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

Cesar Felipe Martínez Cisneros, Jesús Ulises Quiroz Bautista, Claudia Anahí Guzmán Solano et al.

The integration of Large Language Models (LLMs) into biomedical research offers new opportunities for domainspecific reasoning and knowledge representation. However, their performance depends heavily on the semantic quality of training data. In oncology, where precision and interpretability are vital, scalable methods for constructing structured knowledge bases are essential for effective fine-tuning. This study presents a pipeline for developing a lung cancer knowledge base using Open Information Extraction (OpenIE). The process includes: (1) identifying medical concepts with the MeSH thesaurus; (2) filtering open-access PubMed literature with permissive licenses (CC0); (3) extracting (subject, relation, object) triplets using OpenIE method; and (4) enriching triplet sets with Named Entity Recognition (NER) to ensure biomedical relevance. The resulting triplet sets provide a domain-specific, large-scale, and noise-aware resource for fine-tuning LLMs. We evaluated T5 models finetuned on this dataset through Supervised Semantic Fine-Tuning. Comparative assessments with ROUGE and BERTScore show significantly improved performance and semantic coherence, demonstrating the potential of OpenIE-derived resources as scalable, low-cost solutions for enhancing biomedical NLP.

Xiangrui Li, Li Deng, Hailun Xie et al.

Abstract Background Systemic inflammation and nutritional status are key factors affecting the prognosis of patients with cancer cachexia. This study aims to evaluate the prognostic value of a new nutritional and inflammatory index, Prognostic Nutritional CRP Ratio (NCR), in patients with cancer cachexia. Methods This prospective multicenter study analyzed 3,447 patients diagnosed with cancer cachexia across over 40 clinical centers in China, from June 2012 to December 2023. The NCR was calculated as BMI × albumin / CRP. The Cox proportional hazards regression model was utilized to analyze hazard ratios (HRs) for all-cause mortality. The relationship between NCR and all-cause mortality was assessed using restricted cubic spline modeling. The optimal cutoff value for NCR was determined through maximally selected rank statistics. Results Among the 3,447 individuals diagnosed with cancer cachexia in our study, 2,296 (66.6%) were men, and 1,151 (33.4%) were women. With a median follow-up duration of 45.33 months, the mean age of the participants was 63.8 ± 11.4 years. We observed that lower NCR levels were prevalent among cachexia patients across a spectrum of cancer types, including lung, colorectal, liver, esophageal, breast, ovarian, and cervical cancers. We observed that lower NCR levels were prevalent among cachexia patients across a spectrum of cancer types, including lung, colorectal, liver, esophageal, breast, ovarian, and cervical cancers. This correlation held true across diverse patient subgroups, delineated by gender, age, smoking status, BMI, TNM stage, and tumor types, underscoring the broad applicability of NCR as a prognostic marker. Moreover, our findings highlighted that cancer cachexia patients with higher NCR levels experienced a significantly improved quality of life. Conclusion The NCR, indicative of nutritional status and inflammation, is associated with reduced all-cause mortality and could be a valuable prognostic marker for patients with cancer cachexia.

Yuenan Wang, Wanwei Jian, Zhidong Yuan et al.

Abstract Background We hypothesize generative adversarial networks (GAN) combined with self‐attention (SA) and aggregated residual transformations (ResNeXt) perform better than conventional deep learning models in differentiating hepatocellular carcinoma (HCC). Attention modules facilitate concentrating on salient features and suppressing redundancies, while residual transformations can reuse relevant features. Therefore, we aim to propose a GAN+SA+ResNeXt deep learning model to improve HCC prediction accuracy. Methods 228 multiphase CTs from 57 patients were retrospectively analyzed with local IRB's approval, where 30 patients were pathologically confirmed with HCC and the rest 27 were non‐HCC. Pre‐processing of automatic liver segmentation and Hounsfield unit (HU) normalization was performed, followed by deep learning training with five‐fold cross validation in a conventional 3D GAN, a 3D GAN+A, and a 3D GAN+A+ ResNeXt, respectively (training: testing ∼ 4:1). Area under receiver operating characteristics curves (AUROC), accuracy, sensitivity and specificity of HCC prediction were evaluated. Results Results showed the proposed method had larger AUROC (95%), better accuracy (91%) and sensitivity (93%) with acceptable specificity (88%) and prediction time (0.04s). Deep GAN with attentions and residual transformations for HCC diagnosis using multiphase CT is feasible and favorable with improved accuracy and efficiency, which harbors clinical potentials in differentiating HCC from other benign or malignant liver lesions.

Zinnat Ara Moni, Zahid Hasan, Md. Shaheen Alam et al.

ABSTRACT Background Cancer is the second leading cause of human mortality worldwide. Extracellular vesicles (EVs) from liquid biopsy samples are used in early cancer detection, characterization, and surveillance. Exosomes are a subset of EVs produced by all cells and present in all body fluids. They play an important role in the development of cancer because they are active transporters capable of carrying the contents of any type of cell. The objective of this review was to provide a brief overview of the clinical implication of exosomes or exosomal components in cancer diagnosis and prognosis. Methods An extensive review of the current literature of exosomes and their components in cancer diagnosis and prognosis were carried out in the current study. Results Tumor cells release exosomes that contribute to the formation of the pre‐metastatic microenvironment, angiogenesis, invasion, and treatment resistance. On the contrary, tumor cells release more exosomes than normal cells, and these tumor‐specific exosomes can carry the genomic and proteomic signature contents of the tumor cells, which can act as tools for the diagnosis and prognosis of patients with cancers. Conclusion This information may help clinicians to improve the management of cancer patients in clinical settings in the future.

Д.Ф. Нарзиева, С. С. Давлатов

Введение. Рак молочной железы (РМЖ) представляет собой значительную причину смертности от онкологических заболеваний среди женщин по всему миру. Опухоле-инфильтрирующие лимфоциты были продемонстрированы как прогностический и предсказательный маркер отклика на лечение у пациентов с тройным негативным раком молочной железы и HER2-положительным раком молочной железы. В многочисленных неоадъювантных клинических испытаниях ОИЛ были идентифицированы как предиктор полного патологического ответа после химиотерапии. Цель. Изучить взаимосвязь между статусами и инфильтрацией лимфоцитов CD4 и молекулярно-биологическими подтипами опухоли рака молочной железы и проанализировать влияние иммунного микроокружения опухоли и его связь с клиническими исходами. Материалы и методы. Исследование проводилось с участием 102 пациенток с диагнозом «рак молочной железы», которые находились на диспансерном учете и проходили лечение в Ташкентском городском филиале Республиканского специализированного научно-практического медицинского центра онкологии и радиологии в период с 2018 по 2021 г. Пациенты были разделены на 2 прогностические группы на основании клинических исходов. Группа I характеризуется неблагоприятным исходом, включающим развитие метастазов, рецидивов и смертельных исходов в течение 5 лет после лечения. В эту группу вошли 57 пациентов, что составляет 55,9% от общей выборки. Группа II включает пациентов с благоприятным исходом, которые демонстрировали отсутствие метастазов, рецидивов и смертельных исходов в течение 5 лет после лечения. В эту группу вошли 45 пациентов, что составляет 44,1% от общей выборки. Результаты. Наши результаты подтверждают, что иммунный профиль опухоли, включающий статусы и типы инфильтрации CD4-лимфоцитами, может служить важным маркером для прогнозирования исходов заболевания. Активный иммунный ответ, характеризуемый положительными статусами и инфильтрацией CD4-лимфоцитами, ассоциируется с благоприятным исходом, тогда как низкий уровень положительных статусов и инфильтрации CD4-лимфоцитами – с неблагоприятным исходом. Выводы. Результаты открывают новые перспективы для дальнейших исследований в области онкологии и могут помочь улучшить результаты лечения пациентов со злокачественными новообразованиями. Introduction. Breast cancer (BC) is a significant cause of cancer-related deaths among women worldwide. Tumor-filtering lymphocytes have been demonstrated as a prognostic and predictive marker of treatment response in patients with triple negative breast cancer and HER2-positive breast cancer. In numerous neoadjuvant clinical trials, TILs has been identified as a predictor of a complete pathological response after chemotherapy. Purpose. To study the relationship between CD4 lymphocyte statuses and infiltration and the molecular biological subtypes of breast cancer tumors and to analyze the effect of the tumor’s immune microenvironment and its relationship to clinical outcomes. Materials and methods. The study was conducted with the participation of 102 patients diagnosed with breast cancer who were registered at a dispensary and were treated at the Tashkent city branch of the Republican Specialized Scientific and Practical Medical Center for Oncology and Radiology and in the period from 2018 to 2021. The patients were divided into two prognostic groups based on clinical outcomes. Group I is characterized by an unfavorable outcome, including the development of metastases, relapses and deaths within 5 years after treatment. This group included 57 patients, which is 55.9% of the total sample. Group II includes patients with a favorable outcome who demonstrated the absence of metastases, relapses and deaths for 5 years after treatment. This group included 45 patients, which is 44.1% of the total sample. Results. Our results confirm that the immune profile of a tumor, including the statuses and types of CD4 lymphocyte infiltration, can serve as an important marker for predicting disease outcomes. An active immune response characterized by positive statuses and infiltration by CD4 lymphocytes is associated with a favorable outcome, while a low level of positive statuses by CD4 lymphocytes is associated with an unfavorable outcome. Conclusions. The results open up new perspectives for further research in the field of oncology and may help improve treatment outcomes for patients with malignant neoplasms.

Brittany File, Anjali Hari

Fernando Guerra, Adriana Rocher, Cintia Gimenez et al.

Wnt/β-catenin and EGFR/PI3K/AKT are signaling pathways frequently activated in cancer. The first is related to epithelial-mesenchymal transition (EMT) phenomena and the second to the processes of cell proliferation, invasion, and mobility. Cervical adenocarcinoma and its possible precursor, adenocarcinoma in situ (AIS), are aggressive tumors that are difficult to diagnose early. For these reasons, the activity of the aforementioned pathways was investigated in relation to the mechanisms of invasion of cervical adenocarcinomas. High-risk human papillomavirus-related adenocarcinomas (HPVA) were selected from surgical materials and biopsies from the archive of the Hospital de Clínicas de C.A.B.A., Argentina. To select HPVA, HPV typing was performed using polymerase chain reaction. The two signaling pathways were analyzed by immunohistochemistry, using antibodies against vimentin, alpha-smooth muscle actin (αSMA), β-catenin, EGFR, PI3K, and AKT. EMT markers (αSMA and vimentin) were negative in adenocarcinomas; vimentin was expressed in 13/55 of the AIS. Components of the ERGR/PI3K/AKT pathway were expressed in adenocarcinomas (EGFR: 70%, PI3K 47%, AKT 67%) and AIS (EGFR: 33%, PI3K 51%, AKT 54%). In total, 47% of adenocarcinomas and 32% of AIS showed full activation of the EGFR/PI3K/AKT pathway. The action of HR-HPVE6 destabilizing intercellular junctions and the activation of AKT would explain the mobility and invasiveness of cervical adenocarcinoma cells, independently of the EMT phenomenon.

Gopinath Sadhu, D C Dalal

Micro-environmental acidity is a common feature of the tumor. One of the causes behind tumor acidity is lactate production by hypoxic cells of the tumor. Hypoxia is a direct result of the establishment of oxygen gradients. It is commonly observed in the tumor in an in-vitro experimental setup and also in-vivo situation. Here, we propose a mathematical model to analyses the production of lactate by hypoxic cells, and it is used as an alternative fuel by normoxic cells in tumor tissue in-vitro and in-vivo conditions. In this article, we study the effects of unequal oxygen concentration at the tumor boundaries on lactate status in the tumor. The effects of presence of the necrotic core in the tumor on the lactate concentration profile is examined. The results have good agreement with experimental data and align with the theoretical findings of previous studies. The analytical results show that lactate levels are elevated in an in-vivo tumor compared to that in an in-vitro tumor. Also, during the onset of necrotic core formation, the effects of necrotic core on lactate levels are noticed. Knowledge of the lactate status in a patient's tumor may be helpful in choosing the rightful and precious medicines for cancer treatment.

Shariq Mohammed, Maria Masotti, Nathaniel Osher et al.

Recent advances in types and extent of medical imaging technologies has led to proliferation of multimodal quantitative imaging data in cancer. Quantitative medical imaging data refer to numerical representations derived from medical imaging technologies, such as radiology and pathology imaging, that can be used to assess and quantify characteristics of diseases, especially cancer. The use of such data in both clinical and research setting enables precise quantifications and analyses of tumor characteristics that can facilitate objective evaluation of disease progression, response to therapy, and prognosis. The scale and size of these imaging biomarkers is vast and presents several analytical and computational challenges that range from high-dimensionality to complex structural correlation patterns. In this review article, we summarize some state-of-the-art statistical methods developed for quantitative medical imaging data ranging from topological, functional and shape data analyses to spatial process models. We delve into common imaging biomarkers with a focus on radiology and pathology imaging in cancer, address the analytical questions and challenges they present, and highlight the innovative statistical and machine learning models that have been developed to answer relevant scientific and clinical questions. We also outline some emerging and open problems in this area for future explorations.

Алмаз Бейшембаев, Б М Ибраев, Н.К. Монолов et al.

В данной статье рассматриваются вопросы эпидемио­ло­гии, классификации и лечения рака предстательной железы – одного из самых распространенных злокачественных но­во­об­ра­зований в мужской популяции. Рак предстательной железы – одно из самых грозных заболеваний в онкоурологии, встре­чает­ся в основном у мужчин среднего и пожилого воз­раста. Внедрение массового скринига в уровне отдельно взято­го го­су­дарства, может привести к значительному снижению запу­щен­ных стадий заболеваний. Приводятся данные за последние десятилетия по росту заболеваемости, анализи­руются гене­ти­ческая предрасположенность и отличия в раз­ных странах. Подробно описана классификация рака пред­ста­тельной же­ле­зы по системе TNM, особое внимание уделено шкале Глисона. Описаны современные методы диагностики, включая ПЭТ/КТ, биохимические методы исследования, в том числе онкомарке­ры и гормоны. Бул макалада эркектердин арасында кеңири та­ралган за­лал­дуу шишиктердин бири болгон эркектин урук безинин рагы­нын эпидемиологиясы, классификациясы жана дарылоосу ка­ра­лат. Урук безинин рагы урологиялык онкология­дагы эң кор­ку­нучтуу оорулардын бири болуп саналат, негизи­нен орто жаш­тагы жана улгайган эркектерде кездешет. Бир­диктүү мамлекеттин деңгээлинде массалык скринингди кирги­зүү оору­лар­дын өнүккөн стадияларын олуттуу кыскартууга алып ке­ли­ши мүмкүн. Оорунун көбөйүшү боюнча акыркы он жыл­дык­тар­дагы маалыматтар берилген, генетикалык ык­туулук жа­на ар кайсы өлкөлөрдө айырмачылыктар талданган. TNM сис­те­масына ылайык простата рагынын классификация­сы Гли­сон баллына өзгөчө көңүл буруу менен деталдуу сүрөт­төлгөн. Заманбап диагностикалык ыкмалар, анын ичинде ПЭТ/КТ, био­­химиялык изилдөө ыкмалары, анын ичинде шишик мар­кер­ле­ри жана гормондор сүрөттөлгөн. This article discusses some questions in epidemiology, classi­fi­cation and treatment of prostate cancer, one of the most common malignant neoplasms in the male population. Prostate cancer is one of the most dangerous diseases in urological oncology, occurring mainly in middle-aged and elderly men. The introduction of mass screening at the level of a single state can lead to a significant re­duc­tion in advanced stages of diseases. The data for the last deca­des on the increase in the incidence are given, the genetic predis­po­si­tion and differences in different countries are analyzed. The clas­si­fication of prostate cancer according to the TNM system is de­scribed in detail, special attention is paid to the Gleason scale. Mo­dern diagnostic methods are described, including PET/CT, bioche­mi­cal research methods, including tumor markers and hormones.

Mohammedazim Bagban, Khanishka Sharma, Sana Saifi et al.

MicroRNAs (miRNAs) are single-stranded RNA molecules of 18-27 nucleotides that regulate gene expression after transcription. The great stability of detectable miRNAs in tissue, blood, and other body fluids provides a rich supply of miRNA-based biomarkers in human malignancies. miRNA dysregulation has been linked to cancer often, especially since they are commonly involved in mechanisms such as transcriptional control, epigenetic regulation and genomic instabilities. Despite the fact that a growing number of potential miRNA biomarkers have been identified, the translation of miRNA-based biomarkers from bench to bedside still faces a number of obstacles. miR-96 is encoded by conserved & paralogous miR-183/-96/-182 cluster that is widely studied in cancer. miR-96 is one of the most important miRNAs that is fast emerging as a novel biomarker with great potential as a diagnostic and therapeutic target in all types of cancers of the body. miR-96 plays a direct or indirect role as an oncogene in various cancers. miR-96 was believed to suppress Epithelial-mesenchymal transition, Osteosarcoma, Gastric adenocarcinoma and Bladder cancer. The miR-96 is also considered to have the function to promote malignancy as well as chemoresistance in Breast cancer. We present the most recent research findings on miR-96's clinicopathological relevance, development, and progress in this review, highlighting its oncogenic and tumor suppressive capabilities and an intermediate role in progressing the development of cancer, being a part of some cancer promoting pathways.

Mengjie Chen, Xinbin Pan, Xinbin Pan et al.

ObjectivesTo study the risk factors for the onset of secondary primary malignancies (SPM) and the latency between SPM and cervical cancer after radiotherapy.MethodsWe selected patients with cervical cancer who underwent radiotherapy between 2000 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. And the data of patients with cervical cancer who underwent radiotherapy in Guangxi Medical University Cancer Hospital during January 1,1997 to December 31,2016 were collected and analyzed. The factors associated with SPM onset and latency were then estimated by nomograms based on logistic regression and a complete risk model. Dynamic risk plots were performed by Poisson regression.ResultsA total of 32,313 cases of cervical cancer who underwent radiotherapy were downloaded from the SEER database; of these, 19,439 cases had a complete dataset and were included in the final analysis. In total, 561 cases suffered from SPM; the remaining 18,878 did not. And a total of 1486 cases of cervical cancer who underwent radiotherapy from Guangxi Medical University Cancer Hospital were analyzed, 27 cases caught SPM and the rest of 1459 cases did not. Patients with SPM were older than those without SPM(p=0.000); significant associations were also identified between SPM and white race(p=0.000), localized stage (p=0.000), squamous carcinoma (SCC)(p=0.003), surgery(p=0.000), and combination radiotherapy (p=0.026). A logistic regression nomogram showed that older age (HR:1.015, 95%CI:1.009-1.021, p=0.000), localized stage (HR:4.056, 95%CI: 2.625-6.269, p=0.000) and regional stage (HR: 3.181, 95%CI:2.094-4.834, p=0.000), white (HR: 1.722, 95%CI:1.145-2.590, p=0.000) and black race (HR: 1.889, 95%CI:1.327-2.689, p=0.000), and the receipt of surgery (HR: 1.381, 95%CI:1.151-1.657, p=0.000) were all independent risk factors for the onset of SPM. The largest proportion of cases involved SPM in the female reproductive system. A dynamic risk plot showed that age, race, stage, and surgery had impacts on the latency of SPM onset. A competing risk regression analysis nomogram showed that age (HR: 1.564, 95%CI: 1.272-1.920, p=0.000), surgery (HR: 1.415, 95%CI: 1.140-1.760, p=0.002), localized stage (HR: 8.035, 95%CI: 4.502-14.340, p=0.000) and regional stage (HR: 4.904, 95%CI: 2.790-8.620, p=0.000), and black race (HR: 1.786, 95%CI: 1.161-2.750, p=0.008) all had significant impacts on the cumulative incidence and latency of SPM.ConclusionsAdvanced age, the receipt of surgery, earlier stages, and white and black race were identified as risk factors for SPM onset and influenced latency in patients with cervical cancer after radiotherapy.

TAN Ruoming, QU Hongping

The current situation of multidrug-resistant bacteria infection in surgical patients is becoming increasingly severe. Effective prevention of cross transmission of multidrug-resistant bacteria and common site infections in ICU patients is the key step. In response to the key issues in the prevention and control of multidrug-resistant bacteria infection, a comprehensive strategy is implemented. Core measures such as early recognition, preemptive isolation, active screening, and graded prevention and control are taken for patients, and targeted preventive measures for common infection sites are combined to form a detection and control system of multidrug-resistant bacteria for ICU patients. By moving forward and extrapolating to the general ward, the prevention and control system effectively reduced the incidence of multidrug-resistant bacteria colonization/infection in surgical patients.

Veronica Jones, Natalie Johnson

Olga Fourkioti, Matt De Vries, Chen Jin et al.

The visual examination of tissue biopsy sections is fundamental for cancer diagnosis, with pathologists analyzing sections at multiple magnifications to discern tumor cells and their subtypes. However, existing attention-based multiple instance learning (MIL) models used for analyzing Whole Slide Images (WSIs) in cancer diagnostics often overlook the contextual information of tumor and neighboring tiles, leading to misclassifications. To address this, we propose the Context-Aware Multiple Instance Learning (CAMIL) architecture. CAMIL incorporates neighbor-constrained attention to consider dependencies among tiles within a WSI and integrates contextual constraints as prior knowledge into the MIL model. We evaluated CAMIL on subtyping non-small cell lung cancer (TCGA-NSCLC) and detecting lymph node (CAMELYON16 and CAMELYON17) metastasis, achieving test AUCs of 97.5\%, 95.9\%, and 88.1\%, respectively, outperforming other state-of-the-art methods. Additionally, CAMIL enhances model interpretability by identifying regions of high diagnostic value.

Ivan Ranđelović, Kinga Nyíri, Gergely Koppány et al.

Mutated genes may lead to cancer development in numerous tissues. While more than 600 cancer-causing genes are known today, some of the most widespread mutations are connected to the RAS gene: RAS mutations are found in approximately 25% of all human tumors. Specifically, KRAS mutations are involved in the three most lethal cancers in U.S.: pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and lung adenocarcinoma. These cancers are among the most difficult to treat, and they are frequently excluded from chemotherapeutic attacks as hopeless cases. The mutated KRAS proteins have specific 3-dimensional conformations, which perturb functional interaction with the GAP protein on the GAP:RAS complex surface leading to a signaling cascade and uncontrolled cell growth. Here we describe a gluing docking method for finding small molecules that bind to both the GAP and the mutated KRAS molecules. These small molecules glue together the GAP and the mutated KRAS molecules and may serve as new cancer drugs for the most lethal, most difficult-to-treat carcinomas. As a proof of concept, we identify two new, drug-like small molecules with the new method: these compounds specifically inhibit the growth of PANC-1 cell line with KRAS mutation G12D in vitro and in vivo. Importantly, the two new compounds show significantly lower IC50 and higher specificity against the G12D KRAS mutant as compared to the recently described MRTX-1133 inhibitor against the G12D KRAS mutant.

Tongxue Zhou, Alexandra Noeuveglise, Romain Modzelewski et al.

Brain tumor is one of the leading causes of cancer death. The high-grade brain tumors are easier to recurrent even after standard treatment. Therefore, developing a method to predict brain tumor recurrence location plays an important role in the treatment planning and it can potentially prolong patient's survival time. There is still little work to deal with this issue. In this paper, we present a deep learning-based brain tumor recurrence location prediction network. Since the dataset is usually small, we propose to use transfer learning to improve the prediction. We first train a multi-modal brain tumor segmentation network on the public dataset BraTS 2021. Then, the pre-trained encoder is transferred to our private dataset for extracting the rich semantic features. Following that, a multi-scale multi-channel feature fusion model and a nonlinear correlation learning module are developed to learn the effective features. The correlation between multi-channel features is modeled by a nonlinear equation. To measure the similarity between the distributions of original features of one modality and the estimated correlated features of another modality, we propose to use Kullback-Leibler divergence. Based on this divergence, a correlation loss function is designed to maximize the similarity between the two feature distributions. Finally, two decoders are constructed to jointly segment the present brain tumor and predict its future tumor recurrence location. To the best of our knowledge, this is the first work that can segment the present tumor and at the same time predict future tumor recurrence location, making the treatment planning more efficient and precise. The experimental results demonstrated the effectiveness of our proposed method to predict the brain tumor recurrence location from the limited dataset.

James Hogg, Jessica Cameron, Susanna Cramb et al.

Cancer is a significant health issue globally and it is well known that cancer risk varies geographically. However in many countries there are no small area level data on cancer risk factors with high resolution and complete reach, which hinders the development of targeted prevention strategies. Using Australia as a case study, the 2017-2018 National Health Survey was used to generate prevalence estimates for 2221 small areas across Australia for eight cancer risk factor measures covering smoking, alcohol, physical activity, diet and weight. Utilising a recently developed Bayesian two-stage small area estimation methodology, the model incorporated survey-only covariates, spatial smoothing and hierarchical modelling techniques, along with a vast array of small area level auxiliary data, including census, remoteness, and socioeconomic data. The models borrowed strength from previously published cancer risk estimates provided by the Social Health Atlases of Australia. Estimates were internally and externally validated. We illustrated that in 2017-18 health behaviours across Australia exhibited more spatial disparities than previously realised by improving the reach and resolution of formerly published cancer risk factors. The derived estimates reveal higher prevalence of unhealthy behaviours in more remote areas, and areas of lower socioeconomic status; a trend that aligns well with previous work. Our study addresses the gaps in small area level cancer risk factor estimates in Australia. The new estimates provide improved spatial resolution and reach and will enable more targeted cancer prevention strategies at the small area level, supporting policy makers, researchers, and the general public in understanding the spatial distribution of cancer risk factors in Australia. To help disseminate the results of this work, they will be made available in the Australian Cancer Atlas 2.0.

A. Mafficini, M. Simbolo, T. Shibata et al.

Pancreatic intraductal tubulopapillary neoplasm (ITPN) is a recently recognized intraductal neoplasm. This study aimed to clarify the clinicopathologic and molecular features of this entity, based on a multi-institutional cohort of 16 pancreatic ITPNs and associated adenocarcinomas. The genomic profiles were analyzed using histology-driven multi-regional sequencing to provide insight on tumor heterogeneity and evolution. Furthermore, an exploratory transcriptomic characterization was performed on eight invasive adenocarcinomas. The clinicopathologic parameters and molecular alterations were further analyzed based on survival indices. The main findings were as follows: 1) the concomitant adenocarcinomas, present in 75% of cases, were always molecularly associated with the intraductal components. These data definitively establish ITPN as origin of invasive pancreatic adenocarcinoma; 2) alterations restricted to infiltrative components included mutations in chromatin remodeling genes ARID2, ASXL1, and PBRM1, and ERBB2-P3H4 fusion; 3) pancreatic ITPN can arise in the context of genetic syndromes, such as BRCA-germline and Peutz–Jeghers syndrome; 4) mutational profile: mutations in the classical PDAC drivers are present, but less frequently, in pancreatic ITPN; 5) novel genomic alterations were observed, including amplification of the Cyclin and NOTCH family genes and ERBB2, fusions involving RET and ERBB2, and RB1 disruptive variation; 6) chromosomal alterations: the most common was 1q gain (75% of cases); 7) by transcriptome analysis, ITPN-associated adenocarcinomas clustered into three subtypes that correlate with the activation of signaling mechanism pathways and tumor microenvironment, displaying squamous features in their majority; and 8) TP53 mutational status is a marker for adverse prognosis. ITPNs are precursor lesions of pancreatic cancer with a high malignant transformation risk. A personalized approach for patients with ITPN should recognize that such neoplasms could arise in the context of genetic syndromes. BRCA alterations, ERBB2 and RET fusions, and ERBB2 amplification are novel targets in precision oncology. The TP53 mutation status can be used as a prognostic biomarker.

Daniel Antunes Moreno, Luciane Sussuchi da Silva, Isabella Gomes et al.

Introduction: Glioblastoma (GBM), isocitrate dehydrogenase ( IDH ) wild-type ( IDH wt ), and grade 4 astrocytomas, IDH mutant ( IDH mut ), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities. Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH wt GBM and IDH mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival. Methods: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator). Results: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH wt GBM compared to IDH mut tumors. Regarding IDH wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1). Conclusion: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients’ prognosis.