Frontiers in Oncology最新文献

{"title":"ER^-/PR⁺ breast cancer: from diagnostic discordance to precision therapy.","authors":"Yuanhao Shao, Meng Zhou, Zhenwei Hu, Bin Wu, Jing Zhou","doi":"10.3389/fonc.2026.1961666","DOIUrl":"https://doi.org/10.3389/fonc.2026.1961666","url":null,"abstract":"<p><p>Estrogen receptor-negative/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER^-/PR⁺/HER2^-)breast cancer is a rare, controversial type that makes up about 0. 3% of all breast cancer cases and does not follow the traditional ER→PR regulatory hierarchy. This review synthesizes the available evidence on the diagnostic evaluation, clinicopathological characteristics, molecular mechanisms, prognosis, and treatment of ER^-/PR⁺/HER2^-(ER^-/PR⁺) breast cancer. Although there are false-negative ER staining results and pre-analytical/analytical factors, a number of clinical and transcriptomic data support the existence of a reproducible ER^-/PR⁺subgroup with molecular heterogeneity. These tumors often have a high histological grade, elevated Ki-67 expression, TP53 alterations, and basal-like features, and are closer to triple-negative breast cancer than luminal disease. Potential drivers include ER-independent non-canonical PR activation, epigenetic dysregulation, kinase-mediated receptor phosphorylation, membrane-associated progesterone signaling and receptor network reprogramming. Direct subtype-specific evidence remains limited, and the effectiveness of conventional endocrine therapy is unknown. Current guidelines classify these tumors as hormone receptor-positive/HER2-negative, obscuring clinically relevant heterogeneity. Standardized repeat testing and multi-omic characterization are thus required. Future studies should prioritize prospective multicenter cohorts with paired pre-treatment and post-treatment receptor testing, spatial or single-cell characterization, biomarker-guided stratification and adaptive clinical trials. A PR-oriented precision-medicine framework may improve diagnostic classification and help identify therapeutic vulnerabilities in biologically distinct patient subsets. In addition, this rare phenotype may serve as a useful model for investigating lineage plasticity and endocrine resistance.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1961666"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223776","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":"Case Report: Heterogeneous endoscopic and histological presentations of gastric and gastroesophageal metastases from breast carcinoma: a three-case series from a Malaysian tertiary center.","authors":"Guo Hou Loo, Yin Ping Wong, Nur Fa'izah Ab Muin, Kean Leong Koay, Mariyam Nahuza, Shahrun Niza Abdullah Suhaimi, Nik Ritza Kosai","doi":"10.3389/fonc.2026.1933062","DOIUrl":"https://doi.org/10.3389/fonc.2026.1933062","url":null,"abstract":"<p><strong>Background: </strong>Gastric metastasis from breast carcinoma is uncommon and is most often associated with invasive lobular carcinoma (ILC), although carcinoma of no special type (NST) and mixed tumors also occur. Metastatic deposits closely mimic diffuse-type gastric adenocarcinoma, and the distinction from a primary gastric tumor carries major therapeutic consequences. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status may differ between the primary tumor and its metastasis, with direct implications for systemic therapy.</p><p><strong>Case descriptions: </strong>We report three women managed at a single Malaysian tertiary center. Case 1 (56 years old; metachronous interval of approximately 4 years) had an ER-positive, HER2 3+ (immunohistochemistry [IHC]) carcinoma of no special type that presented as a circumferential Siewert III gastroesophageal junction (GOJ) tumor with gastric satellites; the metastasis retained E-cadherin and was HER2 2+ with a non-amplified <i>in situ</i> hybridization (ISH) result, a discordance from the HER2 3+ primary. Case 2 (47 years old; synchronous) presented with a linitis plastica-like pattern and gastric outlet obstruction (GOO) from an ER-positive, HER2-negative carcinoma; the primary showed patchy E-cadherin and the metastasis showed focal E-cadherin, consistent with a mixed ductal-lobular phenotype; PR expression was lost between the primary (strong, >90%) and the metastasis (negative). Case 3 (91 years old; effectively synchronous, approximately 6-year course) had a lobular carcinoma with E-cadherin loss and a decline in PR expression (from focal weak positivity in the primary to negative in the metastasis), with a protracted course dominated by recurrent feeding-tube complications. In each case, the diagnosis rested on morphology, a breast-oriented IHC panel, and comparison with the known breast primary rather than on any single marker.</p><p><strong>Conclusion: </strong>This series illustrates that gastric and GOJ metastases from breast carcinoma are morphologically and endoscopically heterogeneous and are not confined to E-cadherin-negative ILC. E-cadherin reflects tumor phenotype and cell cohesion rather than the organ of origin, and it should not be used to distinguish a breast metastasis from a primary gastric carcinoma. Because clinically relevant ER, PR, and HER2 discordance may occur, these biomarkers should be reassessed in metastatic tissue, with results interpreted proportionately to the available evidence.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1933062"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223811","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":"Redefining drug discovery: AI-driven strategies for efficient cancer therapeutics.","authors":"Diptanu De, Sohini Chakraborty, Satarupa Banerjee","doi":"10.3389/fonc.2026.1907591","DOIUrl":"https://doi.org/10.3389/fonc.2026.1907591","url":null,"abstract":"<p><p>The practice of artificial intelligence has recently expanded several social spheres, with the pharmaceutical domain leading the way. Given that AI can facilitate rational drug design, it is plausible to envision its involvement in developing pharmaceutical products from the laboratory to the patient's bedside. AI recognizes hit and lead compounds, followed by validation of therapeutic targets and optimization of molecular design. Artificial intelligence significantly impacts drug discovery and development processes, including target identification, molecule design, drug-drug interactions, drug repurposing, optimization of clinical trials, drug toxicity prediction, drug formulation, and delivery. AI-assisted approaches are progressively being employed for identification and prioritization of targets, biomarker discovery and virtual screening as well as prediction for the interaction of protein and ligand and their molecular properties followed by ADMET screening, molecular design and repurposing to be suited for clinical trial optimization. The significance of automation will be boosted by adopting the most recent artificial intelligence-based technologies, reducing the time it takes for drugs to be available in the market with improved quality, production process safety, and resource utilization. The application of artificial intelligence may not only aid in rapid decision-making but can also enhance the process of incorporating the newly discovered drug into the optimum dosage form, which leads to faster manufacturing of higher-quality drugs and ensures consistency among batches. The potential of artificial intelligence in drug discovery and development, has been explored in this review, encircling several stages from identification of target to its clinical applications, followed by drug development approaches encompassing the future of artificial intelligence in the pharmaceutical sector, along with crosstalk on the tools and tactics used to enforce artificial intelligence, current difficulties, and respective solutions.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1907591"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223736","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":"Beyond chaperoning: HSPA8 modulates alternative splicing of PPP2R2D to drive apoptotic evasion and macrophage-associated immune microenvironment remodeling in triple-negative breast cancer.","authors":"Wenting Xu, Qingwen Zheng, Yu Si, Tian Yao, Hao Lei, Yongtao Li","doi":"10.3389/fonc.2026.1941438","DOIUrl":"https://doi.org/10.3389/fonc.2026.1941438","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular chaperone HSPA8 is classically recognized for its role in protein homeostasis, and while its upregulation correlates with poor prognosis in triple-negative breast cancer (TNBC), whether HSPA8 exerts non-canonical functions beyond chaperoning remains unknown.</p><p><strong>Methods: </strong>Through integrative transcriptomic profiling, RNA immunoprecipitation (RIP), isoform-specific rescue experiments, and <i>in vivo</i> xenograft models, we investigated the functional and mechanistic role of HSPA8 in TNBC pathogenesis.</p><p><strong>Results: </strong>We unveil a paradigm-shifting function for HSPA8 as a modulator of alternative splicing of the PP2A regulatory subunit gene PPP2R2D, promoting exon 2 retention to favor the full-length PPP2R2D-2 isoform over the truncated PPP2R2D-1. These two isoforms exhibit functionally distinct roles: only PPP2R2D-2 possesses pro-survival activity, whereas PPP2R2D-1 lacks this function. Specifically, PPP2R2D-2 rescues HSPA8 depletion-induced apoptosis by modulating the mitochondrial pathway (BAX/BCL-2/cleaved Caspase-3) and restores <i>in vivo</i> tumor growth. Strikingly, this splicing axis also correlates with an immunosuppressive tumor microenvironment, characterized by altered M1/M2 macrophage marker abundance.</p><p><strong>Discussion: </strong>These findings uncover a dual mechanism that simultaneously drives intrinsic survival signaling and is associated with alterations in the tumor immune microenvironment. They transcend the classical chaperone paradigm by establishing HSPA8 as a non-canonical splicing modulator, and the HSPA8-PPP2R2D-2 axis emerges as a critical vulnerability in TNBC, offering a novel therapeutic angle that concurrently targets tumor cell survival and microenvironmental immunosuppression.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1941438"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223784","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":"Case Report: Low-dose radiotherapy as part of multimodal salvage therapy for immunotherapy-resistant SMARCA4-deficient non-small cell lung cancer.","authors":"Tong Bu, Nan Zhang, Tong Jin, Zixuan Wang, Yichen Mao, Dan Zong, Wenjie Guo, Xia He","doi":"10.3389/fonc.2026.1941008","DOIUrl":"https://doi.org/10.3389/fonc.2026.1941008","url":null,"abstract":"<p><p>SMARCA4-deficient non-small cell lung cancer (SD-NSCLC) is a highly aggressive molecular subtype. This malignancy is often diagnosed at an advanced stage, carrying a dismal prognosis and also demonstrating poor responsiveness to traditional treatment. Beyond its primary site, the disease can exhibit unusual metastatic patterns such as metastasis to oral soft tissues. We report a unique case of a 61-year-old male heavy smoker with molecularly confirmed SD-NSCLC who experienced rapid metastatic progression to the right gingiva and neck lymph nodes shortly after radical surgery and initial chemo-immunotherapy. This clinical scenario exemplifies primary resistance to immune checkpoint inhibitors (ICIs), where pre-existing genetic or microenvironmental barriers hinder initial therapeutic success. To overcome this resistance, a salvage multimodal strategy was implemented, integrating ICIs with etoposide/cisplatin (EP) chemotherapy and low-dose radiotherapy (LDRT). Remarkably, this regimen achieved significant regression of the bulky metastatic lesions and has maintained sustained disease stability for over 15 months, with the patient remaining clinically stable as of the latest follow-up in June 2026. This case may hint the potential role of LDRT as an immunomodulatory component to overcome primary resistance in SD-NSCLC, suggesting a potential therapeutic strategy for patients who experience disease progression following first-line chemo-immunotherapy.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1941008"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223818","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":"Case Report: Pelvic-perineal deep angiomyxoma presenting as hematoma-like paravaginal masses: a report of two cases.","authors":"Xiaodan Yang, Fang Wang","doi":"10.3389/fonc.2026.1940480","DOIUrl":"https://doi.org/10.3389/fonc.2026.1940480","url":null,"abstract":"<p><p>Deep angiomyxoma (DAM) is a rare, locally infiltrative mesenchymal tumor of the female pelvic and perineal regions that is often misdiagnosed because of nonspecific clinical and ultrasonographic findings. We report two cases of pelvic-perineal DAM initially interpreted as paravaginal hematomas. One patient underwent ultrasound-guided aspiration and thrombin injection before progressive enlargement prompted further evaluation. Magnetic resonance imaging (MRI) demonstrated marked T2 hyperintensity, internal swirling structures, and extension along pelvic floor tissue planes, raising suspicion of DAM. Both patients underwent surgical resection with histologically negative margins (R0). Histopathology confirmed DAM with estrogen receptor and progesterone receptor positivity. Following multidisciplinary discussion, both patients received six cycles of individualized postoperative gonadotropin-releasing hormone agonist therapy. No radiological recurrence was observed at 11 and 12 months, respectively. Persistent or enlarging hematoma-like pelvic-perineal masses without a clear precipitating factor should prompt consideration of DAM and further MRI evaluation. MRI is useful for suggesting DAM and delineating tumor extent, whereas definitive diagnosis relies on histopathology. The benefit of routine postoperative endocrine therapy after R0 resection remains uncertain.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1940480"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223826","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":"Dynamic changes of serum vascular endothelial growth factor after surgical resection of hepatocellular carcinoma and its application in recurrence monitoring.","authors":"Jirachaya Choovuthayakorn, Phichayut Phinyo, Noraworn Jirattikanwong, Peraphan Pothacharoen, Kanya Udomsin, Anon Chotirosniramit, Worakitti Lapisatepun, Sunhawit Junrungsee","doi":"10.3389/fonc.2026.1865004","DOIUrl":"https://doi.org/10.3389/fonc.2026.1865004","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) recurs frequently after resection. Vascular endothelial growth factor (VEGF) mediates tumor angiogenesis, but its post-operative behavior is poorly described. We compared serum VEGF and alpha-fetoprotein (AFP) trajectories over the first post-operative year.</p><p><strong>Methodology: </strong>In this single-center prospective pilot study, 21 patients undergoing curative resection were assessed and 19 analyzed (8 recurrence, 11 non-recurrence). Both markers were measured before surgery and at 3, 6 and 12 months. Trajectories were compared using mixed-effects models with a group × time interaction (time categorical) and a random intercept; VEGF was modeled on the native scale, AFP on the log₁₀ scale. All analyses are exploratory.</p><p><strong>Results: </strong>Eight of 19 patients (42.1%) recurred, at a median of 177.5 days. VEGF trajectories differed between groups (interaction p = 0.041). In the recurrence group, estimated mean VEGF fell from 188.4 to 82.5 pg/mL by 3 months, rose to 103.9 at 6 months and fell to 67.9 at 12 months. Reductions from baseline were significant in the recurrence group only (all p ≤ 0.003). The 6-month rise was not itself significant (+21.2 pg/mL; p = 0.552). Observed VEGF never differed between groups; AFP was higher in the recurrence group at 12 months (15.61 versus 2.04 IU/mL; p = 0.016).</p><p><strong>Conclusion: </strong>Serum VEGF declines markedly after resection, most steeply in patients who recur, and the groups follow different trajectories. The transient six-month rise coincided with the median time to recurrence but was not significant. Given the small, stage-imbalanced cohort, these findings are hypothesis-generating.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1865004"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223771","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":"Case Report: Diffuse peribiliary metastasis from ovarian cancer mimicking sclerosing cholangitis without a detectable mass.","authors":"Xiao Li, Zhijie Zhang","doi":"10.3389/fonc.2026.1901172","DOIUrl":"https://doi.org/10.3389/fonc.2026.1901172","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer typically spreads via peritoneal seeding, hematogenous, or lymphatic routes. Bile duct metastasis is extremely rare, and peribiliary metastasis manifesting as diffuse Glissonian sheath infiltration without a detectable mass lesion, to our knowledge, has not been well documented.</p><p><strong>Case presentation: </strong>A 42-year-old woman with stage IVB high-grade serous ovarian carcinoma, previously treated with cytoreductive surgery and multiple lines of chemotherapy, presented with fatigue, anorexia, and mild jaundice. Magnetic resonance cholangiopancreatography (MRCP) revealed bile duct wall thickening, peribiliary edema (Glissonian sheath edema), and diffuse inflammatory changes without a discrete mass. Autoimmune and infectious workups were negative. Endoscopic retrograde cholangiopancreatography (ERCP) with biopsy showed micropapillary clusters of atypical cells. Immunohistochemistry was positive for CK7, CK19, PAX-8, P16, and mutant-type p53; CEA focally positive; ER negative; Ki-67 high. This confirmed metastatic high-grade serous carcinoma of ovarian origin involving the common bile duct wall. Imaging (MRI/MRCP) suggested diffuse peribiliary involvement compatible with Glissonian sheath infiltration, although the small biopsy did not directly sample the intrahepatic sheath itself. We hypothesize that the radiological changes reflect peribiliary lymphatic spread, but this remains an inference based on imaging-pathology correlation rather than a histologically proven mechanism. Effective biliary drainage could not be achieved because the patient was unable to tolerate the nasobiliary drain. She was discharged against medical advice and died shortly thereafter, according to family report.</p><p><strong>Conclusions: </strong>In cancer patients with unexplained cholestasis, peribiliary metastasis should be considered even when no mass is seen on cross-sectional imaging. ERCP with biopsy and immunohistochemistry are essential for diagnosis.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1901172"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180704","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":"Case Report: Serplulimab-induced checkpoint inhibitor pneumonitis in extensive-stage small cell lung cancer with underlying COPD: a case report and literature review.","authors":"Jiangang Ju, Qiang Shen, Qingqing Chen, Linfeng Shen, Xiaofang Fu","doi":"10.3389/fonc.2026.1935484","DOIUrl":"https://doi.org/10.3389/fonc.2026.1935484","url":null,"abstract":"<p><strong>Background: </strong>Serplulimab, a first-line therapy for extensive-stage small cell lung cancer (ES-SCLC), can cause checkpoint inhibitor pneumonitis (CIP). The clinical features and outcomes of serplulimab-induced CIP in patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV chronic obstructive pulmonary disease (COPD) remain unclear.</p><p><strong>Case description: </strong>An 80-year-old man with ES-SCLC and preexisting GOLD stage IV COPD received first-line serplulimab plus chemotherapy. After achieving an initial partial response, chemotherapy was discontinued due to reduced tolerance following bacterial pneumonia, and he was continued on serplulimab monotherapy. Three days after the first maintenance dose of serplulimab, he presented with acute severe chest tightness, dyspnea, and hypoxemia and was admitted to the hospital 4 days later. Chest CT revealed new bilateral pulmonary infiltrates. Extensive workup for infection, acute exacerbation of COPD, and tumor progression was negative; the case was ultimately classified as grade 4 serplulimab-induced CIP. He was treated with high-dose methylprednisolone, intravenous immunoglobulin, and empiric anti-infective therapy, with significant clinical improvement. Follow-up CT at 2 months post-discharge showed significant resolution of pulmonary infiltrates.</p><p><strong>Conclusions: </strong>Severe, life-threatening CIP can occur in elderly patients with ES-SCLC and preexisting GOLD stage IV COPD. In this patient, prompt recognition, intensive immunosuppression, and permanent programmed death-1 (PD-1) inhibitor discontinuation contributed to a favorable outcome. Whether preexisting GOLD stage IV COPD confers an increased risk of severe CIP in this understudied population warrants further investigation.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1935484"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223764","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":"Genetic risk stratification reveals distinct first-order radiomic phenotypes in hepatocellular carcinoma.","authors":"Mohamed Eltaher, Zaina Boriek, Rohan Amare, Awj Twam, Prasun Jalal, James Long, Eugene Koay, Khaled M Elsayes, Rikita Hatia, Manal Hassan, David Fuentes","doi":"10.3389/fonc.2026.1754407","DOIUrl":"https://doi.org/10.3389/fonc.2026.1754407","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) exhibits significant morphological heterogeneity that has traditionally been attributed to etiological, environmental, and biological factors. Recent evidence suggests, however, that genetic background may influence tumor characteristics and behavior in HCC.</p><p><strong>Purpose: </strong>To investigate associations between established HCC genetic risk factors and first-order radiomic features.</p><p><strong>Methods: </strong>We evaluated a retrospective cohort of 210 patients with HCC who underwent contrast-enhanced MRI and genetic profiling for three established HCC risk variants (PNPLA3 rs738409-G, TM6SF2 rs58542926-T, and MAU2 rs58489806-T). We screened first-order radiomic features in the full cohort and then focused the primary analysis on 77 treatment-naive patients whose tumor morphology had not been modified by therapy. Patients were stratified into at-risk (≥1 risk allele, n=52) and wild-type (no risk alleles, n=25) groups. Eighteen first-order radiomic features were screened using the Mann-Whitney U test and AUC analysis. The leading feature, kurtosis, was then subjected to univariate and multivariate analysis for clinical and imaging features to identify any confounding effect. In addition, a 10-fold cross-validated cutpoint stability, sensitivity analysis, and Cox/Kaplan-Meier survival analysis were also conducted.</p><p><strong>Results: </strong>Among 18 features, kurtosis best distinguished at-risk from wild-type genotypes in treatment-naive patients (AUC = 0.67, p=0.014), with wild-type tumors showing more uniform, sharply peaked intensity patterns. Tumor volume correlated modestly with kurtosis (Spearman's ρ=0.45, p<0.0001), but volume alone did not discriminate genotype (Mann-Whitney U, p=0.3994). The genotype-kurtosis association remained significant after adjusting for volume and shape (ANCOVA, p=0.029) and strengthened after adjusting for nine clinical/demographic covariates (p=0.003), indicating kurtosis reflects biological information beyond tumor size. The empirical cutpoint was stable across 10-fold cross-validation (mean=3.35, SD = 0.05), and results were unchanged in sensitivity analysis. Kurtosis was not associated with overall survival (Cox HR = 1.19, p=0.13). No genotype-related discrimination was observed in the pooled full cohort, consistent with treatment-related alteration of tumor texture.</p><p><strong>Conclusions: </strong>In a cohort of 210 genetically profiled patients with HCC, genotype-related radiomic features were not apparent when treated and untreated tumors were analyzed together. However, restricting the analysis to the treatment-naive subgroup (n=77) revealed tumor kurtosis as a reproducible, biologically plausible first-order imaging correlate of established HCC genetic risk status.</p>","PeriodicalId":12482,"journal":{"name":"Frontiers in Oncology","volume":"16 ","pages":"1754407"},"PeriodicalIF":3.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223779","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}