Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Analysis of demographics and the impact of adjuvant radiotherapy on a nationwide cohort of patients with high-grade spinal meningiomas.

Background: Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. Methods: The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan-Meier survival analysis was conducted to study overall survival. All analyses were performed on R. Results: A total of 13 184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44-68] versus 65 years [54-75]; P < .001) and were more commonly males (33% vs 20%; P < .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). Conclusions: This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.

Are We the Problem? A Call to Action for Addressing Institutional Challenges to Engaging Community Partners in Research.

Community-engaged research (CEnR) is a potent tool for addressing health inequities and fostering equitable relationships among communities, researchers, and institutions. CEnR involves collaboration throughout the research process, demonstrating improvements in study recruitment and retention, intervention efficacy, program sustainability, capacity building among partners, and enhanced cultural relevance. Despite the increasing demand for CEnR, institutional policies, particularly human participation protection training (HPP), lag behind, creating institutional barriers to community partnerships. Here, we highlight challenges encountered in our ongoing study, Fostering Opportunities in Research through Messaging and Education (FOR ME), focused on promoting shared decision-making around clinical trial participation among Black women diagnosed with breast cancer. Grounded in CEnR methods, FOR ME has a partnership with a community-based organization (CBO) that addresses the needs of Black women with breast cancer. Our CBO partner attempted to obtain HPP training, which was administratively burdensome and time-consuming. As CEnR becomes more prevalent, academic and research institutions, along with researchers, are faced with a call to action to become more responsive to community partner needs. Accordingly, we present a guide to HPP training for community partners, addressing institutional barriers to community partner participation in research. This guide outlines multiple HPP training pathways for community partners, aiming to minimize institutional barriers and enhance their engagement in research with academic partners.

Association of cardiovascular risk profile with premature all-cause and cardiovascular mortality in US adults: findings from a national study.

OBJECTIVE: To assess the association between cardiovascular risk factor (CRF) profile and premature all-cause and cardiovascular disease (CVD) mortality among US adults (age < 65). METHODS: This study used data from the National Health Interview Survey from 2006 to 2014, linked to the National Death Index for non-elderly adults aged < 65 years. A composite CRF score (range = 0-6) was calculated, based on the presence or absence of six established cardiovascular risk factors: hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity. CRF profile was defined as "Poor" (≥ 3 risk factors), "Average" (1-2), or "Optimal" (0 risk factors). Age-adjusted mortality rates (AAMR) were reported across CRF profile categories, separately for all-cause and CVD mortality. Cox proportional hazard models were used to evaluate the association between CRF profile and all-cause and CVD mortality. RESULTS: Among 195,901 non-elderly individuals (mean age: 40.4 ± 13.0, 50% females and 70% Non-Hispanic (NH) White adults), 24.8% had optimal, 58.9% average, and 16.2% poor CRF profiles, respectively. Participants with poor CRF profile were more likely to be NH Black, have lower educational attainment and lower income compared to those with optimal CRF profile. All-cause and CVD mortality rates were three to four fold higher in individuals with poor CRF profile, compared to their optimal profile counterparts. Adults with poor CRF profile experienced 3.5-fold (aHR: 3.48 [95% CI: 2.96, 4.10]) and 5-fold (aHR: 4.76 [3.44, 6.60]) higher risk of all-cause and CVD mortality, respectively, compared to those with optimal profile. These results were consistent across age, sex, and race/ethnicity subgroups. CONCLUSIONS: In this population-based study, non-elderly adults with poor CRF profile had a three to five-fold higher risk of all-cause and CVD mortality, compared to those with optimal CRF profile. Targeted prevention efforts to achieve optimal cardiovascular risk profile are imperative to reduce the persistent burden of premature all-cause and CVD mortality in the US.

ERBB3 Overexpression is Enriched in Diverse Patient Populations with Castration-sensitive Prostate Cancer and is Associated with a Unique AR Activity Signature.

PURPOSE: Despite successful clinical management of castration-sensitive prostate cancer (CSPC), the 5-year survival rate for men with castration-resistant prostate cancer is only 32%. Combination treatment strategies to prevent disease recurrence are increasing, albeit in biomarker-unselected patients. Identifying a biomarker in CSPC to stratify patients who will progress on standard-of-care therapy could guide therapeutic strategies. EXPERIMENTAL DESIGN: Targeted deep sequencing was performed for the University of Illinois (UI) cohort (n = 30), and immunostaining was performed on a patient tissue microarray (n = 149). Bioinformatic analyses identified pathways associated with biomarker overexpression (OE) in the UI cohort, consolidated RNA sequencing samples accessed from Database of Genotypes and Phenotypes (n = 664), and GSE209954 (n = 68). Neutralizing antibody patritumab and ectopic HER3 OE were utilized for functional mechanistic experiments. RESULTS: We identified ERBB3 OE in diverse patient populations with CSPC, where it was associated with advanced disease at diagnosis. Bioinformatic analyses showed a positive correlation between ERBB3 expression and the androgen response pathway despite low dihydrotestosterone and stable expression of androgen receptor (AR) transcript in Black/African American men. At the protein level, HER3 expression was negatively correlated with intraprostatic androgen in Black/African American men. Mechanistically, HER3 promoted enzalutamide resistance in prostate cancer cell line models and HER3-targeted therapy resensitized therapy-resistant prostate cancer cell lines to enzalutamide. CONCLUSIONS: In diverse patient populations with CSPC, ERBB3 OE was associated with high AR signaling despite low intraprostatic androgen. Mechanistic studies demonstrated a direct link between HER3 and enzalutamide resistance. ERBB3 OE as a biomarker could thus stratify patients for intensification of therapy in castration-sensitive disease, including targeting HER3 directly to improve sensitivity to AR-targeted therapies.

Adaptation to volumetric compression drives hepatoblastoma cells to an apoptosis-resistant and invasive phenotype.

Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility. Here we investigate the impact of volumetric compression on liver cancer (HepG2) behavior. We find that conditioning cells under a highly compressed state leads to major transcriptional reprogramming, notably the loss of hepatic markers, the epithelial-to-mesenchymal transition (EMT)-like changes, and altered calcium signaling-related gene expression, over the course of several days. Biophysically, compressed cells exhibit increased Rac1-mediated cell spreading and cell-extracellular matrix interactions, cytoskeletal reorganization, increased YAP and ß-catenin nuclear translocation, and dysfunction in cytoplasmic and mitochondrial calcium signaling. Furthermore, compressed cells are resistant to chemotherapeutics and desensitized to apoptosis signaling. Apoptosis sensitivity can be rescued by stimulated calcium signaling. Our study demonstrates that volumetric compression is a key microenvironmental factor that drives tumor evolution in multiple pathological directions and highlights potential countermeasures to re-sensitize therapy-resistant cells. Significance statement: Compression can arise as cancer cells grow and navigate within the dense solid tumor microenvironment. It is unclear how compression mediates critical programs that drive tumor progression and therapeutic complications. Here, we take an integrative approach in investigating the impact of compression on liver cancer. We identify and characterize compressed subdomains within patient tumor tissues. Furthermore, using in vitro systems, we induce volumetric compression (primarily via osmotic pressure but also via mechanical force) on liver cancer cells and demonstrate significant molecular and biophysical changes in cell states, including in function, cytoskeletal signaling, proliferation, invasion, and chemoresistance. Importantly, our results show that compressed cells have impaired calcium signaling and acquire resistance to apoptosis, which can be countered via calcium mobilization.

Race and Ethnicity Reporting and Enrollment Disparities in Clinical Trials Leading to FDA Approvals for Breast Cancer Between 2010 and 2020.

BACKGROUND: We determined the race and ethnicity demographics and reporting trends of clinical trials leading to Food and Drug Administration (FDA) approvals for breast cancer. METHODS: We collected enrollment and reporting data from clinical trials leading to FDA novel and new use approvals for breast cancer from 2010 to 2020 from Drugs@FDA, ClinicalTrials.gov, and associated journal manuscripts. Enrollment demographics were compared to the US cancer population estimates obtained using National Cancer Institute-Surveillance, Epidemiology, and End Results and 2010 US Census databases. RESULTS: Seventeen drugs received approval based on 18 clinical trials with a total enrollment of 12,334. For approvals from 2010 to 2015 and from 2016 to 2020, there was no significant difference in race (80% vs. 91.6%, P = .34) or ethnicity reporting (20% vs. 33.3%, P = .5) on ClinicalTrials.Gov, manuscripts, and FDA labels. For trials that reported race and ethnicity, White, Asian, Black, and Hispanic patients represented 73.8%, 16.4%, 3.7%, and 10.4% of trial participants. Relative to their US cancer incidence, Black (31% of expected) patients were underrepresented compared with White (90% of expected), Hispanic (115%), and Asian (327% of expected) patients. CONCLUSION: We observed no significant difference in race and ethnicity reporting in pivotal clinical trials leading to FDA approval for breast cancer from 2010 to 2020. Black patients were underrepresented in these pivotal trials relative to White, Hispanic, and Asian patients. Ethnicity reporting remained low throughout the study period. Innovative approaches are needed to ensure equitable benefit of novel therapeutics.

Microfluidic 'brain-on chip' systems to supplement neurological practice: development, applications and considerations.

Among the greatest general challenges in bioengineering is to mimic human physiology. Advanced efforts in tissue engineering have led to sophisticated 'brain-on-chip' (BoC) microfluidic devices that can mimic structural and functional aspects of brain tissue. BoC may be used to understand the biochemical pathways of neurolgical pathologies and assess promising therapeutic agents for facilitating regenerative medicine. We evaluated the potential of microfluidic BoC devices in various neurological pathologies, such as Alzheimer's, glioblastoma, traumatic brain injury, stroke and epilepsy. We also discuss the principles, limitations and future considerations of BoC technology. Results suggest that BoC models can help understand complex neurological pathologies and augment drug testing efforts for regenerative applications. However, implementing organ-on-chip technology to clinical practice has some practical limitations that warrant greater attention to improve large-scale applicability. Nevertheless, they remain to be versatile and powerful tools that can broaden our understanding of pathophysiological and therapeutic uncertainties to neurological diseases.

In this paper, the authors describe the role of microfluidic 'brain-on-chip' systems as a tool to model and study the human brain. While animal studies have provided significant insights, they lack the complexity of human brain tissue in order to verify the effects of drugs on patients, study complex physiological pathways or personalize regenerative therapies. This makes studying diseases of complex human organs challenging. Microfluidics is a field of study that can address these challenges by developing sophisticated and miniaturized devices that can chamber human tissue. These devices could allow scientists to better study diseases on a model that is accurate and controllable, allowing researchers to better understand complex diseases, assess drug efficacy to specific areas of the brain and potentially accelerate the development of new therapies. Herein, we characterize the principles, development and challenges of microfluidics and the role they have served in different neurological diseases.

The role of molecular testing in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is highly aggressive and has few treatment options. To personalize therapy, it is critical to delineate molecular subtypes and understand inter- and intra-tumoral heterogeneity. Germline testing for hereditary genetic abnormalities is recommended for all patients with PDA and somatic molecular testing is recommended for all patients with locally advanced or metastatic disease. KRAS mutations are present in 90% of PDA, while 10% are KRAS wild type and are potentially targetable with epidermal growth factor receptor blockade. KRASG12C inhibitors have shown activity in G12C-mutated cancers, and novel G12D and pan-RAS inhibitors are in clinical trials. DNA damage repair abnormalities, germline or somatic, occur in 5-10% of patients and are likely to benefit from DNA damaging agents and maintenance therapy with poly-ADP ribose polymerase inhibitors. Fewer than 1% of PDA harbor microsatellite instability high status and are susceptible to immune checkpoint blockade. Albeit very rare, occurring in <1% of patients with KRAS wild-type PDAs, BRAF V600E mutations, RET and NTRK fusions are targetable with cancer agnostic Food and Drug Administration-approved therapies. Genetic, epigenetic, and tumor microenvironment targets continue to be identified at an unprecedented pace, enabling PDA patients to be matched to targeted and immune therapeutics, including antibody-drug conjugates, and genetically engineered chimeric antigen receptor or T-cell receptor - T-cell therapies. In this review, we highlight clinically relevant molecular alterations and focus on targeted strategies that can improve patient outcomes through precision medicine.

Defining Vascular Deserts to Describe Access to Care and Identify Sites for Targeted Limb Preservation Outreach.

BACKGROUND: Access to care plays a critical role in limb salvage in chronic limb-threatening ischemia (CLTI). A "medical desert" describes a community lacking access to medical necessities, resulting in increased morbidity and mortality. We sought to describe vascular deserts, which we defined as regions with decreased access to specialty care. METHODS: All California providers performing vascular surgery procedures were identified through online provider and health care facility searches. Facility participation in the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) lower extremity bypass (LEB) and peripheral vascular intervention (PVI) modules was also determined. Addresses were geocoded with a 30-mile surrounding buffer using ArcGIS (Geographic information systems), creating maps based on care type, including all providers performing vascular procedures, board-certified vascular surgeons, and facilities participating in VQI modules. Public census data overlayed on the maps demonstrated population composition in desert versus nondesert regions. Subsequently, data from the Healthy Places Index (HPI) was overlayed, providing data regarding 25 social factors, comprising an overall HPI score and percent, with lower scores corresponding to poorer health and outcomes. RESULTS: Maps depicting care regions demonstrated decreased provider coverage with increasing specialty care, with the VQI provider map showing the most prominent "desert" regions. When comparing nondesert versus desert regions by care type, demographics including race, the percentage of the population 200% below the poverty line, and the rate of uninsured residents were described. Social determinants of health were then described for desert and nondesert regions by care type, including the HPI percentage and specific domain factors. The percentage of uninsured residents was significant only in the desert and nondesert areas served by board-certified vascular surgeons (19.6 vs. 16.8%, P < 0.001). The mean HPI percentile was significantly lower in board-certified provider and VQI facility deserts than nondeserts (50.48% vs. 40.65%, P < 0.001 and 52.68% vs. 43.12%, P < 0.001, respectively). The economic and education factor percentiles were significantly lower in all desert populations, while the housing, social, and pollution factors were significantly higher in nondesert regions. Health care access, transportation, and neighborhood factor percentiles were significantly lower in board-certified and VQI facility deserts than in the nondesert areas. CONCLUSIONS: Access to vascular care plays a significant role in limb salvage. Through mapping vascular deserts, patient demographics, and social factors in desert regions are better understood, and areas that would benefit most from targeted outreach and limb preservation programs for CLTI are identified.

Tunable Mesoscopic Collagen Island Architectures Modulate Stem Cell Behavior.

The extracellular matrix is the biophysical environment that scaffolds mammalian cells in the body. The main constituent is collagen. In physiological tissues, collagen network topology is diverse with complex mesoscopic features. While studies have explored the roles of collagen density and stiffness, the impact of complex architectures remains not well-understood. Developing in vitro systems that recapitulate these diverse collagen architectures is critical for understanding physiologically relevant cell behaviors. Here, methods are developed to induce the formation of heterogeneous mesoscopic architectures, referred to as collagen islands, in collagen hydrogels. These island-containing gels have highly tunable inclusions and mechanical properties. Although these gels are globally soft, there is regional enrichment in the collagen concentration at the cell-scale. Collagen-island architectures are utilized to study mesenchymal stem cell behavior, and it is demonstrated that cell migration and osteogenic differentiation are altered. Finally, induced pluripotent stem cells are cultured in island-containing gels, and it is shown that the architecture is sufficient to induce mesodermal differentiation. Overall, this work highlights complex mesoscopic tissue architectures as bioactive cues in regulating cell behavior and presents a novel collagen-based hydrogel that captures these features for tissue engineering applications.

A Snapshot on Oral and Maxillofacial Surgery Resident Scholarly Activity: Can We Do Better?

BACKGROUND: The Commission on Dental Accreditation (CODA) requires oral and maxillofacial surgery (OMS) residents to engage in scholarly activity. Currently, it is unknown how this mandate translates into research output. PURPOSE: The purpose of this study was to quantify the research output of OMS residents. In addition, we sought to identify characteristics associated with resident productivity. STUDY DESIGN: This was a cross-sectional study of all OMS residents during the 2021-2022 academic year. Attempts were made to obtain resident rosters from every CODA-accredited OMS program. Resident names were searched in PubMed (https://pubmed.ncbi.nlm.nih.gov/) to identify peer-reviewed publications. Postgraduate year (PGY), program name, and total publication count during residency were recorded for each resident. Academic status and fellowship affiliation of the residency program were also included. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor was PGY level of each resident. MAIN OUTCOME VARIABLE: The main outcome variable was the publication count of each OMS resident during the 2021-2022 academic year. COVARIATES: The covariates were the academic status and the fellowship affiliation of the residency program. A program was determined academic if they were associated with a dental or medical school. A program was determined fellowship associated if they had any CODA approved fellowship. ANALYSES: Simple bivariate comparisons were performed using Wilcoxon signed-rank tests. RESULTS: Complete resident rosters were identified for 87 residency programs. One thousand one hundred thirty two residents were queried and a total of 548 peer-reviewed publications were identified. There was a mean of 6.30 publications per program and 0.43 publications per resident. More than half of all residents had no identifiable publication. PGY5 residents averaged the most publications per resident (1.45) followed by PGY6 (1.04) and PGY4 (0.63). Academic programs had significantly more publications per resident than nonacademic programs (median of 3.00 vs 0.00, P = .02). Programs with a fellowship association also had more publications per resident (median of 5.00 vs 2.00, P < .01). CONCLUSION: Current CODA research requirements do not translate into resident publications. Publication counts appeared to slightly increase with PGY level; however, OMS resident productivity still lags far behind that of other surgical subspecialties.

Social Determinants of Health, Cardiovascular Risk Factors, and Atherosclerotic Cardiovascular Disease in Individuals of Vietnamese Origin.

In 2022, the Vietnamese population in the United States (US) comprises 2.2 million individuals, and Vietnam ranks as the sixth most frequent country of origin among immigrants in the US. The American Heart Association and the National Institutes of Health have called for research to define the burden of cardiovascular risk factors, cardiovascular disease, and their determinants across Asian American subgroups, including Vietnamese Americans. Despite these calls, Vietnamese Americans remain remarkably overlooked in cardiovascular research in the US. Studies in Vietnam, small cross-sectional surveys in the US, and research using US mortality data point to a high prevalence of hypertension and tobacco use among men and a high incidence of gestational diabetes among women. Moreover, Vietnamese Americans have one of the highest rates of cerebrovascular mortality in the country. Adverse social determinants of health-including frequent language barriers, limited health literacy, and low average income-have been suggested as important factors that contribute to cardiovascular risk in this group. In this narrative review, we summarize the existing knowledge in this space, highlight the distinct characteristics of cardiac risk in both Vietnamese and Vietnamese American individuals, discuss upstream determinants, and identify key knowledge gaps. We then outline several proposed interventions and emphasize the need for further studies in this underrepresented population. Our aim is to increase awareness of the significant burden of risk factors and cardiovascular disease shouldered by this large-but thus far overlooked-population in the US, boost research in this space, and help inform tailored, effective preventive interventions.

Self-assembly of mesoscale collagen architectures and applications in 3D cell migration.

3D in vitro tumor models have recently been investigated as they can recapitulate key features in the tumor microenvironment. Reconstruction of a biomimetic scaffold is critical in these models. However, most current methods focus on modulating local properties, e.g. micro- and nano-scaled topographies, without capturing the global millimeter or intermediate mesoscale features. Here we introduced a method for modulating the collagen I-based extracellular matrix structure by disruption of fibrillogenesis and the gelation process through mechanical agitation. With this method, we generated collagen scaffolds that are thickened and wavy at a larger scale while featuring global softness. Thickened collagen patches were interconnected with loose collagen networks, highly resembling collagen architecture in the tumor stroma. This thickened collagen network promoted tumor cell dissemination. In addition, this novel modified scaffold triggered differences in morphology and migratory behaviors of tumor cells. Altogether, our method for altered collagen architecture paves new ways for studying in detail cell behavior in physiologically relevant biological processes. STATEMENT OF SIGNIFICANCE: Tumor progression usually involves chronic tissue damage and repair processes. Hallmarks of tumors are highly overlapped with those of wound healing. To mimic the tumor milieu, collagen-based scaffolds are widely used. These scaffolds focus on modulating microscale topographies and mechanics, lacking global architecture similarity compared with in vivo architecture. Here we introduced one type of thick collagen bundles that mimics ECM architecture in human skin scars. These thickened collagen bundles are long and wavy while featuring global softness. This collagen architecture imposes fewer steric restraints and promotes tumor cell dissemination. Our findings demonstrate a distinct picture of cell behaviors and intercellular interactions, highlighting the importance of collagen architecture and spatial heterogeneity of the tumor microenvironment.

Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes.

Drug treatment against liver cancer has limited efficacy due to heterogeneous response among liver cancer subtypes. In addition, the functional biophysical phenotypes which arise from this heterogeneity and contribute to aggressive invasive behavior remain poorly understood. This study interrogated how heterogeneity in liver cancer subtypes contributes to differences in invasive phenotypes and drug response. Utilizing histological analysis, quantitative 2D invasion metrics, reconstituted 3D hydrogels, and bioinformatics, our study linked cytoskeletal dynamics to differential invasion profiles and drug resistance in liver cancer subtypes. We investigated cytoskeletal regulation in 2D and 3D culture environments using two liver cancer cell lines, SNU-475 and HepG2, chosen for their distinct cytoskeletal features and invasion profiles. For SNU-475 cells, a model for aggressive liver cancer, many cytoskeletal inhibitors abrogated 2D migration but only some suppressed 3D migration. For HepG2 cells, cytoskeletal inhibition did not significantly affect 3D migration but did affect proliferative capabilities and spheroid core growth. This study highlights cytoskeleton driven phenotypic variation, their consequences and coexistence within the same tumor, as well as efficacy of targeting biophysical phenotypes that may be masked in traditional screens against tumor growth.

Age-based disparities in telehealth use in an urban, underserved population in cancer and pulmonary clinics: A need for policy change.

BACKGROUND: During the COVID-19 pandemic, telehealth rapidly emerged as an essential health care service and became particularly important for patients with cancer and chronic conditions. However, the benefits of telehealth have not been fully realized for some of the most vulnerable populations due to inequitable access to telehealth capable technology. PURPOSE: This study aimed to assess accessibility and satisfaction with telehealth technology by vulnerable patients with cancer and pulmonary disease. METHODOLOGY: A paper survey and internet-based survey were developed and administered to adult (≥18 years) cancer and pulmonary clinic patients (July 1, 2020 to October 30, 2020). RESULTS: Descriptive statistics and Fisher exact test were performed. Two hundred eleven patients completed the survey. Adults ≥50 years old (older) had reduced access to smartphone video capability and internet connection compared with adults less than 50 years old (59% vs. 90%, p < .01). Older adults reported more challenges with telehealth visits compared with younger adults (50.3%, 28.6%; p < .01). No difference in access to technology and preferences for telehealth versus in-person care was found by race, gender, or education level. CONCLUSIONS: Nearly all patients (95%) who had a previous experience with a telehealth visit felt confident in the quality of care they received via telehealth. Younger adults preferred video visits compared with older adults (75% vs. 50.6%, p < .01). Older adults were less likely to have access to smartphones with internet access, have more challenges with telehealth visits, and were less likely to prefer audio-video telehealth visits compared with younger adults. IMPLICATIONS: Ensuring equitable access to all health care delivery modalities by telehealth, including audio-only visits for patients across the age continuum, is paramount.

Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer.

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, Setting, and Participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main Outcomes and Measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and Relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.