"Long-term effects of center volume on transplant outcomes in adult kidney transplant recipients".

BACKGROUND: The influence of center volume on kidney transplant outcomes is a topic of ongoing debate. In this study, we employed competing risk analyses to accurately estimate the marginal probability of graft failure in the presence of competing events, such as mortality from other causes with long-term outcomes. The incorporation of immunosuppression protocols and extended follow-up offers additional insights. Our emphasis on long-term follow-up aligns with biological considerations where competing risks play a significant role. METHODS: We examined data from 219,878 adult kidney-only transplantations across 256 U.S. transplant centers (January 2001-December 2015) sourced from the Organ Procurement and Transplantation Network registry. Centers were classified into quartiles by annual volume: low (Q1 = 28), medium (Q2 = 75), medium-high (Q3 = 121), and high (Q4 = 195). Our study investigated the relationship between center volume and 5-year outcomes, focusing on graft failure and mortality. Sub-population analyses included deceased donors, living donors, diabetic recipients, those with kidney donor profile index >85%, and re-transplants from deceased donors. RESULTS: Adjusted cause-specific hazard ratios (aCHR) for Five-Year Graft Failure and Patient Death were examined by center volume, with low-volume centers as the reference standard (aCHR: 1.0). In deceased donors, medium-high and high-volume centers showed significantly lower cause-specific hazard ratios for graft failure (medium-high aCHR = 0.892, p<0.001; high aCHR = 0.953, p = 0.149) and patient death (medium-high aCHR = 0.828, p<0.001; high aCHR = 0.898, p = 0.003). Among living donors, no significant differences were found for graft failure, while a trend towards lower cause-specific hazard ratios for patient death was observed in medium-high (aCHR = 0.895, p = 0.107) and high-volume centers (aCHR = 0.88, p = 0.061). CONCLUSION: Higher center volume is associated with significantly lower cause-specific hazard ratios for graft failure and patient death in deceased donors, while a trend towards reduced cause-specific hazard ratios for patient death is observed in living donors.

Phase 2 Study of Sorafenib, Valproic Acid, and Sildenafil in the Treatment of Recurrent High-Grade Glioma.

Here we report the results of a single-center phase 2 clinical trial combining sorafenib tosylate, valproic acid, and sildenafil for the treatment of patients with recurrent high-grade glioma (NCT01817751). Clinical toxicities were grade 1 and grade 2, with one grade 3 toxicity for maculopapular rash (6.4%). For all evaluable patients, the median progression-free survival was 3.65 months and overall survival (OS) 10.0 months. There was promising evidence showing clinical activity and benefit. In the 33 evaluable patients, low protein levels of the chaperone GRP78 (HSPA5) was significantly associated with a better OS (p < 0.0026). A correlation between the expression of PDGFRα and OS approached significance (p < 0.0728). Five patients presently have a mean OS of 73.6 months and remain alive. This is the first therapeutic intervention glioblastoma trial to significantly associate GRP78 expression to OS. Our data suggest that the combination of sorafenib tosylate, valproic acid, and sildenafil requires additional clinical development in the recurrent glioma population.

A monotone single index model for missing-at-random longitudinal proportion data.

Beta distributions are commonly used to model proportion valued response variables, often encountered in longitudinal studies. In this article, we develop semi-parametric Beta regression models for proportion valued responses, where the aggregate covariate effect is summarized and flexibly modeled, using a interpretable monotone time-varying single index transform of a linear combination of the potential covariates. We utilize the potential of single index models, which are effective dimension reduction tools and accommodate link function misspecification in generalized linear mixed models. Our Bayesian methodology incorporates the missing-at-random feature of the proportion response and utilize Hamiltonian Monte Carlo sampling to conduct inference. We explore finite-sample frequentist properties of our estimates and assess the robustness via detailed simulation studies. Finally, we illustrate our methodology via application to a motivating longitudinal dataset on obesity research recording proportion body fat.

Lactic Acid-Induced Colloidal Microrheology of Synovial Fluids.

The presence of colloidal scaffolds composed of proteins and hyaluronic acid engenders unique viscous and elastic properties to the synovial fluid (SF). While the elastic resistance of SF due to the presence of such nanoscale structures provides the load-bearing capacity, the viscous nature enables fluidity of the joints during the movements to minimize the wear and tear of the adjacent muscle, cartilage, or bone tissues. It is well-known that the hypoxic conditions at the bone joints often increase the lactic acid (LA) concentration due to the occurrence of excess anaerobic respiration during either hyperactivity or arthritic conditions. The present study uncovers that in such a scenario, beyond a critical loading of LA, the colloidal nanoscaffolds of SF break down to precipitate higher molecular weight (MW) proteins and hyaluronic acid (HA). Subsequently, the viscosity and elasticity of SF reduce drastically to manifest a fluid that has reduced load bearing and wear and tear resistance capacity. Interestingly, the study also suggests that a heathy SF is a viscoelastic fluid with a mild Hookean elasticity and non-Newtonian fluidity, which eventually transforms into a viscous watery liquid in the presence of a higher loading of LA. We employ this knowledge to biosynthesize an artificial SF that emulates the characteristics of the real one. Remarkably, the spatiotemporal microscopic images uncover that even for the artificial SF, a dynamic cross-linking of the high MW proteins and HA takes place before precipitating out of the same from the artificial SF matrix, emulating the real one. Control experiments suggest that this phenomenon is absent in the case when LA is mixed with either pure HA or proteins. The experiments unfold the specific role of LA in the destruction of colloidal nanoscaffolds of synovia, which is an extremely important requirement for the biosynthesis and translation of artificial synovial fluid.

A phase 1 study of regorafenib and sildenafil in adults with advanced solid tumors.

The purpose of this study is to establish the recommended phase 2 dose for regorafenib in combination with sildenafil for patients with advanced solid tumors. Secondary outcomes included identification of antitumor effects of regorafenib and sildenafil, toxicity of the combination, determination of PDE5 expression in tumor samples, and the impact of sildenafil on the pharmacokinetics of regorafenib. This study was a phase 1, open-label single-arm dose-escalation trial using a 3 + 3 design. Additional patients were enrolled at the maximum tolerated dose (MTD) until a total of 12 patients were treated at the MTD. A total of 29 patients were treated in this study. The median duration of treatment was 8 weeks. The recommended phase 2 doses determined in this study are regorafenib 160 mg daily with sildenafil 100 mg daily. The most common toxicities included palmar-plantar erythrodysesthesia syndrome (20 patients, 69%) and hypophosphatemia (18 patients, 62%). Two patients (7%) experienced grade 4 lipase increase. Objective responses were not observed; however, 14 patients (48%) had a period of stable disease during the study. Stable disease for up to 12 months was observed in patients with ovarian cancer as well as up to 20 months for a patient with cervical cancer. The combination of regorafenib and sildenafil at the recommended phase 2 dose is safe and generally well tolerated. Disease control in patients with gynecologic malignancies was especially encouraging. Further evaluation of the combination of regorafenib and sildenafil in gynecologic malignancies is warranted. Clinical Trial Registration Number: NCT02466802.

Lung Cancer Prevalence in Virginia: A Spatial Zipcode-Level Analysis via INLA.

BACKGROUND: Examining lung cancer (LC) cases in Virginia (VA) is essential due to its significant public health implications. By studying demographic, environmental, and socioeconomic variables, this paper aims to provide insights into the underlying drivers of LC prevalence in the state adjusted for spatial associations at the zipcode level. METHODS: We model the available VA zipcode-level LC counts via (spatial) Poisson and negative binomial regression models, taking into account missing covariate data, zipcode-level spatial association and allow for overdispersion. Under latent Gaussian Markov Random Field (GMRF) assumptions, our Bayesian hierarchical model powered by Integrated Nested Laplace Approximation (INLA) considers simultaneous (spatial) imputation of all missing covariates through elegant prediction. The spatial random effect across zip codes follows a Conditional Autoregressive (CAR) prior. RESULTS: Zip codes with elevated smoking indices demonstrated a corresponding increase in LC counts, underscoring the well-established connection between smoking and LC. Additionally, we observed a notable correlation between higher Social Deprivation Index (SDI) scores and increased LC counts, aligning with the prevalent pattern of heightened LC prevalence in regions characterized by lower income and education levels. On the demographic level, our findings indicated higher LC counts in zip codes with larger White and Black populations (with Whites having higher prevalence than Blacks), lower counts in zip codes with higher Hispanic populations (compared to non-Hispanics), and higher prevalence among women compared to men. Furthermore, zip codes with a larger population of elderly people (age ≥ 65 years) exhibited higher LC prevalence, consistent with established national patterns. CONCLUSIONS: This comprehensive analysis contributes to our understanding of the complex interplay of demographic and socioeconomic factors influencing LC disparities in VA at the zip code level, providing valuable information for targeted public health interventions and resource allocation. Implementation code is available at GitHub.

Partly linear single-index cure models with a nonparametric incidence link function.

In cancer studies, it is commonplace that a fraction of patients participating in the study are cured, such that not all of them will experience a recurrence, or death due to cancer. Also, it is plausible that some covariates, such as the treatment assigned to the patients or demographic characteristics, could affect both the patients' survival rates and cure/incidence rates. A common approach to accommodate these features in survival analysis is to consider a mixture cure survival model with the incidence rate modeled by a logistic regression model and latency part modeled by the Cox proportional hazards model. These modeling assumptions, though typical, restrict the structure of covariate effects on both the incidence and latency components. As a plausible recourse to attain flexibility, we study a class of semiparametric mixture cure models in this article, which incorporates two single-index functions for modeling the two regression components. A hybrid nonparametric maximum likelihood estimation method is proposed, where the cumulative baseline hazard function for uncured subjects is estimated nonparametrically, and the two single-index functions are estimated via Bernstein polynomials. Parameter estimation is carried out via a curated expectation-maximization algorithm. We also conducted a large-scale simulation study to assess the finite-sample performance of the estimator. The proposed methodology is illustrated via application to two cancer datasets.

CYTOR Facilitates Formation of FOSL1 Phase Separation and Super Enhancers to Drive Metastasis of Tumor Budding Cells in Head and Neck Squamous Cell Carcinoma.

Tumor budding (TB) is a small tumor cell cluster with highly aggressive behavior located ahead of the invasive tumor front. However, the molecular and biological characteristics of TB and the regulatory mechanisms governing TB phenotypes remain unclear. This study reveals that TB exhibits a particular dynamic gene signature with stemness and partial epithelial-mesenchymal transition (p-EMT). Importantly, nuclear expression of CYTOR is identified to be the key regulator governing stemness and the p-EMT phenotype of TB cells, and targeting CYTOR significantly inhibits TB formation, tumor growth and lymph node metastasis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, CYTOR promotes tumorigenicity and metastasis of TB cells by facilitating the formation of FOSL1 phase-separated condensates to establish FOSL1-dependent super enhancers (SEs). Depletion of CYTOR leads to the disruption of FOSL1-dependent SEs, which results in the inactivation of cancer stemness and pro-metastatic genes. In turn, activation of FOSL1 promotes the transcription of CYTOR. These findings indicate that CYTOR is a super-lncRNA that controls the stemness and metastasis of TB cells through facilitating the formation of FOSL1 phase separation and SEs, which may be an attractive target for therapeutic interventions in HNSCC.

Concordant care in sentinel lymph node omission following Choosing Wisely® recommendations at a comprehensive cancer center.

BACKGROUND: In 2016, the SSO and ABIM released a Choosing Wisely® guideline stating SLNB can be safely omitted in women ≥70 with HR â€‹+ â€‹HER-invasive breast cancer. No study evaluating concordance of care with this guideline has been performed within a comprehensive cancer center. METHODS: From 2005 to 2020, there were 382 patients with cT1-2N0 invasive carcinoma ER+/PR+ and HER2-identified as having undergone SLNB. These patients were then separated into two groups; those in the pre-guideline concordance cohort (2005-2015) and those in the post-guideline concordance (2016-2020) cohort. Axillary management concordance was trended over time. RESULTS: 382 patients from 2005 to 2020 with HR â€‹+ â€‹HER- IBC were identified. No difference was seen in SLNB pre-versus post-guidelines (p â€‹= â€‹0.35). Increased concordance was noted as age increased (p â€‹= â€‹0.0068) and adjuvant radiation therapy exclusion (p â€‹< â€‹0.0001) post-guideline release. Concordance improved over the years post-guideline release (R2 â€‹= â€‹0.45). CONCLUSIONS: Surgical guideline adoption occurs over time but may also be affected by outside decisions and factors. Further study into patterns of guideline adoption may facilitate improving adherence to guidelines.

Luminal A Versus B After Choosing Wisely: Does Lymph Node Surgery Affect Oncologic Outcomes?

BACKGROUND: In 2016, the Choosing Wisely campaign recommended against routine sentinel lymph node biopsy (SLNB) in women ≥ 70 years old diagnosed with early-stage hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer. No distinction is made between luminal A and luminal B phenotypes, despite luminal B being considered more aggressive. This study evaluates the effect of SLNB on oncologic outcomes in HER2- luminal B versus luminal A breast cancer. PATIENTS AND METHODS: We performed an IRB-approved, single institution, retrospective cohort study from 2010 to 2020 of women aged ≥ 70 years with clinically node negative, HR+ breast cancer undergoing definitive surgical treatment. Luminal status was defined by gene expression panel testing, Ki67%, and/or pathologic grading. Primary endpoints included locoregional recurrence (LRR), disease free survival (DFS), and overall survival (OS). RESULTS: SLNB did not correlate with significant differences in LRR in luminal A (p = 0.92) or luminal B (p = 0.96) disease. SLNB correlated with improved DFS (p < 0.01) and OS (p < 0.001) in luminal A disease, but not in luminal B disease (DFS p = 0.73; OS p = 0.36). On multivariate analysis, age (HR = 1.17; p < 0.01) and tumor size (HR = 1.03; p < 0.05) were associated with DFS, while SLNB was not (p = 0.71). Luminal status (HR = 0.52, p < 0.05), age (HR = 1.15, p < 0.01), and comorbidities (HR = 1.35, p < 0.05) were associated with OS, but not SLNB (p = 0.71). CONCLUSIONS: Our results suggest that SLNB may be safely omitted in patients aged ≥ 70 years with luminal B disease given similar LRR in luminal A disease. Our findings suggest that DFS and OS are driven by tumor biology, patient age, and comorbidities rather than receipt of SLNB.

Higher diet quality relates to better cardiac function in cancer survivors: The multi-ethnic study of atherosclerosis.

BACKGROUND: Cancer therapies induce cardiac injury and increase cardiovascular disease (CVD) risk. In non-cancer populations, higher diet quality is associated with protection against CVD, but the relationship between diet and cardiac function in cancer survivors is unknown. METHODS: This cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort included 113 cancer survivors (55 breast, 53 prostate, three lung, and three blood) and 4233 non-cancer controls. Dietary intake was reported via validated food frequency questionnaire. Alternate healthy eating index (AHEI) was calculated as a measure of quality. Cardiac function, determined as left ventricular ejection fraction (LVEF), was assessed by cardiac magnetic resonance. RESULTS: Cancer survivors had a lower LVEF compared to controls (61.3 ± 6.5% v 62.4 ± 6.1%, p = 0.04). In all participants, total fat (ß ± SE: -0.04 ± 0.01, p = 0.004), saturated fat (-0.11 ± 0.03, p < 0.001), and trans-fat (-0.36 ± 0.12, p = 0.002) intake were inversely associated with LVEF while AHEI (0.03 ± 0.01, p < 0.001) was positively associated with LVEF. Among cancer survivors only, sucrose intake was negatively related to LVEF (-0.15 ± 0.06, p = 0.02), and the ratio of unsaturated fat to saturated fat (2.7 ± 1.1, p = 0.01) and fiber intake (0.42 ± 0.14, p = 0.003) were positively related to LVEF. DISCUSSION: In cancer survivors, improved dietary fat and carbohydrate quality (i.e., greater consumption of unsaturated fatty acids and fiber) was associated with favorable cardiac function, while higher sucrose was associated with worse cardiac function. Further research is needed to confirm these findings and test whether changes in the identified dietary factors will modulate cardiac function in cancer survivors.

Racial/Ethnic Disparities in the Era of Minimally Invasive Surgery for Treatment of Colorectal Cancer.

BACKGROUND: Minimally invasive (laparoscopic and robotic) surgery (MIS) for colorectal cancer is associated with improved outcomes. We sought to characterize possible disparities in surgical approach and outcomes. PATIENTS AND METHODS: In this cross-sectional study, colorectal adenocarcinoma cases among non-Hispanic white (NHW), non-Hispanic Black (NHB), and Hispanic patients were identified using the National Cancer Database (2010-2017). Logistic and Poisson regressions, generalized logit models, and Cox proportional hazards were used to assess outcomes, with reclassification of surgery type if converted to open. RESULTS: NHB patients were less likely to undergo robotic surgery. After multivariable analysis, NHB patients were 6% less likely, while Hispanic patients were 12% more likely to undergo a MIS approach. Lymph node retrieval was higher (> 1.3% more, p < 0.0001) and length of stay was shorter (> 17% shorter, p < 0.0001) for MIS approaches. Unplanned readmission was lower for MIS colon cancer operations compared with open operations, but not for rectal cancer. Race/ethnicity-adjusted risk of death was lower with MIS approaches for colon as well as rectal cancer. After adjusting for surgery type, risk of death was 12% lower for NHB and 35% lower for Hispanic patients compared with NHW patients. Hispanic patients had 21% lower risk of death, while NHB patients had 12% higher risk of death than NHW patients with rectal cancer, after adjusting for surgery type. CONCLUSIONS: Racial/ethnic disparities exist in utilization of MIS for colorectal cancer treatment, disproportionately affecting NHB patients. Since MIS has the potential to improve outcomes, suboptimal access may contribute to harmful and thus unacceptable disparities in survivorship.

Malignant choroidal melanoma with vitreous seeds: supported by histopathology and field emission scanning electron microscopy study.

Aim: To report an exceptionally rare case of malignant choroidal melanoma with vitreous seeding, supported by histopathological and field emission scanning electron microscopic (FESEM) studies. Case report: A 58-year-old male with painless diminution of vision in his left eye for past 1 month was found to have a brown retrolental mass lesion on slit lamp examination in the left eye. Detailed fundus examination revealed choroidal melanoma in the left eye with pigmented seeds extending into the vitreous cavity and associated exudative retinal detachment. Ocular imaging was consistent with the diagnosis. Results: The eyeball was enucleated and the tumor was considered as stage IIB (AJCC 8th edition classification). Metastatic workup of the patient was negative. One half of the eyeball was subjected to field emission scanning electron microscopy to further study the nature and appearance of vitreous seeds. Discussion: Vitreous seeding in choroidal melanoma has been reported only in a handful of cases in literature. Histopathological confirmation of vitreous seeds was done in our case and morphological detailing was performed using FESEM study. Conclusions: Treatment naïve choroidal melanoma can very rarely have vitreous seeds. Early enucleation in such cases carries a favorable prognosis.

Pseudo-value regression of clustered multistate current status data with informative cluster sizes.

Multistate current status data presents a more severe form of censoring due to the single observation of study participants transitioning through a sequence of well-defined disease states at random inspection times. Moreover, these data may be clustered within specified groups, and informativeness of the cluster sizes may arise due to the existing latent relationship between the transition outcomes and the cluster sizes. Failure to adjust for this informativeness may lead to a biased inference. Motivated by a clinical study of periodontal disease, we propose an extension of the pseudo-value approach to estimate covariate effects on the state occupation probabilities for these clustered multistate current status data with informative cluster or intra-cluster group sizes. In our approach, the proposed pseudo-value technique initially computes marginal estimators of the state occupation probabilities utilizing nonparametric regression. Next, the estimating equations based on the corresponding pseudo-values are reweighted by functions of the cluster sizes to adjust for informativeness. We perform a variety of simulation studies to study the properties of our pseudo-value regression based on the nonparametric marginal estimators under different scenarios of informativeness. For illustration, the method is applied to the motivating periodontal disease dataset, which encapsulates the complex data-generation mechanism.

Co-electrolysis of seawater and carbon dioxide inside a microfluidic reactor to synthesize speciality organics.

We report co-electrolysis of seawater and carbon dioxide (CO2) gas in a solar cell-integrated membraneless microfluidic reactor for continuous synthesis of organic products. The microfluidic reactor was fabricated using polydimethylsiloxane substrate comprising of a central microchannel with a pair of inlets for injection of CO2 gas and seawater and an outlet for removal of organic products. A pair of copper electrodes were inserted into microchannel to ensure its direct interaction with incoming CO2 gas and seawater as they pass into the microchannel. The coupling of solar cell panels with electrodes generated a high-intensity electrical field across the electrodes at low voltage, which facilitated the co-electrolysis of CO2 and seawater. The paired electrolysis of CO2 gas and seawater produced a range of industrially important organics under influence of solar cell-mediated external electric field. The, as synthesized, organic compounds were collected downstream and identified using characterization techniques. Furthermore, the probable underlying electrochemical reaction mechanisms near the electrodes were proposed for synthesis of organic products. The inclusion of greenhouse CO2 gas as reactant, seawater as electrolyte, and solar energy as an inexpensive electric source for co-electrolysis initiation makes the microreactor a low-cost and sustainable alternative for CO2 sequestration and synthesis of organic compounds.

Sieve estimation of a class of partially linear transformation models with interval-censored competing risks data.

In this paper, we consider a class of partially linear transformation models with interval-censored competing risks data. Under a semiparametric generalized odds rate specification for the cause-specific cumulative incidence function, we obtain optimal estimators of the large number of parametric and nonparametric model components via maximizing the likelihood function over a joint B-spline and Bernstein polynomial spanned sieve space. Our specification considers a relatively simpler finite-dimensional parameter space, approximating the infinite-dimensional parameter space as n → ∞, thereby allowing us to study the almost sure consistency, and rate of convergence for all parameters, and the asymptotic distributions and efficiency of the finite-dimensional components. We study the finite sample performance of our method through simulation studies under a variety of scenarios. Furthermore, we illustrate our methodology via application to a dataset on HIV-infected individuals from sub-Saharan Africa.

Myocardial Strain during Surveillance Screening Is Associated with Future Cardiac Dysfunction among Survivors of Childhood, Adolescent and Young Adult-Onset Cancer.

Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult (C-AYA) cancer survivors. While serial cardiovascular screening is recommended in this population, optimal screening strategies, including the use of echocardiography-based myocardial strain, are not fully defined. Our objective was to determine the relationship between longitudinal and circumferential strain (LS, CS) and fractional shortening (FS) among survivors. This single-center cohort study retrospectively measured LS and CS among C-AYAs treated with anthracycline/anthracenedione chemotherapy. The trajectory of LS and CS values over time were examined among two groups of survivors: those who experienced a reduction of >5 fractional shortening (FS) units from pre-treatment to the most recent echocardiogram, and those who did not. Using mixed modeling, LS and CS were used to estimate FS longitudinally. A receiver operator characteristic curve was generated to determine the ability of our model to correctly predict an FS ≤ 27%. A total of 189 survivors with a median age of 14 years at diagnosis were included. Among the two survivor groups, the trajectory of LS and CS differed approximately five years from cancer diagnosis. A statistically significant inverse relationship was demonstrated between FS and LS -0.129, p = 0.039, as well as FS and CS -0.413, p < 0.001. The area under the curve for an FS ≤ 27% was 91%. Among C-AYAs, myocardial strain measurements may improve the identification of individuals with cardiotoxicity, thereby allowing earlier intervention.

Outcomes of Cancer Patients with COVID-19: The Virginia Commonwealth University Experience.

PURPOSE: The cancer population is significantly impacted by coronavirus disease 2019 (COVID-19) due to inherent risks of infection imposed by malignancy and therapeutic agents. Evaluating risk factors in this group will lead to improved guidelines for the treatment of malignancy in the setting of a COVID-19 pandemic. PATIENTS AND METHODS: This retrospective study reviewed 295 inpatient cancer patients positive for COVID-19 between February 2020 and December 2021 to determine specific risk factors of mortality and associated complications. Various patient characteristics were collected to evaluate outcomes in patient death, oxygen requirement, ventilatory support, and increased length of stay. RESULTS: 31 (10.5%) of 295 patients died due to COVID-19. Of those that died, the majority had hematologic cancer (48.4%). There was no difference in the odds of death among the cancer groups. Those vaccinated had a reduced risk of death (OR 0.04, CI 0-0.23). Patients with lung cancer (OR 3.69, CI 1.13-12.31), obesity (OR 3.27, CI 1.18-9.27), CHF (OR 2.68, CI 1.07-6.89) were more likely to require ventilation. Those treated with hormonal therapy had higher odds of having a prolonged admission (OR 5.04, CI 1.17-2.53). Otherwise, cancer therapy had no significant difference in any outcome. CONCLUSION: The mortality rate of cancer patients was 10.5%, lower than in other studies. Vaccinations had mortality benefits, but no effect on hypoxia, ventilator use, or LOS. Delaying cancer therapy during peak infection is likely not necessary based on the results of this study. With improved knowledge in the risks of infection and the utility of personalized precautions, both providers and patients can better prepare for another potential wave of COVID-19.

Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.

PURPOSE: Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models. EXPERIMENTAL DESIGN: This was a phase 1 dose-escalation study of belinostat and adavosertib in patients with relapsed/refractory AML and myelodysplastic syndrome (MDS). Patients received both drugs on days 1-5 and 8-12 of a 21-day cycle. Safety and toxicity were monitored throughout the study. Plasma levels of both drugs were measured for pharmacokinetic analysis. Response was determined by standard criteria including bone marrow biopsy. RESULTS: Twenty patients were enrolled and treated at 4 dose levels. A grade 4 cytokine release syndrome at dose level 4 (adavosertib 225 mg/day; belinostat 1000 mg/m2) qualified as a dose-limiting toxicity event. The most common non-hematologic treatment-related adverse events were nausea, vomiting, diarrhea, dysgeusia, and fatigue. No responses were seen. The study was terminated prior to maximum tolerated dose/recommended phase 2 dose determination. CONCLUSIONS: The combination of belinostat and adavosertib at the tested dose levels was feasible but without efficacy signals in the relapsed/refractory MDS/AML population.