Individual Disease Characteristics Research Articles

Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium.

In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Abstract PO2-05-02: Real-world experience of patients receiving treatment for hormone receptor-positive/human epidermal growth factor receptor-2 negative metastatic breast cancer: A global analysis of symptoms and side effects

Abstract Background: Advances in treatment for patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor-2 negative (HER2–) metastatic breast cancer (mBC) have improved overall survival, but treatment resistance is common and median survival remains only a few years. These pts usually need chronic therapy and often experience symptoms and side effects. There is limited knowledge on pts’ experiences outside the clinical trial setting, largely because this information is not routinely reported. This analysis leverages a unique database of physician- and pt-reported data to describe symptoms and side effects among a real-world, geographically diverse population of pts receiving treatment for HR+/HER2– mBC. Methods: This retrospective cohort study used Adelphi Disease Specific Programme Real World Data, comprising validated, linked pt and physician questionnaire data from the US, France, Germany, Italy, Spain, and UK. Eligible pts were ≥18 y, currently receiving treatment for advanced BC and not enrolled in a clinical trial. Data were collected between August 2022 and February 2023. Physician surveys provided data on individual pt demographics and disease characteristics, comorbidities, treatment history, and treatment (including adherence). Physicians also reported presence or absence of symptoms and side effects after treatment initiation for each pt they considered. A subset of pts completed one-time validated quality of life (QOL) instruments, including the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) and EORTC QLQ-breast (BR23). Results: Data from 1578 pts receiving treatment for HR+/HER2– mBC were analyzed. Mean age was 65-y, 91% were white, 71% had de novo mBC, and 82% had ECOG performance status 0-1 at the start of current treatment. Across all lines of therapy, 71% of pts were receiving endocrine-based therapy, 16% were receiving chemotherapy only, and 13% were receiving other therapies; 40% of all pts were receiving second or later lines of any systemic therapy (2L+). Among all pts, the most common physician-reported symptoms and side effects (in ≥10% of pts) were bone pain (30%), change in appetite (13%), weight loss (12%), neutropenia (11%), and joint/muscle pain (11%). Pts on 2L+ therapy experienced a greater frequency of symptoms and side effects than those on first-line therapy (Table). Of 220 pts who completed QOL questionnaires, the most commonly reported symptoms and side effects (in ≥70% of pts) were feeling tired (87%), worry about future health (80%), general worrying (79%), needing to rest during the day (74%), feeling weak (74%), having trouble doing strenuous activity (71%), and trouble taking a long walk (71%). These were common irrespective of pt age, disease state (recurrent vs de novo), current treatment regimen, and line of therapy. Conclusions: This real-world analysis shows that both physicians and pts identified substantial symptoms and side effects during treatment. These were pervasive across the population and more common in those receiving 2L+ therapy, although it remains unclear which were due to treatment or disease. Thus, it is important to continue to develop treatments and supportive care to improve both clinical outcomes and pt QOL. Citation Format: MK Rehnquist, Ann Partridge, Annabel Lambert, Allison Kurian, Natalia Sadetsky, Emily Freeman, Lisa Carey. Real-world experience of patients receiving treatment for hormone receptor-positive/human epidermal growth factor receptor-2 negative metastatic breast cancer: A global analysis of symptoms and side effects [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-02.

Cholangiocyte Organoids: The New Frontier in Regenerative Medicine for the Study and Treatment of Cholangiopathies.

Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell's original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies.

Deciphering the complex links between inflammatory bowel diseases and NAFLD through advanced statistical and machine learning analysis

Background and Objective:Accurate classification of liver disease stages provides crucial insights into patient prognosis, aiding in the prediction of disease outcomes and influencing clinical decision-making. There is an urgent need for non-invasive methods to diagnose various stages of liver dysfunction and uncover hidden pattern based on individual disease characteristics. Method:One popular and effective approach is collecting serum biomarker samples. The study was conducted on collected serum biomaker samples of 81 patients with Inflammatory Bowel Disease (IBD) of Changhua Christian Hospital in China, including 36 with Crohn’s disease (CD) and 45 with Ulcerative Colitis (UC) using Latent Semantic Analysis(LSA) and machine learning (ML) techniques.Machine Learning algorithms Random Forest (RF), Logistic Regression (LR), XGBoost (XGB), and Support Vector Classifier (SVC), were utilized to predict liver risk associated with conditions including Hepatitis, Autoimmune Hepatitis (AIH), Alcoholic Liver Disease (ALD), and Non-Alcoholic Fatty Liver Disease (NAFLD). Models’ accuracy was assessed using K-Fold Cross-Validation (CV).Distinct pattern were identified using Latent Semantic Analysis(LSA). Furthermore, SHAP plots were utilized for enhanced interpretability, highlighting essential features for liver dysfunction levels. Results:The inflammatory profile, mixed disease profile, and healthy profile were the three distinct clusters were identified with LSA. The RF model achieved high accuracy of 0.94±0.06. Serum Glutamate Pyruvate Transaminase (GPT), Age at Diagnosis (AAD), Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP) were found the most key important features in liver disease staging increment. Conclusion:The research significantly contributes to the fields of biomedical informatics and clinical decision-making. The developed model offers valuable decision-making tools for clinicians, enabling early and targeted interventions.

Clinical outcomes of intensive versus less intensive first-line chemotherapy for metastatic colorectal cancer.

Aims: Physicians determine the treatment regimen for metastatic colorectal cancer on a case-by-case bases, according to the individual disease characteristics. We retrospectively compared the baseline characteristics and efficacies of first-line treatment among patients with metastatic colorectal cancer who received intensive therapy involving fluoropyrimidine plus oxaliplatin and/or irinotecan, potentially with molecularly targeted agents as well, versus less intensive fluoropyrimidine and/or bevacizumab therapy. Materials & methods: Data were collected from a medical claims database. The efficacy outcomes were: time to treatment failure, time to first subsequent therapy and overall survival. Results: The less intensive therapy group (n=633) had higher median age, lower daily activity levels and shorter time to treatment failure, time to first subsequent therapy and overall survival than the intensive therapy group (n=3829). Combination therapy with molecularly targeted agents and bevacizumab improved treatment efficacy outcomes in the intensive and less intensive groups, respectively. Conclusion: Patient age and daily activity levels were important factors for determining treatment intensity.

Extracellular vesicles as personalized medicine.

Extracellular vesicles (EVs) are released from all cells in the body, forming an important intercellular communication network that contributes to health and disease. The contents of EVs are cell source-specific, inducing distinct signaling responses in recipient cells. The specificity of EVs and their accumulation in fluid spaces that are accessible for liquid biopsies make them highly attractive as potential biomarkers and therapies for disease. The duality of EVs as favorable (therapeutic) or unfavorable (pathological) messengers is context dependent and remains to be fully determined in homeostasis and various disease states. This review describes the use of EVs as biomarkers, drug delivery vehicles, and regenerative therapeutics, highlighting examples involving viral infections, cancer, and neurological diseases. There is growing interest to provide personalized therapy based on individual patient and disease characteristics. Increasing evidence suggests that EV biomarkers and therapeutic approaches are ideal for personalized medicine due to the diversity and multifunctionality of EVs.

Research Strategy for the Development of a Quality-of-Life Decision-Making Model for Older Patients With Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a deadly cancer, especially for patients over 60 years of age who face the dilemma of choosing the best treatment during a time of crisis. Current research in the older AML population is focused on survival without addressing quality of life (QOL). Survival and QOL data are essential for patients to decide which treatment best aligns with their goals, whether for survival or improved QOL. Research aims: The aims of this study are to: (1) Describe differences in QOL among newly diagnosed older AML patients receiving intensive chemotherapy compared with nonintensive chemotherapy (at baseline, and days 30, 60, 90, and 180 post treatment); (2) Identify the individual clinical disease characteristics and patient factors of newly diagnosed AML patients that predict QOL among those receiving two treatment intensities; and (3) Design a patient decision-making model that integrates the significant clinical disease and patient factor predictors of QOL for newly diagnosed older AML patients. Methods: An exploratory observational design will be used to address aims 1 and 2. Data will be collected from 200 patients ≥ 60 years of age with newly diagnosed AML. Subjects will complete the Functional Assessment of Cancer Therapy-Leukemia, Brief Fatigue Inventory, and Memorial Symptom Assessment Short Form within 7 days of beginning new treatment and at days 30, 60, 90 and 180. Clinical disease characteristics will be completed by the health-care team. A patient decision-making model will be developed to provide survival and quality-of-life data for intensive and nonintensive chemotherapy.

P109 Personalised comprehensive care packages for people with rheumatoid arthritis: a survey-based study

Abstract Background/Aims Socioeconomic and clinical factors are closely associated with long-term disease outcomes in rheumatoid arthritis (RA). There is increasing evidence for holistic, targeted management of people with RA, including at first presentation. This study aimed to determine how people with, and those involved in the treatment of RA, benefit from personalised care packages and treatment programmes. Methods An online survey was developed by an expert panel comprising physicians, psychologists, epidemiologists and patients, following three multidisciplinary workshops which included patients. Questions were designed to evaluate participants’ views on multidisciplinary Team (MDT) involvement in the care of patients at early-stage RA and onwards. The online survey underwent extensive revisions by patients and clinicians, before dissemination to patients and healthcare professionals (HCPs) in the UK. Results We received 41 complete responses: 23 (57.5%) rheumatology consultants/trainees, seven (17.5%) rheumatology specialist nurses, five (12.5%) occupational therapists, three (7.5%) physiotherapists, one dietician (2.5%) and one patient (2.5%). 82.9% of respondents agreed that people with RA need access to the same “early” care package (comprising a core MDT) at time of diagnosis. On subsequent clinical reviews, 85.4% of respondents agreed that the care package for people with early RA may need to be tailored to an individual’s clinical, psychological and social needs. 58.5% of respondents confirmed that a standard core packaging with input from a consultant rheumatologist, clinical nurse specialist/patient educator, general practitioner and pharmacist is appropriate for patients with early RA, irrespective of patient or disease-related factors; 36.6% disagreed and 4.9% were unsure. Of those disagreeing with this statement, 36.7% agreed not all of these healthcare professionals are relevant to patient care at time of diagnosis, whilst 53.3% gave another reason and 10% were unsure. 68.3% of participants suggested additional involvement of 1-6 MDT members in patient care, specifically occupational therapists, physiotherapists and psychologists. Other posited that primary care may be included occasionally, and additional MDT members’ expertise in early disease may be overwhelming and require frequent review. There was strong agreement (median 10/10 on Likert scale) for the following two statements: ‘A care package with core members of the multidisciplinary rheumatology team need to be available to people newly diagnosed with RA’; ‘Personalised comprehensive care packages, comprising a core plus various additional members of the multidisciplinary team, need to be offered and adapted according to a person’s individual disease characteristics and socio-economic circumstances’. Conclusion HCPs caring for people with RA overwhelmingly agree with a tailored MDT involvement from an early stage of disease, reviewed regularly and adapted. Care packages need to be personalised to account for bio-psycho-social factors. HCPs need to acknowledge that the “ideal” care package may vary markedly between patients to maximise impact and benefit for patients. Disclosure M. Dey: None. A.D. Busby: None. H. Lempp: None. E. Nikiphorou: None.

Prognostic value of CT-derived coronary artery disease characteristics varies by ASCVD risk: insights from the PROMISE trial.

To compare the prognostic value of individual CT-derived coronary artery disease (CAD) characteristics across categories of clinical cardiovascular risk. The central core laboratory assessed coronary artery calcium (CAC), obstructive CAD (stenosis ≥ 50%), and high-risk plaque (HRP) in stable outpatients with suspected CAD enrolled in the PROMISE trial. Multivariable Cox regression models (endpoint: unstable angina, nonfatal myocardial infarction, or all-cause mortality; median follow-up: 2years) were used to compare hazard ratios (HR) of the CT measures between low-borderline (< 7.5%) and moderate-high (≥ 7.5%) atherosclerotic cardiovascular disease (ASCVD) risk based on the pooled cohort equation. Among 4356 included patients (aged 61 ± 8years, 52% women), 67% had ASCVD risk ≥ 7.5%. Stratified by ASCVD risk, CAD ≥ 50% had nearly threefold greater HR in individuals with ASCVD < 7.5% (aHR, 6.85; 95% CI, 2.33-20.15; p < 0.001) vs. ASCVD ≥ 7.5% (aHR: 2.66, 95% CI: 1.67-4.25, p < 0.001; interaction p = 0.041). CAC predicted events solely in ASCVD ≥ 7.5% patients (aHR: 1.92, 95% CI: 1.01-3.63, p = 0.045; interaction p = 0.571), while HRP predicted events only in ASCVD < 7.5% (aHR: 3.11, 95% CI: 1.09-8.85, p = 0.034; interaction p = 0.034). Prognostic values of CT-derived CAD characteristics differ by ASCVD risk categories. While CAD ≥ 50% has the highest prognostic value regardless of ASCVD risk, CAC is prognostic in high and HRP in low ASCVD risk. These findings suggest that CAD ≥ 50% and HRP detection rather than CAC scoring may better risk-stratify symptomatic low-risk patients and thus potentially improve downstream care. • Prognostic value of individual CT-derived CAD characteristics differs by categories of cardiovascular risk. • Presence of obstructive coronary artery stenosis ≥ 50% has the highest prognostic value regardless of cardiovascular risk. • Coronary artery calcium is independently prognostic in high and high-risk plaque features in low cardiovascular risk.

Nuclear medicine in pheochromocytoma and paraganglioma: at a crossroads with precision medicine.

Precision medicine (PM) aims to maximize the risk-benefit balance of medical decisions by integrating individual patient and disease characteristics. This approach is gaining increasing recognition from clinicians, healthcare systems, pharmaceutical companies, patients, and governments. Nuclear medicine plays a critical role in PM by its virtue of providing critical information at every step of disease management, digital markers, and companion diagnostics/therapeutics. It is anticipated that technological breakthroughs and new tracers will continue to position nuclear medicine among the significant players in PM.

Medical Treatment Options for Ulcerative Colitis.

The landscape of management of ulcerative colitis, a type of inflammatory bowel disease, continues to change with advancement in pharmaceutical options as well as clinical treatment targets. Ulcerative colitis primarily involves the superficial layers of the large bowel, and cause active inflammation that can affect the colon from the rectum to the cecum in a relapsing and a remitting course. In this review, we provide evidence-based guidance on the selection of appropriate medical therapies based on individual patient and disease characteristics, with a focus on biologics and small molecules. We also review the role of surgery and management of acute severe ulcerative colitis.

Neurons derived from individual early Alzheimer's disease patients reflect their clinical vulnerability.

Establishing preclinical models of Alzheimer's disease that predict clinical outcomes remains a critically important, yet to date not fully realized, goal. Models derived from human cells offer considerable advantages over non-human models, including the potential to reflect some of the inter-individual differences that are apparent in patients. Here we report an approach using induced pluripotent stem cell-derived cortical neurons from people with early symptomatic Alzheimer's disease where we sought a match between individual disease characteristics in the cells with analogous characteristics in the people from whom they were derived. We show that the response to amyloid-β burden in life, as measured by cognitive decline and brain activity levels, varies between individuals and this vulnerability rating correlates with the individual cellular vulnerability to extrinsic amyloid-β in vitro as measured by synapse loss and function. Our findings indicate that patient-induced pluripotent stem cell-derived cortical neurons not only present key aspects of Alzheimer's disease pathology but also reflect key aspects of the clinical phenotypes of the same patients. Cellular models that reflect an individual's in-life clinical vulnerability thus represent a tractable method of Alzheimer's disease modelling using clinical data in combination with cellular phenotypes.

Benefits of Contralateral Patent Processus Vaginalis Closure During Laparoscopic Surgery for Inguinal Hernia in Female Children.

After more than a decade, an accurate description of the current state of pediatric inguinal hernia repair still an issue of contention. Improvement of techniques together with patient-entered intervention that account for the experiences related to individual disease characteristics have become an important factor of which the surgeon must be aware. Therefore, the aim of this study is to analyze a potential treatment for metachronous contralateral inguinal hernia (MCIH) in children during laparoscopic assisted percutaneous internal inguinal ring suturing (PIRS). In a prospective clinical study, carried out at the University Clinic for Pediatric Surgery in Skopje, Republic of North Macedonia, we analyzed the data from 49 female children, aged 1-14 years old, with clinically diagnosed congenital inguinal hernia treated via PIRS. The position of hernias on the right side was 29 (59.2%) on the left side was 19 (38.8%) and on both sides was 1 (2.0%). With intraoperative assessment, it was determined that in 33 (67.3%) participants there was no presence of a hidden hernia, while in 16 (32.7%), there was indeed the presence of a hidden hernia. Of the hidden hernias determined laparoscopically [16 (100%)], 8 (50%) were left and right hidden hernias, all treated laparoscopically. The PIRS technique is a procedure where the basic advanced treatment is exploration. This also included the adequate treatment of other pathologies, such as the prophylactic closure of a contralateral patent processus vaginalis with simultaneous treatment as there is the potential for hernia in future, therefore reducing the number of metachronous inguinal hernias.

Custom CARs: Leveraging the Adaptability of Allogeneic CAR Therapies to Address Current Challenges in Relapsed/Refractory DLBCL.

Cellular therapies have transformed the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), which typically does not respond well to salvage chemotherapy. Recently, approximately 40% of r/r DLBCL patients across three different trials achieved a complete remission at 1 year after receiving treatment with autologous chimeric antigen receptor (CAR) T cells (auto-CARs). These successes have prompted studies of auto-CARs in second-line settings, in which axicabtagene ciloleucel and lisocabtagene maraleucel both showed improved event-free survival over autologous hematopoietic cell transplantation (AHCT). While encouraging, this data also highlights that 60% of patients relapse or progress following treatment with auto-CARs. Individual disease characteristics and logistical challenges of cell engineering also limit patients’ eligibility for auto-CARs. Allogeneic CAR T cells (allo-CARs) may address some of these limitations as they may mitigate delays associated with auto-CARs, thereby reducing the need for bridging chemotherapies and increasing availability of cellular products for patients with aggressive lymphomas. By being sourced from healthy donors who have never been exposed to cytotoxic chemotherapy, allo-CARs can be created from T cells with better fitness. Allo-CARs made from specific cellular subsets (e.g., stem cell memory or naïve/early memory T cells) may also have increased efficacy and long-term persistence. Additionally, allo-CARs have been successfully created from other cell types, including natural killer cells, gamma-delta T-cells and induced pluripotent stem cells. These cell types can be engineered to target viral antigens, enabling precision targeting of virally driven DLBCL. As allogeneic donor cells can be banked and cryopreserved in batches, they can be made more readily available, potentially reducing logistical hurdles and costs compared to engineering auto-CARs. This may ultimately create a more sustainable platform for cell therapies. Challenges with allo-CARs that will need to be addressed include graft versus host disease, alloimmunization, potentially decreased persistence relative to auto-CARs, and antigen escape. In short, the adaptability of allo-CARs makes them ideal for treating patients with r/r DLBCL who have progressed through standard chemotherapy, AHCT, or auto-CARs. Here, we review the published literature on patients with r/r DLBCL treated with allogeneic CAR products manufactured from various cell types as well as forthcoming allogeneic CAR technologies.

Perceived utility and disutility of genomic sequencing for pediatric patients: Perspectives from parents with diverse sociodemographic characteristics.

Given the limited therapeutic options for most rare diseases diagnosed through genomic sequencing (GS) and the proportion of patients who remain undiagnosed even after GS, it is important to characterize a broader range of benefits and potential harms of GS from the perspectives of families with diverse sociodemographic characteristics. We recruited parents of children enrolled in the Undiagnosed Diseases Network. Parents completed an in-depth interview, and we conducted a comparative content analysis of the data. Parents (n=30) were demographically diverse, with 43.3% identifying as Hispanic, 33.3% primarily Spanish-speaking, and widely variable household income and education. Parents reported minimal changes in their child's health status following GS but did report a range of other forms of perceived utility, including improvements in their child's healthcare management and access, in their own psychological well-being, and in disease-specific social connections and research opportunities. Parents who received a diagnosis more frequently perceived utility across all domains; however, disutility also was reported by both those with and without a diagnosis. Impacts depended on multiple mediating factors, including parents' underlying expectations and beliefs, family sociodemographic characteristics, individual disease characteristics, and prior healthcare access. Our study suggests that the perceived utility of GS varies widely among parents and may depend on multiple individual, sociodemographic, and contextual factors that are relevant for pre- and post-GS counseling, for value assessment of GS, and for policymaking related to access to new genomic technologies.

UVB phototherapy in the treatment of vitiligo: State of the art and clinical perspectives.

Vitiligo is a chronic pigmentary skin disorder that results in white, hypopigmented macules and patches. It causes a considerable psychological and emotional burden on the affected individuals and their families. Several therapeutic options have been employed in vitiligo including topical and oral drugs, surgical techniques, and phototherapy which is considered the cornerstone treatment. Different wavelengths and modalities are available, but narrowband UVB (NB-UVB) is considered the safest and the most effective phototherapy alternative. NB-UVB acts on multiple steps in vitiligo pathogenesis, and it is capable of inducing stabilization and repigmentation of vitiligo lesions. Technological advances have led to the development of both new phototherapy devices and new medical and surgical therapeutic options that can be combined with phototherapy to achieve optimal results. There is no standard treatment, and individual patient and disease characteristics should be considered. We review the current evidence in what concerns UVB phototherapy for vitiligo treatment, including novel combination treatments that may help to provide the best care for these patients.

Predictors of clinical trial enrollment and impact on outcome in children and adolescents with acute lymphoblastic leukemia: A population based study.

7031 Background: Outcomes in pediatric acute lymphoblastic leukemia (ALL) have shown remarkable improvements in large part due to sequential clinical trials. Concerns however persist around whether access to clinical trials is equitable. It is also unclear whether patient outcomes are improved simply by enrolling on a clinical trial. Our objective was to therefore determine which patient and disease-related factors are associated with enrollment, and whether enrollment was associated with clinical outcomes among children and adolescents with ALL in a single-payer health system in Ontario, Canada. Methods: We included all Ontario patients diagnosed with ALL between 0-18 years of age from 2002-2012 treated at a pediatric center, identified through a provincial pediatric cancer registry. Clinical trial availability was determined by whether each patient’s primary institution had an open frontline trial for which the patient was eligible at the time of their diagnosis, considering individual disease characteristics such as lineage, central nervous system (CNS) status and risk group. Demographic, disease, trial enrolment, and outcome data were obtained through chart abstraction. Logistic regression models determined factors associated with trial enrolment, while Cox proportional hazard models determined factors associated with event-free and overall survival (EFS, OS). Results: Of 858 patients, 693 (81%) were eligible for an open clinical trial at their time of diagnosis. 476 (69%) enrolled on a trial. In adjusted analyses, age &gt; 15 years (odds ratio 0.4 vs. age 5-9, 95th confidence interval (95CI) 0.2-0.8; p = 0.01) and CNS3 disease (OR 0.38 vs. CNS1, 95CI 0.17-0.83; p = 0.01) were significantly associated with decreased likelihood of enrolment, while sex and neighborhood income quintile were not associated with enrolment. Adjusted for disease and demographic factors, clinical trial enrolment was not significantly associated with either EFS (hazard ratio (HR) 1.1, 95CI 0.7-1.7; p = 0.83) or OS (HR 1.3, 95CI 0.7-2.5; p = 0.44). Conclusions: The majority of patients with ALL eligible for available clinical trials at their time of diagnosis were enrolled. While no disparities in enrolment by income status were noted, adolescents were substantially less likely to participate in trials even within pediatric centers. Studies of mechanisms underlying this disparity are warranted in order to design and implement effective interventions targeting increased enrolment rates in this patient population. Our results however also suggest that clinical trial enrolment on its own is not associated with improved outcomes in the context of a single payer health system.

Risk-Adapted, Individualized Treatment Strategies of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML).

Simple SummaryMyelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two blood cancers with variable symptoms of low blood counts (fatigue, bleeding, infection risk) and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk stratification tools. Supportive care with red blood cell transfusions and medications to stimulate blood cell production remains the mainstay of therapy for lower-risk MDS and CMML patients. For higher-risk patients, a bone marrow transplant is the only potentially curative option, but most patients are not candidates for this intensive therapy. In this case, the hypomethylating agents (HMA) azacitidine and decitabine are standard of care. However, response rates to HMA are low and responses are only transient highlighting the need for novel approaches. While an oral version of decitabine has been recently approved, several targeted therapies are in development, but none has been approved to date.Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two distinct blood cancers with a variable clinical symptom burden and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk stratification tools. While supportive care with red blood cell transfusions, erythropoiesis-stimulating agents, and iron chelation remains the mainstay of therapy for lower-risk (LR)-MDS patients, luspatercept has recently been approved for transfusion-dependent anemic LR-MDS patients ending a decade without any new drug approvals for MDS. For higher-risk patients, allogeneic hematopoietic cell transplant (allo-HCT) remains the only curative therapy for both MDS and CMML but most patients are not eligible for allo-HCT. For those patients, the hypomethylating agents (HMA) azacitidine and decitabine remain standard of care with azacitidine being the only agent that has shown an overall survival benefit in randomized trials. Although early results from novel molecularly driven agents such as IDH1/2 inhibitors, venetoclax, magrolimab, and APR-246 for MDS as well as tagraxofusp, tipifarnib, and lenzilumab for CMML appear encouraging, confirmatory randomized trials must be completed to fully assess their safety and efficacy prior to routine clinical use. Herein, we review the current management of MDS and CMML and conclude with a critical appraisal of novel therapies and general trends in this field.

Abstract OT-11-01: The informed genetics annotated patient registry: The iGAP registry

Abstract Background Interest and knowledge about the genetics and biology of inherited risk of and progression of disease is growing. Physicians are increasingly using tests and technology, including germline genetic, genomic, and biomarker testing, to provide insight into a healthy individual's risk and an affected individual's disease characteristics, in order to provide personalized clinical management. However, many barriers to adoption of precision medicine still exist in the clinical setting, including rapid advances in technology and research, complex guidelines for eligibility, variable quality and cost, and adequate understanding of appropriate implementation by medical professionals. Methods The iGAP Registry uses an innovative digital platform to collect genetic, genomic, biomarker data and correlates it with clinical, pathologic and outcome data to inform providers of an individual’s risk of developing cancer, guide them to appropriate clinical grade testing and provide clinical decision support to providers for prevention and management strategies over time. The iGAP Registry’s digital platform minimizes technological barriers to longitudinal research participation and is available in mobile and desktop formats, allowing for easy implementation in a wide variety of clinic and hospital settings. The risk tool uses predictive analytics to identify and curate patients at risk who are eligible for initial and further testing. The tool additionally can generate letters of medical necessity, each individualized by personal and family history, for eligibility for genetic testing (based on national guidelines) and additional imaging (based on validated cancer risk calculators). The insights tool provides physicians with decision support on how to interpret and manage abnormal genetic testing results on an individual level and supports improved understanding across lab terminology through variant classification. The insights tool also supplies letters of medical necessity and supporting evidence across many specialties. The platform connects the information stored in the risk and insights tools to a unique participant record and automatically feeds the data into a digital case report form for the research registry. Additional clinical data is entered for patients who consent to be a part of the Registry. This allows for seamless longitudinal data collection over time without disrupting typical clinical workflows, and is further enriched by emailed patient-reported outcomes and physician decision impact questionnaires. Follow-up occurs over 5 years after initial data entry for the 10,000 expected subjects in the Registry (Table 1). Conclusion The iGAP Registry is a multi-center longitudinal, observational research database with an integrated platform of clinically-useful tools designed to address gaps for providers specifically for identifying individuals at elevated risk based on clinical and pathologic factors, guiding them to appropriate genetic, genomic, and biomarker testing and providing clinical insights on actionable results for personalized management and prevention for the individual and their family members over time. The iGAP Registry is currently enrolling and accepting new sites at www.igapregistry.org or https://clinicaltrials.gov/ct2/show/NCT04419896. Table 1: Eligibility CriteriaRetrospective18 years or older;Is/was a patient at participating practice previously tested with germline, genomic, or biomarker tests;For germline patients, have a diagnosis of cancer or P/LP result.Prospective18 years or older;§Presents consecutively to a participating practice and who has previously been screened and tested;Receives/has received germline, genomic, or other biomarker testing, either through a prior provider or a participating practice;Consents to be a part of the registry. Citation Format: Rakesh Patel, Peter Beitsch, Pat Whitworth, Chloe Wernecke, Mary Kay Hardwick. The informed genetics annotated patient registry: The iGAP registry [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-11-01.

Impact of access to care on 1-year mortality following allogeneic blood or marrow transplantation.

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.