Frontiers in Oncology最新文献

{"title":"CBCT-based adaptive radiotherapy and automated radiotherapy decision-making systems: development and current status.","authors":"Shang Wang, Xin Wang","doi":"10.3389/fonc.2026.1957030","DOIUrl":"10.3389/fonc.2026.1957030","url":null,"abstract":"<p><p>Cone-beam computed tomography (CBCT)-based adaptive radiotherapy (ART) has emerged as a promising strategy for addressing inter-fractional anatomical and physiological changes during treatment. By incorporating on-treatment imaging, ART enables treatment plans to be adapted to the anatomy of the day, with the potential to improve target coverage and reduce dose exposure to organs at risk (OARs). However, routine implementation remains constrained by the limited image quality of CBCT, uncertainties in dose calculation, labour-intensive workflows and the lack of reliable criteria for determining when adaptation is clinically necessary. This review summarises the development, current status and future prospects of CBCT-based ART, with particular emphasis on artificial intelligence (AI)-assisted automated delineation and automated radiotherapy decision-making systems. CBCT is widely available on modern linear accelerators and remains the most practical imaging basis for ART in many centres. Nevertheless, poor soft-tissue contrast, noise, artefacts, field-of-view truncation and unstable Hounsfield unit values limit its performance in target delineation and dose reconstruction. Recent advances in image-quality enhancement, deformable image registration and synthetic CT generation have partially addressed these limitations. AI-based auto-segmentation models, including convolutional neural networks, Transformers, generative adversarial networks and diffusion models, have demonstrated increasingly favourable geometric accuracy and workflow efficiency. Automated decision-making systems can advise clinicians whether treatment-plan adaptation is required and how it should be implemented according to each patient's circumstances, representing a prerequisite for more efficient ART. Current research has mainly focused on two approaches: adaptation triggered by predefined dosimetric thresholds, and artificial-intelligence-based models that learn from prior knowledge and predict potential dosimetric changes for the current patient based on previous experience. Both approaches have their respective strengths and limitations, but require further refinement, including the systematic exploration of decision thresholds. Moreover, the realisation of fully automated adaptive radiotherapy will require the integration of additional systems, including automated treatment planning and automated QA. Overall, CBCT-based ART assisted by AI is technically feasible and may improve dosimetric quality and treatment efficiency. Future progress requires improved CBCT-specific algorithms, integrated automated planning and QA, multicentre validation, standardised safety frameworks and stronger evidence of clinical benefit.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1957030"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MYH9 confers doxorubicin resistance by stabilizing GRP78 and suppressing the PERK signaling-driven apoptotic pathway in breast cancer.","authors":"Jing Jiang, Tianzi You, Ziyi Zhao, Binlei Sheng, Zhanqi Sun, Xujun Li","doi":"10.3389/fonc.2026.1923603","DOIUrl":"10.3389/fonc.2026.1923603","url":null,"abstract":"<p><strong>Background: </strong>MYH9 is upregulated in various malignancies, but its role in breast cancer chemoresistance remains unclear. We investigated whether MYH9 regulates doxorubicin (ADR) resistance via GRP78 stabilization and PERK pathway modulation.</p><p><strong>Methods: </strong>MYH9 expression was analyzed in breast cancer tissues and cell lines by immunohistochemistry and western blot. ADR-resistant MCF-7 and MDA-MB-231 cell lines were established. MYH9 knockdown/overexpression and GRP78 overexpression were achieved by lentiviral transduction. Protein interactions, degradation assays, PERK signaling, apoptosis, and <i>in vivo</i> drug responses were evaluated.</p><p><strong>Results: </strong>MYH9 was significantly upregulated in breast cancer tissues, particularly in triple-negative breast cancer (95.2%), and further elevated in ADR-resistant cells. MYH9 overexpression enhanced ADR tolerance, while knockdown sensitized resistant cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, MYH9 directly bound GRP78 (but not CALR or GRP94), inhibiting ubiquitin-mediated proteasomal degradation. MYH9 depletion reduced GRP78 levels and activated the PERK pathway (p-eIF2α, ATF4, CHOP), promoting apoptosis via Bax/Bad upregulation and Bcl-2 downregulation. ERS induction with thapsigargin enhanced ADR sensitivity, whereas 4-PBA attenuated it. GRP78 overexpression rescued ADR resistance, confirming GRP78 dependency.</p><p><strong>Conclusion: </strong>MYH9 confers ADR resistance in breast cancer by stabilizing GRP78 and suppressing PERK-driven apoptosis, identifying the MYH9/GRP78 axis as a potential therapeutic target for overcoming chemoresistance.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1923603"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic treatment strategies for BRAF wild-type metastatic unresectable melanoma: a network meta-analysis.","authors":"Yishan Zhou, Yuanmin He, Xiaoqi Tan","doi":"10.3389/fonc.2026.1967814","DOIUrl":"10.3389/fonc.2026.1967814","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to provide new insights into systemic treatment for BRAF wild-type metastatic unresectable melanoma, thereby offering a basis for personalized clinical decision-making.</p><p><strong>Methods: </strong>PubMed, Embase, Cochrane Library, and Web of Science were searched. Eligible participants were adults with pathologically confirmed BRAF V600 wild-type metastatic unresectable melanoma. Outcomes included progression-free survival (PFS) and overall survival (OS). Network meta-analysis (NMA) results were presented as league tables and the surface under the cumulative ranking curve (SUCRA) values.</p><p><strong>Results: </strong>In total, 8 randomized controlled trials (RCTs) involving 3,418 patients and 9 systemic treatment strategies were included. One open-label study was rated as having some concerns, while the remaining seven were rated as low risk of bias across all domains and overall. The NMA results showed that, compared to ipilimumab, pembrolizumab, nivolumab, nivolumab + relatlimab, and nivolumab + ipilimumab demonstrated significant advantages in improving OS. Notably, nivolumab + relatlimab ranked first in prolonging OS (SUCRA = 93.94%). In the PFS analysis, this regimen had the highest SUCRA value only within the connected network consisting of dacarbazine, nivolumab, and the combination of nivolumab and relatlimab (SUCRA = 98.86%), although no comparisons or standardized rankings were performed between different PFS networks.</p><p><strong>Conclusions: </strong>The results of OS primary analysis for nivolumab plus relatlimab, as well as its ranking within the corresponding PFS network, are exploratory in nature. They are intended solely to generate research hypotheses and should not be interpreted as evidence of superiority over other treatments or as a basis for changing the current standard of care. Direct head-to-head RCTs are still needed to further clarify the comparative efficacy of the relevant regimens.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1967814"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid biopsy using circulating miRNAs for the identification of recurrence-associated biomarkers in glioblastoma CNS WHO grade 4.","authors":"Razan Muhtadi, Christian D Diehl, Nikolai Schmid, Gabriele Multhoff, Denise Bernhardt, Stephanie E Combs, Lisa Hönikl, Sandro M Krieg, Jens Gempt, Bernhard Meyer, Philipp Karschnia, Arthur Wagner, Vahe Barsegian, Monika Lindemann, Samantha Stewart, Sabrina Fischer, Patrick Ostheim, Stefan Friedrich Eder, Michael Abend","doi":"10.3389/fonc.2026.1938611","DOIUrl":"10.3389/fonc.2026.1938611","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma CNS WHO Grade 4 (GBM) is associated with poor prognosis and high recurrence rates despite the current therapeutic approaches. Conventional imaging, in particular Magnetic Resonance Imaging (MRI), is primarily used during follow-up to detect tumor recurrence but has limited ability to distinguish recurrence from therapy-related changes, such as tissue necrosis and postoperative scar tissue. Liquid biopsy using circulating tumor-specific serological biomarkers, such as miRNAs, provides a gene expression signature for early identification of GBM recurrence. This pilot \"proof-of-concept\" study investigated the potential of circulating tumor-derived miRNA in whole blood samples for early detection of tumor recurrence.</p><p><strong>Methods: </strong>In a previous whole-transcriptome screening (NGS) study, whole-blood samples (n = 33) from seven patients and tumor biopsies (n = 4) were used to identify biomarkers. Corresponding to tumor surgery and recurrence, miRNA expression was examined in pre-surgical blood samples and tumor tissues. In whole blood, we investigated whether a pattern could be identified indicating post-surgery downregulation, consistent with reduced tumor burden, followed by a return to pre-surgery levels at recurrence. We identified 1-19 miRNA species per patient (a total of 72 miRNAs) showing this pattern. In this manuscript, we present the qRT-PCR validation results. The 45 most promising miRNAs identified by NGS study were selected and quantified using qRT-PCR. In addition, <i>miR-21</i> was included as a promising candidate reported in the literature. To address challenges in miRNA normalization, five normalization strategies and unnormalized raw Ct values were compared.</p><p><strong>Results: </strong>Two normalization approaches (median DCt normalization and unnormalized raw Ct values) showed no systematic bias. Depending on the normalization method, the agreement between NGS and qRT-PCR ranged from 23.6 to 27.9%. Although the concordance between NGS and qRT-PCR was low at the individual-patient level, qRT-PCR identified a common set of 24 miRNAs differentially regulated across patients. Notably, <i>miR-424-3p</i> and <i>miR-362-5p</i> were shared by five of seven patients, followed by <i>miR-1307-3p</i> and <i>miR-22-5p</i>, each shared by four patients. Interestingly, <i>miR-21</i> did not show the predefined recurrence-associated pattern in any patient.</p><p><strong>Discussion: </strong>Blood-based miRNA profiling may complement imaging in longitudinal monitoring of GBM patients, although clinical benefits have not been confirmed, and validation in a larger independent cohort is required.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1938611"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of treatment response to PSMA radioligand therapy using Ga-68 PSMA-11 and F-18 DCFPyL PET imaging.","authors":"Chae Moon Hong, Abuzar Moradi Tuchayi, Mansour Abtahi, Stellamaris Nwihim, Surekha Yadav, Robert R Flavell, Thomas A Hope","doi":"10.3389/fonc.2026.1932583","DOIUrl":"10.3389/fonc.2026.1932583","url":null,"abstract":"<p><strong>Purpose: </strong>Multiple prostate-specific membrane antigen (PSMA) PET tracers are used for patient selection in radioligand therapy (RLT). This study compared treatment response to RLT across different PSMA tracers.</p><p><strong>Methods: </strong>We retrospectively analyzed patients who underwent Lu-177 PSMA-617 RLT with baseline imaging using either Ga-68 PSMA-11 or F-18 DCFPyL PET. PET parameters were measured, including SUV_mean, SUV_max, and total tumor volume (TTV). Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with PSA50 response, and Cox proportional hazards regression analyses were performed to evaluate factors associated with overall survival.</p><p><strong>Results: </strong>Of 140 patients analyzed (Ga-68 PSMA-11: n=51; F-18 DCFPyL: n=89), SUV_max and SUV_mean did not differ significantly between groups; however, TTV was significantly higher in the Ga-68 PSMA-11 group (p=0.038). In multivariable analysis adjusted for age, baseline PSA, PET tracer type, SUVmean, and log-transformed TTV, PET tracer type was not significantly associated with PSA50 response (OR, 1.318; 95% CI, 0.585-2.970; p=0.505), whereas higher SUVmean was associated with greater odds of PSA50 response (OR, 1.285; 95% CI, 1.126-1.466; p<0.001). Overall survival did not differ significantly between tracer groups (HR, 0.760; 95% CI, 0.507-1.138; p=0.183), with median overall survival of 8.4 and 12.6 months. In multivariable analysis, PET tracer type was not significantly associated with overall survival (HR, 0.736; 95% CI, 0.475-1.139; p=0.168), whereas higher SUVmean was associated with a lower risk of death (HR, 0.886; 95% CI, 0.825-0.950; p<0.001) and higher log-transformed TTV was associated with a higher risk of death (HR, 1.415; 95% CI, 1.194-1.678; p<0.001).</p><p><strong>Conclusion: </strong>PET tracer type was not significantly associated with PSA50 response or overall survival following RLT. Higher SUV_mean was associated with greater odds of PSA50 response and a lower risk of death, whereas higher TTV was associated with overall survival.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1932583"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-stratified gradients of colorectal neoplasia and an exploratory endoscopic red-flag composite in a lesion-confirmed screening colonoscopy cohort.","authors":"Lina Du, Jingzhi Su, Jihua Dai, Peipei Pu, Li Meng, Feiyan Zhao, Lili Pang, Sizhu Li, Yanxia Zhang, Xin Rong, Huihong Zhai, Sufang Shen","doi":"10.3389/fonc.2026.1842525","DOIUrl":"10.3389/fonc.2026.1842525","url":null,"abstract":"<p><strong>9objective: </strong>To characterise age-related gradients in colorectal lesion severity and prespecified high-risk endoscopic features in a lesion-confirmed screening colonoscopy cohort and to evaluate an investigator-defined red-flag composite as an exploratory marker of advanced pathology. <i>Helicobacter pylori</i> was assessed as a secondary exposure.</p><p><strong>Methods: </strong>This retrospective cohort included 291 participants with histologically confirmed lesions in four age groups (36-45, 46-55, 56-65 and 66-72 years). Logistic regression evaluated predictors of advanced neoplasia (high-grade dysplasia [HGD] or adenocarcinoma); adenocarcinoma-only and age × <i>H. pylori</i> interaction analyses were exploratory because events were sparse.</p><p><strong>Results: </strong>With advancing age, body mass index, <i>H. pylori</i> positivity, adenoma, sessile serrated lesions, HGD, adenocarcinoma and high-risk endoscopic features increased, whereas hyperplastic polyps decreased (all P < 0.05). Age (per 10 years), male sex, <i>H. pylori</i> positivity, lesion size ≥10 mm, proximal location and JNET 2B/3 pattern were independently associated with advanced neoplasia. Red-flag positivity (≥2 of four features) increased from 5.2% to 32.7% and enriched for adenocarcinoma, although positive predictive values were imprecise and non-monotonic.</p><p><strong>Conclusions: </strong>Colorectal lesion severity and high-risk endoscopic features showed an age-related gradient. The red-flag composite is an exploratory descriptive construct, not a validated predictive score. <i>H. pylori</i> findings, especially interaction analyses, are hypothesis-generating and require prospective validation.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1842525"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD163-positive macrophage enrichment is associated with mismatch repair deficiency and adverse pathologic features in early-stage endometrioid endometrial carcinoma: a retrospective cohort study.","authors":"Donglian Chen, Xiaojuan Huang, Yu Zhang, Linhong Liao, Qianqian Ye, Yu Guo","doi":"10.3389/fonc.2026.1954599","DOIUrl":"10.3389/fonc.2026.1954599","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mismatch repair deficiency defines an immunologically distinct subgroup of endometrioid endometrial carcinoma, but its relationship with CD163-positive macrophage infiltration in early-stage disease remains incompletely characterized. We evaluated the association between MMR status and quantitative CD163-positive TAM infiltration, together with secondary clinicopathologic and exploratory DFS analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This single-center retrospective cohort included patients with surgically treated FIGO 2009 stage I-II endometrioid endometrial carcinoma and available formalin-fixed paraffin-embedded tumor tissue. Immunohistochemistry for MLH1, PMS2, MSH2, MSH6, and CD163 defined MMR status and quantified macrophage density. CD163-positive TAM density was analyzed quantitatively as the principal measure, with a cohort-median low/high categorization retained for secondary phenotypic analyses. Median regression evaluated the association between MMR status and continuous CD163-positive TAM density, whereas logistic regression was used for the secondary binary TAM analysis and the composite adverse pathologic endpoint. Exploratory DFS analyses included single-marker and combined Cox models, formal MMR-by-TAM interaction testing, and comparison of models with and without continuous CD163-positive TAM density.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 254 patients assessed, 236 were included. MMR protein expression was retained in 172 tumors (72.9%), whereas 64 (27.1%) were classified as dMMR. CD163-positive TAM density was higher in dMMR than pMMR tumors (median, 76 vs 47 cells/HPF; P&lt;0.001), and high TAM infiltration was more frequent in dMMR tumors (44/64, 68.8% vs 71/172, 41.3%; P&lt;0.001). After adjustment for age, FIGO stage, tumor grade, tumor size, and deep myometrial invasion, dMMR remained associated with high macrophage infiltration (adjusted OR, 2.27; 95% CI, 1.19-4.18; P = 0.008). High macrophage infiltration was associated with grade 3 histology, deep myometrial invasion, LVSI, and the composite adverse pathologic feature; the association with the composite endpoint persisted after adjustment (adjusted OR, 1.78; 95% CI, 1.01-3.14; P = 0.047). During follow-up, 26 DFS events occurred. In exploratory Cox analyses, dMMR was associated with DFS (adjusted HR, 2.76; 95% CI, 1.25-6.10; P = 0.012), whereas continuous CD163-positive TAM density was not (adjusted HR per 10 cells/HPF, 1.04; 95% CI, 0.97-1.12; P = 0.281), and addition of CD163-positive TAM density did not significantly improve model fit beyond MMR status (likelihood-ratio P = 0.279). The dMMR/high-TAM phenotype retained an exploratory association with DFS in the conventional model (adjusted HR, 2.21; 95% CI, 1.02-4.81; P = 0.044), but the association was attenuated after additional adjustment for adjuvant therapy (HR, 2.04; 95% CI, 0.93-4.52; P = 0.075).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;IHC-defined dMMR was associated with increased CD163-po","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1954599"},"PeriodicalIF":3.4,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular profiling and prognostic significance of gastric cancer subtypes based on extracellular vesicle-related characteristics.","authors":"Guangyu Ding, Chenjie Xu, Xingmao Huang, Federico Maria Mongardini, Pengfei Yu, Chengkang Zhu, Hongtao Wang, Zequan Wu, Shengxin Fang, Xinyi Lei, Minji Xu, Salvatore Tolone, Ludovico Docimo, Li Min, Ling Huang","doi":"10.3389/fonc.2026.1948199","DOIUrl":"10.3389/fonc.2026.1948199","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a molecularly heterogeneous disease. This study aims to explore whether endocytosis pathway-associated genes and immune checkpoint-related features were linked to GC subtypes and prognosis.</p><p><strong>Methods: </strong>Public transcriptomic datasets from TCGA and GEO were analyzed. ssGSEA was applied to predefined endocytosis-related gene sets, and NMF was used to identify molecular subtypes. Survival, tumor microenvironment features, tumor mutation burden, microsatellite instability, and differentially expressed genes were evaluated. A three-gene prognostic model was developed and assessed through retrospective internal and external validation across public cohorts for prognostic association only.</p><p><strong>Results: </strong>Two endocytosis-related subtypes were identified. The Group 1 subtype showed higher pathway activity, more immunosuppressive microenvironmental features, higher expression of selected immune checkpoint-related markers, and poorer survival. The Group 2 subtype showed lower pathway activity and more favorable outcomes. A three-gene signature (NRP1, SERPINE1, and MISP3) stratified patients into higher-risk and lower-risk groups across retrospective cohorts. Higher-risk cases were associated with worse overall survival and enrichment of epithelial-mesenchymal transition- and immune evasion-related pathways. This retrospective cross-cohort validation suggests that the prognostic signal was not restricted to a single dataset, but it does not demonstrate prospective clinical validity, analytical validity, or readiness for clinical implementation.</p><p><strong>Conclusions: </strong>Endocytosis-related molecular patterns may be associated with distinct biological and prognostic features in GC. The identified subtypes and prognostic signature should be interpreted as exploratory, hypothesis-generating findings that warrant further prospective, functional, and assay-level validation.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1948199"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histologic heterogeneity in synchronous bilateral breast cancer: a case report and literature review.","authors":"Xuedi Yuan, Wen Liu, Xiuxia Liu, Chuyun Sun, Yuwen Cao","doi":"10.3389/fonc.2026.1936986","DOIUrl":"10.3389/fonc.2026.1936986","url":null,"abstract":"<p><p>Synchronous bilateral primary breast cancer (sBPBC) accounts for 2.9%-3.9% of newly diagnosed breast cancers, while cases with discordant histologic subtypes are exceptionally rare. We report on a 59-year-old woman with synchronous left-sided invasive ductal carcinoma (IDC) and right-sided invasive lobular carcinoma (ILC). The patient underwent bilateral breast-conserving surgery with sentinel lymph node biopsy, followed by adjuvant radiotherapy and endocrine therapy. No recurrence or metastasis was observed during the 12-month follow-up. To place the present case in the context of the existing literature, we comparatively reviewed seven previously reported cases of synchronous bilateral IDC and ILC. The comparison illustrated considerable heterogeneity in the clinicopathological characteristics, molecular profiles, nodal involvement, treatment strategies, and clinical outcomes. These findings support independent characterization of each breast lesion and individualized treatment planning based on the features of both tumors.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1936986"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival and prognostic factors analysis of carbon ion radiotherapy for limited-stage small cell lung cancer.","authors":"Xuexue Liang, Qinli Gong, Yihe Zhang, Ling Tian, Xiaoli Zhao, Bole Wang, Zhenglin Li, Pengqing Li, Yancheng Ye, Yanshan Zhang","doi":"10.3389/fonc.2026.1898779","DOIUrl":"10.3389/fonc.2026.1898779","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the clinical efficacy, safety and prognostic influencing factors of carbon ion radiotherapy (CIRT) in patients with limited-stage small-cell lung cancer (LS-SCLC).</p><p><strong>Methods: </strong>The clinical data of 39 patients with LS-SCLC who received CIRT from June 2020 to August 2026 were retrospectively analyzed. Survival outcomes and adverse reactions were evaluated, and Cox regression was used to analyze prognostic factors.</p><p><strong>Results: </strong>All patients completed the treatment. The 3-month objective response rate (ORR) was 64.10%. The 1- and 2-year local control rates were both 91.2%. The 1- and 2-year overall survival (OS) rates were 91.65% and 62.45%, with a median OS of 44 months. The 1- and 2-year progression-free survival (PFS) rates were 72.00% and 47.77%, with a median PFS of 24 months. Serum levels of NSE, CYFRA21-1, SCC and CEA decreased significantly after treatment. Acute treatment-related adverse reactions were mainly grade I-II and could be relieved after symptomatic treatment. Stratified Cox regression indicated that KPS score was an independent protective factor for OS. Univariate analysis suggested that the magnitude of post-treatment reduction in SCC and CYFRA21-1 was potentially associated with survival outcomes.</p><p><strong>Conclusion: </strong>CIRT achieves favorable local tumor control with low acute radiotherapy-related toxicity, and can serve as an alternative therapeutic option for LS-SCLC. This is a single-center, small-sample retrospective study, and the conclusions regarding efficacy and prognosis need to be further verified in larger-sample cohorts.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1898779"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}