tbuckley/cabot-search huggingface dataset:
Prophylaxis of neutropenia with mecapegfilgrastim in patients with non-myeloid malignancies in a real-world setting.
Authors: Jun Ma, Huiqiang Huang, Peifen Fu, Nong Xu, Chenyu Mao, Gang Cheng, Haijiao Yan, Yongqing Li, Yanxia Shi, Yongsheng Wang, Yumin Yao, Liang Chen, Yong Chen, Ningling Zhang, Guifang Zhang, Zhangxia Ren, Zengjun Li, Lihua Song, Shukui Qin
Journal: Journal of Clinical Oncology (2021)

e24072 Background: The prophylaxis of neutropenia has been evolving from short acting granulocyte colony-stimulating factors (G-CSFs) to long acting G-CSFs. The safety and effectiveness of long acting G-CSF in a real-world setting were still lacking. Methods: We performed a multi-center, non-interventional, real-world study to explore the tolerability and effectiveness of mecapegfilgrastim. Different prophylactic strategy (primary or secondary prophylaxis) were compared. The effect of mecapegfilgrastim by means of continuous administration was also explored. Results: This study included 638 patients who had complete the study from May 2019 to November 15, 2020. About half of the participants were breast cancer patients. The mean age of the patients were 56 years. The most frequently reported adverse event possibly related to study drug was white blood cell increase (6.2 %). No unexpected adverse events were reported. Overall, thirty-six (5.6 %) patients experienced grade ≥ 3 neutropenia in chemotherapy cycle one. The patients in the primary and secondary prophylaxis subgroups had incidence of grade ≥ 3 neutropenia of 4.3 % and 9.2 % in chemotherapy cycle one respectively. There was a decreasing trend of neutropenia from cycle one to cycle four when mecapegfilgrastim were administrated continuously. Conclusions: The mecapegfilgrastim was well tolerable and no unexpected adverse events were observed in real-world setting. Primary prophylaxis using mecapegfilgrastim had lower incidence of neutropenia than secondary usage.
Medicaid patients more likely to die at home without hospice during the pandemic versus before, exacerbating disparities with commercially insured patients.
Authors: Laura Elizabeth Panattoni, Li Li, Qin Sun, Catherine R. Fedorenko, Hayley Sanchez, Karma L. Kreizenbeck, Veena Shankaran, Scott David Ramsey
Journal: Journal of Clinical Oncology (2021)

6502 Background: The COVID-19 pandemic dramatically reduced family access to hospitals and created new barriers to home hospice care, raising concerns about how the pandemic has impacted cancer patients’ place of death and end of life home hospice support. Hypothesizing that Medicaid-enrolled cancer patients may be at greater risk of disruptions in end-of-life care compared to commercially insured patients, we examined changes in place of death and home hospice support for Medicaid and Commercial enrollees following the pandemic. Methods: We linked WA State cancer registry records with claims from Medicaid and approximately 75% of commercially insured cancer patients in the state. Patients ages 18-64 with solid-tumor malignancies who died March-June 2020 (COVID) were compared to those who died March-June 2017-2019 (Pre-COVID). Place of death was categorized as hospital, home with hospice, and home without hospice; nursing home deaths were excluded. Given our sample size, we examined differences in the likelihood of place of death with Fisher’s exact tests and multinomial logistic regressions stratified by payer and by COVID period, controlling for age, gender, race, stage, cancer type, and census tract-level neighborhood deprivation. We report marginal effects. Results: In Fisher’s exact analyses, Medicaid but not commercial patients were significantly less like to die in hospital and more likely to die at home without hospice during COVID (Table). In pre-post adjusted analysis of Medicaid patients, the probability of dying in the hospital was 12.3% (p=0.03) percentage points lower during the pandemic versus before, while the probability of dying at home without hospice was 11.1% (p=0.04) greater. Place of death did not change significantly pre-post for commercial patients. In addition, Pre-COVID, the probability of dying in the hospital was 10.7% (p=0.03) greater for Medicaid than commercial patients. During COVID, the probability of dying at home without hospice was 15.8% (p=0.04) greater for Medicaid versus commercial patients but lower for women (ME=20.2%; p=0.01) and colorectal versus breast cancer patients (ME=39.2%; p=0.01). Conclusions: Following COVID, Medicaid patients place of death shifted from hospital to homes, but without an increase in the use of home hospice services. In contrast, place of death and hospice use among commercial patients did not significantly change. This widening disparity in home deaths without hospice services raises concerns that the pandemic disproportionately worsened end of life experience for low income patients with cancer.[Table: see text]
Primary urachal carcinoma: A systematic review.
Authors: Dawood Findakly, Jue Wang
Journal: Journal of Clinical Oncology (2021)

e16502 Background: Primary urachal carcinoma (PUC) is a rare cancer of unknown definite cause, and various treatment approaches given its very low incidence and the scarcity of prospective studies. This review aimed to assess the clinicopathologic findings, treatment, and outcomes of PUC cases reported in the literature. Methods: We performed PubMed, Medline, ScienceDirect, and Scopus literature search for "urachus cancer" in adults (19+ years) from data inception through 2020, pooled with six cases from our institution. Results: We included 152 patients with a male: female ratio of 1.61:1 and mean age at diagnosis (±SD, range) of 50.0 (±13.5, 20–86) years. Most common presenting symptoms were hematuria, irritative voiding, abdominal pain, mucinuria, and a palpable mass in 49.5%, 17.3%, 10.2%, 8.7%, and 6.6% of patients, respectively, with a median duration of symptoms of 3 (range 0.25-240) months. Most common locations were the urinary bladder dome (83.6%), supero-anterior (7.03%), and the anterior wall (3.9%), with a median size of 4.9 (range 0.5–96) cm. Subgroups, according to tumor size, were divided into &lt; 4 cm (n = 54, 35.5%) vs ≥4 cm (n = 98, 64.5%) with a significant survival differences according to a log-rank test (p-value &lt; 0.0001). Histologically, the most common diagnoses were urachal adenocarcinoma (43.4%), followed by mucinous adenocarcinoma (24.1%), adenocarcinoma of enteric type (8.9%), and adenocarcinoma with signet ring cell (6.9%). 17.5% and 72.2% of patients were diagnosed at an early stage (stage I and II) while 82.5% and 27.8% were diagnosed at an advanced stage ( III and IV) using Sheldon staging system and Mayo staging system, respectively. Only 9.9% of patients lived for more than five years after their diagnosis. Early Sheldon stage is associated with a high survival probability based on a log-rank test (p-value: 0.003). Overall, most common treatment modalities included surgery alone (71.0%), followed by surgery with chemotherapy (18.6%), and surgery with chemoradiation (4.1%). Patients underwent partial cystectomy (65.4%), en bloc radical resection/exenteration (25.7%), local resection (8.8%), pelvic lymphadenectomy (38.2%), and umbilectomy (16.9%). Almost 79% of patients were alive with an average duration of follow-up of 12 (range 0.9-240) months, and 20.9% were deceased with an average time to death of 23.9 (range 5-139) months. Conclusions: Early Sheldon stage and smaller tumor size were notable predictors of higher survival probability in PUC patients. Hence, early and correct diagnosis is crucial in improving outcomes. This review serves as real-world evidence to promote our understanding of this rare entity and shed light on future clinical trial design.
Arterolane–piperaquine–mefloquine versus arterolane–piperaquine and artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial
Authors: Mainga Hamaluba, Rob W van der Pluijm, Joseph Weya, Patricia Njuguna, Mwanajuma Ngama, Peter Kalume, Gabriel Mwambingu, Caroline Ngetsa, Juliana Wambua, Mwanamvua Boga, Neema Mturi, Altaf A Lal, Arshad Khuroo, Walter R J Taylor, Sónia Gonçalves, Olivo Miotto, Mehul Dhorda, Brian Mutinda, Mavuto Mukaka, Naomi Waithira, Richard M Hoglund, Mallika Imwong, Joel Tarning, Nicholas P J Day, Nicholas J White, Philip Bejon, Arjen M Dondorp
Journal: The Lancet Infectious Diseases (2021)

Triple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children.
Racial Adjustment Adversely Affects Glomerular Filtration Estimates in Black Americans Living with HIV
Authors: Mohamed G. Atta, Katie Zook, Todd T. Brown, Dhananjay Vaidya, Xueting Tao, Paula Maier, George J. Schwartz, Gregory M. Lucas
Journal: Journal of the American Society of Nephrology (2021)

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimating equations are commonly reported by clinical laboratories and used by clinicians to estimate GFR from intrinsic biomarkers (creatinine [eGFRcr], cystatin C, or both biomarkers [eGFRcr-cys]).[1][1][⇓][2]–[3][3] In the
Towards racial equity in global mental health research
Authors: Dixon Chibanda, Helen E Jack, Lisa Langhaug, Atalay Alem, Melanie Abas, Walter Mangezi, Charlotte Hanlon, Katherine Sorsdahl, Ashraf Kagee, Helen Weiss, Rosemary Musesengwa, Khameer Kidia, Michael Udedi, Definate Nhamo, Wubalem Fekadu, Mekdes Demissie, Crick Lund
Journal: The Lancet Psychiatry (2021)
Edward Sumner: paediatric anaesthetist who developed intensive care at Great Ormond Street Hospital
Authors: Joanna Lyall
Journal: BMJ (2021)

Ted Sumner, who has died aged 80, attributed his successful career to a fall from the top of a climbing rope in childhood. Having broken both legs he had to repeat a year at school and discovered the joy of studying. “I became academic,” he later recalled.

Appointed as consultant paediatric anaesthetist at Great Ormond Street Hospital (GOSH) in 1973 he found postoperative care “19th century.” Ventilated patients were spread throughout the hospital with huge, primitive ventilators being wheeled to wards as needed. Fourteen years after his arrival at the hospital he wrote that paediatric intensive care—for the needs of children from 4 weeks to 16 years—was still in its infancy in the UK. “Newborns and adults are well catered for, but at least one third of paediatric admissions to intensive care in Britain are still into adult, …
Methylated DNA markers for monitoring palliative chemotherapy response in advanced colorectal cancer.
Authors: Mojun Zhu, Douglas W. Mahoney, Kelli Burger, Patrick H. Foote, Karen A. Doering, William R. Taylor, Sara S. Then, Hao Xie, Hatim T. Allawi, Michael W. Kaiser, Graham P. Lidgard, Joleen M. Hubbard, John B. Kisiel
Journal: Journal of Clinical Oncology (2021)

e15511 Background: Aberrantly methylated DNA marker (MDM) candidates are strongly associated with primary colorectal cancer (CRC) before treatment and detect CRC recurrence with high sensitivity when assayed from plasma. The relationship of these MDMs in association to chemotherapy treatment response is unknown. Methods: In a prospective cohort of patients receiving systemic therapy for advanced CRC, peripheral blood was collected serially during restaging visits. 15 patients were retrospectively identified to have partial response (PR), stable disease (SD) and progressive disease (PD) to treatment (n=5 for each group) based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Using paired samples from each patient before and after response assessment, we analyzed 11 MDMs ( GRIN2D, ZNF671, ANKRD13B, QKI, VAV3, JAM3, SFMBT2, CHST2, ZNF568, FER1L4 and CNNM1) to assess correlation with treatment response. Cell-free DNA was extracted and bisulfite treated before MDMs were quantified by target enrichment long-probe quantitative-amplified signal assay and normalized to a methylated sequence of B3GALT6. Continuous variables are summarized as a median with corresponding interquartile ranges (IQR) and comparisons between subgroups were based on the Wilcox Rank Sums test. Results: The median interval between pre- and post-response assessment visits was 69 days (IQR: 63-83 days) and the level of tumor burden at pre-assessment was similar across all response types (Table 1). Patients with PD had higher levels of methylated GRIN2D, ZNF671 and ANKRD13B than those with PR or SD at baseline and may offer additional prognostic value over CEA which was similar in the PR and PD groups before treatment (Table 1). Elevation of pre-assessment MDMs preceded radiographic evidence of disease progression by 82 days (IQR 69-83 days). Conclusions: Three MDMs, GRIN2D, ZNF671 and ANKRD13B, were found to reflect treatment response (PD vs. PR + SD) as shown in the table. Although this pilot study was limited by a small sample size, it demonstrated the feasibility of using plasma-based MDMs in monitoring treatment response to systemic therapy for advanced CRC and should be compared to CEA in a larger study.[Table: see text]
Analysis of patients (pts) with in-transit metastases treated with nivolumab (NIVO) or ipilimumab (IPI) in CheckMate 238.
Authors: James Larkin, Helen Gogas, Michele Del Vecchio, Michele Maio, Petr Arenberger, Ana Maria Arance, Jean-Jacques Grob, Vanna Chiarion-Sileni, Karl D. Lewis, Laurent Mortier, Patrick Alexander Ott, Georgina V. Long, Alfonsus Van Den Eertwegh, C. Lance Cowey, Michael Schenker, Marcus O. Butler, Maurice Lobo, Margarita Askelson, Paolo Antonio Ascierto, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2021)

9569 Background: In the phase 3 CheckMate 238 study, NIVO has demonstrated improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) vs IPI in pts with resected stage IIIB–C or IV melanoma, which was sustained at the 4-y analysis. Having in-transit metastases/satellites (ITM) is a poor prognostic factor, and pts with ITM are generally omitted from clinical trials. This study was the first and only adjuvant checkpoint inhibitor trial to include pts with ITM. Here, we present post hoc outcomes in this subgroup. Methods: Pts aged ≥15 y with completely resected stage IIIB–C or IV melanoma stratified by stage and tumor PD-L1 status were randomized 1:1 to NIVO (3 mg/kg Q2W; n = 453) or IPI (10 mg/kg Q3W for 4 doses, Q12W thereafter; n = 453) for a maximum of 1 y or until disease recurrence/unacceptable toxicity. Pts with ITM, with or without synchronous nodal involvement, were included. The primary study endpoint was RFS; overall survival (OS) was a secondary endpoint; and DMFS was exploratory. Results: Each of the 2 treatment groups had 164 pts with ITM. Baseline characteristics were generally similar between treatment groups in pts with or without ITM; in pts with ITM vs without ITM, tumor ulceration was less frequent in NIVO-treated pts, and fewer IPI-treated pts had PD-L1 expression ≥5%. RFS and DMFS favored NIVO vs IPI in all ITM subgroups (table). OS was similar to the intention-to-treat (ITT) population with no differences noted between treatment groups or between ITM subgroups. Among pts with or without ITM, dominant metastatic sites were lung and lymph nodes, followed by brain, liver, and soft tissue (in varying order). Similar metastasis patterns were observed in pts with ITM regardless of nodal involvement. Treatment-related adverse events (any grade and grade 3/4) in pts with ITM were similar to those of the ITT population. Conclusions: Results of this post hoc 4-y analysis of CheckMate 238 showed that safety and efficacy were similar in pts with or without ITM, supporting the use of adjuvant NIVO in pts with ITM, regardless of nodal involvement. Clinical trial information: NCT02388906. [Table: see text]
A phase 1 study of RTX-321, an engineered red blood cell as an artificial antigen-presenting cell expressing HLA-A*02 with the HPV-16 E7 peptide and 4-1BB ligand with membrane-bound IL-12 for the treatment of HPV 16-positive cancers.
Authors: Johanna C. Bendell, Alexander I. Spira, Ramez Nassef Eskander, Ezra E.W. Cohen, Geoffrey Kuesters, Christopher Plescia, Karen Campbell, Tiffany Chen, Omid Hamid
Journal: Journal of Clinical Oncology (2021)

TPS2664 Background: High-risk strains of HPV (HPV 16/18) have been associated with the development of multiple cancers, and the associated viral antigens are validated targets from immunotherapy approaches. We engineered red blood cells into allogeneic, off-the-shelf, artificial antigen-presenting cells (aAPCs) that express a human papillomavirus (HPV) 16 E7 peptide bound to human leukocyte antigen (HLA)-A*02:01, the costimulatory molecule 4-1BB ligand (L), and the cytokine interleukin (IL)-12 on the cell surface. This aAPC, RTX-321, activated HPV specific T-cells and promoted effector function in vitro. In animal models using a murine surrogate system, this aAPC approach resulted in robust antigen-specific T-cell expansion, NK cell expansion, tumor control, memory formation and antigen spreading, which led to a broad and robust antitumor immune response . The presence of 4-1BBL and IL-12 induced minimal toxicities in these models due to restriction of the biodistribution of the aAPC to the vasculature and spleen. RTX-321 is a potential in vivo cellular immunotherapy for treating HPV 16-positive cancers including cervical, head and neck and anal cancers. Methods: The RTX-321-01 study is a phase 1 multi-center, dose-escalation study of RTX-321 administered intravenously every 3 weeks in HLA-A*02:01-positive patients with relapsed or refractory HPV 16-positive cancers of the cervix or anal canal, or squamous cell cancers of the head and neck (HNSCC). Patients with cervical cancer or HNSCC will undergo testing for the presence of the HPV 16 virus or provide confirmation from archival tumor tissue prior to enrollment. Patients with anal cancer will not be required to have prospective determination of HPV 16-positive status prior to enrollment given the high incidence in this indication (approximately 80-85 percent of anal cancers). Approximately 18 patients will be enrolled across dose level cohorts to identify the recommended phase 2 dose (RP2D) of RTX-321, followed by RP2D expansion cohorts in specific indications. The starting dose is 1 billion (1x10 9 ) cells administered intravenously every 3 weeks (Q3W) and the dose will escalate by half-log increments, following a Bayesian logarithmic regression model (BLRM) with overdose control. Translational studies will investigate the activation and expansion of HPV16 E7 antigen-specific responses as well as broad innate and adaptive responses in multiple peripheral blood samples over the first 3 cycles of therapy as well as in optional paired tumor biopsies. At this time, the study is open and enrolling patients in the first dose escalation cohort (NCT04672980). Clinical trial information: NCT04672980.
Description of asymptomatic cancer patients with COVID-19 infection: Experience of the ACHOCC-19 study in one Latin American country.
Authors: Aylen Vanessa Ospina Serrano, Ricardo Elias Bruges Maya, William Armando Mantilla, Ivan Camilo Triana, Pedro Ramos, Sandra Aruachan, Alicia Quiroga, Isabel Munevar, Juan Ortiz, Nestor Llinas, Paola Pinilla, Henry Vargas, Henry Idrobo, July Andrea Russi Noguera, Ray Manneh Kopp, Giovanna Patricia Rivas, Hector Alirio Gonzalez Florez, Daniel Andres Santa, Jesus Insuasty, Gilberto Lopes
Journal: Journal of Clinical Oncology (2021)

e18761 Background: Cancer has been described as a risk factor for worse prognosis in people with Covid-19. However, there are few studies informing on the characteristics of cancer patients that have asymptomatic SARS-cov2 infection. The ACHOCC-19 study included asymptomatic patients. Methods: Analytical cohort study of patients with cancer and SARS-cov2 infection in Colombia. From April 1 to October 31, 2020, we collected data on demographic and clinical variables related to cancer and COVID-19 infection. We describe the characteristics and outcomes of patients who had no symptoms of COVID19. Association between outcomes and prognostic variables was analyzed using logistic regression models. Results: We included 742 patients, of which 205 (27.6%) were asymptomatic. Of these 62.2% were older than 61 years, 66% were women, 1.42% were smokers. The most frequent malignancy was breast cancer (25%), followed by colon-rectum (14.6%), sarcoma/soft tissues (5.66%) and lung cancer (5.19%). Patients were more likely to be asymptomatic if they had fewer comorbidities (0-1 comorbidities: 84% asymptomatic, 2 comorbidities: 10.85%, more than 2 comorbidities: 5.15%). 90.5% lived in urban areas and 53.37% had low income. 35.4% of patients had metastatic disease, 8.7% had progressive cancer, 40% had stable disease or partial response. No patient had an ECOG PS of 4 or more, and only 1.91% had ECOG 3. In logistic regression analysis statistically significant associations for having symptomatic disease included: man, presence of 1, 2 or &gt; 2 comorbidities, ECOG 1,2 or 3 and cancer in progression. On the other hand, the statistically significant ORs for having asymptomatic disease were age between 18 and 30 years old, cancer in remission and receiving non-cytotoxic treatment. Table sumarizes ORs and their respective 95% CIs of the variables adjusted in the logistic regression model. Conclusions: In our stumdy, cancer patients had a higher probability of asymptomatic COVID-19 infection if they were women, between the ages of 18 and 30 years, had cancer in remission , ECOG 0 and no comorbidities. This is the first cohort of patients with cancer and asymptomatic covid 19 with a significant sample size in Latin America.[Table: see text]