Adult Malignancies Research Articles

Pulsed focused ultrasound alters the proteomic profile of the tumor microenvironment in a syngeneic mouse model of glioblastoma.

Glioblastoma (GBM), a lethal primary adult malignancy, is difficult to treat because of the restrictive nature of the blood-brain barrier (BBB), blood-tumor barrier (BTB), and the immunosuppressive tumor microenvironment (TME). Since pulsed focused ultrasound (pFUS) is currently used to improve therapeutic deliveries across these barriers, this study aims to characterize the impact of pFUS on the TME proteomics upon opening the BBB and BTB. We utilized MRI-guided, pFUS with ultrasound contrast microbubbles (termed 'pFUS' herein) to selectively and transiently open the BBB and BTB investigating proteomic modifications in the TME. Utilizing an orthotopically-allografted mouse GL26 GBM model (Ccr2RFP/wt - Cx3cr1GFP/wt), pFUS's effect on glioma proteomics was evaluated using a Luminex 48-plex assay. pFUS treated tumors exhibited increases in pro-inflammatory cytokines, chemokines, and trophic factors (CCTFs). Proteomic changes in tumors tend to peak at 24 h after single pFUS session (1x), with levels then plateauing or declining over the subsequent 24 h. Tumors receiving three pFUS sessions (3x) showed elevated CCTFs levels peaking as early as 6 h after the third session. pFUS together with microbubbles induces a sterile inflammatory response in the TME of a mouse GBM tumor. Moreover, this proinflammatory shift can be sustained and perhaps primed for more rapid responses upon multiple sessions of pFUS. These findings raise the intriguing potential that pFUS-induced BBB and BTB opening may not only be effective in facilitating the therapeutic agent delivery, but also be harnessed to modify the TME to assist immunotherapies in overcoming immune evasion in GBM.

Stereotactic Ablative Radiation Therapy (SABR) for Adolescent and Young Adult Malignancies.

There are limited studies examining local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for adolescent and young adult (AYA) populations/histologies with local recurrences or metastatic disease. The RSSearch® Patient Registry, an international SABR registry, was evaluated for AYA patients treated with SABR. AYA patients with adult histologies/primaries were excluded. Kaplan-Meier analyses were employed to characterize LC and OS following SABR. Potential prognostic factors were assessed with log-rank tests for initial univariate analysis (UVA). For multivariate analyses (MVA), a Cox proportional hazards multivariate model was utilized. A total of 19 AYA patients with 39 lesions treated with SABR were identified and included in the analysis. Four lesions (10.3%) were treated with SABR for primary tumor recurrence and 35 lesions were treated for metastatic disease. The median patient age was 34 years (range: 16-39 years). Common lesion locations included lung (11 lesions; 28.2%), non-spinal bone (nine lesions; 23.1%), and spine (six lesions; 15.4%). The median biological effective dose (BED10) was 61.5 Gy (range: 26.4-180). One-year LC and OS following SABR were 77.7% (95% CI: 58.5-88.7) and 72.7% (95% CI: 46.3-87.6), respectively. On UVA, BED10 ≥ 60 Gy was associated with superior one-year LC (94.4% vs. 47.6%; p<0.0001) as were sarcoma primaries (two-year LC: 92.3% vs. 42.2%;p = 0.0002). Central nervous system (CNS) primaries had significantly poorer one-year LC (20% vs 87.5%; p<0.0001) as well as spinal metastases (33.3% vs. 87.0%; p<0.0001). On MVA, BED10 < 60 Gy was associated with inferior LC (hazard ratio (HR) = 5.51;p = 0.01) with sarcoma primaries associated with superior LC (HR = 0.04;p = 0.008). SABR with BED10 ≥ 60 Gy resulted in durable LC for AYA patients, particularly those with sarcoma primaries, though poor outcomes were noted in metastatic CNS malignancies.

Uveal Melanoma: Comprehensive Review of Its Pathophysiology, Diagnosis, Treatment, and Future Perspectives.

Uveal melanoma (UM) is the most common intraocular malignancy in adults. Recent advances highlight the role of tumor-derived extracellular vesicles (TEV) and circulating hybrid cells (CHC) in UM tumorigenesis. Bridged with liquid biopsies, a novel technology that has shown incredible performance in detecting cancer cells or products derived from tumors in bodily fluids, it can significantly impact disease management and outcome. The aim of this comprehensive literature review is to provide a summary of current knowledge and ongoing advances in posterior UM pathophysiology, diagnosis, and treatment. The first section of the manuscript discusses the complex and intricate role of TEVs and CHCs. The second part of this review delves into the epidemiology, etiology and risk factors, clinical presentation, and prognosis of UM. Third, current diagnostic methods, ensued by novel diagnostic tools for the early detection of UM, such as liquid biopsies and artificial intelligence-based technologies, are of paramount importance in this review. The fundamental principles, limits, and challenges associated with these diagnostic tools, as well as their potential as a tracker for disease progression, are discussed. Finally, a summary of current treatment modalities is provided, followed by an overview of ongoing preclinical and clinical research studies to provide further insights on potential biomolecular pathway alterations and therapeutic targets for the management of UM. This review is thus an important resource for all healthcare professionals, clinicians, and researchers working in the field of ocular oncology.

Construction and validation of a SASP-related prognostic signature in patients with acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a common and highly aggressive haematological malignancy in adults. Senescence-associated secretory phenotype (SASP) plays important roles in tumorigenesis and progression of tumour. However, the prognostic value of SASP in patients with AML has not been clarified. The present study aims to explore the prognostic value of SASP and develop a prognostic risk signature for AML. The RNA-sequencing data was collected from the TCGA, GTEx and TARGET databases. Subsequently, differentially expressed gene analysis, univariate Cox regression and LASSO regression were applied to identified prognostic SASP-related genes and construct a prognostic risk-scoring model. The risk score of each patient were calculated and patients were divided into high- or low-risk groups by the median risk score. This novel prognostic signature included 11 genes: G6PD, CDK4, RPS6KA1, UBC, H2BC12, KIR2DL4, HSF1, IFIT3, PIM1, RUNX3 and TRIM21. The patients with AML in the high-risk group had shorter OS, demonstrating that the risk score acted as a prognostic predictor, which was validated in the TAGET-AML dataset. Univariate and multivariate analysis revealed the risk score was an independent prognostic factor in patients with AML. Furthermore, the present study revealed that the risk score was associated with immune landscape, immune checkpoint gene expression and chemotherapeutic efficacy. In the present study, we constructed and validated a unique SASP-related prognostic model to assess therapeutic effect and prognosis in patients with AML, which might contribute to understanding the role of SASP in AML and guiding the treatment for AML.

Extended survival in a case of metastatic choroidal melanoma with immunotherapy.

Uveal melanoma is the most common intraocular malignancy in adults. Despite advances in local treatments, approximately 50% of all cases eventually die from metastatic disease. In cases with metastasis, 2- and 5-year survival rates are approximately 10% and <1%, respectively. Advances in molecular biology have led to the identification of a number of promising drugs including immune checkpoint inhibitors (ICIs). Ipilimumab and nivolumab are ICIs targeting the cytotoxic T-lymphocyte-associated antigen-4 and the programmed-cell death protein-1, respectively. Herein, we present a case of choroidal melanoma having liver metastasis treated with nivolumab and ipilimumab and transarterial radioembolization, achieving a 3-year survival.

Increased risk of haematological malignancy in adults over age 60 with thrombocytopenia compared with matched controls: Time for an upfront bone marrow evaluation?

International societies have conflicting recommendations on whether bone marrow aspirate/biopsy (BMB) is needed during workup for isolated thrombocytopenia. Our objective was to determine if thrombocytopenia in patients aged ≥60 years is associated with an increased incidence of haematological malignancy. We performed a retrospective population-based cohort study in patients aged ≥60 years between January 1, 2009 to December 31, 2019. Exposed patients had specialist consultation for thrombocytopenia, with platelet count <100 × 109/L, but normal haemoglobin and white blood cell count. Unexposed patients were those who never had specialist consultation for thrombocytopenia and whose platelets were ≥100 × 109/L. The primary outcome was the diagnosis of haematological malignancy using a competing risk of death model. During 4.0 years (IQR 2.2-6.7) of follow-up, 378/4930 exposed (19.1/1000PY, 95% CI 17.1-21.0), and 204/17556 unexposed patients (2.5/1000PY, 95% CI 2.2-2.8) were diagnosed with haematological malignancy (HR 15.5 (95% CI 11.3-21.4, p < 0.0001) in year 1, and 5.3 (95% CI 4.4-6.6, p < 0.0001) in years 2+). This finding persisted in analyses stratified by sex, age, severity, or duration of thrombocytopenia, and treatment with corticosteroids within 2 weeks of consultation. This study found a strong association between isolated thrombocytopenia and haematological malignancy in patients ≥60 years, supporting consideration of diagnostic testing including BMB during outpatient specialist consultation.

Recent Updates in the Diagnosis and Management of Kidney Diseases in Multiple Myeloma

Multiple myeloma (MM) represents a difficult-to-treat plasma cell malignancy and the second most common hematologic malignancy in adults, significantly impacting kidney function. The spectrum of kidney involvement in MM is broad, encompassing electrolyte imbalances, tubular injury, and even rare glomerular diseases. The evolution of MM treatment modalities has led to notable improvements in the long-term survival of patients experiencing kidney-related complications. Over the past decade, groundbreaking therapeutic agents have emerged, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, selective inhibitors of nuclear export, and antibody-drug conjugates. These novel therapies have revolutionized the landscape of MM management, offering new hope for patients and challenging the traditional treatment paradigms. This comprehensive review explores recent advances in the diagnosis and management of MM, emphasizing the pivotal role of these innovative therapeutic agents in improving patient outcomes. We delve into the intricacies of diagnosing MM, highlighting the significance of early detection and precise diagnostic tools. We elucidate the evolving treatment strategies, emphasizing the mechanisms of action and clinical efficacy of the latest agents. This manuscript provides valuable insights into the ever-evolving field of MM management, shedding light on the remarkable progress achieved in enhancing the prognosis and quality of life of MM patients.

Miniaturized Sniffing Device based on an Array of Fluorescent Carbon Quantum Dots and Metallic Nanoclusters Efficiently Identifies Hematologic Malignancy in Adults.

The study demonstrates the potential of an optical nose made by depositing an array of fluorescent nanomaterials on a paper substrate for the early detection of leukemia in adults. This is based on the fact that blood volatile organic compounds (VOCs) are useful leukemia biomarkers. The integrated design was miniaturized and comprised both sensing zones and a sample holding zone, which were installed on a small sheet of paper within a miniature cubic reaction chamber fabricated by using 3D printing technology. The sensing device, comprising seven fluorescent sensing elements, namely, metal nanoclusters, quantum dots, and carbon dots was capable of detecting VOCs in the blood headspace and providing a colorimetric signature that could discriminate between blood samples from healthy and cancerous individuals. A total of 70 new leukemia cases and 51 healthy controls aged 20-50 years were studied. The device required a 60 μL portion of the blood sample and reacted to blood VOCs after 3 h when kept at 50 °C. The imaging data from the device was processed by linear discriminant analysis, and the results confirmed efficient identification of patient samples from healthy samples with 100% accuracy. Overall, the array system is noninvasive (or minimally invasive), portable, fast, inexpensive, and requires only a small amount of blood sample.

Atrial Natriuretic Peptide as a Biomarker and Therapeutic Target in Cancer: A Focus on Colorectal Cancer

Abstract: One of the most prevalent cancers throughout the world is colorectal cancer (CRC). Natriuretic peptides are important hormones that have a crucial role in the physiology of humans and other animals. There are a variety of treatments for colon cancer. However, conventional therapies have many side effects and low efficacy in the treatment of this disease. Atrial Natriuretic Peptide (ANP) is one of the most well-known natriuretic peptides involved in regulating blood pressure and blood volume. Studies have demonstrated that ANP has a therapeutic effect on different cancer types. The anti-tumor effect of ANP is exerted by inhibiting DNA synthesis but not inducing apoptosis. The anti-proliferative role of ANP has been reported in human breast, prostate, colon, pancreatic, lung, and ovarian cancer and in many other tumors. Therefore, we review the recent papers on natriuretic peptides in CRC as a common malignancy in adults to assess the pathways of ANP involved in the progression of CRC and its effects on the prevention or treatment of CRC and other cancer types.

BIOM-11. TUMOUR SUPPRESSIVE ROLES OF MIR-206 AND MIR-383 VIACORO1C ANDSV2B IN AGGRESSIVE PAEDIATRIC AND ADULT BRAIN MALIGNANCIES

Abstract Medulloblastoma (MB), the most prevalent brain malignancy in children, poses challenges in paediatric oncology due to its aggressiveness and potential for metastasis. Tailored treatment strategies are essential due to the impact of treatment-related toxicities and long-term side effects on children’s developing brains. This study aimed to identify therapeutic targets for paediatric MB and explore common biosignatures with glioblastoma multiforme (GBM), the most aggressive adult brain tumour. Total RNA and microRNAs (miRNAs) were extracted from eleven paediatric brain tissues (normal brain tissues, n=2; MB tumour tissue, n=8; pilocytic astrocytoma, n=1). High-throughput small-RNA sequencing (sRNA-seq) and transcriptomics were performed to identify the most deregulated miRNAs in paediatric MB tissue samples. Selected miRNAs, gene targets and encoded proteins were evaluated in vitro and ex vivo via real-time polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry (IHC). The sRNA-seq demonstrated that miR-383 and miR-206 were highly down regulated in MB samples suggesting their tumour suppressor properties. Bioinformatics analysis using miRSystem and TargetScan identified SV2B and CORO1C as their direct targets, respectively. Transcriptomics showed significant upregulation of SV2B and CORO1C in MB tissue samples. RT-qPCR analysis confirmed overexpression of SV2B and CORO1C within GBM cell lines and IHC depicted significant overexpression of SV2B and CORO1C proteins in paediatric MB and GBM patient cohorts (n=28) compared to their normal brain counterparts (n=32). Elevated CORO1C expression was also detected in adult MB (n=23) and GBM (n=73) tissue samples, when compared to normal brain tissue. Western blotting further verified the significant overexpression of CORO1C and SV2B within GBM cells, suggesting their role as potential oncoproteins. Collectively, our preliminary study proposes the clinical significance of miR-206 and miR-383 when overexpressed in the therapy of aggressive paediatric and adult brain malignancies.

The Epidemiology and Survival Outcomes of Adult Conjunctival Malignancies in Germany: A Decade-Long Population-Based Analysis (2009–2019)

ABSTRACT Purpose This study aims to evaluate the epidemiological patterns, treatment strategies, and survival outcomes of conjunctival malignancies in Germany between 2009 and 2019. Methods A total of 1,532 cases were analyzed, with the crude incidence rate calculated. The survival rates were investigated using life tables and Cox regression analysis. Results The overall incidence rate was 1.7 per million. Incidence rates varied across age groups, peaking in the 75+ age group. Carcinomas (43%), melanomas (30%), and lymphomas (20%), were the most prevalent malignancies. Of the total cases with reported treatment, surgical intervention was undertaken in 64.5% of the patients. The 5-year overall survival rates were 90.4% for lymphomas, 73.8% for melanomas, and 72.9% for carcinomas. Age at diagnosis emerged as a significant prognostic factor in the Cox regression analysis. Conclusions This study provides the first population-based incidence data on conjunctival malignancies in Germany, noting a generally low incidence with survival rates comparable to other regions. The findings underscore the importance of consistent reporting and further research into risk factors for a deeper understanding of these malignancies. The study calls for improved reporting systems and further investigations into genetic factors and targeted prevention strategies for high-risk groups.

The importance of ultrasound-guided biopsy: lesson from a case of liver metastasis from uveal melanoma

Melanoma is an extremely aggressive malignant neoplasm. Uveal melanoma is the most common primary intraocular malignancy in adults, representing 3–5% of all melanomas. Liver metastases can be clinically detected in 10–20% of patients with metastatic disease from cutaneous melanoma. However, while liver is typically not the first site of disease spread in cutaneous melanoma, ocular melanoma has been showed to primarily metastasize from the eye to the liver; indeed, liver metastases are detected in approximately 87% of patients with metastatic uveal melanoma. Therefore, liver metastasis can be challenging to identify in early stages, thus being essentially asymptomatic until the disease has advanced. Here we report the case of a patient who came to our ultrasound unit reporting a large liver mass. Both contrast-enhanced abdominal computed tomography and magnetic resonance imaging did not establish a definitive diagnosis. The final diagnosis was made only through an ultrasound-guided biopsy of the mass, thus revealing a uveal melanoma metastasis. This is followed by a review of the literature on imaging follow-up of patients with melanoma.

AMLdb: a comprehensive multi-omics platform to identify biomarkers and drug targets for acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the huge amount of data from NGS platforms requires a comprehensive AML platform to streamline literature mining efforts and save time. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve, and analyse AML related multi-omics data. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines, and information on 41 experimentally validated biomarkers. In this study, we have reported five genes, i.e. CBFB, ENO1, IMPDH2, SEPHS2, and MYH9 identified via our analysis using AMLdb. ENO1 is uniquely identified gene which requires further investigation as a novel potential target while other reported genes have been previously confirmed as targets through experimental studies. Top of form we believe that these findings utilizing AMLdb can make it an invaluable resource to accelerate the development of effective therapies for AML and assisting the research community in advancing their understanding of AML pathogenesis. AMLdb is freely available at https://project.iith.ac.in/cgntlab/amldb.

Epidemiology of Oral Cavity Malignancies in Adolescents and Young Adults in Jordan: A Population-Based Study

Background: Oral cavity malignancies mostly affect older adults and the elderly. Adolescents and young adults (15–39 years) are less affected. However, there is a paucity of studies addressing the epidemiology of oral cavity malignancies in these age groups.Objectives: To describe the epidemiology of oral cavity malignancies in adolescents and young adults in Jordan.Patients and methods: The records of ordinarily resident patients in Jordan aged between 15 and 39 years, with histologically confirmed oral cavity malignancies, between the years 2000 and 2017, were analyzed. The frequency of each type of malignancy, incidence, annual percentage, site, age, sex and trends were analyzed.Results: Between the years 2000 and 2017, 406 adolescents and young adults fulfilled the inclusion criteria. This comprised 2.9% of all cancers in this age category during the same period. The mean age was 28.5 ± 7.6 years. Some 59.4% were male and 40.6% female. Regarding marital status, 34.2% were single, 61.6% married, and 0.7% divorced, while the marital status of 3.4% was unknown. Most (98.3%) were Jordanian nationals. The number of cases increased from 4.7% in 2000 to 6.2% in 2017, with no statistically significant trend. The overall age-adjusted incidence rate was 7.8 per 1,000,000. It decreased from 9.4 in 2000 to 6.2 in 2017, with no statistically significant trend over the study period. Nasopharyngeal cancer was the most common (56.9%), followed by cancers of the salivary gland (16.7%), tongue (10.3%), gums (6.2%), lips (5.2%), hypopharynx (2.7%), other oral cavity and pharynx (1.0%), oropharynx (0.5%), floor of mouth (0.2%), and tonsils (0.2%). Overall, the incidence of cancers of the oral cavity and pharynx was higher in males. The incidence of cancers of the nasopharynx, tongue, and lips was higher in males, while salivary gland cancer was higher in females. The incidence of cancers of the gum, hypopharynx, and pharynx did not differ between the sexes.Conclusions: The incidence of oral malignancies in adolescents and young adults in Jordan is relatively high compared to worldwide estimates but is not increasing. Risk factors for these malignancies should be the target of primary prevention interventions.

Tumor Control Probability and Time-Dose-Response Modeling for Stereotactic Radiosurgery of Uveal Melanoma

IntroductionUveal melanoma (UM), while a rare malignancy, stands as the most prevalent intraocular malignancy in adults. Controversies persist regarding the dose dependency of local control (LC) through radiotherapy. This study seeks to elucidate the significance of the prescription dose by employing time-dose response models for UM patients receiving photon-based stereotactic radiosurgery (SRS). Materials and MethodsInclusion criteria comprised UM patients treated between 2005 and 2019. All patients underwent single-fraction SRS. Datapoints were separated into three dose groups, with Kaplan-Meier analysis performed on each group, from which time-dose response models for LC were created at 2, 4, and 7 years using maximum-likelihood fitted logistic models. ResultsOutcomes from 594 patients with 594 UM were used to create time-dose response models. The prescribed doses and the number of patients were as follows: 17-19 Gy (24 patients), 20 Gy (122 patients), 21 Gy (442 patients), and 22 Gy (6 patients). Averaged over all patients and doses, LC rates at 2, 4, and 7 years were 94.4%, 88.2%, and 69.0%, respectively. Time-dose response models for LC demonstrated a dose-dependent effect, showing 2-year LC rates of more than 90% with 20 Gy and 95% with 22 Gy. For four years and a LC of 90%, a dose of approximately 21 Gy was required. After seven years, the 21 Gy prescription dose is predicted to maintain a LC above 70%, sharply declining to less than 60% LC with 19 Gy and less than 40% with 18 Gy. ConclusionIn contrast to prior findings, the time-dose response models for UM undergoing photon-based SRS emphasize the critical role of the prescription dose in achieving lasting LC. The dose selection must be carefully balanced against toxicity risks, considering tumor geometry and individual patient characteristics to tailor treatments accordingly.

Initial results from phase I trial of a novel oncolytic adenovirus Ad-TD-nsIL12 in recurrent glioblastoma connecting to ventricular system.

2057 Background: Glioma is the most common primary central nervous system malignancy in adults, of which glioblastoma (GBM) accounts for more than 50% of the incidence and is the most aggressive subtype of glioma, with a median survival of about 15 months. Oncolytic virus emerges as a promising therapy for recurrent GBM (rGBM), but its safety and efficacy are not evaluated in patients with rGBM connecting to ventricular system. Methods: This is a dose-escalating trial to study the safety and efficacy of Ad-TD-nsIL12, a novel oncolytic adenovirus, in patients with rGBM connecting to the ventricular system. The assigned dose levels of Ad-TD-nsIL12 were 5x109vp, 1x1010vp, and 5x1010vp. Adverse events (AEs) associated with the virus were graded using the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), and Grade ≥ 3 AEs identified the dose-limiting toxicity (DLT). Tumor response was evaluated based on the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Eight patients, aged from 45 to 71 years, were enrolled between December 2019 and September 2022, with treatment doses ranging from 5x109 to 5x1010vp. Grade 3 seizure according to CTCAE occurred in two patients from Cohort 3 (5x1010vp) after AD-TD-nsIL12 injection. Minimal adverse events were observed at a treatment dose of 1x1010 vp, even after multiple injections. Complete response (CR) was demonstrated in one patient, partial response (PR) in one patient, stable disease (SD) in four patients and progressive disease (PD) in two patients. Immunohistochemical staining showed higher infiltrations of CD3+, CD4+ and CD8+ T cells and positivity of E1A and Hexon in virus post-treated tissues. Inflammation associated cytokines in the blood were not significantly elevated by Ad-TD-nsIL12. Conclusions: AD-TD-nsIL12 treatment was safe and effective in patients with rGBM and warrants examination in a phase II clinical study. Clinical trial information: ChiCTR2000032402.

Personalized neoantigen-pulsed autologous dendritic cells vaccine as an adjuvant treatment for patients with newly-diagnosed glioblastoma multiforme: A phase I trial.

e14025 Background: Glioblastoma Multiforme (GBM) is the most common and aggressive primary brain malignancy in adults. We herein report a phase I trial using personalized neoantigen-pulsed autologous dendritic cells (nDC) vaccine as an adjuvant treatment for patients with newly-diagnosed GBM. Methods: It is a single-center, single-arm phase I trial, enrolling patients aged 18-75 years old, with newly-diagnosed GBM and tumor resection extent ≥90%. Tumor specimens were sequenced for identification of personalized neoantigens. A total of 3-10 neoantigen peptides were loaded into DC to generate the nDC vaccine. The vaccine was administered subcutaneously for 5-6 doses at 1×10^7 cells following concomitant radiotherapy plus temozolomide. The primary objective is safety. Secondary objectives include survival outcomes and T cell immune response against the neoantigens. Results: As of Dec. 31, 2023, eleven patients completed at least one dose of vaccination and were included in the safety analysis; eight patients completed planned doses and were included in the efficacy analysis. All the patients reported Treatment-emergent adverse events (TEAEs). Most TEAEs were grade 1 or 2. One patient reported two grade 3 TEAEs: decreased white blood cell count and decreased lymphocyte count. Pyrexia was considered as treatment-related adverse event (TRAE) that was reported in two (18.2%) patients. No treatment-related deaths occurred. Among eight efficacy-assessable patients, seven (87.5%) patients kept progression-free for at least 5.4-27.3 months; one patient progressed at 10.2 months after surgery and achieved complete remission after receiving anti-PD1 plus bevacizumab therapy; compared to the baseline level, a median 15-fold (3 to 506-fold) increase of neoantigen-specific cytotoxic T cells was detected in their peripheral blood samples post-vaccination, indicating strong anti-tumor T cell responses elicited by the nDC vaccine. Conclusions: The nDC vaccine, combined with the standard treatments for GBM, was well tolerated. Initial results from this ongoing study have exhibited encouraging survival outcome of the nDC vaccine for patients with newly-diagnosed GBMs. Clinical trial information: NCT04968366 . [Table: see text]

Procollagen C-protein enhancer 1 (PCPE-1) as a potential serum biomarker for osteosarcoma.

e23518 Background: Osteosarcoma (OS) is the most common bone malignancy in children and young adults. Treatment with perioperative systemic chemotherapy has improved patient outcome but a third of patients will eventually develop incurable metastatic disease. Currently, there are no biomarkers for monitoring patients’ response to neo-adjuvant (NA) chemotherapy or for patients under active surveillance following treatments. Procollagen C-Proteinase Enhancer-1 (PCPE-1) is an extra-cellular matrix glycoprotein which promotes the maturation of pro-collagen into collagen in various tissues. Elevated serum levels of PCPE-1 are found in bone diseases such as Paget’s disease and Osteoporosis and in patients with breast cancer with bone metastases. Serum PCPE-1 has not been described in patients with OS. We aimed to describe PCPE-1 serum levels in patients with OS compared with healthy volunteers, and across different time points in their treatment and disease course. Methods: We collected serum samples from the Israeli national biobank of 18 adult OS patients. Serum samples were also collected from 6 healthy individuals. Additionally, we obtained serial samples from 4 OS patients prior to and after initiating NA therapy. Quantification of serum PCPE-1 levels was performed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: We successfully analyzed serum PCPE-1 levels from all patients and healthy volunteers. Mean PCPE-1 levels of 553ng/ml (range 479-614ng/ml) were observed in OS patients, compared with 313ng/ml (285-339ng/ml) in healthy volunteers. Of 4 patients undergoing treatment who had serial samples, a decrease in serum levels was observed 2 responding patients, while an increase in PCPE-1 levels were observed in one patient after NA treatment who had no response to treatment at the time of surgery. Of notice, serum levels nearly doubled in a patient during active surveillance who experienced local disease recurrence (274ng/ml and 423ng/ml, respectively). Conclusions: This is the first study to show elevated PCPE-1 serum levels in patients with OS. Our study also demonstrates potential changes in PCPE-1 levels in response to treatment. We are expanding our study to include a pediatric population to investigate the role of PCPE-1 as a potential tumor biomarker for monitoring treatment and surveillance of OS.

Use of artificial intelligence (Al) in augmenting prior authorisation process for financial support in hemato-lymphoid malignancies: Joint project of Navya Al and Indian Cancer Society Cancer Cure Fund (ICS-CCF).

11086 Background: Hemato-lymphoid malignancies have a special urgency on time to initiate treatment and prior authorisation has relied on rapid review by domain experts. Since 2011, ICS-CCF has contributed over $32 million to cover the treatment costs of 14,600 underprivileged patients, including hematolymphoid malignancies. A mandate of ICS-CCF for this philanthropic funding is to choose beneficiaries who have a high chance of cure with standard of care. For this, a Due Diligence Team (DDT) of expert oncologists and the Governing Advisory Council (GAC) of ICS-CCF sequentially adjudicate every application. To augment and scale up this process, in Feb 2021, ICS-CCF evaluated and implemented the use of Al for prior-authorizations. Navya Al is a clinically validated Al model that matches clinical data of applicants with available evidence and registry data to predict survival, and generates payor/national guidelines based optimal treatment plans. Since Feb 2021, 80% of applications are adjudicated by Navya Al with a 99% concordance with GAC. Methods: This study was planned to assess the impact of Navya Al on the process of prior authorisation in a cohort of adult and pediatric hemato-lymphoid malignancies. All patients evaluated by Navya AI alone or with DDT from February 2021 to July 2023 were analyzed. Adjudication rates reflecting effort and time savings were calculated as the % of patients for whom Navya Al could make a decision on its own without referring to the DDT for review. Results: Of the 5775 applications reviewed by Navya Al, 2255(39.04%) were hematolymphoid malignancies. 37.16%(838/2255) of patients were pediatric (Age&lt;=15years) and 62.8%(1417/2255) were adults (Age&gt;15 years). Of these 2255, Navya AI alone adjudicated 73.61%(1660/2255) cases and 25.36%(572/2255) were referred to DDT for adjudication. Analysis was done on 2232 cases excluding the 1.01%(23/2255) reapplication cases. Details in table. Conclusions: With Al, only one fourth of beneficiary applications with hematolymphoid malignancies need expert review for prior authorisation. Implementation of AI has potential to save time in the authorization process for philanthropic funding for governmental and non governmental health care schemes. [Table: see text]

Establishing palliative care in tribal and rural Indian setting: A participatory action research approach.

e24085 Background: We established a palliative care center in the tribal area of Santhal Pargana, India, under a tertiary care facility, as a crucial step in addressing the palliative needs of oncology patients. This study assesses the center's inaugural year, focusing on referral patterns, morphine consumption, and pain management. Methods: Data from all patients visiting the palliative care outpatient department (OPD) in 2023 were prospectively collected and analyzed. The study focused on key palliative care indicators, including morphine consumption, patient referrals, and the mean Numeric Rating Scale (NRS) pain score after initial consultation. The PAR approach was utilized to tailor services to the community's needs. Results: The center observed an increase in patient referrals, from 8 new patients in January to 19 by December. The patient demographic primarily comprised individuals with head and neck cancer (43%), followed by breast cancer (28%) and gall bladder cancer (12%), alongside other types such as cervix, sarcomas, lung, and adult hematolymphoid malignancies. Bone metastasis was present in 46 (55.4%) patients at initial presentation. Morphine consumption demonstrated a notable rise, from 840 mg in May to 2860 mg in December, totaling 9800 mg for the year. The mean NRS pain score improved significantly from 6.5 in January to 4.3 post-initial consultation. The center maintained an overall median of 3 consultations per patient, and bereavement support was provided to 13 (15.7%) patients. Conclusions: The integration of the Participatory Action Research approach, specifically the CTC-5, was instrumental in the successful initiation and expansion of palliative care services within the center. The structured training, mentorship, and organizational restructuring, facilitated by the program, were crucial in establishing a modest palliative care infrastructure. This comprehensive approach not only enhanced care delivery but also ensured the sustainability and adaptability of palliative services, effectively addressing the gap in palliative care in rural, tribal settings.