Vobra duo, a duocarmycin-based humanized ADC (drug-to-antibody ratio is ∼2.7) targeting B7-H3, shows robust in vivo activity against a range of adult cancer models, and a favorable pharmacokinetic and safety profile in cynomolgus monkeys. Initial results from the single agent phase 1 clinical trial of vobra duo (NCT03729596) showed manageable side effects and promising objective response rates in metastatic castration-resistant prostate cancer. B7-H3 is highly expressed in pediatric solid tumors, and it is emerging as a key target for pediatric oncology. Here we report the antitumor activity of vobra duo against preclinical xenograft models of pediatric solid tumors. Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and neuroblastoma (NB) xenograft models were tested with n=1 or n=2 designs. Osteosarcoma (OS) models, due to their slower growth kinetics and lower rates of tumor regression, were tested with n=10 mice per arm. The study was extended to include malignant rhabdoid tumor (MRT), hepatoblastoma (HB), and Wilms tumor (WT) models using n=5 mice per treatment group. vobra duo and control ADC (SYD988 anti-CD20 ADC with the same linker and payload as vobra duo) were provided by MacroGenics, Inc., and were administered at 6 mg/kg as a single administration IP. Time-to-event was defined as 4-fold increase in tumor xenograft volume from the day of treatment. The Kaplan-Meier method was used to compare event-free survival (EFS) between treated and control groups. Objective response categories were determined as described previously (Ped Blood Cancer 2007;49:928-940), with objective responses including partial, complete, and maintained complete responses (PR, CR, and MCR). Vobra duo induced objective responses in 4 of 11 NB models (3 CR and 1 MCR) and in 3 of 5 OS models (2 MCR). ES models showed objective responses in 2 of 6 models (1 MCR) and 4 of 6 RMS models showed objective responses, all MCR. Control ADC was less active than vobra duo and showed objective responses in 0 of 11 NB, 1 of 5 OS, 1 of 6 ES, and 2 of 4 RMS models. The study was extended to MRT, HB, and WT models. Vobra duo induced objective responses in 2 of 4 MRT with 1 MCR, 2 of 5 HB with 2 MCR, and 3 of 4 WT with 3 MCR. Control ADC only induced objective responses in 1 of 4 MRT and 2 of 4 WT models (all PR), with no objective responses for the 5 HB models. Vobra duo is potently efficacious across a broad panel of pediatric solid tumor xenograft models supporting clinical development of this agent and other agents targeting B7-H3 for children with cancer. Haiying Tang, Edward Favours, Samson Ghilu, Peyton Wong, Vanessa Del Pozo, Abhik Bandyopadhyay, Elena Mironova, Eric J. Earley, Stephen W. Erickson, David Groff, Beverly A. Teicher, Kateryna Krytska, Matthew Tsang, Yael P. Mosse, E. Anders Kolb, Matthew Stephens, Steve Neuhauser, Tim Stearns, Jeff Chuang, Emily L. Jocoy, Jee Young Kwon, Carol Bult, Malcolm A. Smith, John M. Maris, Richard G. Gorlick, Peter J. Houghton, Raushan Kurmasheva. The B7-H3 targeting antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) is potently effective against a broad panel of pediatric solid tumor xenograft models: A study from the Pediatric Preclinical In Vivo Testing (PIVOT) Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7040.
Background and objective: Radical cystectomy (RC) in bladder cancer patients is associated with considerable short-term morbidity. Although RC is known to impair health-related quality of life (HRQOL), the impact of complication severity on HRQOL in the long term remains unclear. The aim of this study is to investigate the relationship between perioperative cumulative complication burden and HRQOL after RC using data from a prospective registry, given the limited existing evidence. Methods: The Comprehensive Outcome Measures and Perioperative Morbidity After CystecTomy (COMPACT) registry (DRKS00024929) prospectively collects standardized data on perioperative morbidity and longitudinal patient-reported outcome measures. The study includes patients undergoing open RC with pelvic lymph node dissection and urinary diversion for bladder cancer. According to the European Association of Urology guidelines, 90-d morbidity was assessed using both the Clavien-Dindo classification (CDC) and the Comprehensive Complication Index (CCI). HRQOL was measured at baseline and 3, 6, and 12 mo using the Functional Assessment of Cancer Therapy—Bladder—Cystectomy (FACT-BL-CYS) scores (range 0–168). Patients treated between 2020 and 2022 were included. Multivariable linear regression was used to evaluate the associations of 90-d CDC grade ≥IIIb (ie, “major complications”) and 90-d CCI with the 6-mo FACT-BL-CYS total score, adjusting for clinical and pathological confounders. Key findings and limitations: Among 82 patients, one (1.2%) had no complications, and 47 (57%) had CDC grade ≤II, 22 (27%) grade III, and 11 (13%) grade IV complications. The 90-d mortality rate was 1.2%. The median 90-d CCI was 35 (interquartile range [IQR] 26–45). The median 6-mo FACT-BL-CYS total score was 119 (IQR 90–142). Only comorbidity (age-adjusted Charlson index) was significantly associated with HRQOL (coefficient: –4.76, p = 0.02); neither CDC ≥IIIb (p = 0.7) nor CCI (p = 0.2) was significant. Limitations include uncertainty in effect sizes due to the low number of major complications. Conclusions and clinical implications: Open RC is associated with a high rate of perioperative complications when assessed with standardized methods. However, our findings suggest that their impact on HRQOL at 6 mo is limited. HRQOL appears to be more closely related to age-adjusted comorbidity. These insights should inform preoperative counseling and guide individualized postoperative care planning. Patient summary: We looked at whether complications after bladder removal surgery (radical cystectomy) affect patients’ quality of life. We found that most patients have complications, but these usually do not reduce quality of life 6 mo after surgery. Instead, pre-existing health conditions had a stronger impact on recovery.
Diseases of the genitourinary system. Urology, Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Alberto Busetto, Giorgio Cannone, Luigi Lione
et al.
ABSTRACT Chylothorax is a rare but insidious condition, characterized by the accumulation of chyle in the pleural space, which is particularly common after cardiothoracic surgeries. It presents significant challenges in both diagnosis and treatment. In this technical report, we present our experience in managing four cases of postsurgical chylothorax, each one treated with a different approach. The first and second cases were successfully managed with Lipiodol lymphangiography, which allowed for the visualization and occlusion of the injured lymphatic duct, leading to the resolution of the chylothorax. The third case involved thoracic duct embolization, a procedure that resulted in the closure of the duct responsible for the chylous effusion. The last case involved a patient who developed left‐sided chylothorax following a pulmonary resection. The patient experienced chylous leakage early in the postoperative period and underwent a revision thoracoscopy for hemostasis and thoracic duct ligation. During the procedure, indocyanine green (ICG) fluorescence was used to effectively identify and ligate the injured chylous duct. This case series highlights the variety of therapeutic strategies available for the management of chylothorax, emphasizing the importance of a structured, stepwise approach tailored to the specific needs of each patient.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Vladimir Vinarsky, Stefania Pagliari, Bacel Aldabash
et al.
Abstract Cardiac diseases are fueled by extracellular matrix (ECM) remodelling. Together with the altered ECM chemical composition, the mechanical turmoil associated with ECM maladaptive remodelling in the pathological heart drives the shuttling of Yes Associated Protein 1 (YAP1) into cardiomyocyte (CM) nuclei that results either in cell cycle re-entry or cardiomyocyte hypertrophy. The mechanism of YAP1 reactivation and factors driving qualitatively different cellular outcomes is not well understood. Here we employed mechanical actuation as a proxy reproducing ECM remodelling in vitro to trigger YAP1 nuclear shuttling in contractile cardiomyocytes derived from human embryonic and induced pluripotent stem cells (hPSCs). By using hPSC lines in which YAP1 expression has been genetically depleted, super-resolution microscopy and electrophysiological measurements, we show that ECM-triggered nuclear presence of endogenous YAP1 contributes to cardiomyocyte maturation, participates in the formation and alignment of myofibrils, as well as in the maturation of their electrophysiological properties and calcium dynamics. We eventually exploit engineered heart tissues (EHTs) to demonstrate that the net effect of YAP1 deficiency in cardiomyocytes is the inability to respond to physiological stimuli by compensatory growth that results in reduced force development. These results suggest that the re-activation of endogenous YAP1 following ECM maladaptive remodelling promotes cardiomyocyte contractility by restructuring the sarcomere apparatus and the maturation of electrophysiological properties via transcriptionally dependent and independent mechanisms.
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cytology
Introduction: Traditional models of carcinogenesis based on genetic mutations and direct exposure to carcinogens cannot explain all cases of cancer. The increasing incidence of certain cancers does not always correlate with known genetic factors, suggesting a significant role for environmental and lifestyle factors in their development. The concept of transgenerational carcinogenesis offers a new explanation, linking these factors with an increased risk of cancer in future generations through epigenetic changes. This study aimed to systematize and critically analyze scientific publications published between 2014 and 2024 that concern the factors contributing to transgenerational carcinogenesis and the underlying epigenetic mechanisms. Methods: To identify relevant publications, extensive searches were conducted in electronic databases, including PubMed/MEDLINE, Scopus, and Web of Science. Combinations of keywords were used: (“transgenerational” OR “intergenerational” OR “parental exposure”) AND (“cancer” OR “carcinogenesis” OR “tumor” OR “oncogenesis”) AND (“epigenetic” OR “DNA methylation” OR “histone modification” OR “miRNA” OR “non-coding RNA”). Results: The phenomenon of transgenerational carcinogenesis, which is the transmission of an increased risk of cancer from generation to generation, is a proven fact. Epigenetic changes that persist in the germline affect gene expression in subsequent generations, and they can be caused by various factors affecting the parents. Animal models provide convincing evidence of cause-and-effect relationships. Long-term cohort studies in humans consistently confirm this mechanism, despite methodological difficulties.Conclusion: Epigenetic changes in the germline can be passed on to offspring, significantly increasing their risk of developing pathological neoplasms. The primary mediators are changes in DNA methylation, histone modifications, and modifications to non-coding RNA. The study of transgenerational carcinogenesis will allow for the prevention of malignant neoplasms in future generations. Cause-and-effect relationships are convincing in models; in human populations, evidence is limited by associations and requires multigenerational cohorts with admixture control
Background: Despite advancements in precision oncology, only a minor subset of patients can be matched with effective targeted therapy, and even fewer experience sustained benefits. This is partly because current approaches, such as genomic profiling alone, do not fully capture the complexity of tumor biology. Integrating ex vivo drug sensitivity testing of patient-derived tumor cells with genomic profiling may offer a more comprehensive solution, helping identify effective treatments for patients with limited standard options or failed therapies. Objective: This prospective, non-randomized, single-arm observational study aims to evaluate the feasibility and clinical utility of integrating ex vivo drug sensitivity testing with genomic profiling to support real-time treatment decision-making for pediatric and adult patients with advanced solid tumors. The primary objective is to determine if treatment recommendations based on ex vivo drug testing can be delivered within a clinically actionable timeframe. The secondary objective is to evaluate if these patient-derived organoids (PDO)-guided recommendations improve clinical outcomes, specifically progression-free survival (PFS) and overall survival (OS). Methods: Tumor biopsies or resection specimens from patients with advanced solid tumors undergoing genomic profiling (matched tumor-normal WGS, total RNAseq) at our center will be processed to establish PDOs. Drug sensitivity will be tested using a luminescence-based viability assay (CellTiterGlo). Drug panels will be tailored for each patient by including on- and off-label options relevant to each diagnosis. If possible, drugs in clinical trials will also be included. Patients lacking effective standard-of-care treatments will receive alternative recommendations informed by both PDO drug sensitivity profiles and genomic data. Feasibility will be assessed by tracking the time required to return actionable recommendations to the clinical team within a predefined window (<4 weeks). For patients with resistant tumors, transcriptomic profiling will be used to explore the molecular mechanisms underlying resistance and potential alternative therapies. Approximately 30 patients will be enrolled over two years for an initial assessment of the clinical impact of this approach. Currently, we are performing a pilot study to optimize tissue processing and drug screening protocols across various tumor types, correlating ex vivo drug response with patient treatment outcomes. Conclusion: We hypothesize that PDO-guided treatment will lead to improved clinical outcomes compared to those treated without ex vivo guidance. This study will provide foundational evidence for integrating functional precision oncology into clinical practice and support future large-scale trials that could enhance the standard of care for patients with advanced and treatment-resistant cancers. Citation Format: Malene Blond, Maria E Skjøtt, Aram Arshadi, Søren B Poulsen, Ronja Carstensen, Kirstine J Elbæk, Anders R Korshøj, Britt E Laursen, Eva A Sædder, Ole H Larsen, Torben Mikkelsen, Kasper Thorsen, Martin K Thomsen, Maria Rusan. Advancing precision medicine: A prospective feasibility study integrating ex vivo drug testing and genomic profiling to improve outcomes in children and adults with advanced cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B024.
Childhood tumors comprise only about 1% of all diagnosed tumors and every year, approximately 400,000 children are diagnosed with cancer globally. In India, childhood malignancies range from 1.6-4.8% between 0-15 years of age. The records of all the tumors diagnosed histopathologically in children ≤14 years of age during a period of 5 years were retrieved and analyzed. For classification, the International Classification of Childhood Cancers (ICCC-3), based on International Classification of Diseases for Oncology (ICD-O-3), was followed. Written informed consent for publication of their clinical details and histopathological images was obtained from the parent/legal guardian of the patients. A total number of 160 cases were included in the study among which 99 were males (62%). The highest occurrence (48.13%) of malignancies was observed in 10-14 years of age in which most common malignancies noted were lymphoma (24.37%), followed by malignant bone tumors (21.27%) and CNS neoplasm (20.63%). Next common age group was between 0-4 years (31.7%) in which embryonal tumors including medulloblastoma, neuroblastoma, Wilms tumor and hepatoblastoma were more common. It can be concluded from our study that male predominance is a salient feature of childhood tumors. Most common childhood tumors originate from embryonal tissue while tumors of epithelial origin are rare. This large pediatric population based Indian study would provide us with greater insight details into pediatric tumors, and would play a pivotal role in facilitating early diagnosis and implementing effective disease management strategies for pediatric patients.
Navid Mohammad Mirzaei, Panayotis G. Kevrekidis, Leili Shahriyari
Breast cancer is one of the most challenging global health problems among women. This study investigates the intricate breast tumor microenvironment (TME) dynamics utilizing data from Mammary-specific Polyomavirus Middle T Antigen Overexpression mouse models (MMTV-PyMT). It incorporates Endothelial Cells (ECs), oxygen, and Vascular Endothelial Growth Factors (VEGF) to examine the interplay of angiogenesis, hypoxia, VEGF, and the immune cells in cancer progression. We introduce an approach to impute the immune cell fractions within the TME using single-cell RNA-sequencing (scRNA-seq) data from MMTV-PyMT mice. We further quantify our analysis by estimating cell counts using cell size data and laboratory findings from existing literature. Parameter estimation is carried out via a Hybrid Genetic Algorithm (HGA). Our simulations reveal various TME behaviors, emphasizing the critical role of adipocytes, angiogenesis, hypoxia, and oxygen transport in driving immune responses and cancer progression. The global sensitivity analyses highlight potential therapeutic intervention points, such as VEGFs' critical role in EC growth and oxygen transportation and severe hypoxia's effect on the cancer and the total number of cells. The VEGF-mediated production rate of ECs shows an essential time-dependent impact, highlighting the importance of early intervention in slowing cancer progression. These findings align with the observations from the clinical trials demonstrating the efficacy of VEGF inhibitors and suggest a timely intervention for better outcomes.
Yuhan Zheng, Jessie A Elliott, John V Reynolds
et al.
Esophageal cancer is a major cause of cancer-related mortality internationally, with high recurrence rates and poor survival even among patients treated with curative-intent surgery. Investigating relevant prognostic factors and predicting prognosis can enhance post-operative clinical decision-making and potentially improve patients' outcomes. In this work, we assessed prognostic factor identification and discriminative performances of three models for Disease-Free Survival (DFS) and Overall Survival (OS) using a large multicenter international dataset from ENSURE study. We first employed Cox Proportional Hazards (CoxPH) model to assess the impact of each feature on outcomes. Subsequently, we utilised CoxPH and two deep neural network (DNN)-based models, DeepSurv and DeepHit, to predict DFS and OS. The significant prognostic factors identified by our models were consistent with clinical literature, with post-operative pathologic features showing higher significance than clinical stage features. DeepSurv and DeepHit demonstrated comparable discriminative accuracy to CoxPH, with DeepSurv slightly outperforming in both DFS and OS prediction tasks, achieving C-index of 0.735 and 0.74, respectively. While these results suggested the potential of DNNs as prognostic tools for improving predictive accuracy and providing personalised guidance with respect to risk stratification, CoxPH still remains an adequately good prediction model, with the data used in this study.
Aakash Tripathi, Asim Waqas, Matthew B. Schabath
et al.
HONeYBEE (Harmonized ONcologY Biomedical Embedding Encoder) is an open-source framework that integrates multimodal biomedical data for oncology applications. It processes clinical data (structured and unstructured), whole-slide images, radiology scans, and molecular profiles to generate unified patient-level embeddings using domain-specific foundation models and fusion strategies. These embeddings enable survival prediction, cancer-type classification, patient similarity retrieval, and cohort clustering. Evaluated on 11,400+ patients across 33 cancer types from The Cancer Genome Atlas (TCGA), clinical embeddings showed the strongest single-modality performance with 98.5% classification accuracy and 96.4% precision@10 in patient retrieval. They also achieved the highest survival prediction concordance indices across most cancer types. Multimodal fusion provided complementary benefits for specific cancers, improving overall survival prediction beyond clinical features alone. Comparative evaluation of four large language models revealed that general-purpose models like Qwen3 outperformed specialized medical models for clinical text representation, though task-specific fine-tuning improved performance on heterogeneous data such as pathology reports.
Rising breast cancer (BC) occurrence and mortality are major global concerns for women. Deep learning (DL) has demonstrated superior diagnostic performance in BC classification compared to human expert readers. However, the predominant use of unimodal (digital mammography) features may limit the current performance of diagnostic models. To address this, we collected a novel multimodal dataset comprising both imaging and textual data. This study proposes a multimodal DL architecture for BC classification, utilising images (mammograms; four views) and textual data (radiological reports) from our new in-house dataset. Various augmentation techniques were applied to enhance the training data size for both imaging and textual data. We explored the performance of eleven SOTA DL architectures (VGG16, VGG19, ResNet34, ResNet50, MobileNet-v3, EffNet-b0, EffNet-b1, EffNet-b2, EffNet-b3, EffNet-b7, and Vision Transformer (ViT)) as imaging feature extractors. For textual feature extraction, we utilised either artificial neural networks (ANNs) or long short-term memory (LSTM) networks. The combined imaging and textual features were then inputted into an ANN classifier for BC classification, using the late fusion technique. We evaluated different feature extractor and classifier arrangements. The VGG19 and ANN combinations achieved the highest accuracy of 0.951. For precision, the VGG19 and ANN combination again surpassed other CNN and LSTM, ANN based architectures by achieving a score of 0.95. The best sensitivity score of 0.903 was achieved by the VGG16+LSTM. The highest F1 score of 0.931 was achieved by VGG19+LSTM. Only the VGG16+LSTM achieved the best area under the curve (AUC) of 0.937, with VGG16+LSTM closely following with a 0.929 AUC score.
Paola Sanchez-Moreno, Juan Luis Ortega-Vinuesa, Jose Manuel Peula-Garcia
et al.
Despite all the advances achieved in the field of tumor-biology research, in most cases conventional therapies including chemotherapy are still the leading choices. The main disadvantage of these treatments, in addition to the low solubility of many antitumor drugs, is their lack of specificity, which explains the frequent occurrence of serious side effects due to nonspecific drug uptake by healthy cells. Progress in nanotechnology and its application in medicine have provided new opportunities and different smart systems. Such systems can improve the intracellular delivery of the drugs due to their multifunctionality and targeting potential. The purpose of this manuscript is to review and analyze the recent progress made in nanotherapy applied to cancer treatment. First, we provide a global overview of cancer and different smart nanoparticles currently used in oncology. Then, we analyze in detail the development of drug-delivery strategies in cancer therapy, focusing mainly on the intravenously administered smart nanoparticles with protein corona to avoid immune-system clearance. Finally, we discuss the challenges, clinical trials, and future directions of the nanoparticle-based therapy in cancer.
Soft tissue sarcomas are a rare and heterogeneous group of solid tumors originating from the mesenchyme and accounting for only 1 % of all malignant neoplasms in adults. The modern clinical and morphological World Health Organization of soft tissue sarcomas classification includes more than 100 forms of these tumors. Neurofibromatosis is a group of hereditary, autosomal dominant diseases characterized by the development of multiple tumor formations, often benign. Currently, there are 3 types: neutrophibromatosis type I, neurofibromatosis type II and schwannomatosis. The estimated risk of developing sarcoma in patients with neurofibromatosis type 1 at age 30 years is 25.1 %, and by age 50 years it is 38.8 %. Treatment of soft tissue sarcomas associated with neurofibromatosis fully complies with the standard recommendations of National Comprehensive Cancer Network, NCCN (NCCN), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO) and RUSSCO and does not have its own peculiarities. Over the past 15 years, at the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center, more than 190 patients with locally advanced, high-grade soft tissue sarcomas have been treated, including five patients with sarcomas associated with neurofibromatosis. The article presents clinical cases of treatment of soft tissue sarcomas associated with neurofibromatosis.
Gallbladder cancer often arises from somatic mutations in cells of the biliary epithelium, which can be precipitated by chronic inflammation (as in chronic cholelithiasis and cholecystitis), infections (e.g., by Salmonella spp. or Helicobacter spp.), and exposure to carcinogens. Adenocarcinomas represent more than 90% of gallbladder cancer cases, with other histological subtypes including squamous cell carcinomas, adenosquamous carcinomas, and neuroendocrine tumors.
Background Dendritic cells are nonlymphoid, nonphagocytic, antigen-presenting cells present in lymphoid and nonlymphoid tissue. There are 4 types of dendritic cells: follicular, interdigitating, Langerhans, and fibroblastic cells. The WHO 2022 classification system groups dendritic cell and histiocytic neoplasms into 3 categories: plasmacytoid dendritic cell neoplasms, Langerhans cell and other dendritic cell neoplasms, and histiocytic neoplasms. The 2nd category is subdivided into “Langerhans cells neoplasms” and “other dendritic cell neoplasms”, which contains indeterminate dendritic cell tumor (IDCT) and interdigitating dendritic cell sarcoma (IDCS). The 2022 classification eliminated follicular dendritic cell sarcoma (FDCS) as it is no longer thought to be of hematopoietic origin. A prior Surveillance, Epidemiology, and End Results (SEER) review published in 2013 by Perkins and Shinohara grouped FDCS and IDCS and included 20 cases of IDCS diagnosed between 2001 and 2008. To our knowledge, this is the first update of epidemiologic and survival data for non-Langerhans cell and non-plasmacytoid dendritic cell neoplasms since the WHO reclassification. Methods We used the SEER 22 database, which collects data from cancer registries covering approximately 47.9% of the U.S. population. We selected all patients with cancers falling in the “other dendritic cell neoplasms” category according to the WHO 2022 classification from 2000-2020 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code of 9757/3, which codes for IDCS but also includes IDCT. The Kaplan-Meier method was used to display the survival curves. The Cox proportional hazards model was used to determine p values. Results A total of 72 cases of IDCS/IDCT were identified. Median follow up was 19 months and median OS for the entire cohort was 24 months (95% CI 10-92 months). Of these patients, 61.1% (n=44) were White, 16.7% (n=12) were Hispanic, 13.8% (n=10) were Black, 5.6% (n=4) were Asian or Pacific Islander, and 2 patients were of unknown race. IDCS/IDCT was more common in males than females with a ratio of 1.77. The most common primary sites of involvement were connective tissue in 40.2% (n=29), head and neck in 16.7% (n=12), lymph nodes in 11.1% (n=8), and bone marrow in 8.3% (n=6). Patients with bone marrow involvement had a trend towards worse OS (median OS of 5 months). IDCS/IDCT is more common in adults but does occur in children and adolescents. Only 6 cases were diagnosed in patients under the age of 20 years. Patients who were under the age of 60 years at diagnosis had a median OS of 155 months compared to a median OS of only 10 months for patients who were 60 years or older at diagnosis (Figure 1, p<0.001). Staging was unknown in 12 patients. Of patients with known staging, 56.7% (n=34) had localized disease and 43.3% (n=26) had metastatic disease. Patients with localized disease at diagnosis had a better prognosis with a median OS of 120 months compared to 5 months for patients with metastatic disease at diagnosis (Figure 2, p<0.001). Treatment modality was unknown in 29 of the patients. Of patients with known treatment, 34.9% (n=15) had surgery alone, 20.9% (n=9) had chemo alone, 16.3% (n=7) had radiation alone, and 27.9% (n=12) had combination treatment. Single modality treatment regimens were most popular in patients with localized disease with 48% (n=12) of the patients with known treatment modality getting surgery alone, followed by radiation alone at 24% (n=6).The most common cause of death in this cohort was IDCS/IDCT with 76% of deaths being attributed to the cancer (n=35, there were 46 total deaths). Conclusions Though cases of IDCS and IDCT have more than tripled since 2008, it still remains the rarest type of dendritic cell neoplasm. Connective tissue, head and neck, and lymph nodes were the most common sites involved. Surgical resection was the most common treatment modality followed by chemotherapy. Clinical presentation is rare in patients under the age of 20 years. Age 60 years and older and metastatic disease were associated with poor outcomes with a signal towards worse survival when bone marrow was involved. Our study updates current knowledge of IDCS/IDCT and highlights some of the unknowns in this type of neoplasm, particularly regarding other prognostic factors including treatment effect on survival.