A Comparison between Silver Nanosquare Arrays and Silver Thin-Films as a Blood Cancer Prognosis Monitoring Electrode Design Using Optical and Electrochemical Characterization

The development of silver (Ag) thin films and the fabrication of Ag nanosquare arrays with the use of an anodic aluminum oxide (AAO) template and leaf extracts were successfully carried out using the DC sputtering and spin coating deposition methods. Ag thin films and Ag nanosquare arrays are developed to monitor cancer prognosis due to the correlation between serum albumin levels and prognostic factors, as well as the binding of serum albumin to the surface of these electrodes. Nanosquare structures were fabricated using AAO templates with varying diameters and a gap distance between adjacent unit cells of 100 nm. The nanosquare array with a diameter of 250 nm and irradiated with electromagnetic waves with a wavelength of around 800 nm possessed the greatest electric field distribution compared to the other variations of diameters and wavelengths. The results of the absorption measurement and simulation showed a greater shift in absorption peak wavelength when carried out using the Ag nanosquare array. The absorption peak wavelengths of the Ag nanosquare array in normal blood and blood with cancer lymphocytes were 700–774 nm and 800–850 nm, respectively. The electrochemical test showed that the sensitivity values of the Ag thin-film electrode deposited using DC sputtering, the Ag thin-film electrode deposited using spin coating, and the Ag nanosquare array in detecting PBS+BSA concentration in the cyclic voltammetry (CV) experiment were 1.308 µA mM−1cm−2, 0.022 µA mM−1cm−2, and 39.917 µA mM−1cm−2, respectively. Meanwhile, the sensitivity values of the Ag thin film and the Ag nanosquare array in detecting the PBS+BSA concentration in the electrochemical impedance spectroscopy (EIS) measurement were 6593.76 Ohm·cm2/mM and 69,000 Ohm·cm2/mM, respectively. Thus, our analysis of the optical and electrochemical characteristics of Ag thin films and Ag nanosquare arrays showed that both can be used as an alternative biomedical technology to monitor the prognosis of blood cancer based on the concentration of serum albumin in blood.

Perceptions of Hospice and Transfusion Access Among Patients with Advanced Blood Cancers: Results from a Best-Worst Scaling Survey

Background: Patients with hematologic malignancies have low rates of hospice use, and when they do enroll, they often do so in the last three days of life. While lack of access to transfusions in hospice has been posited to be a key barrier to hospice use for this population, data are lacking regarding the perception of patients with blood cancers about the importance of transfusion access compared to traditional hospice services. We sought to characterize the utility of transfusions and hospice services from the perspective of patients with advanced blood cancers, who would potentially be eligible for hospice care. Methods: In October 2020, we began a web-based survey of patients with hematologic malignancies recruited from the clinics of two large cancer centers. Eligible patients were at least 18 years of age, had at least two outpatient visits to the cancer center, and had a physician-estimated prognosis of six months or less based on their hematologic oncologist answering "no" to a modified "surprise" question (Hudson KE, JPM 2018): "would you be surprised if this patient died within the next six months?" A physician-estimated prognosis of ≤ 6 months was used for study inclusion as this is an eligibility criterion for hospice. The survey was developed through literature review, a series of patient/caregiver focus groups (n=27) and cognitive debriefing with blood cancer patients (n=5). The survey included a best-worst scaling (BWS) section to assess patients' perceptions of the utility of various services routinely provided in hospice (visiting nurse, case manager, home health aide, chaplain, social worker, respite care) as well as non-routine services (transfusion access, transportation, peer support, telemedicine through videoconferencing). We asked patients to imagine a program developed to support quality of life for patients with blood cancers just like them. We then presented them with 10 questions with different combinations of the services in groups of 4 and participants were asked to select the service they considered "most important" and "least important" in deciding whether to sign up for the program. The BWS questions were constructed using a near balanced incomplete block design (Louviere JJ, Patient 2010). We conducted a hierarchical Bayesian analysis to ascertain a standardized utility score assigned to each service, a measure of the average propensity to choose a service as most important more often than least important. Analyses were conducted using Sawtooth (Sawtooth Software, Inc). Results: As of July 2021, 102 patients had completed the survey (response rate: 64.6%). The median age of respondents was 71 years (IQR 63, 77). The majority of respondents were male, white, and married/living with partner (Table). The most common diagnosis was acute leukemia (38.2%). Patients considered access to blood transfusions to have the highest importance (Figure) with a standardized utility score of 21.1, 95% confidence interval [CI] [19.6-22.6], followed by telemedicine (19.4, 95% CI [17.8-20.9]), transportation to/from medical appointments (13.4, 95% CI 11.7-15.1), and visiting nurses (10.8, 95% [9.5-12.2]. The three least important services perceived by respondents were access to respite care (4.7, 95% CI [3.9-5.6]), social workers (4.5, 95% CI [3.5-5.5]), and chaplains (2.3, 95% CI [1.3-3.3]). Conclusions: In this cohort of blood cancer patients who would potentially be eligible for hospice care, access to blood transfusions had the greatest level of importance relative to services routinely provided in hospice settings. The high value placed on transfusion access suggests that this factor plays a crucial role in hospice decision making. Accordingly, lack of transfusion access in many hospices likely reduces the propensity of patients with blood cancers to choose hospice. Innovative hospice delivery models that include access to palliative transfusions may have strong potential to increase hospice use and optimize end-of-life care for this patient population. Figure 1 Figure 1. Disclosures Huntington: Genentech: Consultancy; SeaGen: Consultancy; Thyme Inc: Consultancy; Servier: Consultancy; Novartis: Consultancy; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy; DTRM Biopharm: Research Funding; TG Therapeutics: Research Funding; Flatiron Health Inc.: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding.

Social Media Validation for Pre-Screened Ontologies As a Driver for Biomolecular Interaction Significance in COVID-19 and Hematological Malignancies

With the rise of social media use during the COVID-19 pandemic, impressions from online content can affect behavioral changes resulting in exacerbating disparities in care. Thus, there exists a need to utilize social media platforms, like Twitter, to help augment preparedness, especially at the intersection between oncology and COVID-19, where tweets could help hint at potential biomolecular interactions. To address this, a study was developed to assess relationship and ontologies on the interaction between hematological malignancies and COVID-19 on Twitter. Ontologies are groupings of terms and related identifiers, such as genes, for general search terms, such as "Blood Cancer", were found utilizing the Human Phenotype Ontology. These were combined with the term "COVID-19" and used as search terms for Twitter's Standard Search API. The resulting tweets were cross-checked to assess if they included any of the other terms or genes related to the starting ontologies to then determine how many terms or genes each tweet was associated with. Once the most associated tweets to the ontologies were found, the genes related to those ontologies were utilized to find biological structures within the AlphaFold EMBL database, before being used in binding using HEX Docking software's shape based binding tool in 3D. Finally, Root Mean Square (RMS) Deviations were performed between the top 2000 conformations for each bound structure to determine if the binding was statistically significant. Results showed strong clustering of top tweets around keyword combinations. In the case of the starting entry, "Blood COVID-19", the ontologies that were found were linked to 45 terms that each had 100 or more tweets linked to them (Figure 1a). One such term of significance was Acute Myeloid Leukemia, which was linked to the gene BRCA1. The biological significance of the molecular interaction between BRCA1 and SARS CoV-2 was determined using the predicted protein structure from the AlphaFold-EMBL database for BRCA1 and the RCSB Protein Bank structure for the SARS CoV-2 spike (PDB# 6VSB), which can be found in Figure 1b. This interaction was found to be significant based on the average RMS Deviation of 82.97 Angstroms that ranged across the top 2000 conformation. Each model had an average RMS of 85.05 Angstroms between BRCA1 and the COVID-19 spike, with binding occurring on the spike's carbohydrate recognition domain within its S1 segment that is typically used for cell entry. Thus, human phenotype ontology was effective in classifying tweets to specific biomolecular interactions. Therefore, this approach could be utilized to proactively influence treatment designs for blood cancer patients infected with COVID-19, as well as in other areas where medical illnesses are already well defined by ontologies or other literature data. Forward looking, future studies will help to ensure that terms that are not well characterized by ontologies can still be utilized in this type of analysis by employing de novo ontology production methods. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Utilization of Cardiac Surveillance in Pediatric Blood Cancer Survivors Who Received Anthracycline-Based Therapy Differs By Age: A Claims-Based Analysis

Background: The Children's Oncology Group Long-Term Follow-up Guidelines recommend surveillance for late effects in pediatric cancer survivors based on therapeutic exposures. In particular, the Guidelines recommend an echocardiogram, or comparable imaging, every 2 to 5 years to evaluate cardiac function in survivors exposed to anthracycline chemotherapy. However, little is known about the real-world utilization of cardiac surveillance tests following the completion of cancer therapy. Objective: This study fills this gap by describing the proportion of anthracycline-treated survivors of pediatric cancer who received surveillance for cardiac function following the completion of their cancer therapy. Method : We developed an algorithm to identify a cohort of pediatric cancer survivors using the IBM MarketScan ® Commercial Claims and Encounters Database (a nationwide private insurance enrollment and claims database). The cohort for inclusion was enrollees who (1) received anthracycline for blood cancer (leukemia or lymphoma); (2) aged ≤21 years at cancer diagnosis; (3) completed all cancer therapy between 2009 and 2018; and (4) remained continuously insured for at least one year post-therapy. Outcomes assessed included the receipt of: (1) echocardiogram, (2) cardiac magnetic resonance imaging (MRI), (3) multiple gate acquisition (MUGA) scan, and (4) any of the aforementioned cardiac surveillance tests over the 5-year period after the completion of all cancer therapy. The Kaplan-Meier (K-M) method was used to estimate the cumulative incidence of an event post-therapy, where the event was defined as the initial healthcare claim for a cardiac surveillance test. Individuals were censored if they had not received a test by study termination or were lost to follow-up at any time during the 5 years post-therapy. Multivariate Cox proportional hazard models were estimated to identify the demographic and cancer-related factors strongly associated with the initial test receipt. Results : Among 1,914 eligible blood cancer survivors, 259 (13.5%) survivors received a hematopoietic stem cell transplantation (HSCT; Table 1). The K-M estimated probability of receiving a cardiac surveillance test by 5 years post-therapy was 61.0% (95% Confidence Interval [CI]: 57.2% to 64.7%), with the median time to the initial test being 2.6 years (95% CI: 2.2 to 3.1 years) from therapy completion. The vast majority of cardiac surveillance test users underwent an echocardiogram (n=850; versus only 10 who had a cardiac MRI, and 14 who had a MUGA scan) by the end of their follow-up period. The proportion of survivors who had an initial cardiac test increased over time but varied by age at cancer therapy completion and the receipt of HSCT. The K-M estimated probability of receiving an initial test by 5 years post-therapy was: 86.0% (95% CI: 77.3% to 91.6%) for children (ages ≤11 years), 85.0% (95% CI: 75.4% to 91.1%) for adolescents (ages 12-17 years), and 36.8% (95% CI: 32.6% to 41.0%) for young adults (ages 18-28 years; Figure 1). Multivariate Cox models showed that compared with children, adolescents were more likely to receive an initial cardiac test (Hazard Ratio [HR] = 1.3; 95% CI: 1.1 to 1.5), while young adults were less likely to receive a test (HR = 0.4; 95% CI: 0.3 to 0.5). In addition, survivors who received a HSCT were more likely than those who did not to complete an initial cardiac test (HR=1.8; 95% CI: 1.5 to 2.2). Conclusions: This nationwide, claims data-based study showed that a substantial proportion of anthracycline-exposed survivors of blood cancers had not completed a cardiac surveillance test within 5 years post-therapy. Within this high-risk population, young adults were significantly less likely to receive surveillance testing for the prevention and early detection of cardiac dysfunction. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Identifying and Overcoming Barriers in Clinical Trial Enrollment for Veterans with Blood Cancers

Introduction Equitable and diverse clinical trials participation is essential for practice-changing results to be applicable to all patients. However, patients who identify as minorities, who live in rural areas, and who have low income are typically underrepresented in clinical trials. Increasing clinical trial participation in general and among underrepresented patients in particular is a goal of The Leukemia & Lymphoma Society's (LLS) Clinical Trial Support Center (CTSC), a clinical trial nurse navigation service for patients with blood cancers and their oncologists. The Veterans Health Administration (VA) is a national network of health care facilities. Approximately 3% of cancers in the United States are diagnosed in the VA. The prevalence of certain blood cancers is higher in the VA, in part due to military exposures. Veterans who receive care in the VA are more likely to have lower income, live in rural areas, and have comorbidities than patients who receive care in the private sector. Clinical trial participation among Veterans may be hampered by VA-specific factors (e.g. relatively fewer clinical trial options in the VA, lack of awareness that Veterans may be referred to participate in clinical trials outside of the VA) and patient-specific factors (e.g. income, rurality, comorbidities, and minority status). This study aimed to characterize and overcome barriers to Veteran enrollment in blood cancer clinical trials. Methods The LLS CTSC performs clinical trial searches using a database with information from clinicaltrials.gov and other proprietary data. To assess the impact of geography and rurality on the availability of clinical trials, we performed simulated searches for clinical trials in proximity of 13 VA facilities (6 rural, 7 urban), six blood cancers (AML, CLL, DLBCL, FL, MDS, MM), and two disease statuses (new diagnosis, relapsed/refractory). To further evaluate barriers to CTSC referral and clinical trial enrollment among Veterans who receive care in the VA, we collected data about referral patterns of VA hematologist-oncologists and Veterans' treatment choices at four VA facilities between September 2020 through May 2021. Results When evaluating both 100- and 200-mile radii from the VA facilities in simulated searches, there were significantly more clinical trials available for Veterans who receive care in urban compared to rural areas and on the East or West Coast compared to the Midwest, in aggregate (all cancers) and by disease type or status (p unadj < 0.0001). Forty-eight Veterans with blood cancers at the Durham NC, Salem VA, Sioux Falls SD, and Clarksburg WV VA facilities had consideration of clinical trials as a treatment option by oncology providers over a nine-month period. All Veterans were male, with 33 White/15 African-American, 47 non-Hispanic/1 Hispanic, age 41-93 years (median 71), living 0.2-186 miles from their VA facility (median 33.1), with diverse diseases and stages represented. Of the 48 patients, 14 patients were not asked if they wanted clinical trials information; reasons were need for immediate therapy, co-morbidities, or patient circumstances. Of 34 patients who were asked if they wanted clinical trials information, 14 did not agree to a referral to the CTSC; reasons were preference for immediate therapy, wanting care in the VA, wanting standard therapy, and lack of transportation. Of 20 referred Veterans, two enrolled in clinical trials outside the VA (for CLL and PMF), with investigational therapy provided by the study sponsors. Conclusions Using data from simulated and actual patient referrals to the LLS CTSC, we identified patient, provider, and location specific barriers for Veteran referral and enrollment in blood cancer clinical trials. When offered information about clinical trials, the majority of patients agreed to an LLS CTSC referral, suggesting that patients are generally willing to receive education and information about trial participation if given the opportunity. The LLS CTSC nurse navigators can overcome barriers to enrollment by providing education and identifying potential clinical trials within a desired geographic area. In addition to resources provided by the LLS CTSC, opening additional clinical trials in rural areas and within the VA system could help increase Veteran participation in clinical trials for blood cancers. Disclosures Rodgers: MJH Lifesciences: Consultancy. Weiss: AbbVie Inc.: Research Funding; Amgen Inc.: Research Funding; AstraZeneca Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding.

The Atlas of Blood Cancer Genomes (ABCG) Project: A Comprehensive Molecular Characterization of Leukemias and Lymphomas

Introduction Blood cancers are collectively common and strikingly heterogeneous diseases both clinically and molecularly. According to the WHO taxonomy, there are over 100 distinct myeloid and lymphoid neoplasms. Genomic profiling of blood cancers has been applied in a somewhat ad hoc fashion using diverse sequencing approaches including the use of targeted panels, whole exome sequencing, whole genome sequencing, RNA sequencing, etc. The lack of data uniformity has made it difficult to comprehensively understand the clinical and molecular spectrum within and across diseases. Systematic genomic approaches can address the central challenges in the diagnosis and treatment of blood cancers. For the diagnosis of blood cancers, the incorporation of genomics could greatly enhance the accuracy and speed of clinical diagnostics. Genomics could also inform their pathology classification. However, these applications must be preceded by a clear understanding of the particular genetic aberrations and expression profiles that unite and distinguish different leukemias and lymphomas. Therapeutic development can also be aided by genomic approaches through identification of new targets and establishing the relevance of existing targets and treatments. Targeted therapies including those directed at specific surface markers (e.g. CD19, CD30 and CD123) or molecular targets (e.g. BCR-ABL fusions, IDH1 mutations and EZH2 mutations) are rarely restricted to a single disease, with most occurring in multiple blood cancers. A systematic understanding of the presence or overlap of these targets within or across blood cancers would significantly expand the therapeutic possibilities and better enable the use of existing therapies in both common and rare cancers. However, such therapeutic possibilities need to be established through a rigorous, data-driven approach. We initiated the Atlas of Blood Cancers Genomes (ABCG) project to systematically elucidate the molecular basis of all leukemias and lymphomas by building upon advances in genomic technologies, our capabilities for data analysis and economies of scale. Using a uniform approach to systematically profile all blood cancers through DNA and RNA sequencing at the whole exome/whole transcriptome level, we aim to link genomic events with clinical outcomes, disease categories and subcategories, thereby providing a complete molecular blueprint of blood cancers. Methods/Results The ABCG project consists of collaborators from 25 institutions around the world who have collectively contributed samples from 10,481 patients comprising every type of blood cancer in the current WHO classification. The samples include thousands of myeloid leukemias and mature B cell lymphomas, hundreds of Hodgkin lymphoma and plasma cell myeloma, as well as every rare type of hematologic malignancy (along with case-matched normal tissue). All cases were de-identified and their associated pathology and detailed clinical information entered into a purpose-built web-based system that included disease-specific data templates. All cases were subjected to centralized pathology review and clinical data review by experienced hematopathologists and oncologists. All 10,481cases are being sequenced at the DNA and RNA level, and are being profiled to define the genetic alterations and expression changes that are characteristic of each disease. Analysis will include translocations, copy number alterations, and viral status. These molecular features will be examined in conjunction with genetic events, pathologic factors, and the clinical features. We have already generated results for ALK-negative anaplastic large B cell lymphoma and primary mediastinal B cell lymphomas (N=210). These data demonstrate novel subgroup and molecular discoveries that are enabled by integrative DNA and RNA sequencing analysis and the examination of molecular features across different diseases as well as within individual entities. In addition, other disease entities and the collective data will be presented in the meeting. Conclusion The ABCG project will comprehensively study the genetic and clinicopathological features of all blood cancers using systematic genomic approaches. We anticipate our data, approaches and results will serve as a lasting resource for the molecular classification and therapeutic development for leukemias and lymphomas. Disclosures McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau.