Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

Jhommara Bautista, Ricardo Bedón-Galarza, Francisco Martínez-Hidalgo et al.

Pancreatic cancer (PC) represents one of the most formidable challenges in oncology, characterized by its asymptomatic onset, delayed clinical detection, and dismal prognosis. Among pancreatic neoplasms, pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of cases and remains the most aggressive form, driven by late diagnosis, intrinsic chemoresistance, and a profoundly immunosuppressive tumor microenvironment. Recent advances have reframed the human microbiome not as a passive bystander but as an active architect of pancreatic tumor biology. This review delineates the mechanistic axes through which microbial ecosystems orchestrate PDAC progression across four key anatomical niches-gastrointestinal, oral, urogenital, and intrapancreatic. We elucidate how microbial dysbiosis fosters oncogenesis through immune evasion, metabolic reprogramming, and chronic inflammation, implicating specific taxa such as Fusobacterium nucleatum, Malassezia spp., and Porphyromonas gingivalis in immune suppression and chemoresistance. Microbial enzymatic inactivation of gemcitabine and modulation of cytokine networks further underscore the microbiome’s pivotal role in therapeutic failure. Conversely, commensal and probiotic species may potentiate immunosurveillance and enhance treatment efficacy. This review also explores microbiota-derived biomarkers for early detection and the translational promise of microbiome-targeted interventions, including fecal microbiota transplantation, probiotics, and selective antibiotics. By decoding the microbial blueprint of PC, we propose a paradigm in which the microbiome emerges as both a biomarker and a therapeutic axis, offering novel avenues for precision oncology. Furthermore, this integrative synthesis emphasizes the multi-omic, immunometabolic, and therapeutic dimensions of the pancreatic cancer-microbiome interface, where metagenomic, transcriptomic, metabolomic, and immunomic layers converge to shape tumor evolution and therapeutic response, advancing the vision of microbiome-informed precision oncology.

Yuxuan Zhang, Lijun Jia

Malignant tumors exhibit complex pathogenesis, yet classical oncological theories remain fragmented, failing to provide a unifying framework to address this complexity. This gap limits the utility and translational potential of the prevailing "confront-and-eradicate" therapeutic paradigm, constraining transformative therapeutic breakthroughs and driving the emergence of acquired and recurrent drug resistance. Here, we propose the Tumor Existential Crisis-Driven Survival (ECDS) theory, anchored in the core proposition that impairment of Existential Stability drives the compensatory hyperactivation of Survival Capacity. This framework defines three foundational constructs (Existential Stability, Survival Capacity, and Existence Threshold) and three guiding principles, unifying and integrating canonical core theories of tumorigenesis. It delineates the dynamic coupling between declining Existential Stability and escalating Survival Capacity during tumor evolution, reinterprets the hierarchical activation of the well-established 14 cancer hallmarks, elucidates the redundancy of survival signaling pathways that underpins intratumoral and intertumoral heterogeneity, and unravels the "hierarchical leap" in therapeutic resistance. By reframing tumors as "Existential Stability erosion-driven passive survival systems" rather than "intrinsically aggressive cellular aggregates", ECDS challenges prevailing dogma, uncovers tumors' intrinsic vulnerability, and establishes a robust meta-theoretical foundation for both basic cancer research and translational clinical management.

Belinda Cairns, A. Woolley, Joseph Lewis et al.

Many biotechnology and pharmaceutical companies rely on mRNA expression as a key to finding novel oncology targets for therapeutic intervention. One of the challenges with this approach is the mismatch that can occur quite frequently between mRNA expression and protein expression and abundance. While it is established that you need mRNA for protein expression, there can be a huge mismatch mainly due to factors such as translational and transcriptional delays, post-transcriptional modifications, degradations and structural or physical alterations. These discrepancies highlight the significant limitations of relying solely on mRNA data to predict protein targets. Here we provide specific examples demonstrating how our proprietary OGAP-Verify target discovery platforms uniquely identifying targets overlooked by RNA-based predictions using a variety of protocols including RNAseq, qPCR and in situ hybridization. A prime example in the public domain is Type 1 Collagen which, while not a membrane protein, exhibits significant mismatch between low RNA levels and high protein expression. Here, we present data of proprietary membrane specific targets which have significant RNA-Protein level mismatch as examples of the effectiveness of OGAP-Verify in identifying such novel oncology targets. OGAP-Verify has enabled OBT with a unique approach to identify membrane specific protein expression on patient tumors which has resulted in identifying a large number of new specific cancer targets that do not correlate with their RNA expression profiles. Immunohistochemistry (IHC) data shows direct correlation with OGAP-Verify proteomics results. Leveraging OGAP-Verify—the world’s largest cancer membrane protein expression database—OBT has exclusive access to unique oncology targets, including cancer-specific isoforms, unavailable elsewhere in the industry. Belinda Cairns, Andrew Woolley, Joseph Lewis, Daniel Davies, Lindsey Hudson, Somdatta Basu, Ben Thomas, Christian Rohlff. OGAP-verify protein database can identify and highlight mRNA and protein mis-matched oncology targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 458.

Kristen Fousek, Lucas A Horn, Haiyan Qin et al.

Neuroendocrine neoplasms (NEN) consist of slow growing neuroendocrine tumors and highly proliferative neuroendocrine carcinomas. The incidence of NEN continues to rise, yet there remains a lack of effective treatments for this disease. Immune checkpoint blockade (ICB) in combination with chemotherapy is approved in extensive stage small cell lung cancer (SCLC), a very aggressive tumor classically known as NE, but only a subset of patients experiences improved survival. Lack of response to ICB is often attributable to low expression of MHC-class I. Our group recently published that the lack of MHC-class I can instead be utilized to facilitate targeting by NK cells. We found that NK cells stimulated with an IL-15 cytokine superagonist (N-803) were able to effectively target SCLC of all phenotypes. This led us to hypothesize that cytokine stimulated memory-like NK cells may be effective in targeting SCLC and other types of NE tumors. In the present study, the ability of memory cytokine enriched NK cells (M-ceNK) to target human NE cell line models is evaluated. M-ceNK are derived from an apheresis product (from healthy donors or cancer patients) and exposed to a cocktail of cytokines including N-803, IL-12, and IL-18 until a highly purified CD3NEGCD56HIGH cell population results. Characterization across many donors indicates that M-ceNK are highly activated NK cells exhibiting increased natural cytotoxicity receptors (NKp30, NKp44, NKp46), minimal inhibitory markers (KLRG1, TIGIT), elevated IFN-gamma and Granzyme B production, and increased reliance on glycolysis for their metabolic activity compared to healthy donor NK cells. The functional killing capacity of M-ceNK was assessed via in vitro immune cytotoxicity assays; M-ceNK demonstrated a median of 69% lysis (range 35-89%) at an effector to target ratio of 5:1 across 5 SCLC models (DMS79, H69, H446, H1048, H841) as well as 66% and 42% lysis respectively in NE prostate cancer (H660) and lung cancer (H720, H727) models as compared to 6% lysis (range 0-58%) with healthy donor NK cells. Furthermore, M-ceNK provided significant anti-tumor efficacy in two xenograft models of SCLC (H69, DMS79) when administered with N-803 in vivo. To better understand the efficacy of M-ceNK and their role upon encountering tumor cells, we co-cultured M-ceNK and NE tumors together and subsequently performed single cell RNA-sequencing on pairs of matched donor M-ceNK pre- and post- tumor exposure. We observed rapid upregulation of a gene signature indicative of tumor-infiltrating NK cells as well as increases in the expression of chemokines that play a key role within the tumor microenvironment. Further studies will evaluate the functional importance of these changes in gene expression and how they affect the ability of M-ceNK to target tumor cells, secrete cytokines, and proliferate; M-ceNK will also be tested in combinatorial immunotherapy approaches to treat NE and other ICB-refractory tumors. Kristen Fousek, Lucas A. Horn, Haiyan Qin, Nika Rajabian, Miriam Marlene Medina Enriquez, Shantel Angstadt, Manju Saxena, Lennie Sender, Patrick Soon-Shiong, Claudia Palena. Characterization of the anti-tumor efficacy of memory cytokine enriched NK cells against tumors with neuroendocrine features [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A018.

Y. Lyashchuk, K. I. Romanov, K. Ivanishchev et al.

This study analyzes approaches to the diagnosis and treatment of mammary cancer in animals. The authors examined carcinogenesis using small domestic animals as a study subject to ensure adherence to bioethical principles and to enhance the statistical validity of the results obtained in a clinical setting using modern equipment and data recording in electronic medical records. It should be noted that the incidence of malignant neoplasms in the mammary gland depends on the individual characteristics of the animals, as well as the duration of exposure and the type of carcinogen. Since the development of malignant neoplasms is a significant issue not only for pet owners but also for veterinarians treating farm animals, the chosen research topic is relevant. Mammary cancer is widespread among food-producing animals, causing significant losses in both dairy and meat production due to the culling of carcasses or parts affected by tumors, and is a frequent cause of disruption to the normal reproduction of healthy livestock, including the feeding of young animals. One of the most common types of malignant tumors in farm and domestic animals, arising from carcinogenesis, is mammary cancer. Comparing data on the etiology, pathogenesis, clinical presentation, and morphology of mammary tumors in various animal species is an extremely important process for the development of comparative oncology. The obtained data can be used to diagnose and treat mammary cancer in various animal species.

A. J. Xu, B. Dwivedi, E. Kalashnikova et al.

Brain metastases in breast cancer (BC) present significant clinical challenges. The utility of circulating tumor DNA (ctDNA) in detecting intracranial progression is not well established. This study investigated ctDNA kinetics before and after brain relapse from early-stage BC in pts undergoing routine surveillance with a tumor-informed ctDNA assay. To identify pts with brain metastases from early-stage breast cancer and relevant ctDNA timepoints, we utilized Natera’s proprietary real-world database, which is linked to Komodo's Healthcare Map® claims database and available results of tumor-informed ctDNA testing (SignateraTM, Natera, Inc.) from 2019 to 2024. Hormone receptor and HER2 status and date of relapse were inferred from ICD-10 claims codes associated with interventions and secondary neoplasms. We evaluated ctDNA kinetics before and after brain relapse, including relative timing of ctDNA positivity, ctDNA levels (mean tumor molecules (MTM)/mL), and ctDNA clearance after initiation of therapy. We identified 77 pts with early-stage breast cancer who developed subsequent brain relapse, including 28 pts with brain-only metastasis (BOM) and 49 pts with brain and extracranial metastases (BM+ECM) at the time of initial metastatic diagnosis. Among 28 pts with BOM, TNBC was the most represented subtype (40%; 11/28), followed by HER2+ (32%; 9/28) and ER+/HER2- (28%; 8/28). BOM were diagnosed at a median of 21.2 months (range: 1.8 - 87.0) and BM+ECM at a median of 19.2 months (range: 1.21 - 90.4) after surgery. The overall ctDNA detection rate prior to relapse was 54% (15/28) for pts with BOM and 92% (45/49) for pts with BM+ECM. Median time from ctDNA detection to BOM was 3.21 months (range: 0.2 to 14.5 months) and to BM+ECM was 2.66 (range: 0.03 to 39.2 months), acknowledging that the timing of ctDNA assessments was not controlled in this real-world dataset. Median ctDNA level prior to BOM was 1.27 MTM/mL (range: 0.04 - 227) compared to a median of 47.7 MTM/mL (range: 0.09 - 3854) in pts with BM+ECM. Among pts with BOM with matching pre- and post-relapse timepoints (n=17), 9 pts were ctDNA positive prior to BOM; of these, ctDNA clearance was observed in 44.4% (4/9) following post-relapse treatment, while the remaining pts were persistently ctDNA-positive [55.5% (5/9)]. Eight pts were ctDNA negative at BOM, and 25% (2/8) converted to positive after the diagnosis of isolated brain relapse. Among 34 pts with BM+ECM and matching pre- and post-relapse ctDNA timepoints, 30 pts were ctDNA positive prior to BM+ECM; of these, 13.3% (4/30) achieved clearance following post-relapse treatment, and 86.6% (26/30) remained positive. Four pts were ctDNA negative at BM+ECM, and 25% (1/4) converted to ctDNA-positive after the diagnosis of BM+ECM. Our RWD study provides evidence that tumor-informed ctDNA test results were positive in >50% of early-stage BC pts with BOM and >90% of early-stage BC pts with BM+ECM prior to the date of metastatic relapse. As expected, median ctDNA levels were generally lower in those with BOM compared to BM+ECM. Our data confirm the utility of ctDNA to identify pts who are at high risk of relapse, and provide evidence that ctDNA can detect CNS-limited recurrences. Given the potential for CNS involvement in pts with BC, pts with ctDNA-positivity and negative extracranial scans should be considered for CNS imaging to exclude BOM. A. J. Xu, B. Dwivedi, E. Kalashnikova, J. Ortiz, J. McKenzie, A. Rodriguez, M. C. Liu, L. A. Huppert, C. K. Anders, N. U. Lin, S. L. Sammons. Circulating tumor DNA (ctDNA) Dynamics in Early-stage Breast Cancer Patients (pts) with Brain Metastases [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-08-21.

D. Fischerová, F. Frühauf, Andrea Burgetová et al.

Simple Summary Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Abstract Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer.

Takuma Imakita, Kohei Fujita, Yuki Yamamoto et al.

Abstract Tarlatamab, a bispecific T-cell engager (BiTE), effectively activates the immune system but often causes cytokine release syndrome (CRS). To understand the early in vivo cytokine dynamics of post-BiTE therapy, we analyzed serum from three SCLC patients before and after tarlatamab administration using the Bio-Plex Pro Human Cytokine Screening Panel, 48-Plex. CRS occurred once in case 1, twice in case 2, and not at all in case 3. During the initial CRS in cases 1 and 2, IL-6, IL-1Ra, IL-10, granulocyte colony-stimulating factor, MIG, and IP-10 increased from baseline. Of these, MIG and IP-10 were also elevated during the second CRS episode in case 2. Some cytokines (hepatocyte growth factor, IFN-α2, IFN-γ, IL-2Rα, MIP-1α, MCP-1, and TRAIL) rose during CRS in either case 1 or 2 but showed little change in the other. RANTES decreased during CRS in case 1, yet increased and remained high in case 2, and stayed elevated in case 3. This cytokine profiling highlights the complex pathophysiology of CRS and the involvement of diverse cytokine networks beyond the IL-6 axis. These findings may guide future biomarker development, disease classification, and therapeutic strategies beyond IL-6 inhibition, advancing personalized CRS management.

Yu Li, Yu Chen, Gansheng Xie et al.

BackgroundComputed tomography (CT) Hounsfield units (HUs) of pathologically confirmed metastatic inguinal lymph nodes (ILNs) were proved to be higher than negative ones. We designed this study to explore the clinical value of CT HU for diagnosing palpable ILN metastasis in patients with penile cancer.MethodsA total of 32 patients with penile cancer, including 84 palpable ILNs, were recruited in this study. They all performed 5-mm layer pelvic contrast-enhanced CT (CE-CT) before treatment. The palpable ILNs were matched with CT image. By using radiologic software PACS, the layer with a maximum cross-sectional area of target lymph node was selected, and the short axis was defined as diameter. We outlined the edge of target lymph nodes, and the software automatically calculated its area, maximum CT HU, and average CT HU. All target ILNs were biopsied by surgery to confirm the presence of metastasis.ResultsCompared with non-metastatic ILNs, metastatic ILNs had larger diameter, area, maximum non-contrast CT (NC-CT) HU, maximum arterial-phase CE-CT (ACE-CT) HU, average NC-CT HU, and average ACE-CT HU, with statistically significant differences (P < 0.05). Receiver operating characteristic analysis showed the all six parameters (maximum NC-CT HU, maximum ACE-CT HU, average NC-CT HU, average ACE-CT HU, diameter, and area) had significant diagnostic value for ILN metastasis, with an area under the curve of 0.847, 0.853, 0.900, 0.919, 0.809, and 0.789, respectively. The average ACE-CT HU (cutoff: 40.5) had the highest accuracy as 0.857, and maximum NC-CT HU (cutoff: 51.5) had the highest sensitivity of 0.897.ConclusionILN CT HU was clinically valuable for the diagnosis of palpable ILN metastasis in patients with newly diagnosed penile cancer.

Chengfei Zhang, Yufei Bo, Ting Zhang et al.

Abstract Cancer stem cells (CSCs) play a pivotal role in driving colorectal cancer (CRC) progression and therapeutic resistance. However, the molecular mechanisms regulating CRC-CSC properties are not fully understood. Proline-rich Akt substrate 40 (PRAS40) is involved in various tumorigenic processes, yet little is known about its contribution to cancer stemness. In this study, we demonstrated that PRAS40 was overexpressed in CRC tissues and its elevated expression positively correlated with poor patient survival. Genetic ablation of PRAS40 suppressed tumorigenesis in CRC mouse models. Notably, PRAS40 enhanced the stemness of CRC cells, as evidenced by increased sphere formation, upregulation of stem cell markers, enrichment of the CD133+CD44+ cell population, and enhanced tumor initiation capacity in vivo. Mechanistically, PRAS40 induced a glycolytic phenotype by interacting with and activating the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Furthermore, PRAS40 enhanced the interaction between PGK1 and the acetyltransferase p300/CBP-associated factor (PCAF), thereby promoting PGK1 acetylation, which contributes to glycolysis activation and the maintenance of CRC stemness. Pharmacological inhibition of acetylation attenuated PRAS40-mediated CRC stemness and colorectal carcinogenesis. Collectively, our findings uncover a novel PRAS40/PGK1 regulatory axis that promotes CRC stemness and tumorigenesis through enhanced glycolysis, suggesting potential therapeutic strategies targeting this axis for CRC treatment.

Zhen Yu, Wenxing Xun, Pan Ren et al.

Abstract Objective The purpose of our study was to evaluate the clinical effect of a facelift combined with a modified overlapping superficial musculoaponeurotic system (SMAS) flap for repairing facial depression caused by the resection of benign parotid lesions. Methods This retrospective, non-randomized observational study included 87 patients diagnosed with benign parotid tumors who underwent surgical treatment between June 2014 and September 2023. All patients were treated in our department or by the same surgical team after institutional transfer. All patients received surgery via a standardized facelift incision approach.; All patients underwent surgery using a standardized facelift incision. Of them, 58 patients received reconstructive surgery with the modified SMAS flap, and 29 patients were treated using the classical SMAS flap. The degree of satisfaction with scarring and facial depression was assessed 6 months postoperatively using the Vancouver Scar Scale (VSS) and a 10-point scale (0 = no obvious depression; 10 = severe depression), respectively. Results There was no significant difference regarding the degree of satisfaction with scarring between the two groups (P > 0.05), while the modified SMAS flap group was significantly more satisfied with the facial depressions than the classical SMAS flap group (P < 0.001). Surgical complications and tumor recurrence were not significantly different between the two groups. Conclusions A facelift combined with a modified SMAS flap can effectively repair the facial depressions caused by the resection of benign parotid lesions and achieve good aesthetic results.

Jarett Dewbury, Chi-en Amy Tai, Alexander Wong

Prostate cancer (PCa) is the most prevalent cancer among men in the United States, accounting for nearly 300,000 cases, 29\% of all diagnoses and 35,000 total deaths in 2024. Traditional screening methods such as prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) have been pivotal in diagnosis, but have faced limitations in specificity and generalizability. In this paper, we explore the potential of enhancing PCa gland segmentation using a novel MRI modality called synthetic correlated diffusion imaging (CDI$^s$). We employ several state-of-the-art deep learning models, including U-Net, SegResNet, Swin UNETR, Attention U-Net, and LightM-UNet, to segment prostate glands from a 200 CDI$^s$ patient cohort. We find that SegResNet achieved superior segmentation performance with a Dice-Sorensen coefficient (DSC) of $76.68 \pm 0.8$. Notably, the Attention U-Net, while slightly less accurate (DSC $74.82 \pm 2.0$), offered a favorable balance between accuracy and computational efficiency. Our findings demonstrate the potential of deep learning models in improving prostate gland segmentation using CDI$^s$ to enhance PCa management and clinical support.

Xizhe Zhang, Weixiong Zhang

Cancer research has traditionally focused on identifying driver genes, those with mutations that initiate tumorigenesis. The Cancer Driver Gene (CDG) paradigm, further supported by the observation of oncogene addiction in tumors, has successfully guided the development of targeted therapies. However, the limitations of this driver-centric view, highlighted by the broad emergence of frequent therapeutic resistance, the presence of driver mutations in healthy tissues or individuals, and the lack of identifiable drivers in many tumors, call for a shift in perspective and clinical practice. The latest network controllability perspective on cancer cells introduced the concept of Cancer Keeper Genes (CKGs) and a CKG-based paradigm for cancer therapeutics. The new concept encompasses the concept of non-oncogene addiction, emphasizing reliance on non-mutated pathways crucial for maintaining oncogenic cellular states. Here, we explore the transition towards a system-level understanding of cancer based on the CKG paradigm, emphasizing the essential role of genes required for tumor maintenance, irrespective of their initiating function or mutational capacity. We discuss clinical implications of this paradigm shift, highlighting the progress made so far and potential of targeting non-driver CKGs, genes involved in processes like DNA damage response, proteostasis, and metabolism, as a promising strategy to overcome therapeutic challenges and achieve more durable cancer control. Targeting these maintenance vulnerabilities represents a critical evolution in precision oncology, moving towards therapies designed to dismantle the networks sustaining malignancies.

Soheil Hashtarkhani, Yiwang Zhou, Fekede Asefa Kumsa et al.

Breast cancer screening plays a pivotal role in early detection and subsequent effective management of the disease, impacting patient outcomes and survival rates. This study aims to assess breast cancer screening rates nationwide in the United States and investigate the impact of social determinants of health on these screening rates. Data on mammography screening at the census tract level for 2018 and 2020 were collected from the Behavioral Risk Factor Surveillance System. We developed a large dataset of social determinants of health, comprising 13 variables for 72337 census tracts. Spatial analysis employing Getis-Ord Gi statistics was used to identify clusters of high and low breast cancer screening rates. To evaluate the influence of these social determinants, we implemented a random forest model, with the aim of comparing its performance to linear regression and support vector machine models. The models were evaluated using R2 and root mean squared error metrics. Shapley Additive Explanations values were subsequently used to assess the significance of variables and direction of their influence. Geospatial analysis revealed elevated screening rates in the eastern and northern United States, while central and midwestern regions exhibited lower rates. The random forest model demonstrated superior performance, with an R2=64.53 and root mean squared error of 2.06 compared to linear regression and support vector machine models. Shapley Additive Explanations values indicated that the percentage of the Black population, the number of mammography facilities within a 10-mile radius, and the percentage of the population with at least a bachelor's degree were the most influential variables, all positively associated with mammography screening rates.

Garazi Retegui, Jaione Etxeberria, María Dolores Ugarte

Cancer data, particularly cancer incidence and mortality, are fundamental to understand the cancer burden, to set targets for cancer control and to evaluate the evolution of the implementation of a cancer control policy. However, the complexity of data collection, classification, validation and processing result in cancer incidence figures often lagging two to three years behind the calendar year. In response, national or regional population-based cancer registries (PBCRs) are increasingly interested in methods for forecasting cancer incidence. However, in many countries there is an additional difficulty in projecting cancer incidence as regional registries are usually not established in the same year and therefore cancer incidence data series between different regions of a country are not harmonised over time. This study addresses the challenge of forecasting cancer incidence with incomplete data at both regional and national levels. To achieve this, we propose the use of multivariate spatio-temporal shared component models that jointly model mortality data and available cancer incidence data. We evaluate the performance of these multivariate models using lung cancer incidence data and the corresponding number of deaths reported in England for the period 2001-2019. Model performance was assessed using different predictive measures to select the best model.

Kevin Mallery, Nathaniel R. Bristow, Nicholas Heller et al.

Circulating tumor cells (CTCs) are cancer cells found in the bloodstream that serve as biomarkers for early cancer detection, prognostication, and disease monitoring. However, CTC detection remains challenging due to low cell abundance and heterogeneity. Digital holographic microscopy (DHM) offers a promising, label-free method for high-throughput CTC identification by capturing superior morphological information compared to traditional imaging methods, while remaining compatible with in-flow data acquisition. We present a streamlined DHM-based system that integrates microfluidic enrichment with deep learning-driven image analysis, supplemented by immunofluorescent profiling, to improve the sensitivity and specificity of CTC enumeration. Specifically, our platform combines inertial microfluidic preprocessing with dual-modality imaging, integrating holography with fluorescence sensing of up to two markers. A deep learning model, trained on a diverse set of healthy blood samples and cancer cell lines, and executed in real-time, provides a morphological confidence on a cell-by-cell basis that may then be combined with immunofluorescence criteria for enumeration. In a pilot study, we demonstrate significantly higher CTC counts in patients with late-stage prostate cancer (n=13) compared to healthy controls (n=8), with a patient-level false positive rate of 1 cell/mL. Notably, nearly two-thirds of identified CTCs were EpCAM-negative but PSMA positive (a prostate specific epithelial marker), suggesting that traditional use of EpCAM as an epithelial marker for CTCs may lead to false negatives. These findings highlight the potential of DHM for applications including but not limited to screening, diagnostics, and precision oncology.

D. Ferguson

N. Kitsera, Sviatoslav Yu. Karp, O. Tril et al.

Aim. To analyze thyroid cancer cases among individuals over 85 years old in the Lviv region (Ukraine) during 1991–2024. Materials and methods. Our retrospective study analyzed thyroid cancer cases among 22 patients aged 85+ living in urban and rural areas of the Lviv region (Ukraine) within 34 years based on the Cancer Registry of Lviv Oncology Regional Treatment and Diagnostic Center. Results. As of January 1, 2022, the population of the Lviv region was 2.478 million, including 37,757 individuals aged over 85. The database registered 6,499 long-lived patients with cancer and 22 patients (19 women and three men) with thyroid cancer aged 85+ (median age 87.5 ± 2.3 years). The male-to-female ratio was 1 to 6.3. We analyzed demographics, cancer stage, treatment approaches, and survival outcomes. All cases were diagnosed by ultrasound because biopsy was considered too risky for the elderly due to the high risk of life-threatening complications. Three women had a history of multiple myeloma, malignant neoplasm of the cervix uteri, and breast cancer. Thyroid cancer developed from 13 to 33 years after the women were diagnosed with the first tumor. Urban residents over 85 were more frequently diagnosed with thyroid cancer than rural residents (p = 0.045), likely due to better diagnostic access in cities. Survival was generally poor (median 3 months), with men (p = 0.029) showing better outcomes than women. Untreated patients sometimes exhibited unexpectedly longer survival, possibly reflecting biological or care-related differences. Conclusions. This study highlights the increasing diagnosis of thyroid cancer in the elderly over 85, particularly among women, with a very short survival time averaging 2-3 months. This research underscores the importance of balancing treatment decisions with quality of life for elderly patients and emphasizes the need for targeted approaches to manage thyroid cancer in the aging population.

Sabrina Testa, Akiko Shimamura, J. Kamihara et al.

Germline genetic testing is increasingly recommended at the time of a pediatric cancer diagnosis for children with solid tumors, but not routinely performed for patients with hematologic malignancies (HM). Studies regarding incidence of hereditary hematologic malignancies (HHM) are limited with variable rates reported in pediatric and adult cohorts (4-39%). In this retrospective study, we evaluated the prevalence of HHM in children and young adults with newly diagnosed or relapsed HM and the impact of these diagnoses on treatment decisions. Methods Patients with newly diagnosed or relapsed HM treated between 1/1/2020 and 12/31/2024 in the Pediatric Oncology Clinic at Dana-Farber Cancer Institute were eligible. We performed focused retrospective chart review on all patients in our study cohort with additional chart abstraction done for those patients identified with a HM who received genetic counseling (GC). All germline genetic testing was done using cell sources suitable for accurate detection of germline variants. Germline testing primarily consisted of multi-gene panels that screened >200 genes with known association to cancer predisposition and bone marrow failure. Results were obtained from a CLIA certified lab and variants were classified according to American College of Medical Genetics variant classification guidelines. Results 571 patients with a HM were included in our study cohort. 207/571 patients (36%) were referred for genetic counseling (GC). Of those seen for GC, 127 had a lymphoid neoplasm (acute lymphoblastic leukemia 48%, Hodgkin lymphoma 6%, non-Hodgkin lymphoma 4%, lymphoblastic lymphoma 3%) while 80 had a myeloid neoplasm (acute myeloid leukemia (AML), 32%, myelodysplastic syndrome 5%, myeloproliferative neoplasms 2%). The mean age of the GC-evaluated cohort at initial diagnosis of their HM was 9.1 years (0.2-28.4) with male predominance (62%). All 207 patients seen for GC were offered germline testing, and 141 patients (68%) consented. A pathogenic or likely pathogenic (P/LP) variant was identified in 67/141 (48%) patients. Specifically, 16 patients (16/141, 11%) of the tested cohort had a P/LP variant in a gene associated with a HHM and 11 patients (11/141, 8%) had a P/LP variant in a gene associated with solid tumor risks. One patient harbored two germline variants: one with HHM risk and the other with solid tumor risk. The remaining 41 patients (41/141, 29%) had a P/LP variant associated with carrier status of an autosomal recessive syndrome or risk for non-cancer phenotypes only. An additional 7 patients had a variant of uncertain significance (VUS) in a gene associated with HHM that was highly consistent with their phenotype and met at least one additional suggestive feature: functional evidence of pathogenicity, rarity in population databases, or familial segregation. In summary, 33 patients (33/141, 23%) had a P/LP variant or highly suspicious VUS in a cancer risk gene. Of that cohort, 54% (18/33) presented with myeloid disease while 45% (15/33) had a lymphoid malignancy. The P/LP variants associated with HHM included 3 patients with GATA2, two patients each with RUNX1, DDX41, POT1, and MPO, and one patient each with CBL, TP53, PAX5, CDKN2A and constitutional mismatch repair deficiency (PMS2 biallelic). For the 7 patients with highly suspicious VUS, the genes involved included ETV6, GATA2, LCP1, CEBPA, GATA1, TP53, and PIK3CD. AML treatment was upstaged to include hematopoietic stem cell transplantation in 2 patients due to their germline results. For all other patients, the germline results did not impact therapy but did lead to subsequent cancer surveillance and other practice changes, including cascade testing recommendations for family members, where applicable. ConclusionPrevalence of germline predisposition to pediatric HM remains unclear. Acknowledging the referral bias of this cohort, our findings show a significant rate (23%) of pediatric HM patients with a HHM, cancer predisposition syndrome, or VUS highly suggestive of such risk. Our data supports universal germline testing at time of HM diagnosis. In doing so, we will more accurately define the prevalence of HHM and determine if HHMs confer higher risk of relapse and adverse treatment effects in specific disease subsets.

A. A. Lykova, L. Khidirova, N. Sulaimanov

Results. This analytical review provides a comprehensive assessment of current Russian and international scientific literature focused on the problem of coronary artery disease progression in cancer patients. The literature search was conducted in authoritative domestic and international databases, including PubMed, Scopus, Elsevier, Cochrane Library, Clinical Evidence, Best Evidence, and RSCI, ensuring the representativeness and reliability of the data presented. The relevance of this issue is underscored by a significant increase in the frequency of cardiovascular complications in patients with malignant neoplasms, which is directly linked to both the direct effects of anticancer therapy and the indirect influence of the cancer itself. The review details the key pathogenetic mechanisms contributing to the development and exacerbation of coronary artery disease: Direct cardiotoxicity of anticancer drugs: Particular attention is paid to anthracyclines, which induce oxidative stress and cardiomyocyte apoptosis, leading to myocardial dysfunction. VEGF inhibitors are associated with the development of arterial hypertension and thromboembolic complications, as well as direct damage to the endothelium of coronary arterioles, impairing vasodilatory reserve. HER2-targeted drugs, in turn, can block crucial pathways for cardiomyocyte survival and repair. Systemic effects of the malignant process: Tumor progression is accompanied by chronic systemic inflammation, the release of pro-inflammatory cytokines, and a prothrombotic state, which accelerates atherothrombosis and endothelial dysfunction. Furthermore, the work analyzes epidemiological data on the frequency of coronary artery disease progression and identifies key risk factors in oncology patients, including comorbid conditions (e.g., hypertension, diabetes), cumulative doses of chemotherapeutic agents, the type of targeted therapy received, and the baseline state of the cardiovascular system. Conclusion. Thus, the conducted analysis confirms that the problem of coronary artery disease progression in cancer patients requires a multidisciplinary approach (onco-cardiology) and the development of strategies for active monitoring, early diagnosis of microvascular dysfunction, and cardioprotection at all stages of anticancer treatment.