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Last Modified, May 09, 2021
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A balancing act between primate lentiviruses and their receptor

Proc Natl Acad Sci U S A

2021 Molly OhAinle; Harmit Malik


"I Made All Decisions Myself": Breast Cancer Treatment Decision-Making by Receivers and Decliners

Asia Pac J Oncol Nurs

2021 Robyn Andersen

Objective: Many women with breast cancer refuse adjuvant treatments. How they arrive at their respective decisions and whether they are passively or actively involved in making decisions is less known. We explored the different decision-making behaviors of women who received treatments (receivers) after being diagnosed with breast cancer and those who refused (decliners). Methods: Seven women (four receivers and three decliners) were recruited from the Breast Cancer Integrative Oncology Study. We conducted an inductive content analysis based on in-depth semi-structured interviews with open-ended questions. Results: Receivers reported that doctors and family members influenced their decision-making. Decliners perceived their doctors as supportive of their decisions and reported that the experience of adjuvant therapy of family and friends, the results of Oncotest, and concerns about side effects influenced their decision-making. Receivers expressed discomfort about their decisions, relied on books, whereas decliners used various sources to find information. Both receivers and decliners believed that they had made the decisions themselves. However, receivers were somewhat negative about doctors' advice. Receivers also reported that, sometimes, the decision-making process was lacking and reported discomfort with the treatment process. Conclusions: Women with breast cancer need support in understanding the care they are prescribed and getting essential care.

Association between Menopausal Hormone Therapy and Incidence of Psoriasis: A Secondary Analysis from the Women's Health Initiative Randomized Clinical Trials

Br J Dermatol

2021 Aaron Aragaki

Estrogen level fluctuations have been linked to psoriasis (1); however, the association between menopausal hormone therapy and risk of psoriasis is largely unexplored. We analyzed data from the Women's Health Initiative's (WHI) randomized controlled trials comparing conjugated equine estrogens (CEE) vs. placebo and CEE plus medroxyprogesterone acetate (MPA) vs. placebo to investigate the association between hormone therapy use and psoriasis.

Biomarker evaluation under imperfect nested case-control design

Stat Med

2021 Yingye Zheng

The nested case-control (NCC) design has been widely adopted as a cost-effective sampling design for biomarker research. Under the NCC design, markers are only measured for the NCC subcohort consisting of all cases and a fraction of the controls selected randomly from the matched risk sets of the cases. Robust methods for evaluating prediction performance of risk models have been derived under the inverse probability weighting framework. The probabilities of samples being included in the NCC cohort can be calculated based on the study design ``a previous study'' or estimated non-parametrically ``a previous study''. Neither strategy works well due to model mis-specification and the curse of dimensionality in practical settings where the sampling does not entirely follow the study design or depends on many factors. In this paper, we propose an alternative strategy to estimate the sampling probabilities based on a varying coefficient model, which attains a balance between robustness and the curse of dimensionality. The complex correlation structure induced by repeated finite risk set sampling makes the standard resampling procedure for variance estimation fail. We propose a perturbation resampling procedure that provides valid interval estimation for the proposed estimators. Simulation studies show that the proposed method performs well in finite samples. We apply the proposed method to the Nurses' Health Study II to develop and evaluate prediction models using clinical biomarkers for cardiovascular risk.

Antibodies to vaccine-preventable infections after CAR-T-cell therapy for B-cell malignancies

JCI Insight

2021 Michael Boeckh; Alexandre Hirayama; Cameron Turtle; Jacob Keane-Candib; Justin Taylor; Damian Green; Joshua Hill; Terry Stevens-Ayers; Merav Bar; Elizabeth Krantz; David Maloney; Andrew Cowan; Rebecca Gardner; Joyce Maalouf; Laurel Joncas-Schronce; Carla Walti; Jim Boonyaratanakornkit; Sayan Dasgupta

BACKGROUND: Little is known about pathogen-specific humoral immunity in individuals with long-term remission after treatment with chimeric antigen receptor-modified T-cells (CAR-T-cells) for B-cell lineage malignancies. METHODS: We conducted a prospective cross-sectional study of CD19-targeted or BCMA-targeted CAR-T-cell therapy recipients 6 months post-treatment and in remission. We measured lymphocyte subsets, immunoglobulins, pathogen-specific IgG for 12 vaccine-preventable infections, and the total number of viral and bacterial epitopes to which IgG was detected ('epitope hits') using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections. RESULTS: We enrolled 65 children and adults a median of 20 months after CD19- (n=54) or BCMA- (n=11) CAR-T-cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. Despite this, these individuals had seroprotection to a median of 67% (IQR, 59-73%) of tested vaccine-preventable infections. Proportions of participants with seroprotection per-pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared to CD19-CAR-T-cell recipients, BCMA-CAR-T-cell recipients were half as likely to have seroprotection to vaccine-preventable infections (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22). CONCLUSIONS: Seroprotection for vaccine-preventable infections in adult CD19-CAR-T-cell recipients was comparable to the general population, but BCMA-CAR-T-cell recipients have fewer pathogen-specific antibodies. Deficits in both groups support the need for randomized vaccine and IGRT trials to determine efficacy and risk-benefit.

Sclerotic chronic GVHD: you may WANT to block WNT


2021 Stephanie Lee


Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors

Sci Rep

2021 Petros Grivas; Namrata Singh; Ali Khaki

Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population. In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD), chronic infection and pre-existing systemic steroid use (regardless of dose). Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count > 2.6 k/ul (adjusted [a]OR: 4.30), absolute monocyte count > 0.29 k/ul (aOR: 2.34) and platelet count > 145 k/ul (aOR: 2.23), neutrophil to lymphocyte ratio (NLR) ≤ 5.3 (aOR: 2.07) and monocyte to lymphocyte ratio (MLR) ≤ 0.73 (aOR: 2.96), as well as platelet to lymphocyte ratio ≤ 534 (aOR: 5.05). Patients with pre-existing AD (aOR: 2.57), family history of AD (aOR: 5.98), and ICI combination (aOR: 2.00) had higher odds of irAEs. Baseline NLR ≤ 5.3 (aHR: 0.68), MLR ≤ 0.73 (aHR: 0.43), PLT > 145 (aHR: 0.48) and PLR ≤ 534 (aHR: 0.48) were associated with longer OS. irAEs were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR, MLR and PLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.

Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma

Blood Adv

2021 Donald Patrick; David Maloney

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion. There were no clinically meaningful changes in physical functioning and pain, whereas clinically meaningful improvements were observed in fatigue at 2, 12, and 18 months. The proportion of patients with clinically meaningful improvement in global health status/QoL was generally higher for treatment responders than for nonresponders. A trend toward decreased mean EQ-5D-5L index scores was observed at 1 month after liso-cel infusion, followed by subsequent increases through 18 months. Mean EQ-5D-5L visual analog scale scores increased from 2 through 18 months. In summary, patients with relapsed/refractory LBCL treated with liso-cel had early, sustained, and clinically meaningful improvements in HRQoL and symptoms that correlated with antitumor activity. This study was registered at as #NCT02631044.

Impact of novel systemic therapies on the first-year costs of care for melanoma among Medicare beneficiaries


2021 Ruth Etzioni

BACKGROUND: Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras. METHODS: The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged 67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars. RESULTS: Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients. CONCLUSIONS: The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families

BMC Public Health

2021 Lu Qian

BACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

Last Modified, February 20, 2020