Cancers最新文献

{"title":"Cognitive Stimulation Interventions for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients: A Systematic Review and Meta-Analysis.","authors":"Macarena C Cáceres, Miguel Ángel Martín-Parrilla, Jesús Montanero-Fernández, Aitana Santos-Fernández, Casimiro Fermín López-Jurado, Noelia Durán-Gómez","doi":"10.3390/cancers17183001","DOIUrl":"10.3390/cancers17183001","url":null,"abstract":"<p><p><b>Background</b>: A considerable proportion of breast cancer (BC) patients experience chemotherapy-related cognitive impairment (CRCI) and other symptoms even after the completion of treatment. The persistence of CRCI throughout the oncological process highlights the need for routine assessment of its severity, impact on quality of life, and the effectiveness of interventions aimed at addressing it. <b>Objectives</b>: To analyse the effectiveness of cognitive stimulation interventions on CRCI in BC patients and to identify the characteristics of such interventions, including the most appropriate timing for their implementation, the most suitable techniques, and their duration. <b>Methodology</b>: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Randomized controlled trials published between 1 January 2020 and 31 December 2024 were searched across three electronic databases. Studies involving cognitive stimulation interventions for the management of CRCI in BC patients were included. <b>Results</b>: A total of 12 eligible studies were identified for the systematic review and 10 for the meta-analysis. The review revealed a wide range of cognitive stimulation interventions, differing in techniques, duration, format, and timing of implementation. Group-based therapies lasting between 6 and 12 weeks predominated, with cognitive outcomes primarily assessed using the FACT-Cog scale. The meta-analysis demonstrated a moderate positive effect of cognitive stimulation interventions on cognitive functioning in BC patients (d = 0.59), although not statistically significant (<i>p</i> = 0.07), and showed high heterogeneity across studies (I² = 93%). <b>Conclusions</b>: Cognitive stimulation interventions show potential benefits in improving cognitive functioning in BC patients following chemotherapy. However, the high methodological heterogeneity limits the strength of the evidence. Further research is needed to develop standardized and personalized early intervention protocols.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Turning the Tide-Artificial Intelligence in the Evolving Landscape of Liver Cancer.","authors":"Cristiana Grapă, Tudor Mocan, Lavinia Patricia Mocan, Andrei Motofelea, Raluca Stănciulescu, Rareș Crăciun, Andrei Vârciu, Zeno Spârchez, Teodora Mocan","doi":"10.3390/cancers17183003","DOIUrl":"10.3390/cancers17183003","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Liver cancer is an exceedingly heterogeneous malignancy with high mortality rates, and despite extensive research, there have been no significant improvements in treatment outcomes. In the process of navigating the complex landscape of liver cancer, AI has arisen as the \"knight in shining armour\", sparking hope and offering invaluable insight into early detection, diagnosis, staging, treatment selection, and post-treatment surveillance. By integrating imaging, clinical, pathological, and molecular data, AI emerges as a transformative tool that offers unique opportunities to enhance patient care. <b>Methods:</b> A comprehensive literature search of PubMed and Scopus, was conducted using the terms \"artificial intelligence,\" \"machine learning,\" \"deep learning,\" \"radiomics,\" and \"liver cancer.\" Eligible studies included peer-reviewed original research applying AI to detection, diagnosis, prognosis, treatment planning, or surveillance of liver cancer. Key findings are organized along the clinical continuum. <b>Results:</b> Imaging-based AI models for tumor detection were the most advanced, with several achieving diagnostic accuracy above 90% in retrospective studies. Applications for treatment decision-making are emerging, but most remain at proof-of-concept stages. Generally, few of these innovations have progressed to large-scale clinical trials or received regulatory approval, slowing their integration into clinical practice. <b>Conclusions:</b> This narrative review highlights AI's potential to transform liver cancer management and addresses the ethical, regulatory, and logistical barriers to its clinical adoption, serving as a call to action for integrating AI into practice to improve patient outcomes.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Repurposing for Targeting Cancer Stem-like Cells in Glioblastoma.","authors":"Ana Luísa De Sousa-Coelho, Brigita Solaković, Alexandra Diogo Bento, Mónica Teotónio Fernandes","doi":"10.3390/cancers17182999","DOIUrl":"10.3390/cancers17182999","url":null,"abstract":"<p><p>Glioblastoma (GBM) is one of the deadliest types of cancer, characterized by a short life expectancy after diagnosis, mostly related to therapy resistance and recurrence. GBM stem-like cells (GSCs) reside within the tumor and contribute to these features; therefore, finding drugs that specifically target such cells holds promise to halt GBM progression. The primary objective of this work is to comprehensively review and discuss the potential of hard drug repurposing to target GSCs. Several studies evaluating drugs showing anti-GSC activity, originally approved for non-cancer indications, were identified. These mainly included antidiabetics (e.g., Metformin, Phenformin, and Sitagliptin), antihypertensives (e.g., Nicardipine, Doxazosin, and Prazosin), antimicrobials (e.g., Pyrvinium pamoate, Flubendazole, and Clofazimine), and central nervous system-acting drugs (e.g., Chlorpromazine, Fluvoxamine, and Disulfiram). Relevant candidates include those that disrupt GSC metabolism, namely impairing mitochondrial function, such as Metformin, Chlorpromazine, and Pyrvinium pamoate. Multiple signaling pathways may be involved, namely the Wnt, PI3K/AKT, and STAT3 pathways, among others. Also significant were those drugs tested in combination, resulting in increased sensitivity to Temozolomide (TMZ), the standard pharmacological treatment available for GBM. Some repurposed agents, such as Disulfiram and Metformin, have already reached clinical testing, although none have yet been incorporated into clinical practice. Importantly, major translational barriers remain, like limited blood-brain barrier penetration and the lack of robust clinical trials. In conclusion, drug repurposing is an affordable and suitable strategy to target GSCs, impairing cell viability, reducing stemness, and enhancing their sensitivity to TMZ, which has potential that should be further explored to improve patients' clinical outcomes.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumol Targets the VHL/HIF-1α Axis to Suppress Glycolysis-Driven Progression in Colorectal Cancer.","authors":"Gang Wang, Zengyaran Yue, Gang Yin, Lifeng Zhu, Wen Zhou, Ruiqian Sun, Tingting Bi, Lin Zhao, Yong Bian, Decai Tang","doi":"10.3390/cancers17183000","DOIUrl":"10.3390/cancers17183000","url":null,"abstract":"<p><p><b>Background</b>: Hypoxia-induced glycolysis represents a hallmark of colorectal cancer (CRC) progression and contributes significantly to therapeutic resistance. Curcumol, a natural sesquiterpenoid derived from Curcumae Rhizoma, has demonstrated promising anti-tumor properties. However, its impact on metabolic reprogramming under hypoxic conditions remains largely undefined. <b>Objective</b>: The objective of this study was to elucidate the potential of Curcumol in inhibiting glycolytic reprogramming and impede CRC progression via regulation of the VHL/HIF-1α signaling pathway. <b>Methods</b>: CRC cells and orthotopic mouse models were treated with Curcumol under chemically induced hypoxic conditions. Metabolic alterations were evaluated using Seahorse extracellular flux analysis, Western blot analysis, quantitative real-time PCR (qRT-PCR), immunohistochemistry (IHC) and co-immunoprecipitation (Co-IP). Functional validation of glycolysis and epithelial-mesenchymal transition (EMT) phenotypes was conducted through in vitro and in vivo assays. <b>Results</b>: Curcumol inhibited HIF-1α-mediated metabolic reprogramming by upregulating VHL expression, thereby promoting HIF-1α degradation. This effect led to the downregulation of key glycolytic genes (HK2, LDHA, and GLUT1), decreased glycolytic flux, and lactate production, ultimately suppressing CRC cell proliferation and invasion. The anti-tumor efficacy of Curcumol was validated in both in vitro and in vivo models. Moreover, Curcumol effectively reversed the hypoxia-induced epithelial-mesenchymal transition (EMT) phenotype, suggesting that its metabolic regulatory effects may contribute to reduced metastatic potential. <b>Conclusions</b>: Curcumol suppresses glycolysis and CRC progression by activating the VHL/HIF-1α signaling axis. These findings underscore the potential of Curcumol as a natural metabolic regulator capable of reversing tumor metabolic reprogramming, offering a promising therapeutic strategy for CRC treatment.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Derivation of Genetically Defined Murine Hepatoblastoma Cell Lines with Angiogenic Potential.","authors":"Keyao Chen, Ahmet Toksoz, Colin Henchy, Jessica Knapp, Jie Lu, Sarangarajan Ranganathan, Huabo Wang, Edward V Prochownik","doi":"10.3390/cancers17183002","DOIUrl":"10.3390/cancers17183002","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Hepatoblastoma (HB), the most common pediatric liver cancer, often bears mutations in and/or otherwise deregulates the oncogenic transcription factors β-catenin (B), YAP (Y) and NRF2 (N). HB research is hampered by a paucity of established cell lines, particularly those possessing these molecular drivers. All combinations of B, Y and N (BY, BN, YN and BYN) are tumorigenic when overexpressed in murine livers, but it has not been possible to establish cell lines from primary tumors. Recently, we found that concurrent, in vivo Crispr-mediated targeting of the <i>Cdkn2a</i> tumor suppressor locus allows for immortalized cell lines to be efficiently generated. <b>Methods</b>: We derived and characterized five immortalized cell lines from <i>Cdkn2a</i>-targeted BN and YN HBs. <b>Results:</b> Four of the above five cell lines retained their ability to grow as subcutaneous or \"pseudo-metastatic\" pulmonary tumors in the immunocompetent mice from which they originated. Most notably, when maintained under hypoxic conditions for as little as 2 days, BN cells transiently upregulated the expression of numerous endothelial cell (EC)-specific genes and acquired EC-like properties that benefited tumor growth. These lines and those from previously derived BY and BYN HBs also possessed similar sensitivities to four commonly employed chemotherapeutic drugs. <b>Conclusions</b>: The above-described approach is currently the only means to generate HB cell lines with pre-selected and clinically relevant oncogenic drivers. Its generic nature should also allow bespoke HB cell lines with other oncogenic drivers to be readily produced. A collection of such cell lines will be useful for studying tumor cell-to-EC trans-differentiation, interactions with the immune environment and drug sensitivities.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The EBV-Positive Tumor Methylome Is Distinct from EBV-Negative in Diffuse Large B-Cell Lymphoma.","authors":"Ashley K Volaric, Ramiro Barrantes-Reynolds, Karine Sahakyan, Yuri Fedoriw, Seth Frietze","doi":"10.3390/cancers17182994","DOIUrl":"10.3390/cancers17182994","url":null,"abstract":"<p><p><b>Backgrounds</b>: Epstein-Barr virus (EBV) is implicated in the pathogenesis of different B-cell lymphomas and lymphoproliferative disorders, including diffuse large B-cell lymphoma (DLBCL) arising in immunodeficiency settings. Despite its clinical significance, the mechanisms of EBV-mediated lymphomagenesis across different disease subtypes remain poorly understood. Global DNA methylation profiling can provide insight into tumor heterogeneity and disease mechanisms. <b>Methods</b>: To further characterize the underlying biology of EBV(+) DLBCL, we performed a global methylome analysis of a cohort of EBV(+)/(-) DLBCL. Illumina MethylationEPIC array data were generated from a curated set of DLBCL tissue samples (<i>n</i> = 43) from a rural patient population with defined EBV status and immunodeficiency background. Differential methylation analyses were conducted using linear mixed models to identify significant methylation changes associated with EBV status. <b>Results</b>: Principle component analysis (PCA) and probe-level comparisons revealed a distinct, globally hypermethylated DNA methylome in EBV(+) DLBCL compared to EBV(-) cases, and an overall hypomethylated profile in all DLBCL relative to control tissues. We identified a total of 117,334 differentially methylated probes mapping to 1557 cancer-associated genes in EBV(+) versus EBV(-) DLBCL, and 330,872 probes mapping to 4230 cancer-associated genes in all DLBCL versus controls. Pathway enrichment analysis highlighted distinct biological processes in EBV(+) DLBCL, including P53 feedback loops (hypermethylated genes) and MAPK signaling (hypomethylated genes). <b>Conclusions</b>: These findings demonstrate that EBV(+) DLBCL is epigenetically distinct from EBV(-) disease, with alterations that may contribute to clinical heterogeneity and potentially serve as biomarkers for disease classification and therapeutic targeting.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterisation of mAb104 Antibody-Drug Conjugates Targeting a Tumour-Selective HER2 Epitope.","authors":"Sagun Parakh, Nhi Huynh, Laura D Osellame, Diana D Cao, Angela Rigopoulos, Benjamin Gloria, Nancy Yanan Guo, Fiona E Scott, Zhanqi Liu, Hui K Gan, Andrew M Scott","doi":"10.3390/cancers17182995","DOIUrl":"10.3390/cancers17182995","url":null,"abstract":"<p><strong>Background: </strong>The novel anti-HER2 antibody 104 (mAb104) targets a unique tumour-specific epitope, lacks normal tissue binding and can internalise into tumour cells, thus supporting its development into antibody drug conjugates (ADCs).</p><p><strong>Methods: </strong>We now describe the binding properties and preclinical activity of mAb104-ADCs developed through the conjugation of mAb104 via linkers to the anti-microtubule drug maytansoinoid ematansine (DM1-SMCC; DM1), topoisomerase I inhibitor, exatecan derivative (MC-GGFG-DX8951; DX8951) or microtubule disruptor monomethyl auristatin E (MC-vc-PAB-MMAE; MMAE).</p><p><strong>Results: </strong>Mab104-ADCs demonstrate dose-dependent cytotoxicity in vitro. The safety of single-dose mAb104-DX8951 was demonstrated in vivo at doses up to 10 mg/kg. MAb104-ADCs also demonstrated potent and prolonged anti-tumour activity in a range of tumour types with variable HER2 expression. Mab104-DX8951 showed significant responses in trastuzumab-resistant HER2-positive breast cancer, low HER2-expressing cancers, as well as HER2-overexpressing cancers.</p><p><strong>Conclusion: </strong>These findings indicate the potential for tumour-specific targeting of HER2-expressing tumours with mAb104-ADCs.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Occupational Carcinogens and Non-Oncogene Addicted Phenotype in Lung Cancer: Results from a Real-Life Observational Study.","authors":"Enrico Oddone, Luca D'Amato, Roberta Pernetti, Domenico Madeo, Luca Toschi, Sara Farinatti, Giulia Riva, Lucrezia Spina, Luigia Ferrante, Catharina Conde, Laura Deborah Locati, Federico Sottotetti, Franca Barbic","doi":"10.3390/cancers17182997","DOIUrl":"10.3390/cancers17182997","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Lung cancer (LC) remains one of the most lethal malignancies worldwide, with both environmental and occupational exposures contributing to its incidence. While oncogene-addicted tumors-defined by single driver mutations-have garnered attention due to their therapeutic implications, less is known about the mutational landscape of tumors potentially arising from occupational exposure to carcinogens. This real-life observational study aimed to assess whether previous occupational exposure to lung carcinogens correlates with distinct LC phenotypes, particularly non-oncogene-addicted (nOA) profiles. <b>Methods</b>: A total of 199 LC patients were enrolled across two specialized oncology centers in Northern Italy between 2021 and 2023. Each participant underwent detailed occupational history taking and molecular characterization using next-generation sequencing. Patients were stratified into nonexposed (NE), low exposed (LE), and high exposed (HE) to carcinogens for lung based on standardized questionnaires and sector-specific assessments. <b>Results</b>: No significant differences were found in histological subtypes across exposure groups. However, people with adenocarcinoma and high occupational exposure to lung carcinogens were more frequently characterized by a nOA phenotype compared to those with low occupational exposure. Logistic regression models-adjusted for age, sex, and smoking habits-confirmed that HE patients had a significantly higher likelihood of developing nOA tumors (OR = 3.07; 95% CI: 1.16-8.11; <i>p</i> = 0.023). This association persisted after adjusting for smoking habits Exposures occurring 5-10 years before diagnosis seemed to be associated with an increased nOA profile. <b>Conclusions</b>: These findings suggest that high levels of exposure to occupational carcinogens impact LC phenotypes. Indeed, these phenotypes are more complex to treat and show the worst prognosis. Assessing the occupational exposure to lung carcinogens during work may offer prognostic insights and support the request for more adequate compensation for the patients. Further studies are warranted to validate these results and to explain the mechanisms that produce the differences observed in LC phenotypes in people with high exposure to occupational carcinogens.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Real-World Evidence on the Safety and Effectiveness of Lutathera^TM for Treating Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs): Insights from Post-Marketing Surveillance.","authors":"Yong-Il Kim, Hoon Young Suh, Yehrim Kang, Hojin Cho, Seung Hyup Hyun, Yoo Sung Song, Seunggyun Ha, Keon Wook Kang","doi":"10.3390/cancers17182992","DOIUrl":"10.3390/cancers17182992","url":null,"abstract":"<p><p><b>Background/Objectives:</b> This post-marketing surveillance study was conducted to evaluate the safety and effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE in patients with GEP-NETs in real-world practice in South Korea. <b>Methods:</b> From July 2020 to July 2024, a total of 89 patients from 6 institutions diagnosed with GEP-NETs, as outlined in the approved indication for [¹⁷⁷Lu]Lu-DOTA-TATE, were enrolled. Safety was the primary objective, whereas effectiveness was a secondary objective. In this article, findings were analyzed and compared with the NETTER-1 and NETTER-2 trials. <b>Results:</b> Baseline characteristics were comparable to NETTER-1 and NETTER-2 except for the notably high proportion of G2 (77.1%) among participants. Less than half of patients (41.0%) completed four cycles of [¹⁷⁷Lu]Lu-DOTA-TATE treatment, presenting a lower portion of completion rate compared to 75.7% in NETTER-1 and 87.8% in NETTER-2. Among the 83 patients, 60 patients (72.3%, 239 cases) had at least 1 AE, with 6 patients (7.2%, 8 cases) experiencing SAEs. The most common AE was nausea (34.9%, 46 cases), and most AEs were mild in severity (94.6%, 226 cases). Overall, the safety profile in this study presented minimal differences from NETTER-1 and NETTER-2. This study reports 37.7% of ORR which was between 14.7% in NETTER-1 and 43.0% in NETTER-2. <b>Conclusions:</b> This nationwide post-marketing surveillance study complemented the safety and effectiveness of [¹⁷⁷Lu]Lu-DOTA-TATE among Koreans, which was not probed in two pivotal trials. The data would support the clinical implication of [¹⁷⁷Lu]Lu-DOTA-TATE for the GEP-NETs treatment.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Deep Learning Framework for Classification of Neuroendocrine Neoplasm Whole Slide Images.","authors":"Amir Hadjifaradji, Michael Diaz-Stewart, Jenny Chu, David Farnell, David Schaeffer, Hossein Farahani, Ali Bashashati, Jonathan M Loree","doi":"10.3390/cancers17182991","DOIUrl":"10.3390/cancers17182991","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Neuroendocrine neoplasms (NENs) are uncommon neoplasms. Grading informs the prognosis and treatment decision of NENs and is determined by cell proliferation, which is measured by mitotic count and Ki-67 index. These measurements present challenges for pathologists as they suffer inter- and intra-observer variability and are cumbersome to quantify. To address these challenges, we developed a machine learning pipeline for identifying tumor areas, proliferating cells, and grading NENs. <b>Methods</b>: Our study includes 385 samples of gastroenteropancreatic NENs from across British Columbia with two stains (247 H&E and 138 Ki-67 images). Labels for these cases are at the patient-level, and there are 186 patients. We systematically investigated three settings for our study: H&E, H&E with Ki-67, and pathologist-reviewed and corrected cases. <b>Results</b>: Our H&E framework achieved a three-fold balanced accuracy of 77.5% in NEN grading. The H&E with Ki-67 framework yields a performance improvement to 83.0% on grading. We provide survival and multivariate analysis with a c-index of 0.65. Grade 1 NENs misclassified by the model were reviewed by a pathologist to assess reasons. Analysis of our AI-graded NENs for the subset of pathologist-assessed G1s demonstrated a significant (<i>p</i>-value = 0.007) survival difference amongst samples the algorithm assigned to a higher grade (<i>n</i> = 20; median survival 4.22 years) compared to concordant G1 samples (<i>n</i> = 60; median survival 10.13 years). <b>Conclusions</b>: Our model identifies NEN grades with high accuracy and identified some grade 1 tumors as prognostically unique, suggesting potential improvements to standard grading. Further studies are needed to determine if this discordant group is a different clinical entity.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}