tbuckley/cabot-search huggingface dataset:
Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma
Authors: Antoine Hollebecque, Stefania Salvagni, Ruth Plummer, Nicolas Isambert, Patricia Niccoli, Jaume Capdevila, Giuseppe Curigliano, Victor Moreno, Patricia Martin-Romano, Eric Baudin, Marina Arias, Sheila Mora, Juan de Alvaro, Jorge Di Martino, Josep L. Parra-Palau, Tania Sánchez-Pérez, Ida Aronchik, Ellen H. Filvaroff, Manisha Lamba, Zariana Nikolova, Johann S. de Bono
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types, and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Patients and Methods: CC-90011-ST-001 (NCT02875223; 2015-005243-13) is a phase I, multicenter, first-in-human dose-escalation study. Nine dose levels of CC-90011 (1.25–120 mg) given once per week were explored. Primary objectives were to determine safety, maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D). Secondary objectives were to evaluate preliminary efficacy and pharmacokinetics. Results: Fifty patients were enrolled, 49 with solid tumors (27 neuroendocrine tumors/carcinomas) and 1 with R/R NHL. Median age was 61 years (range, 22–75). Patients received a median of three (range, 1–9) prior anticancer regimens. The RP2D was 60 mg once per week; the nontolerated dose (NTD) and MTD were 120 mg once per week and 80 mg once per week, respectively. Grade 3/4 treatment-related toxicities were thrombocytopenia (20%; an on-target effect unassociated with clinically significant bleeding), neutropenia (8%; in the context of thrombocytopenia at the highest doses), and fatigue (2%). The patient with R/R NHL had a complete response, currently ongoing in cycle 34, and 8 patients with neuroendocrine tumors/carcinomas had stable disease ≥6 months, including bronchial neuroendocrine tumors, kidney tumor, and paraganglioma. Conclusions: CC-90011 is well tolerated, with the RP2D established as 60 mg once per week. The MTD and NTD were determined to be 80 mg once per week and 120 mg once per week, respectively. Further evaluation of CC-90011 is warranted.
Hypoxia Alters the Response to Anti-EGFR Therapy by Regulating EGFR Expression and Downstream Signaling in a DNA Methylation–Specific and HIF-Dependent Manner
Authors: Mahelet Mamo, I. Chae Ye, Josh W. DiGiacomo, Je Yeon Park, Bradley Downs, Daniele M. Gilkes
Journal: Cancer Research (2020)

Abstract Intratumoral hypoxia occurs in 90% of solid tumors and is associated with a poor prognosis for patients. Cancer cells respond to hypoxic microenvironments by activating the transcription factors, hypoxia-inducible factor 1 (HIF1) and HIF2. Here, we studied the unique gene expression patterns of 31 different breast cancer cell lines exposed to hypoxic conditions. The EGFR, a member of the ErbB (avian erythroblastosis oncogene B) family of receptors that play a role in cell proliferation, invasion, metastasis, and apoptosis, was induced in seven of the 31 breast cancer cell lines by hypoxia. A functional hypoxia response element (HRE) was identified, which is activated upon HIF1 binding to intron 18 of the EGFR gene in cell lines in which EGFR was induced by hypoxia. CpG methylation of the EGFR HRE prevented induction under hypoxic conditions. The HRE of EGFR was methylated in normal breast tissue and some breast cancer cell lines, and could be reversed by treatment with DNA methyltransferase inhibitors. Induction of EGFR under hypoxia led to an increase in AKT, ERK, and Rb phosphorylation as well as increased levels of cyclin D1, A, B1, and E2F, and repression of p21 in an HIF1α-dependent manner, leading to cell proliferation and migration. Also, increased EGFR expression sensitized cells to EGFR inhibitors. Collectively, our data suggest that patients with hypoxic breast tumors and hypomethylated EGFR status may benefit from EGFR inhibitors currently used in the clinic. Significance: Hypoxia sensitizes breast cancer cells to EGFR inhibitors in an HIF1α- and a methylation-specific manner, suggesting patients with hypoxic tumors may benefit from EGFR inhibitors already available in the clinic.
Pharmacoeconomic savings associated with alternate dosing strategy of nivolumab and ipilimumab combination therapy.
Authors: Allison Kupsh, Laura Alwan, Eve M. Segal, Kathryn J. Hammer, Evan Thomas Hall
Journal: Journal of Clinical Oncology (2020)

79 Background: Nivolumab (NIVO) plus ipilimumab (IPI) is a commonly used therapy for advanced melanoma. Original weight-based dosing of NIVO 1 mg/kg plus IPI 3 mg/kg (NIVO1+IPI3) was approved in 2017. Recently, the CHECKMATE 511 trial demonstrated improved tolerability of NIVO 3 mg/kg plus IPI 1 mg/kg (NIVO3 + IPI1) compared to the original dosing regimen without observed differences in efficacy.Objective: To determine the pharmacoeconomic implications of NIVO1+IPI3 and NIVO3+IPI1 with a dose banding strategy applied. Methods: Patients with advanced melanoma (N = 21) who received IPI and NIVO in combination between 4/2019 – 7/2019 were evaluated via a single-center retrospective chart review. A total of 118 checkpoint inhibitor doses (59 NIVO, 59 IPI) were analyzed.Weapplied a dose banding strategy to both NIVO1+IPI3 and NIVO3+IPI1 regimens to examine pharmaceutical expenditures using the two dosing regimens, whichincluded our organization 10% dose-vial rounding policy. Pharmaceutical expenditure using average wholesale price (AWP), which was $32.42 per mg of NIVO and $180.03 per mg of IPI, was calculated for each dosing strategy (NIVO1+IPI3 and NIVO3+IPI1). Results: The anticipated cost savings of patients receiving NIVO3+IPI1 combination therapy compared to NIVO1+IPI3, (both with dose rounding strategy applied), was $1,459,473 or &gt;$70,000 per patient, representing a 47.2% savings from the original NIVO1 +IPI3 regimen (Table). Conclusions: In addition to improved tolerability and comparable efficacy for NIVO3+IPI1 vs NIVO1+IPI3, our study shows that adoption of the NIVO3+IPI1 regimen results in significant savings in drug costs. Considerations should be made in future combination trials to compare NIVO3+IPI1 as a treatment arm to NIVO1+IPI3 to see if comparable clinical results can be obtained with less toxicity and decreased pharmaceutical spending. [Table: see text]
CiRCL: A psychosocial programfacilitating communication and care to patients, families, and frontline health care teams during COVID-19
Authors: Kauser Ahmed, Peter Phung, Noah Goldstein, John Glaspy
Journal: Clinical Cancer Research (2020)

The need for strict social distancing measures preventing visitors on inpatient oncology, ICU, and COVID unitsduring the COVID-19 pandemic has had the unintended consequence of leading to significant psychological andspiritual distress for patients and families and “moral distress” for frontline health care teams tasked with supportingpatients who are suffering or dying alone without the support of their loved ones  The trauma of these deaths issometimes further compounded for families by their inability to provide the final rituals of patients' faith communitiesin their last moments, leading to complicated and ongoing grief after the loss  To address these complexpsychosocial needs among COVID-19 and advanced cancer oncology patients, and the health care teams caring forthem, the Simms/Mann UCLA Center for Integrative Oncology, in collaboration with colleagues at the UCLAAnderson School of Business and a team of diverse faith leaders, developed an innovative digitally mediatedprogram for connection, communication, and care  This program, CiRCL (Caring in Remote Communities of Love), leveraged ZOOM and smartphone recording technology to accomplish the following goals: 1) provide psychologicalsupport to family members and friends to facilitate the recording of meaningful personal messages to the patient, including curated playlists of evocative songs from the patient's life to be played at the bedside;2) facilitate moremeaningful communication between loved ones and frontline workers, including messages of gratitude and supportto reduce feelings of isolation and moral distress for frontline workers;and 3) create a liturgical library of recordedecumenical and faith-based blessings from various traditions, available during illness and at time of dying  Blessingsinclude and encompass the health care teams as well as patients  This program, recently developed and beingpiloted at UCLA, is intended to extend compassion to all within the health care system during the unique challengesof COVID-19 and, by facilitating connection and support among patients, families, and frontline teams, extend thedefinition of healing and mitigate the impact of loss and grief for all during the many phases of this pandemic
Two subsets of stem-like CD8+ memory T cell progenitors with distinct fate commitments in humans
Authors: Giovanni Galletti, Gabriele De Simone, Emilia M. C. Mazza, Simone Puccio, Claudia Mezzanotte, Timothy M. Bi, Alexey N. Davydov, Maria Metsger, Eloise Scamardella, Giorgia Alvisi, Federica De Paoli, Veronica Zanon, Alice Scarpa, Barbara Camisa, Federico S. Colombo, Achille Anselmo, Clelia Peano, Sara Polletti, Domenico Mavilio, Luca Gattinoni, Shannon K. Boi, Benjamin A. Youngblood, Rhiannon E. Jones, Duncan M. Baird, Emma Gostick, Sian Llewellyn-Lacey, Kristin Ladell, David A. Price, Dmitriy M. Chudakov, Evan W. Newell, Monica Casucci, Enrico Lugli
Journal: Nature Immunology (2020)
Characterizing participants in the North Carolina Breast and Cervical Cancer Control Program (NC BCCCP): A review of 90,000 women.
Authors: Sarah D Tait, Yi Ren, Cushanta C. Horton, Sachiko M. Oshima, Samantha M. Thomas, Sherry Wright, Awanya Caesar, Jennifer Kay Plichta, Eun-Sil Shelley Hwang, Rachel Adams Greenup, Laura Horst Rosenberger, Gayle DiLalla, Carolyn S. Menendez, Lisa Tolnitch, Terry Hyslop, Debi Nelson, Oluwadamilola Motunrayo Fayanju
Journal: Journal of Clinical Oncology (2020)

101 Background: Overall breast cancer mortality in the US has declined since 1990, but racial/ethnic disparities have worsened. Since 1992, NC BCCCP has provided free/low-cost breast cancer screening to underserved women as part of a national effort by the Centers for Disease Control and Prevention (CDC) to mitigate these disparities. We sought to characterize and evaluate benchmarks for this previously unstudied, state-level cohort. Methods: We identified women ≥18y who underwent their first breast cancer screening via NC BCCCP from 2009-2018. Univariate analysis was used to compare differences in timeline of care and rates of breast pathology (i.e., cancer or atypia) by race/ethnicity and age. Logistic and negative binomial regression were used to identify factors associated with cancer diagnosis and time from enrollment to diagnosis (TTD) and treatment (TTT), respectively. Results: 88,893 women with complete records were identified (median age 50y, IQR 44-56): 45.5% were Non-Hispanic (NH) white, 30.9% NH black, 19.5% Hispanic, 1.7% American Indian (AI), and 1.1% Asian. Overall participation peaked in 2012 but steadily increased among Hispanic women over time (p &lt; 0.001). Breast pathology was diagnosed in 2,016 (2.3%) women, with rates ranging from 1% in Hispanic women to 2.7% in NH whites. After adjustment, Hispanic women were least likely (vs NH white women: OR 0.40; 95% CI 0.34-0.47) to be diagnosed with breast cancer. Median TTD was 19d and TTT was 33d, both within the CDC’s 60d standard. In univariate analyses, women &lt; 50 had shorter TTD (median 18d vs 21d) and TTT (median 30d vs 35d) vs women ≥50 (both p &lt; 0.01), and there were no significant differences by race/ethnicity or between women with atypia vs cancer. In multivariate models, however, older age and NH black race were associated with longer TTD and TTT. Conclusions: NC BCCCP meets national quality benchmarks for TTD and TTT. These data also highlight broader opportunities to achieve racial/ethnic parity and improve equity for breast cancer prevention. [Table: see text]
Effectiveness of immunotherapy given to cancer patients in the hospitalized setting.
Authors: Mojisola O Araoye, Brian J. Byrne
Journal: Journal of Clinical Oncology (2020)

74 Background: Immunotherapy is a type of cancer treatment that uses an individual’s immune system to fight cancer. Most clinical trials involving immunotherapy have been done on healthy patients, thus excluding many hospitalized patients. Many oncologists feel there are less significant toxicities to immunotherapy and thus may give them to sicker patients. This may delay discussions regarding goals of care and contribute to increased costs at end of life. This exploratory study focuses specifically on the use of immune checkpoint inhibitors in hospitalized patients to determine outcomes of patients treated in the inpatient setting. Methods: This is a retrospective chart-review study. Data on patients from the Hartford Healthcare system was extracted from EPIC. Patients were eligible if they had received at least one dose of a PD1 or PDL1 inhibitor (pembrolizumab, nivolumab, atezolizumab) during a hospital stay. The number of doses received in total, side effects, as well as discharge status was also recorded. Results: A total of 74 patients received at least one dose of a PD1 or PDL1 inhibitor during a hospital stay. 46% of the total patients treated either died in the hospital (16.2%) or were discharged to hospice (29.3%). 54 percent of patients were discharged with a plan to continue with therapy. For the subgroup of the 27 patients whose treatment was initiated in the hospital, 48% of them received only one cycle of treatment and 74% received less than 4 treatments total. The average number of cycles was 5.3. The percentage of patients who died in the hospital was 11.1% and the percentage of patients discharged to hospice was 33.3%. 55.5% were successfully discharged with a plan to continue with therapy. Conclusions: For patients who receive immunotherapy in the hospital setting there is a questionable benefit with more than 45% dying in the hospital or being discharged to hospice. Further evaluation can be done looking at increasing the cost, delaying palliative care, and patient/family satisfaction with their end of life care by giving immunotherapy in the hospital. A new quality measure looking at time from last immunotherapy to hospice enrollment or death may need to be followed in the future due to these poor outcomes in the hospitalized setting. [Table: see text]
EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II—2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer
Authors: Philip Cornford, Roderick C.N. van den Bergh, Erik Briers, Thomas Van den Broeck, Marcus G. Cumberbatch, Maria De Santis, Stefano Fanti, Nicola Fossati, Giorgio Gandaglia, Silke Gillessen, Nikolaos Grivas, Jeremy Grummet, Ann M. Henry, Theodorus H. van der Kwast, Thomas B. Lam, Michael Lardas, Matthew Liew, Malcolm D. Mason, Lisa Moris, Daniela E. Oprea-Lager, Henk G. van der Poel, Olivier Rouvière, Ivo G. Schoots, Derya Tilki, Thomas Wiegel, Peter-Paul M. Willemse, Nicolas Mottet
Journal: European Urology (2020)
Understanding the supportive care needs of early-phase cancer clinical trial (CT) participants.
Authors: Debra Lundquist, Dejan Juric, Rachel Jimenez, Virginia Capasso, Casandra McIntyre, Barbara J. Cashavelly, Andrew Johnson, Megan Healy, Ryan David Nipp
Journal: Journal of Clinical Oncology (2020)

26 Background: Early phase CTs investigate novel therapeutic approaches for patients with cancer, but little is known about the use of supportive care services among participants in early phase CTs. Methods: We conducted a retrospective chart review of consecutive patients enrolled in Phase 1 CTs from 2017-2019, capturing sociodemographics, clinical data, and use of supportive care services from the electronic health record. We calculated the Royal Marsden Hospital (RMH) prognostic score using data at the time of CT trial enrollment based on patients’ lactate dehydrogenase, albumin, and number of sites of metastasis. The RMH score ranges from 0-3, with scores of 2+ indicating a poor prognosis. We explored differences in patient characteristics, supportive care use, and clinical outcomes based on the RMH prognosis score. Results: Among 426 patients treated on Phase 1 CTs during the study period, the median age was 63.0 years (range 20.5-85.2 years), and most were female (56.1%), white race (85.1%), and had metastatic cancer (97.7%). The most common cancer types were gastrointestinal (22.1%), lung (20.0%), and breast (10.6%) cancer. Under half (31.6%) had an RMH score indicating a poor prognosis. Patients with a poor prognosis score had a worse performance status (ECOG ≥1: 80.2% v 58.3%, p &lt; .001) and more prior treatment (3+ prior lines: 49.5% v 35.0%, p = .001) compared to those without a poor prognosis score. Those with a poor prognosis score were more likely to receive palliative care before or during CT participation (40.5% v 27.1%, p = .011). We observed no significant differences in the rates of nutrition (69.1% v 64.0%), social work (62.2% v 63.8%), or physical therapy (64.5% v 61.7%) consults between those with and without a poor prognosis score. We found that those with an RMH score indicating a poor prognosis had a shorter time on trial (median: 49 vs 87 days, p &lt; .001) and worse survival (median: 139 v 379 days, p &lt; .001). Conclusions: Early phase CT participants represent an advanced cancer population with unique supportive care needs, and we identified a group with a particularly poor prognosis for whom earlier intervention with supportive care services may be needed. Our findings highlight the need to prospectively examine these characteristics along with patient-reported outcomes to better understand the distinct supportive care needs of this population and guide the development of targeted interventions.
Patient safety: NHS trusts report multiple risks linked to lack of staff and funding
Authors: Jacqui Wise
Journal: BMJ (2020)

NHS trusts in England have reported various risks to the safety of patients linked to staffing shortages, lack of funding, or problems with buildings and failing equipment, shows an analysis of risk registers carried out by the Labour Party.

Labour says the documents show that the NHS entered the covid-19 pandemic with major problems, and that urgent action is now needed for it to cope with a second wave of covid-19 on top of the usual winter pressures.

Jonathan Ashworth, the shadow health and social care secretary, said, “In a normal winter these risks would be worrying. In the coming winter … they take on a whole new meaning.”

The Labour Party analysed 114 risk registers from non-specialist …
NIR light-assisted phototherapies for bone-related diseases and bone tissue regeneration: A systematic review
Authors: Zhuqing Wan, Ping Zhang, Longwei Lv, Yongsheng Zhou
Journal: Theranostics (2020)

Recently, the rapid development of biomaterials has induced great interest in the precisely targeted treatment of bone-related diseases, including bone cancers, infections, and inflammation. Realizing noninvasive therapeutic effects, as well as improving bone tissue regeneration, is essential for the success of bone‑related disease therapies. In recent years, researchers have focused on the development of stimuli-responsive strategies to treat bone-related diseases and to realize bone regeneration. Among the various external stimuli for targeted therapy, near infrared (NIR) light has attracted considerable interests due to its high tissue penetration capacity, minimal damage toward normal tissues, and easy remote control properties. The main objective of this systematic review was to reveal the current applications of NIR light-assisted phototherapy for bone-related disease treatment and bone tissue regeneration. Database collection was completed by June 1, 2020, and a total of 81 relevant studies were finally included. We outlined the various therapeutic applications of photothermal, photodynamic and photobiomodulation effects under NIR light irradiation for bone‑related disease treatment and bone regeneration, based on the retrieved literatures. In addition, the advantages and promising applications of NIR light-responsive drug delivery systems for spatiotemporal-controlled therapy were summarized. These findings have revealed that NIR light-assisted phototherapy plays an important role in bone-related disease treatment and bone tissue regeneration, with significant promise for further biomedical and clinical applications.
Organizational partnership to expand the ASCO Quality Training Program to oncology pharmacists.
Authors: Emily R. Mackler, Amy Morris, George W. Carro, Vedner Guerrier, Gene Cunningham, Terry Gilmore, Michael Kenneth Keng
Journal: Journal of Clinical Oncology (2020)

198 Background: Pharmacists have a recognized role in optimizing medication management and enhancing patient quality of care. In an effort to enhance knowledge related to oncology quality improvement (QI), the Hematology/Oncology Pharmacy Association (HOPA) partnered with the American Society of Clinical Oncology (ASCO) Quality Training Program (QTP) to provide a 1-day HOPA-ASCO QTP Workshop. Methods: HOPA’s Quality Oversight Committee identified several areas of priority focus, including identifying and developing opportunities for members to participate in education focused on oncology value and quality-based patient care. The ASCO QTP program most closely met HOPA goals for training due to the practical outcomes associated with the program, the interdisciplinary focus, the successful experience of prior HOPA-member participants, and expertise of the faculty. In addition, both organizations have a unified goal in improving the care of cancer patients. Surveys were formulated to assess knowledge pre- and post-participation and actionable efforts participants made given knowledge gained from the workshop. Results: A total of 24 HOPA members participated in the 1-day workshop with 40% having been in oncology practice for 15+ years and 70% involved in some aspect of QI within their role. Primary reasons for participation were – to help lead oncology multidisciplinary initiatives in my organization (44%), to increase skills to complete QI projects (28%), and to help lead oncology pharmacy practitioners in my organization (20%). Measures of knowledge and competence increased after participation. Knowledge increased by an average of 3 points from 4.57 to 7.55 (0-10 scale) and competence increased an average of 2.8 points from 4.48 to 7.32. In a 3-month follow-up survey (67% response rate), the majority (93%) of participants indicated they were very likely or extremely likely to use the skills gained from the workshop in practice and 88% of respondents indicated they used the skills gained from the program somewhat often, very often or extremely often. Since the 9 months from the workshop, 2 pharmacists who participated have enrolled in the ASCO QTP 6-month course. Conclusions: The 1-day HOPA-ASCO QTP Workshop proved to be a successful partnership between the two organizations, providing excellent training and education to HOPA members. Next steps of this collaboration include additional 1-day workshops available to more members and a modified 6-month ASCO QTP program for HOPA members with oncology pharmacists serving as the interdisciplinary team leader.