Oncologic Conditions Research Articles

P-276 Endometrial microbiome diversity and the local macrophages populations during the mid-secretory phase

Abstract Study question Are there any quantitative associations between endometrial macrophages populations and microorganisms’ diversity? Summary answer The quantities and spatial distribution of endometrial macrophages populations correlated significantly with several microbiome diversity indices. What is known already Numerous studies have linked the relative abundance of Lactobacilli with a receptive endometrium, while the presence of multiple other bacterial species has been implicated in implantation failure. Another determinant of endometrial receptivity is the local immune cell composition and its inflammatory status. Knowing that the microbiome affects the immune system, it is worth studying the potential interplay between bacterial composition and immune cell populations in the endometrium during its receptive state. The present study aimed to investigate associations between the quantity and distribution of endometrial macrophages populations and the local microbiome diversity during the mid-secretory phase of the menstrual cycle. Study design, size, duration This prospective observational study was conducted between April 2021 and January 2023. Endometrial biopsies were collected from 25 female patients of reproductive age on day 7 after luteinising hormone surge. Eligibility criteria included no endometrial pathologies, no history of recent or chronic inflammatory or infectious disease, no recent antibiotic treatment, and no endocrinological, autoimmune or oncological conditions. Participants/materials, setting, methods Half of each biopsy was used for immunohistochemistry with CD11c + (Proteintech) and CD163 + (Quartett) to reveal pro- and anti- inflammatory macrophages, respectively. Their quantities and spatial distribution were analysed by HALO® image analysis software. The remaining endometrial tissue underwent DNA isolation and subsequent 16S rRNA (v4-v5 region) gene sequencing to determine endometrial microbiota composition. Alpha diversity indices - Good’s coverage, Shannon and phylogenic diversity - were evaluated and tested for correlation with the macrophages metrics. Main results and the role of chance The observed median percentage and range of the studied macrophages populations in the endometrial stroma were: 1.16% (2.98) CD11c+ macrophages and 1.96% (4.48) CD163+ macrophages. The evaluated alpha diversity indices were: 0.99±0.01 Good’s coverage, 2.53±1.20 Shannon and 38.56±15.43 phylogenic diversity.The CD11c+ macrophages percentage was not related to the microbial diversity of the studied samples. The percentage of the CD163+ macrophages, however, showed significant correlation with the Good’s coverage alpha diversity index (R = 0.397, p = 0.04). The median distance between CD11c+ and CD163+ cells in the endometrial stroma was 63.7µm (108.36) and it was significantly related to the Shannon alpha diversity index (R=-0.347, p = 0.05) and phylogenic diversity whole tree index (R=-0.367, p = 0.05).In summary, the anti-inflammatory macrophages percentage in the mid-secretory endometrial stroma is positively related to the local microbial diversity. Moreover, the distances between the pro- and anti-inflammatory macrophages populations in the endometrium are negatively associated to Shannon and PD whole tree alpha diversity indices. Limitations, reasons for caution The results of this study should be confirmed in a larger study population. Wider implications of the findings This study’s findings indicate that there is a correlation of the endometrial macrophages quantity and stromal distribution with the endometrial microbiome diversity. The association between these determinants of endometrial receptivity could help in understanding the fine tuning of the endometrium for accepting the embryo. Trial registration number The current research was funded by the National Science Fund, Ministry of Education, Bulgaria, Contract № KP-06-N53/14/16.11.2021.

The expanding role of artificial intelligence in the histopathological diagnosis in urological oncology: a literature review.

The ongoing growth of artificial intelligence (AI) involves virtually every aspect of oncologic care in medicine. Although AI is in its infancy, it has shown great promise in the diagnosis of oncologic urological conditions. This paper aims to explore the expanding role of artificial intelligence in the histopathological diagnosis in urological oncology. We conducted a focused review of the literature on AI in urological oncology, searching PubMed and Google Scholar for recent advancements in histopathological diagnosis using AI. Various keyword combinations were used to find relevant sources published before April 2nd, 2024. We approached this article by focusing on the impact of AI on common urological malignancies by incorporating the use of different AI algorithms. We targeted the capabilities of AI's potential in aiding urologists and pathologists in histological cancer diagnosis. Promising results suggest AI can enhance diagnosis and personalized patient care, yet further refinements are needed before widespread hospital adoption. AI is transforming urological oncology by improving histopathological diagnosis and patient care. This review highlights AI's advancements in diagnosing prostate, renal cell, and bladder cancer. It is anticipated that as AI becomes more integrated into clinical practice, it will have a greater influence on diagnosis and improve patient outcomes.

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe.

This study presents the biodistribution, clearance and dosimetry estimates of [64Cu]Fibrin Binding Probe #8 ([64Cu]FBP8) in healthy subjects. This prospective study included 8 healthy subjects to evaluate biodistribution, safety and dosimetry estimates of [64Cu]FBP8, a fibrin-binding positron emission tomography (PET) probe. All subjects underwent up to 3 sessions of PET/Magnetic Resonance Imaging (PET/MRI) 0-2 hours, 4h and 24h post injection. Dosimetry estimates were obtained using OLINDA 2.2 software. Subjects were injected with ~400 MBq of [64Cu]FBP8. Subjects did not experience adverse effects due to the injection of the probe. [64Cu]FBP8 PET images demonstrated fast blood clearance (half-life = 67 min) and renal excretion of the probe, showing low background signal across the body. The organs with the higher doses were: the urinary bladder (0.075 vs. 0.091 mGy/MBq for males and females, respectively); the kidneys (0.050 vs. 0.056 mGy/MBq respectively); and the liver (0.027 vs. 0.035 mGy/MBq respectively). The combined mean effective dose for males and females was 0.016 ± 0.0029 mSv/MBq, lower than the widely used [18F]fluorodeoxyglucose ([18F]FDG, 0.020mSv/MBq). This study demonstrates the following properties of the [64Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; low background signal; and whole-body acquisition within 20 minutes in a single session. These properties provide the basis for [64Cu]FBP8 to be an excellent candidate for whole-body non-invasive imaging of fibrin, an important driver/feature in many cardiovascular, oncological and neurological conditions.

Staged wound reconstruction utilizing regenerative dermal matrix followed by split-thickness skin grafting in the setting of local radiation: A case series with review of the literature

The use of radiation for local control following tumor extirpation has improved outcomes across the spectrum of oncologic conditions. Reconstructive strategies that improve short-term healing rates and long-term results in these complicated wound healing environments are paramount to success. Regenerative dermal matrices (RDM) have emerged as viable options to improve reconstructive outcomes in the field of radiology. Here, we present a case series highlighting our algorithm of staged reconstruction using regenerative dermal matrix followed by split-thickness skin grafting to reconstruct skin deficits following excision of tumors either before or after radiation. A systematic review of the literature pertaining to irradiated wound closure and the application of dermal regenerative templates is presented to better understand its emerging role to manage these complex cases and impact future outcomes. Six patients underwent staged reconstruction using our algorithm, all of which went on to heal completely without additional procedures or evidence of skin breakdown in the short and long term. RDMs seem to improve the radioresistance of surgically reconstructed wounds following excision of cancer. The mechanism for this is likely related to the creation of additional tissue layers beyond those replaced with skin graft alone and should be the subject of future study.

P2X7 Variants in Pathophysiology.

P2X7 receptor activation by extracellular adenosine triphosphate (eATP) modulates different intracellular pathways, including pro-inflammatory and tumor-promoting cascades. ATP is released by cells and necrotic tissues during stressful conditions and accumulates mainly in the inflammatory and tumoral microenvironments. As a consequence, both the P2X7 blockade and agonism have been proposed as therapeutic strategies in phlogosis and cancer. Nevertheless, most studies have been carried out on the WT fully functional receptor variant. In recent years, the discovery of P2X7 variants derived by alternative splicing mechanisms or single-nucleotide substitutions gave rise to the investigation of these new P2X7 variants' roles in different processes and diseases. Here, we provide an overview of the literature covering the function of human P2X7 splice variants and polymorphisms in diverse pathophysiological contexts, paying particular attention to their role in oncological and neuroinflammatory conditions.

Essential Review of Oncological Emergencies

Innovations in oncology have expanded treatment eligibility, leading to a rise in cancer patients requiring critical care. This necessitates that all critical care clinicians possess a fundamental knowledge of prevalent oncological conditions and identify emergent scenarios requiring immediate action. This article will explore key oncological complications and their management approaches.

OncoGPT: Enhancing oncological decision-making with ASCO guideline–trained AI.

e13607 Background: General-purpose language models like ChatGPT, while proficient in a wide array of topics, often lack the specialized knowledge and precision required for specific fields such as oncology. The American Society of Clinical Oncology (ASCO) guidelines offer a comprehensive resource for oncology professionals, yet sifting through extensive documents for specific information can be daunting. To bridge this gap, we introduce OncoGPT, a specialized GPT model, tailored to provide precise and guideline-adherent oncological advice. Methods: We leveraged GPT-4's advanced language understanding capabilities as the foundation for OncoGPT. This customization involved an extensive training regimen using the complete text of the ASCO clinical guidelines. The training process was meticulously designed to ensure that OncoGPT not only assimilates the detailed information within these guidelines but also understands the context and intricacies of oncological care. Additionally, we created disease-specific versions of OncoGPT, each fine-tuned with guideline subsets pertinent to particular oncological conditions. Further, the training was augmented with specific prompts to foster kind, sincere, and respectful interactions, especially for patient-oriented responses. The model was designed to discern whether the user is a healthcare professional or a patient and adjust the complexity of its responses accordingly. For patients, additional emphasis was placed on delivering information in a kind, responsible, and empathetic manner. Results: OncoGPT's performance was rigorously evaluated for accuracy and reasoning against real-world clinical scenarios. The responses generated by the model were meticulously reviewed by an experienced oncologist to confirm adherence to ASCO guidelines and clinical relevance. This assessment revealed a high level of precision and contextual understanding in OncoGPT's outputs, demonstrating its potential as a valuable tool for oncology practitioners. Importantly, it showed a remarkable ability to tailor its communication style based on the user's background, providing simplified explanations for patients and more detailed responses for professionals. An example of a specific OncoGPT: Breast Cancer OncoGPT: https://chat.openai.com/g/g-VcuECT3jg-oncogpt-breast-cancer Conclusions: OncoGPT represents a significant advancement in the application of AI for medical decision-making. By integrating the depth of ASCO guidelines into a responsive and accurate AI model, OncoGPT offers oncology professionals a powerful tool for accessible, guideline-compliant advice. This development marks a crucial step towards integrating AI more profoundly into specialized medical fields, enhancing both the efficiency and accuracy of clinical decision-making.

Impact of a 1-day disease overview session on knowledge and preparedness for incoming hematology/oncology fellows.

e21011 Background: The start of hematology/oncology fellowship involves an abrupt transition in disease management and a steep learning curve. Many fellowship programs have introductory lecture series over the first weeks or months, but fellows often need specialty knowledge prior to the completion of these. Methods: A 1-day session for incoming first year fellows at our institution was developed to provide brief overviews of common conditions in classical hematology, malignant hematology, and oncology, subdivided into a total of 12 topics. Fellows were surveyed before and after the session regarding their feelings of preparation for fellowship and having good disease frameworks for each of the 3 major content areas. Fellows also evaluated the content and length of each topic. Pre- and post-course knowledge assessments were conducted. Feedback was sought later in the year as well. Results: The session was well-received by fellows. Post-course assessments increased by a mean of 32% (SD 6%). The majority of topics were well-reviewed for length and content. Fellow responses to feelings of preparedness and disease frameworks were improved or unchanged from pre-course surveys. All fellows agreed that it was a good use of their time and would recommend it being a part of future orientation sessions. Fellows recommended splitting the session into 2 days. Conclusions: A 1-day introductory course for incoming hematology/oncology fellows is feasible and rapidly improves baseline knowledge to prepare fellows for clinics, consults, and being on call.

Implementation of hematology oncology lecture series for nursing staff.

e21005 Background: Westchester Medical Center has an oncology unit that provides care for hundreds of patients annually. Inpatient cancer patients often have especially complex medical treatment plans that require interdisciplinary collaboration and specialized knowledge of oncologic conditions. There is a need to implement formal teaching tailored to nursing staff devoted to topics in hematology and oncology. Our goal was to develop a monthly lecture series for nursing that deepened their understanding of cancer treatments, enabling them to assess and monitor patients with greater expertise. Methods: Topics were chosen based on relevance and are listed in the table. Speakers included full-time faculty, fellows and residents, pharmacists, and medical students. Ten lectures were completed and scheduled approximately once monthly in the mornings just prior to sign out for nursing shift change. Nursing staff were asked to complete a set of questions prior to each lecture (Pre-Test) They were given the same set of questions after each lecture (Post-Test) to determine whether there was an improvement in understanding of the topic. Informational handouts were distributed at the end of each lecture to provide participants with a summary of key points. A survey administered at the conclusion of the lecture series was collected to assess attitudes towards the lectures. Results: Overall test scores improved after each lecture was given, as demonstrated in the table: Pre and Post Lecture Test Scores. Additionally, feedback regarding the lectures was positive. 100% agreed that they gained a better understanding of topics related to hematology oncology and 92% agreed that participation in these lectures has improved their ability to function collaboratively on interprofessional healthcare teams. Conclusions: A didactic lecture series is a valuable component of hematology oncology education for nursing staff and will improve quality of care of the oncology service. Some limitations of this lecture series concerned nursing staff scheduling conflicts and their availability for lecture attendance. Possible interventions in the future may include setting aside time dedicated for monthly lectures and scheduling lectures for afternoons to avoid conflicts with shift changes and morning rounds. Nevertheless, our findings highlight the value of continued education in empowering nursing staff to deliver quality care to hematology oncology patients.[Table: see text]

#1490 Long-term health outcomes in non-dialysis dependent chronic kidney disease patients with cognitive impairment or dementia

Abstract Background and Aims A decline in cognitive function, with a spectrum ranging from mild cognitive impairment to dementia (CI-D), is common in patients with chronic kidney diseases (CKD), rendering them frailer. Whether the coexistence of CKD and CI-D increases the health risk profile remains unclear. Our work aims to clarify how this association increases adverse outcomes for CKD patients (stages 3-5). Method This retrospective observational cohort study was conducted on CKD patients (stages 3-5) from the Global Collaborative Network (GCN) of the TriNetX research platform between 2004 and 2024. TriNetX provides access to anonymized electronic medical records from over half a million CKD patients in large healthcare organizations (HCOs) across the world. Our report includes patients from 110 HCOs with different demographic backgrounds. The study compared outcomes of patients with CKD stages 3-5, aged 18-70 years, with and without pre-existent CI-D (diagnosed within 5 years). The two cohorts were propensity score-matched (PSM) for age, sex, ethnicity, comorbidities (neurological, haematological, musculoskeletal, respiratory including smoking history, oncological, cardiovascular, gastroenterological and endocrine conditions) and CKD stage. The proportional hazard assumption was tested using the generalized Schoenfeld approach built in the TriNetX platform. A 95% confidence interval (95% CI) was considered evidence of statistical significance throughout the analyses. Kaplan- Meier (KM) was used for survival probability. Statistical significance was defined as p-value < 0.05. Outcome events were included from 1 day after the index event (CKD diagnosis) until 3650 days after. Results Of the total of 503,298 CKD patients, 7,891 had a co-existent diagnosis of CI-D made within 5 years (prevalence rate 1.56%). A PSM generated a matched cohort of 7,890 patients each. The mean age of the cohort was 60.7 ± 7.0 years, with a predominance of white ethnicity (53.7%) and an equal male-to-female ratio. Standardized difference (Std diff) was used to evaluate the balance of baseline characteristics in the PSM populations. Generally, Std diff < 0.1 is considered a small difference and all comorbidities fell below this threshold after PSM (Table 1). The comparison of the outcomes at follow-up between the matched cohorts is illustrated in Table 2. CKD patients with concomitant CI-D had higher all-cause mortality (18.4% vs 12.1%, p < 0.0001), a higher risk of cerebrovascular disease (10.8% vs 7.8%), malnutrition (6.7% vs 4.3%), mood disorders (13.7% vs 8.9%), anxiety (13.2% vs 10.9%), encephalopathy (9.6% vs 4.5%), epilepsy (4.3% vs 1.3%). All findings were statistically significant with a p < 0.0001. Proportional hazard models showed that CI-D was a strong risk factor associated with all-cause mortality (HR: 1.761; 95% CI (1.621-1.913, p < 0.0001)) and other cerebrovascular and mental health illnesses. Conclusion Our “real-world data” demonstrate that a concomitant CI-D diagnosis is a strong risk factor for negative health outcomes and mortality in patients with CKD stages 3-5. These results highlight the need for routine cognitive assessments in patients with advanced CKD to deliver personalised care.

#2910 Renal toxicities in oncology at a secondary level hospital within the first 6 months of outpatient consultation establishment

Abstract Background and Aims In recent years the discovery of targeted therapies in oncology have been a revolution with spectacular results for patients with advanced neoplasia and metastasis. Representing a more precise approach to interfering with tumorigenesis, these therapies exhibit superior tolerability profile in terms of toxicity and have significantly improved overall survival (1). Numerous studies have demonstrated the increased risk of cancer patients developing acute renal failure and progressing to chronic kidney disease, both contributing to higher mortality. The use of these novel drugs, alongside traditional chemotherapy, coupled with the extended survival of patients with neoplasms has led to a rise in kidney pathologies (2.3). Addressing the need to provide a comprehensive and optimized treatment to this group of patients, the field of Onconephrology has emerged. Its primary objective is to assist in the diagnosis and management of kidney diseases associated with the underlying oncological condition and/or oncotherapeutics. While well-established Onconephrology Clinics predominantly operate in tertiary hospitals worldwide, acknowledging the growing significance of this field, we established an Onconephrology outpatient consultation at our secondary level hospital. In this study, we aim to delineate the incidence of renal toxicities secondary to oncotherapeutics within the first six months of initiating our Onconephrology outpatient consultation. Method Forty-six patients were retrospectively included, and an analysis of oncological and renal variables was conducted to determine the incidence of renal toxicities. Results Out of the forty-six patients evaluated, 12 exhibited renal toxicity secondary to oncotherapeutics, with a mean age of 73.3 years. The most frequent malignancy was lung cancer (n = 6), followed by gastrointestinal tract cancer (n = 2). Most patients presented with metastatic disease (n = 9), and their malignant disease was either in remission (n = 4) or stable (n = 5). Reasons for referral included acute kidney injury (n = 7), acute kidney injury over chronic kidney disease (n = 3), proteinuria (n = 1), and electrolyte abnormalities (n = 1). The diagnoses included acute immune-mediated tubulointerstitial nephritis secondary to checkpoint inhibitors (n = 5), cisplatin renal toxicity (n = 3), acute tubular necrosis secondary to tyrosine kinase inhibitors (n = 2), hypomagnesemia induced by EGFR inhibitor (n = 1), and nephrotic syndrome related to anti-VEGF. Following multidisciplinary intervention, most patients experienced recovery of kidney function (n = 9), while some progressed to chronic kidney disease (n = 2), and other maintained electrolyte imbalances (n = 1). Conclusion This study describes 12 patients with renal toxicities secondary to oncotherapeutics over a 6-month period at a secondary hospital. Most patients exhibited recovery of kidney function, emphasizing the positive outcomes achievable through multidisciplinary care, particularly in the context of the Onconephrology outpatient consultation, even in institutions with limited resources.

QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7nm and 182.0nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.

Profile and Outcomes of Pediatric Hematology and Oncology Patients Diagnosed with COVID-19 in the Philippine General Hospital.

The coronavirus pandemic has affected millions worldwide. Better understanding of COVID-19 in pediatric hematology-oncology patients in a resource-limited setting is crucial to improve care as the pandemic ensues. This study describes the clinical profile and outcomes of pediatric hematology oncology patients with COVID-19 seen at the Philippine General Hospital (PGH). A retrospective, descriptive review of pediatric hematology oncology patients with COVID-19 seen between March 2020 to March 2021 in PGH was done. Forty patients were identified. Seventeen percent had non-malignant hematologic conditions, 40% had leukemias, and 42.5% had solid tumors. Fever and cough were the most common manifestations. Seventy-six percent were on treatment, 9% were newly diagnosed, and 7% were in relapse or disease progression. Fifty-five percent had mild COVID-19; 5% and 2.5% had severe and critical COVID-19, respectively. Thirty-seven percent were asymptomatic. Cancer-related therapy was placed on hold for most patients. There were two mortalities, none was due to COVID-19. Results suggest that patients with hematologic and oncologic conditions have a mild course, with majority showing recovery from COVID-19. Delays in cancer-related therapy however, may contribute to disease progression and mortality.

Preferential HDAC6 inhibitors derived from HPOB exhibit synergistic antileukemia activity in combination with decitabine

Histone deacetylase 6 (HDAC6) is an emerging drug target to treat oncological and non-oncological conditions. Since highly selective HDAC6 inhibitors display limited anticancer activity when used as single agent, they usually require combination therapies with other chemotherapeutics. In this work, we synthesized a mini library of analogues of the preferential HDAC6 inhibitor HPOB in only two steps via an Ugi four-component reaction as the key step. Biochemical HDAC inhibition and cell viability assays led to the identification of 1g (highest antileukemic activity) and 2b (highest HDAC6 inhibition) as hit compounds. In subsequent combination screens, both 1g and especially 2b showed synergy with DNA methyltransferase inhibitor decitabine in acute myeloid leukemia (AML). Our findings highlight the potential of combining HDAC6 inhibitors with DNA methyltransferase inhibitors as a strategy to improve AML treatment outcomes.

Dysphagia After Anterior Cervical Spine Surgery: Pathophysiology, Diagnosis, and Management.

Anterior cervical spine surgery (ACSS) is a surgical intervention widely used for a myriad of indications including degenerative, oncologic, inflammatory, traumatic, and congenital spinal conditions. A primary concern for surgeons performing ACSS is the postoperative development of oropharyngeal dysphagia. Current literature reports a wide incidence of this complication ranging from 1 to 79%. Dysphagia after ACSS is multifactorial, with common risk factors being prolonged duration of operation, revision surgeries, multilevel surgeries, and use of recombinant human bone morphogenetic protein-2. Many technical strategies have been developed to reduce the risk of postoperative dysphagia, including the development of low-profile implants and retropharyngeal local steroid application. In this article, we review the most recent literature regarding the epidemiology and pathophysiology, diagnostic criteria, risk factors, and management of dysphagia after ACSS.

The preliminary analysis of lymphatic flow around the connective tissues surrounding SMA and SpA elucidates patients’ oncological condition in borderline-resectable pancreatic cancer

BackgroundIn pancreatic ductal adenocarcinoma (PDAC), invasion of connective tissues surrounding major arteries is a crucial prognostic factor after radical resection. However, why the connective tissues invasion is associated with poor prognosis is not well understood.Materials and methodsFrom 2018 to 2020, 25 patients receiving radical surgery for PDAC in our institute were enrolled. HyperEye Medical System (HEMS) was used to examine lymphatic flow from the connective tissues surrounding SMA and SpA and which lymph nodes ICG accumulated in was examined.ResultsHEMS imaging revealed ICG was transported down to the paraaortic area of the abdominal aorta along SMA. In pancreatic head cancer, 9 paraaortic lymph nodes among 14 (64.3%) were ICG positive, higher positivity than LN#15 (25.0%) or LN#18 (50.0%), indicating lymphatic flow around the SMA was leading directly to the paraaortic lymph nodes. Similarly, in pancreatic body and tail cancer, the percentage of ICG-positive LN #16a2 was very high, as was that of #8a, although that of #7 was only 42.9%.ConclusionsOur preliminary result indicated that the lymphatic flow along the connective tissues surrounding major arteries could be helpful in understanding metastasis and improving prognosis in BR-A pancreatic cancer.

512 Understanding Expanded Access: Who are the Patients?

OBJECTIVES/GOALS: The FDA allows physicians to request clinical use of investigational drugs, biologics, and devices for patients with no satisfactory treatment options through a pathway called Expanded Access (EA). TEAMSS (Transforming Expanded Access to Maximize Support and Study) sought to examine single-patient cases to better characterize these patients. METHODS/STUDY POPULATION: We prospectively collected data on requests for single-patient EA at any one of the four collaborating TEAMSS institutions (Duke University, University of Rochester, University of Michigan, and University of Texas Southwestern) between September 1, 2021 and February 28, 2023. Regulatory and health records were reviewed for past cases that occurred between June 1, 2018 and August 31, 2021. Descriptive statistics were performed on data from the submission process, the patient demographics, the indication for treatment, and patient health status over time. RESULTS/ANTICIPATED RESULTS: The patient population was representative with respect to the largest racial groups (69.3% White / 13.0% Black or African American) and legal sex (51.3% male / 48.7% female). All ages were represented, with overrepresentation of those 60-70 years old (16.8%) and under 10 (14.8%). Patients were most often treated for infectious diseases (44.2%) or oncologic conditions (39.0%). Those who received more than one dose stayed on treatment for 76 days (median) and up to 1427 days (maximum). At the end of study, 53.9% had completed treatment as planned, moved to commercial product, or continued treatment. Death, disease progression, or failure to respond occurred for 31.9% of patients. DISCUSSION/SIGNIFICANCE: The population that receives Expanded access treatments is heterogeneous in both demographics and medical conditions. Some successful treatments are continued for years. Many patients complete their treatment, and a minority experience death or disease progression during treatment.

342 Systematic Review of Disparities in Treatment, Surgical Management, Outcomes by Race and Insurance Status Disparities in Spine Oncology

INTRODUCTION: Healthcare disparities within neurosurgery and spine surgery have been documented with respect to race and insurance type. To date, there has not been a systematic review of disparities in spinal oncology access, treatment and outcomes. METHODS: A systematic review was performed following PRISMA guidelines with a strategy to identify disparities broadly within spine oncology using the following MeSH terms: “spinal neoplasms,” “healthcare disparities,” “race,” “insurance status,” and “socioeconomic status.” Studies were included and excluded based on pre-established criteria. RESULTS: Out of a total of 400 papers, 17 papers were reviewed. Black patients with spine oncologic conditions experienced decreased access to care and disparities in treatment modalities offered when compared to non-Black patients. Further, when minority and white patients were compared, differences were seen in the clinical presentation of symptoms and in-hospital outcomes. Minority patients were found to have longer postoperative length of stay and higher rates of surgical complications. A similar trend is seen when comparing Medicaid patients versus privately insured patients with respect to access to treatment and differences in treatment modality. Furthermore, patients with public insurance experienced higher rates of postoperative mortality compared to those with private insurance. CONCLUSIONS: Disparities within the treatment of spine oncology patients are present with respect to factors such as race, socioeconomic status, and insurance type. Further exploration into the root causes for these disparities should be performed to inform policy and programs aimed at establishing equity for the care of spine oncology patients.

Characterization of accelerated approval status, trial endpoints and results, and recommendations in guidelines for oncology drug treatments from the National Comprehensive Cancer Network: cross sectional study

ObjectivesTo evaluate National Comprehensive Cancer Network (NCCN) guideline recommendations for oncology drug treatments that have been granted accelerated approval, and to determine whether recommendations are updated based on the results...

Abstract 2246: The impact of a waitlist control group on physical activity level in the activity after cancer treatment exercise oncology randomized pilot study

Abstract Background: In randomized clinical trials, control conditions such as blinding are essential for mitigating threats to validity. In exercise oncology trials, researchers are unable to blind participants to randomization, which may confer unintended consequences (i.e., crossover or dropout) that may threaten validity. Despite prior suggestions that a waitlist control is optimal for lessening these consequences, to date there is little agreement concerning control conditions in exercise oncology. Further, the use of a waitlist control is complicated by concerns regarding the ethical implications of instructing participants to delay healthy behavior change. Herein, we leveraged data from the Activity after Cancer Treatment (ACT) study to evaluate the impact of randomization to a waitlist control group on objectively assessed physical activity (PA) levels in breast cancer (BC) survivors. Methods: The ACT Study (PI: Ambrosone) was a 12-week, four-arm pilot study at Roswell Park Comprehensive Cancer Center. Participants included 37 BC survivors who were randomized to either a waitlist control group (n=10), or one of three exercise interventions of varying intensities including home-based walking (n=9), home-based Zumba (n=9), or a supervised high-intensity interval training treadmill protocol (n=9) delivered by study personnel at Roswell Park Comprehensive Cancer Center. The waitlist group was asked to maintain their usual PA during the 12-week intervention. All participants received weekly phone calls to optimize engagement and ensure Fitbit data were properly synced. For the current analysis, the primary analytic exposure was randomization assignment (control or active intervention); the analytic outcomes included steps/day, moderate-to-vigorous PA (MVPA) minutes/week and total active minutes/week as measured by the Fitbit Charge 2. ANOVA was used to assess mean group differences in steps and active minutes. Results: At study conclusion, the control group accumulated significantly fewer steps/day [6,087 (±1,353)] than the active intervention groups [8,729 (±2,585), p=0.0003]. The control group also accumulated significantly fewer MVPA minutes/week [146.2 (±114.9) vs. 264.1 (±192.3), p=0.045] and total active minutes/week [1,478 (±291.0) vs. 1,976.8 (±658.6), p=0.003] in comparison to the active intervention groups, respectively. Conclusions: BC survivors randomized to active intervention accumulated significantly more steps, MVPA and total active minutes than the waitlist group. Although the waitlist was effective for minimizing PA relative to the active arms, waitlisted participants exceeded the national step average of 4800 steps/day by 1200 steps and nearly met the minimum PA recommendation of 150 minutes of MVPA/week, potentially assuaging ethical or public health concerns regarding the delay of health-seeking behavior. Citation Format: Rikki Cannioto, Evan Davis, Karen Hulme, Chi-Chen Hong, Carol DeNysschen, Tracey O'Connor, Christine Ambrosone. The impact of a waitlist control group on physical activity level in the activity after cancer treatment exercise oncology randomized pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2246.