities in National Institute of Health funding for hematologic malignancies, hematopoietic stem cell transplantation, and cellular therapeutics.
Authors: Raheel Sufian Siddiqui, Moazzam Shahzad, Mahrukh Majeed, Ali Hussain, Faryal Murtaza, Farhan Khalid, Ayesha Habib, Zobia Aijaz, Syeda Sadia Bukhari, Iqra Anwar, Sehar Altaf, Faiz Anwer, Sibgha Gull Chaudhary, Ramesh Balusu, Nausheen Ahmed, Siddhartha Ganguly, Sunil H. Abhyankar, Joseph McGuirk, Faisal Khosa, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2021)

11020 Background: Gender inequality in research funding has been studied extensively; however, the literature lacks evidence in Hematology. We investigated trends in National Institutes of Health (NIH) funding for hematologic malignancies (HM), hematopoietic stem cell transplantation (HSCT), and cellular therapeutics (CT). Methods: The data on Hematology funding was retrieved from NIH Research Portfolio Online Reporting Tools (RePORT) Categorical Spending for fiscal years 2018 and 2019. A total of 6351 entries were reported. Only grants (n=1834) that were related to HM, HSCT, and CT were included. After excluding non-relevant, 975 principal investigators (PIs) were included in the analysis. Additional data regarding PIs was ascertained from the Scopus database, LinkedIn, Doximity, and departmental websites, including the number of publications, number of years of active research, H-index, highest degree, gender, and institution. Data were analyzed using SPSS version 21. Bivariate analyses, using chi-square and t-test, and linear regression analyses were performed. Results: In 2018 and 2019, 1834 grants totaling $799.4 million were awarded by the NIH for malignant hematology research (men 1301, 71% vs women 533, 29%). Of 975 PIs, 680 (70%) were men and 295 (30%) were women. Table highlights gender disparities in NIH funding and associated factors. Most of the grant recipients were Ph.D. or M.D./Ph.D. About 70% of total funding was awarded to male PIs. There were no gender differences in the mean number of grants and mean grant amount. Women had significantly lower years of active research and academic productivity. Conclusions: Although the gender gap in academic hematology has decreased in recent years, the latest trend suggests significant gender inequality in NIH funding for malignant hematology, transplantation, and cellular therapy.[Table: see text]
Bosutinib in combination with pemetrexed in patients with selected metastatic solid tumors: A phase I study (NCT03023319).
Authors: Nagla Fawzy Abdel Karim, Mahran Shoukier, Ihab Eldessouki, Ahmed Khaled, John Morris
Journal: Journal of Clinical Oncology (2021)

3022 Background: Activation of the Src kinase pathway has been observed in about 50% of cancers of the colon, liver, lung, breast and pancreas. Ceppi, et al, explored that Src inhibitors might be synergistic in combination with pemetrexed. Bosutinib is an approved oral ATP-competitive Bcr-Abl tyrosine-kinase inhibitor with an inhibitory effect on Src kinases. Methods: In this phase 1, dose-escalation study, we enrolled 10 patients with advanced metastatic solid tumors who progressed on standard of care chemotherapy, 9 of whom were evaluable, to receive bosutinib and pemetrexed. Bosutinib was administered once daily in a 3 + 3 dose-escalation study design where the first cohort started at an oral dose of 200 mg daily with I.V. pemetrexed 500 mg/m2 on a three weekly schedule. The primary objective was to determine the dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of bosutinib with pemetrexed, and the type and frequency of adverse events. Secondary objective(s) were to estimate tumor response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: All patients had progressed on prior chemotherapy and included 9 patients with adenocarcinoma of the lung, and 1 patient with metastatic adenocarcinoma of the appendix. Two patients (22%) had prior pemetrexed exposure. Median age was 62 years (range, 58-44). The median number of bosutinib and pemetrexed cycles received was 2 (range, 1-4). Nine patients were evaluable. The MTD of bosutinib was 300 mg daily in this combination as 2 out of the 3 patients who received 400 mg experienced elevated liver transaminases (&gt;CTCAE Grade 3) and one patient experienced grade 3 fatigue. Two patients (22%) had a partial response, and 6 patients (67%) had stable disease, including 2 patients with prior pemetrexed exposure, and 1 patient had disease progression. The two responders and the subject with the longest stable disease duration demonstrated Src overexpression on immunohistochemical staining of their tumor. Two patients died of sepsis; both had stable disease. Median PFS was 4.1 months (range, 1.2-11.6), and the median OS was 11.9 months (range, 4-36.7). Adverse events included pneumonia/sepsis, diarrhea, fatigue, rash, weakness, transaminitis, hypertension, and thrombocytopenia. Conclusions: The MTD of oral bosutinib was 300 mg daily in combination with pemetrexed 500 mg/m2 every 3 weeks. Despite the limitations of this phase I study there appears potential efficacy of this combination in pretreated patients. We are currently enrolling patients in the expansion cohort. Clinical trial information: NCT03023319.
Role of C reactive protein and procalcitonin in the diagnosis of lower respiratory tract infection in children in the outpatient setting
Authors: Andrés Pérez-López, Adam Irwin, Carlos Rodrigo, Cristina Prat-Aymerich
Journal: BMJ (2021)

### What you need to know

A previously healthy and fully vaccinated (including 13-valent pneumococcal conjugate vaccine) 22 month old boy is brought to the emergency department because of a 12 hour history of high fever (up to 40°C). He had had low grade fever, runny nose, cough, and decreased oral intake for the past two days. On examination, he did not look severely ill but was febrile (38.3°C). His respiratory rate was 45 breaths/minute (normal range 25-40 breaths/min at 18-24 months old), heart rate was 140 beats/minute (normal range 98-135 beats/min at 18-24 months), and blood oxygen level was 95%. Although breath sounds were not decreased, some bibasilar crackles were noted on chest auscultation. A chest x ray was interpreted as having bilateral peribronchial infiltrates and haziness in the right lower lobe. To aide their decision whether to initiate antibiotic therapy, clinicians requested blood tests, which revealed a white blood cell count of 22.5×109/L (60.0% neutrophils), a CRP of 30 mg/L (normal <5 mg/L), and a PCT of 0.25 μg/L (normal <0.5 μg/L). 

Lower respiratory tract infections (LRTIs) in childhood are commonly of viral aetiology. Distinguishing viral from bacterial LRTI in children—and thus appropriately …
Toward Greater Precision in Cancer Radiotherapy
Authors: Jac A. Nickoloff
Journal: Cancer Research (2021)

Abstract The cellular DNA damage response (DDR) is a key factor in tumor suppression and tumor responses to genotoxic chemo- and radiotherapy. Master DDR regulators include three phosphatidyl inositol 3′ kinase–related kinases (PIKK) called ATM, ATR, and the catalytic subunit of DNA-dependent protein kinase, DNA-PKcs. Among their many functions, PIKKs regulate repair of DNA double-strand breaks (DSB) by homologous recombination (HR) and nonhomologous end-joining (NHEJ). Ionizing radiation induces DSBs that are either widely dispersed and efficiently repaired, or clustered and poorly repaired by the dominant NHEJ pathway. The inefficient repair of clustered DSBs by NHEJ shifts repair toward the competing HR pathway. In this issue of Cancer Research, Zhou and colleagues revealed a novel synthetic lethal approach in which the greater dependency on HR to repair clustered DSBs induced by protons is exploited to enhance killing of tumor cells and tumor xenografts by suppressing HR with an ATM inhibitor or mutant BRCA1. This is an important step toward precision cancer radiotherapy. See related article by Zhou et al., p. 3333
Abstract 17101: An Enhanced Recovery Protocol (ERP) For All Cardiac Surgeries Reduces Postoperative Length Of Stay (postopLOS) And Perhaps The Incidence Of New Onset Postoperative Atrial Fibrillation
Authors: Jonathan Parmet, Satoshi Furukowa, Pietro Colonna-Romano
Journal: Circulation (2019)

Introduction: Previously, we reported a decreased postopLOS in CABG patients undergoing “on table extubation” (OTE) in the operating room from 2015-2017 (avg OTE CABG postopLOS = 5.6 ± 2.8 days vs....
Transcriptome Alterations of Prospectively Isolated Bone Marrow Stromal Cells Provide Potential Cues to MGUS and Multiple Myeloma Pathobiology
Authors: Dimitra Zacharaki, Roshanak Ghazanfari, Hongzhe Li, Hooi Ching Lim, Sofia Von Palffy, Shamit Soneji, Thoas Fioretos, Stefan Scheding
Journal: Blood (2017)
Psychostimulant Use Among Myeloproloferative Neoplasm Patients
Authors: Robyn M. Scherber, Blake T. Langlais, Heidi Elizabeth Kosiorek, Amylou Dueck, Holly Geyer, Zhenya Senyak, Archie McCallister, Mary Cotter, Barbara VanHusen, Jeanne Palmer, Leslie Padrnos, Claire N. Harrison, Angela G. Fleischman, Ruben A Mesa
Journal: Blood (2017)
Real-world first-line (1L) treatment patterns in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) in a U.S. health insurance database.
Authors: Umang Swami, Agnes Hong, Nader N. El-Chaar, David Nimke, Krishnan Ramaswamy, Elizabeth J. Bell, Rickard Sandin, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2021)

5072 Background: Over the past 6 years, intensification of androgen deprivation therapy (ADT) with docetaxel (DOC) and novel hormonal therapies (NHT) [abiraterone, enzalutamide, and apalutamide], has been shown to improve survival outcomes in men with mCSPC. This study assessed the real-world utilization of effective combination therapies as 1L treatment in insured pts in the U.S. with mCSPC. Methods: This retrospective study used the Optum health insurance claims database, which includes pt claims data from both commercially insured and Medicare Advantage populations. Eligible pts were adult men with ≥1 claim with a metastatic International Classification of Diseases diagnostic code (first claim was index date) within 90 days (d) prior to, or any time after, a prostate cancer diagnosis between January 2014 and June 2019. Pts with evidence of systemic anticancer therapy during the 1-year pre-index baseline period were excluded, unless the first drug claim occurred within 90 d prior to the diagnosis of metastatic disease. The 1L treatments were identified as any treatment for mCSPC within 90 d pre-index, plus any other treatment received within 180 d of the first, and were grouped by regimen: ADT only; ADT + first-generation antiandrogens (AA); ADT + DOC; ADT + NHT; and ADT + NHT + DOC. Results: Of 4221 men with mCSPC, 2364 (56.0%) received ADT only; 892 (21.1%) ADT + AA; 577 (13.7%) ADT + NHT; 348 (8.2%) ADT + DOC; and 40 (0.9%) ADT + NHT + DOC. Pts who received ADT + DOC or ADT + DOC + NHT were generally younger than the other treatment groups (Table). By 2019, use of ADT only and ADT + AA had declined, while the use of ADT + NHT and ADT + NHT + DOC had increased (Table). However, in 2018 and 2019, the majority of men with mCSPC still received either ADT alone, or ADT + AA, including those with visceral metastases (Table). Survival analysis across treatment cohorts is ongoing. Conclusions: Despite level 1 evidence demonstrating improved survival with intensified treatment (ADT + DOC or NHT), this study shows its underutilization in pts with mCSPC. This is evident even in those with more aggressive disease (visceral metastases) as recently as 2019. These data highlight that a minority of pts with mCSPC received optimal life-prolonging therapies in a commercially insured and Medicare Advantage U.S. population. Further studies are needed to identify the reasons for this underutilization of intensified treatments.[Table: see text]
Timing of steroid use and outcomes of immune checkpoint inhibitor: A population based study.
Authors: Nikita Nikita, Jennifer Maria Johnson, Melissa Wilson, Joshua Banks, Scott W. Keith, Swapnil Sharma, Grace L. Lu-Yao
Journal: Journal of Clinical Oncology (2021)

6590 Background: Immune checkpoint inhibitors (ICIs) have rapidly become the treatment of choice for multiple cancer types. However, the relationship between the timing of immunosuppressive agents, such as steroids use, preceding ICI initiation and subsequent treatment outcomes remains unknown due to lack of data. This study was undertaken to address this knowledge gap. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked data to identify patients with melanoma receiving Ipilimumab, Nivolumab, Pembrolizumab, or Ipilimumab/Nivolumab combination in 2010-2015. Last steroid exposure within 12 months prior to ICI use was categorized (none, 0-1, 1-3, and 3-12 months prior). Cox models were used to generate covariate-adjusted hazard ratios of overall mortality following ICI initiation. Because the hazards were not proportional over time, we allowed the hazard ratios to differ in three periods (&lt;3, 3-6, and more than 6 months post ICIs). Results: We identified 3,149 melanoma patients (median age 68 years) using ICIs; among these 1,352 received steroid within 12 months prior. Steroid use within 1 month prior to using ICIs was associated with a 93% and 102% increased risk in overall mortality within 3 months and 3-6 months post ICI initiation. The risk diminished over time (Table). A similar pattern was observed for steroid use 1-3 months prior. Steroid use beyond 4 months prior to ICI was not associated with increased mortality. Conclusions: This was the first major study to document that timing of steroid use prior to ICI is associated with the risk of mortality and how the increased risk diminishes over time. Further studies are warranted to confirm the findings and understand potential mechanisms.[Table: see text]
A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies.
Authors: Scot Anthony Niglio, Daniel da Motta Girardi, Lisa M. Cordes, Lisa Ley, Marissa Mallek, Olena Sierra Ortiz, Jacqueline Cadena, Carlos Diaz, Heather Chalfin, Andre Kydd, Rene Costello, Ariel E. Marciscano, Jennifer C Jones, Kilian Elizabeth Salerno, Vladimir Valera, William Douglas Figg, William L. Dahut, James L. Gulley, Jeffrey Schlom, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2021)

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.