tbuckley/cabot-search huggingface dataset:
Trends in use of ovarian suppression (OS) for premenopausal patients with early-stage hormone positive breast cancer and Intermediate Risk (IR) Oncotype Recurrence Scores (RS) from 2006-2020: A retrospective database analysis.
Authors: Sara Malin Hovstadius, Brittney Shulman Zimmerman, Shana Berwick, Julia Blanter, Natalie F Berger, Erin Moshier, Asem Berkalieva, Shabnam Jaffer, Krystal Pauline Cascetta, Amy Tiersten
Journal: Journal of Clinical Oncology (2021)

e12522 Background: Oncotype RS is a 21-gene assay used to predict the risk of recurrence and benefit from chemotherapy in early-stage, hormone positive (HR+), node-negative breast cancer (BC). The TAILORx trial showed that many patients with RS&lt;25 can avoid chemotherapy and the small absolute benefit may be due to chemotherapy-induced menopause in premenopausal patients. The SOFT-TEXT trials found that premenopausal women have higher rates of freedom from recurrence and 8-year survival when receiving OS with endocrine therapy (ET). These studies suggest that premenopausal women with IR RS (16-25) benefit from aggressive ET with OS but trends in OS use have not been adequately studied. We predict that OS use has increased in premenopausal patients over time. Methods: We identified 87 premenopausal patients with early-stage, HR+ BC with IR Oncotype RS (16-25) who were treated with ET between 2006-2020 at our large NYC academic cancer center. The Cochran-Armitage test was used for trends in the proportions of patients receiving OS and chemotherapy over time. The log-rank test was used to compare distributions of recurrence rates between RS groups. Results: Median age was 46 years and median RS was 19. Overall, 23 (26%) patients received chemotherapy and 30 (34%) received OS (via leuprolide, goserelin or surgical oophorectomy) with ET. 55 (63%) received tamoxifen alone, 10 (11%) tamoxifen + OS, and 20 (23%) aromatase inhibitor (AI) + OS. Between 2006-2010, 2 (17%) patients received OS and 2 (17%) received chemotherapy compared to 9 (24%) and 12 (32%) between 2011-2015, and 19 (51%) and 9 (24%) between 2016-2020, respectively (Table). There was a significant increasing proportion of patients receiving OS; p=0.0064, but no significant trend in chemotherapy receipt; p=0.8910. There were 8 (9%) patients that recurred, with a borderline significant difference in secondary invasive breast event rates in patients receiving tamoxifen alone (8, 15%) compared to those on tamoxifen + OS or AI + OS (0, 0%), (p=0.0520). There were no significant differences in recurrence rates based on chemotherapy receipt (p=0.1868) or RS group 16-20 vs 21-25 (p= 0.1836). Conclusions: There has been a significant increase in the use of OS with ET in premenopausal women with IR RS in our study population. This study shows how the results of the SOFT-TEXT trial have been adapted into current practice. Future studies are needed to evaluate real-world recurrence rates with the use of increased OS and whether chemotherapy rates have decreased over time.[Table: see text]
Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial
Authors: Siddharth Jain, Varun Dhir, Amita Aggarwal, Ranjan Gupta, Bidyalaxmi Leishangthem, Shankar Naidu, Aastha Khullar, Supriya Maurya, Veena Dhawan, Shefali Khanna Sharma, Aman Sharma, Sanjay Jain
Journal: Annals of the Rheumatic Diseases (2021)

There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX.This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat.178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen.A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially.CTRI/2018/12/016549.
Are SARS-CoV-2 Human Challenge Trials Ethical?
Authors: Daniel P. Sulmasy
Journal: JAMA Internal Medicine (2021)

A clinical trial is underway in the UK in which young, healthy participants are exposed deliberately to SARS-CoV-2 to assess the viral inoculum needed to produce an infection and to test vaccine efficacy (NCT04740320). 1 Each participant will be paid approximately $6200.Although the very idea of such a study might seem unethical, there is a long history of deliberate infection of humans for research. 2Such studies are called challenge studies or controlled human infection trials and involve deliberate exposure to pathogens to study the natural history, treatment, or prevention of infectious diseases.Challenge trials have a checkered ethical history, such as German and Japanese experiments during World War II, US sexually transmitted disease experiments in Guatemala after the war, and the Willowbrook hepatitis experiments that only ended in 1972. 2 Yet most recent studies have been conducted ethically, ensuring consent and participants' welfare. 3Challenge trials have contributed to important medical advances, such as the yellow fever vaccine.They can speed the development of treatments and cut research costs and have the potential to help many people, perhaps hundreds of millions in a pandemic.Yet the end does not necessarily justify the means.The importance of having ethical principles in the first place is that they can be relied on, especially under extraordinary circumstances.Pandemic exceptionalism should be avoided. 4ome have advocated strongly for SARS-CoV-2 challenge trials. 5Therefore, it is important to examine how the UK COVID-19 challenge trial measures up against ethical criteria. 6Informed consent is a necessary, but not a sufficient, protection for research participants, particularly for a challenge trial.Although intended to advance medical knowledge rather than to benefit participants clinically, human medical research is a part of the medical enterprise, which is conditioned by the ethics of medicine as a profession.Physicians have recognized since Hippocrates the ethical importance of avoiding harm.In challenge trials, the participants are deliberately put at risk for the sake of helping unnamed future patients, and there is a special obligation to limit the likelihood and potential magnitude of the harm they might face.Importantly, challenge trials add the risk of the infective agent to the already substantial risks of the experimental intervention being investigated.The ethical mandate to limit the harm to those who volunteer for such trials is very strong.Consent is but one of several ethical considerations that ought to govern a decision to permit a challenge trial.Broadly speaking, these considerations also include the social and scientific warrant for the trial, nonmaleficence, and justice.These ethical considerations also be used to assess the UK COVID-19 challenge trial.
Knitting to improve cognition and reduce stress in cancer survivors: A pilot study.
Authors: Jennifer W Hartzell, Susan Yaguda, Danielle Boselli
Journal: Journal of Clinical Oncology (2021)

e24049 Background: Cancer-related cognitive impairment (CRCI), or “chemo brain,” is defined by mild cognitive changes before, during or after cancer treatment. Objective deficits on neuropsychological tests are mild, while distress about cognitive issues is often high and interventions are lacking. Skill learning, which relies upon implicit memory, promotes functional and structural neuroplasticity. This has not been explored in CRCI. We designed a standardized protocol for learning to knit over 8 weeks and recruited consecutive cancer patients with subjective cognitive concerns. Cognition and perceived stress were assessed before and after learning to knit. Methods: Sixteen cancer survivors (N=16) without any known central nervous system disease or prior knitting experience completed the study. All were female and &gt;80% were Caucasian. Mean age was 54 (SD=7) years. Mean education was 16 (SD=2) years. Neuropsychological tests were selected based on sensitivity to frontal lobe functions and memory and resistance to practice effects. Cognition and perceived stress were measured before and after the intervention, summarized, and compared using paired t-tests. P&lt;0.1 was considered statistically significant. Clinically significant cognitive change was defined by ≥1 standard deviation change between pre- and post-intervention standardized scores. Results: Baseline cognitive function was average across domains. Baseline perceived stress was moderately high. At post-testing, there were statistically significant improvements in perceived stress, cognitive flexibility, and psychomotor speed. After controlling for demographic factors, clinically significant improvements in attention and memory were seen in 38% and 25% of subjects, respectively. 69% had clinical improvement in at least one cognitive domain. Conclusions: Learning to knit produced statistically and clinically significant improvements in cognition and perceived stress in cancer survivors in 8 weeks. Most had clinical improvement in at least one cognitive domain. This skill-based pilot study suggests functional neuroplastic change is possible in selected female, college-educated cancer survivors in a short timeframe and without technology use. Future research on the impact of skill learning on cognition and stress in larger, more diverse samples of cancer survivors may yield much needed interventions for CRCI.[Table: see text]
A precision dosing application for prostate cancer patients treated with docetaxel and G-CSF.
Authors: Claire Villette, Christian Hurry, Hitesh Mistry, Jim Millen, Christophe Chassagnole
Journal: Journal of Clinical Oncology (2021)

e13585 Background: The aim of this study is to produce a precision dosing application for clinicians to control neutropenia in prostate cancer patients treated with both docetaxel and G-CSF. Chemotherapy-induced neutropenia (CIN) poses serious harm to patients due to the heightened risk of severe infection. Accordingly, chemotherapy dose is assessed at the beginning of each cycle. The therapeutic window of chemotherapy is determined from population studies, with an individual’s dose often scaled by their body surface area. This leads to a large number of patients being over- or under- dosed. We previously developed an application [1] which uses weekly neutrophil counts from the first cycle of docetaxel treatment to predict the level of neutropoenia in subsequent cycles for a given dose of docetaxel. However, in the original app the administration of G-CSF, used as a prophylactic treatment for neutropenia, was not considered. G-CSF administration lacks standardisation and the COVID-19 pandemic has created a highly risk adverse environment to infections, raising the prospects that a clinician will administer G-CSF. Methods: We adapted and combined representations of endogenous and exogenous G-CSF action on CIN from the literature [2,3,4] to capture the inherent feedback effect of circulating neutrophils on progenitor proliferation as well as the stimulatory action of G-CSF injection on proliferation and maturation of progenitor cells. Using data in the public domain from the comparator arm of a phase III clinical trial for metastatic hormone-resistant prostate cancer (NCT00617669), we identified 134 patients treated with docetaxel with recorded weekly blood tests in the first and second cycle, including 27 also receiving G-CSF. We calibrated individualised patient models against neutrophil counts measured in the first cycle by minimising a Bayesian objective function and evaluated their ability to predict the levels observed in the second cycle. Results: The model was able to capture the main features of endogenous and exogenous G-CSF action on neutrophil count described in the literature, including endogenous-G-CSF-mediated rebound above baseline after chemotherapy-induced depletion [4], rapid rise in neutrophil count following exogenous G-CSF administration [5], as well as reduced chemotherapy-induced depletion and earlier recovery under G-CSF treatment compared to chemotherapy alone [5]. Conclusions: This tool has the potential to help determine how a docetaxel patient may best benefit from G-CSF treatment and/or a change in dose of docetaxel. References: Villettte C., et al., AACR; Cancer Res, 2019;79(13 Suppl): Abstract nr 677. Pastor, M.L., et al. 2013. Pharm. Res, 30(11), pp.2795-2807. Krzyzanski, W., et al. 2010. J. Clin. Pharmacol, 50(S9), pp.101S-112S. Quartino, A.L et al., 2014. Pharm. Res, 31(12), pp.3390-3403. Crawford, J., et al. 1991. N. Engl. J. Med, 325(3), pp.164-170.
Diffuse cystic lung disease in sickle cell anaemia: a series of 22 cases and a case–control study
Authors: Fatma Kort, Anoosha Habibi, Francois Lionnet, Marie-France Carette, Antoine Parrot, Laurent Savale, Hilario Nunes, Bernard Maitre, Frederic Schlemmer, Jean-Marc Naccache
Journal: Thorax (2021)

Chronic interstitial lung abnormalities have been described in sickle cell disease (SCD) and attributed to repetitive episode of acute chest syndrome. We report a series of 22 cases of diffuse cystic lung disease in SCD with a case-control study to hunt for mechanism. On pathological analysis of a surgical lung biopsy of the index case, the bronchioles had the appearance of constrictive bronchiolitis. Pulmonary function test results revealed lower forced expiratory flow from 25% to 75% of vital capacity in cases versus controls. These findings suggest a bronchiolar mechanism that was not associated with more acute chest syndrome.
Final results from the CAVE (cetuximab rechallenge plus avelumab) mCRC phase II trial: Skin toxicity as a predictor of clinical activity.
Authors: Giulia Martini, Stefania Napolitano, Vincenzo Famiglietti, Filippo G. De Braud, Marinella Terminiello, Carola Borrelli, Pietro Paolo Vitiello, Antonio Avallone, Nicola Normanno, Evaristo Maiello, Alfredo Falcone, Giuseppe Santabarbara, Carmine Pinto, Daniele Santini, Alessandra Di Liello, Daniela Renato, Lucia Esposito, Francesca Marrone, Teresa Troiani, Davide Ciardiello
Journal: Journal of Clinical Oncology (2021)

3578 Background: Promising antitumor activity of so called rechallenge treatment with anti-epidermal growth factor receptor (EGFR) drugs in patients with RAS wild type (RAS WT) metastatic colorectal cancer (mCRC) has been recently reported. Beside the absence of resistance mutations at plasma circulating tumor DNA (ctDNA) analysis, no biomarkers of response to anti-EGFR rechallenge strategy have been identified. Methods: We conducted the single arm phase II CAVE mCRC trial to evaluate the combination of cetuximab as rechallenge plus avelumab treatment in 77 RAS WT mCRC patients, with complete (CR) or partial response (PR) to first line chemotherapy plus anti-EGFR drugs, who developed acquired resistance and received a subsequent line of therapy. A post-hoc baseline analysis of circulating tumor DNA (ctDNA) for KRAS, NRAS, BRAF and EGFR-S492R mutations was performed for 67/77 (87%) patients. The correlation of skin toxicity (ST) and other clinical variables with OS, PFS and response rate (RR) was assessed. Results: Cetuximab plus avelumab provided in the intention to treat population (ITT) median overall survival (mOS) of 11.6 months [95% Confidence Interval (CI), 8.4-14.8] and median PFS (mPFS) of 3.6 months (95% CI, 3.2-4.1) with a manageable toxicity profile. Thirty-three (42.9%) patients experienced grade 2-3 ST with mOS of 17.8 months (CI 95% 14.9-20.7), whereas 44 (57.1%) patients with grade 0-1 ST exhibited mOS of 8.2 months (CI 95% 5.6-11), (HR 0.51, CI 95% 0.29-0.89, P = 0.019). mPFS was 4.6 months (CI 95% 3.5-5.8) in patients with grade 2-3 ST, compared to 3.4 months (CI 95% 2.8-4.1) in patients with grade 0-1 ST (HR 0.49, CI 95% 0.3-0.8, P = 0.004). Grade 2-3 ST and baseline RAS/BRAF/EGFR WT ctDNA were the only variables with statistically significant effect on OS both at univariate and multivariate analyses. ST, number of metastatic sites ≤2, surgery of primary tumor and RAS/BRAF/EGFR WT ctDNA were associated with an improvement in PFS only at univariate analysis. In the 33 patients with grade 2-3 ST, 1 (3%) CR, 2 (6.1%) PR and 24 (72.7%) stable disease (SD) were observed, with disease control rate (DCR) of 81.8%. In the 44 patients with grade 0-1 ST 0 CR, 3 (6.8%) PR, 20 (45.5%) SD, with 52.3% DCR were reported. Conclusions: Cetuximab plus avelumab is effective and well tolerated as rechallenge treatment in mCRC. ST is a clinical biomarker for the identification of RAS/BRAF mCRC patients that could benefit from anti-EGFR rechallenge. Clinical trial information: NCT04561336.
Prevalence and outcomes of sepsis in HIV versus non-HIV patients with diffuse large B-cell lymphoma: A nationwide analysis.
Authors: Muhammad Junaid Tariq, Binav Baral, Prasanth Lingamaneni, Vedavyas Gannamani, Muhammad Usman Almani, Shweta Gupta, Paul G. Rubinstein
Journal: Journal of Clinical Oncology (2021)

e19567 Background: With the advent combined anti-retroviral therapy (ART), the survival of people living with HIV has improved, thereby increasing their prevalence, while concurrently decreasing the incidence AIDS defining malignancies. Despite its decrease, AIDS-related Diffuse Large B-Cell Lymphoma (DLBCL) remains the 3 rd most common malignancy in the HIV population and an important cause of cancer related morbidity and a leading cause cancer attributed mortality. Currently the treatment modalities between HIV and non-HIV DLBCL are similar, however a comparison of the infectious complications has never been assessed. We aim to explore the prevalence and outcomes of sepsis in persons living with HIV and DLBCL versus the non-HIV DLBCL patient population. Methods: We identified all adult DLBCL patients admitted between 2016–2018 from The Nationwide Inpatient Sample (NIS) with a primary diagnosis of sepsis. Patients with and without HIV were identified and compared for demographic differences and primary outcomes of inpatient mortality, length of stay (LOS) and hospital charges. Secondary outcomes studied included rates of septic shock, acidosis, Acute Kidney Injury (AKI), Tumor Lysis Syndrome (TLS) pancytopenia, anemia, neutropenia, protein energy malnutrition (PEM) and history of bone-marrow/stem-cell transplant. Statistics were performed using t-Test, chi-square test and multivariable logistic regression. Results: There was a total of 5740 HIV-DLBCL and 158,445 non-HIV-DLBCL inpatient admissions of which 480 (8.4%) and 16085 (10.1%) respectively had sepsis (p &lt; 0.0001). Compared to non-HIV cohort, HIV-DLBCL patients were significantly younger (47.5 versus 67 years, p &lt; 0.001), more likely to be male (66.7% vs 55.3%, p = 0.02), Black (43% vs 7.7%) or Hispanic (18% vs 11%) (p &lt; 0.001), more likely to be on Medicaid (44.9% vs 8.2%, p &lt; 0.001) and lived-in low-income zip-codes (p &lt; 0.0001). Overall adjusted inpatient mortality was not significantly different between HIV and non-HIV groups (14.6% vs 16.9%, p = NS). But HIV-DLBCL patients had significantly high Chalrson co-morbidity index (p &lt; .0001), longer inpatient LOS (8.75 vs 8.65 days, p &lt; 0.0001) and higher total hospital charges (average $5338 higher for each admission, p &lt; 0.0001). HIV-DLBCL cohort also reported significantly higher TLS (7.3% vs 2.6%, p = 0.005) and PEM (42.7% vs 28.9%, p = 0.004). Other secondary outcomes were not significantly different between the groups. Conclusions: Demographic differences between the two cohorts are reflective of known racial &amp; socio-economic disparities associated with HIV. Lower rates of sepsis in HIV cohort were not translated into improved inpatient mortality. Longer LOS and hospitalization charges in HIV patients likely due to high comorbidity burden.
Career Advancement for Women in Diabetes-Related Research: Developing and Retaining Female Talent
Authors: Darleen A. Sandoval, Laura C. Alonso, Maureen Gannon, Maike Sander, Lori Sussel, Jane E.B. Reusch
Journal: Diabetes Care (2021)

To change the future you need a firm grip on history. Successful implementation of strategies to catalyze evolution of gender parity requires a coherent plan with clear deliverables. The article by Dunne et al. (1,2), simultaneously published in Diabetes and Diabetes Care , provides a much-needed foundation that defines the scope of the problem within the field of diabetes, documents stagnated progress over recent years, and offers suggestions for intervention. We applaud the authors and are encouraged that the American Diabetes Association (ADA) leadership is fully invested in being part of an effective solution. As nationally funded and internationally recognized women leaders in diabetes research, we are compelled to initiate the process of addressing the inequities brought to light by Dunne et al. to enhance the development and retention of female talent in our field. To intiate that process, here we discuss the observations by Dunne et al. and propose a set of concrete measures for achieving gender equity within diabetes-related professions.

Dunne et al. observe that almost half (43%) of the attendees of the annual ADA Scientific Sessions national conference are women, demonstrating strong active participation of women. Women are also well represented in education-focused leadership positions comprising 83% of the then Vice Presidents and now Presidents of Health Care and Education over the last five decades and 89% and 49% of the editorial boards for Diabetes Spectrum and Clinical Diabetes , respectively. In striking contrast, in the last 20 years, only 9% of ADA Presidents of Medicine and Science have been women (1,2), and since the inception of the ADA, only 5 of 81 ADA Presidents of Medicine and Science have been women. Further, women represent one-third or fewer of editorial board members for the highest-impact diabetes journals ( Diabetes Care, Diabetes , and Diabetologia …