Search Results (4,296)

Systemic therapy is the mainstay of treatment in inoperable cholangiocarcinoma (CCA). The aim of this study was to evaluate the overall survival (OS), progression-free survival (PFS), recurrence patterns, and the association between biliary complications and OS in patients with inoperable, localized cholangiocarcinoma treated with radiotherapy (RT) alone. Records of patients treated between 2004 and 2022 who received a minimum of 32.5 Gy BED10 were retrospectively reviewed. Survival was estimated using the Kaplan–Meier method, and prognostic factors were assessed using univariate and multivariable analyses. A total of 56 patients (median age 67.5) were included, most of whom had intrahepatic (78.6%) CCA, and most of whom received SBRT (76.8%). The median dose was 36 Gy (BED 55 Gy), and the median OS and PFS were 20 months and 10 months, respectively. One-year local control was 92.1% and the primary site of progression was intrahepatic (64.9%). On univariate analyses, pre-radiation biliary obstruction, elevated baseline CA 19-9, larger tumor size, and age were associated with worse outcomes; on multivariable analysis, only lesion size was prognostic. Biliary complications were associated with inferior OS. These findings highlight the high intrahepatic out-of-field failure rates and suggest the incorporation of biliary-event-free survival as a clinically relevant endpoint. Full article

Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204⁺ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3⁺ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusions: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies. Full article

Background/Objectives: This systematic review and meta-analysis evaluates the oncological safety and outcomes of minimally invasive versus open interval debulking surgery after neoadjuvant chemotherapy in advanced ovarian cancer, addressing whether laparoscopy represents a safe alternative to the standard open procedure. Methods: The Ovid/Medline, Pubmed, and Cochrane databases were systematically screened for studies investigating surgical resection status and/or patient survival after laparotomy compared to minimally invasive interval debulking surgery for FIGO stage III-IV ovarian cancer. A meta-analysis was performed using a random-effects model and risk of bias was assessed. Results: Overall, 14 observational and randomized studies published between 2015 and 2024 with a total of 16,578 patients (4310 laparoscopy and 12,268 laparotomy) were included. A complete cytoreduction to no visible tumour was achieved significantly more often after minimally invasive surgery compared to laparotomy (RR = 1.12; 95% CI [1.01, 1.23]; p = 0.03). Overall survival showed no significant difference between the two groups (HR = 0.81; 95%CI [0.64, 1.04]); progression-free survival was significantly more common after laparoscopy (HR = 0.67; 95% CI [0.48, 0.94]; p = 0.02; I² = 55%; p = 0.07). Patients undergoing minimally invasive surgery experienced significantly fewer postoperative complications (RR = 0.50; 95% CI [0.33, 0.76]; p ≤ 0.001), a lower mean blood loss (165 mL vs. 325 mL; SMD −0.58, 95% CI [−0.82, −0.35]; p ≤ 0.001), a shorter mean hospital stay (3 days vs. 5 days; SMD −0.79, 95% CI [−1.06, −0.52], p ≤ 0.001), and a faster initiation of adjuvant chemotherapy (mean 25 ± 32 days vs. 33 ± 28 days). Conclusions: This study indicates that laparoscopic interval debulking surgery is an oncologically safe alternative in selected patients with advanced-stage ovarian cancer. However, randomized controlled trials should confirm these findings as certainty of evidence is low and residual confounding cannot be excluded. Trial registration: PROSPERO Identifier CRD42024524725. Full article

Background/Objectives: The treatment of ovarian cancer (OC), which is predominantly diagnosed in advanced stages, poses a significant challenge to modern gynecologic oncology practice. A significant proportion of patients exhibit chemoresistance, underscoring the need for novel therapeutic interventions. This challenge is further compounded by the immunogenic nature of this neoplasm, prompting the exploration of alternative therapies. A notable example is the use of trastuzumab-deruxtecan (T-DXd), an antibody-drug conjugate (ADC), that has demonstrated encouraging outcomes in preliminary studies and has the potential to become a new treatment option. This systematic review aims to prove that. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) structure was employed to systematically search the PubMed and Scopus databases from December 2024. Furthermore, authors employed materials from the FDA’s official website and registry of clinical trials that are currently recruiting participants for T-DXd’s studies. Eligible studies included randomized controlled trials and observational studies assessing T-DXd in patients with OC. Outcomes of interest were objective response rate (ORR), median overall survival, adverse effects, and progression-free survival. Data was synthesized narratively. Results: Following a thorough review of available literature, 30 scientific papers were selected for inclusion. A total of 598 patients participated in clinical trials. The most common adverse effects were blurred vision and nausea, generally manageable. The risk of bias was low in most studies. Conclusions: T-DXd shows promising efficacy. A comparison of T-DXd with the ADC currently approved for OC therapy reveals that both demonstrate similar median overall survival and ORRs. However, the drug has exhibited significant adverse effects in breast cancer trials and has been studied on a relatively small number of patients. Therefore, further clinical trials focusing on OC patients are necessary to better assess the safety and efficacy of T-DXd in this population. Full article

Helicobacter pylori urease (HpU) plays a central role in bacterial survival and virulence by hydrolyzing urea into ammonia and carbon dioxide, neutralizing gastric acidity, and facilitating host colonization. The increasing prevalence of antibiotic resistance underscores the need for alternative strategies targeting essential bacterial enzymes such as urease. In this study, a multistage computational pipeline integrating pharmacophore modeling, machine learning (ML), ensemble docking, and enhanced molecular dynamics simulations were applied to identify novel triazole-based HpU inhibitors. Starting from over seven million compounds in the ZINC15 database, pharmacophore- and ML-based filters progressively reduced the chemical space to 7062 candidates. Ensemble docking across 25 conformational frames of HpU, followed by quantum-polarized ligand docking (QPLD), identified seven promising ligands exhibiting strong binding energies and stable metal coordination. Molecular dynamics (MD) simulations under progressively relaxed restraints revealed three highly stable complexes (CA1, CA3, and CA6). Subsequent well-tempered metadynamics (WT-MetaD) simulations reconstructed free-energy landscapes showing deep, localized basins for CA3 and CA6, comparable to the potent reference inhibitor DJM, supporting their potential as strong urease binders. Finally, unsupervised chemical space mapping using the UMAP algorithm positioned these candidates within molecular regions associated with potent urease inhibitors, further validating their structural coherence and pharmacophoric relevance. An ADMET assessment confirmed that the selected candidates exhibit physicochemical and early safety properties compatible with subsequent in vitro evaluation. This multilevel screening strategy demonstrates the power of combining ML-driven classification, ensemble docking, and enhanced sampling simulations to discover non-hydroxamic urease inhibitors. Although the current findings are computational, they provide a rational foundation for future in vitro validation and for expanding the discovery of triazole-based scaffolds targeting ureolytic enzymes. Full article

Background: Tumor immunogenicity is a concept for modeling the susceptibility of tumors to immune checkpoint inhibitors (ICIs) and other immunotherapies. Single biomarkers, such as tumor mutation burden (TMB) or PDL1 expression, have been shown to correlate with ICI outcomes but are poor predictors of overall and progression-free survival (OS, PFS). Complex machine learning models that integrate multiple biomarkers have shown improved predictions but often lack clear a priori interpretability. In this study, we developed a coherent Multi-Omics Tumor Immunogenicity score (MOTIscore) that combines immunogenicity biomarkers derived from genomic and transcriptomic data and demonstrated its generalizability across multiple cancer types. Methods: Several immunogenicity biomarkers, including TMB, neoantigen burden, T-cell receptor repertoire, PDL1 expression, B2M expression, and variants in pathways of ICI response and resistance, were integrated using a weighted sum scoring scheme. The weights were determined using statistical tests in a large melanoma ICI cohort. We compared the MOTIscore with a machine learning (ML) model trained using the same biomarkers and evaluated the model using melanoma, gastric cancer, and pan-cancer datasets. Results: MOTIscore achieved results similar to those of the ML model in predicting ICI in melanoma and gastric cancer, with both outperforming TMB. Gastric cancer and melanoma patients with high MOTIscores had a significantly extended overall and progression-free survival. Gene set enrichment analysis revealed the enrichment of immune-related pathways in patients with high MOTIscores. Differential expression analysis between patients with high and low immunogenicity identified highly expressed C-X-C motif chemokine ligands as important characteristics associated with successful ICI therapy and significantly improved PFS. MOTIscores varied widely across cancers treated in the molecular tumor board at our hospital and showed distinct distributions between non-immunogenic and immunogenic cancer types. Conclusions: MOTIscore demonstrated improved ICI outcome predictions compared to single-omics biomarkers. Patients with higher tumor immunogenicity also show significantly improved OS and PFS in melanoma and gastric cancer. The results demonstrate the potential use of the MOTIscore to prioritize ICI in personalized cancer treatment. However, ICI outcomes and survival should be investigated in prospective studies, and additional cancer types and larger patient cohorts are needed. Full article

Objectives: This single-center retrospective study evaluates the clinical efficacy and safety of percutaneous ablation using microwave ablation (MWA) and irreversible electroporation (IRE) in patients with breast cancer liver metastases (BCLM). Methods: Between August 2018 and December 2023, 32 patients underwent 40 image-guided ablations for 57 BCLM. Mean age was 61.3 years (range: 32–85), and mean tumor size was 2.9 cm (range: 0.9–7.0 cm). Fifty lesions were treated with MWA and seven with IRE. Clinical efficacy was assessed by m-RECIST response at first follow-up imaging (after ≥1 month) and by monitoring local tumor progression (LTP), local tumor progression-free survival (LTPFS), and overall survival (OS). Safety was evaluated by adverse events according to CTCAE. Kaplan–Meier statistics were used for LTPFS and OS. Results: Median follow-up was 32.4 months (95% CI 16.6–48.0). Complete response was observed in 34 tumors (59.6%), partial response in 14 (24.6%), and progressive disease in 9 (15.8%). LTP occurred in 37 tumors (64.9%), with a median time to progression of 11.1 months (95% CI 1.4–20.8). One- and two-year LTPFS rates were 43.6% and 34.1%. Sixteen patients died during follow-up, with median OS of 27.8 months (95% CI 19.0–36.6) and 1- and 2-year OS rates of 90.1% and 55.9%. No major complications occurred. Complications included eight Grade 1 and two Grade 2 complications. Conclusions: Percutaneous ablation demonstrates clinical efficacy and a favorable safety profile in selected BCLM patients, achieving OS comparable to the current literature. Further studies should clarify its additive role within multimodality treatment. Full article

Importance: Patient with head and neck cancer of the oropharynx (HNC-OROP) undergo curative-intent definitive or post-operative radiation therapy. The systemic inflammation response index (SIRI) has independent prognostic capacity in HNC-OROP. We hypothesized that the use of SIRI may produce a parsimonious model of HNC-OROP outcomes. Objective: We aimed to investigate the prognostic utility of systemic inflammatory response index (SIRI) in oropharyngeal head and neck cancer patients who underwent radiation therapy. Design, Setting, and Participants: Random survival forest (RSF) machine learning was used to model survival in 568 oropharyngeal cancer patients in this retrospective cohort study. SIRI was calculated via pre-treatment bloodwork. Model validation was performed in an external cohort of 421 oropharyngeal cancer patients. Exposures: Exposure was curative-intent definitive or post-operative radiation therapy for head and neck cancer of the oropharynx (HNC-OROP). Results: This is a retrospective study with 568 and 421 patients in the Roswell Park and external Ohio State University cohorts. We evaluated full and reduced RSF models and a robust decision tree model. The C-index of the models was 0.758 (RSF full), 0.725 (RSF reduced), and 0.702 (decision tree). The incorporation of SIRI (with performance status and smoking history) into a machine learning model identified three risk-groups that significantly stratified overall survival (p < 0.0001). These findings were validated in the external validation cohort (p = 0.0019). Progression-free survival was also significantly different for the three groups in the validation cohort (p = 0.0025). Conclusions and Relevance: An integrated machine learning model using SIRI, performance status, and smoking history was successfully developed and externally validated in oropharyngeal head and neck cancer patients. Full article

Background/Objectives: Despite increasing use of upfront decompressive surgery for malignant epidural compression of the myelon (MESCC), a substantial number of affected patients still receive radiotherapy (RT) alone. Many of these patients would benefit from a personalized treatment approach including the most appropriate dose-fractionation regimen. The PRE-MODE trial (NCT03070431) compared precision RT with 5 × 5 Gy (prospective cohort, n = 40) to conventional RT with 5 × 4 Gy (historical control, n = 676)). After propensity-score matching, 5 × 5 Gy resulted in significantly increased local progression-free survival (LPFS) at 6 months than 5 × 4 Gy. The question arose whether this benefit is still present after a longer period of follow-up. Methods: For this additional study, supplementary data were retrospectively captured, resulting in prolongation of follow-up until 24 months. Results: 5 × 5 Gy resulted in LPFS of 80.9% at each investigated time point (12, 18, and 24 months) without reported radiation myelopathy. Moreover, 5 × 5 Gy showed a trend towards improved LPFS after 12 (p = 0.070), 18 (p = 0.060), and 24 (p = 0.054) months. Similarly to the original PRE-MODE trial, OS-rates were not significantly different in the dose groups of this supplementary study. Conclusion: Since 5 × 5 Gy resulted in excellent long-term LPFS and showed a trend towards better outcomes up to 24 months following RT, it appears preferable to 5 × 4 Gy and will contribute to the personalized treatment of patients with MESCC who are assigned to RT alone without upfront neurosurgical intervention. Full article

Objective: We aimed to provide real-world insights into the management of non-small cell lung cancer stage III (NSCLC-SIII) in Spain. Methods: The GOECP-SEOR group conducted an observational, retrospective, multicenter study in which data from patients diagnosed with NSCLC-SIII treated in Spanish radiotherapy departments (RTDs) were collected. Results: A total of 1505 NSCLC-SIII patients from 35 RTDs from 2018 to 2021 were recruited. A total of 871 patients (57.9%) received concurrent chemoradiotherapy (cCRT), and 390 patients (25.91%) received maintenance durvalumab. The immunotherapy (IT) was well tolerated, with Common Terminology Criteria for Adverse Events (CTCAE) Grade 0–2 toxicity observed in 85% of the patients (295 patients). The median overall survival (OS) was 26 months (95% CI 9.4-Not Reached NR). There was a statistically significant difference when patients were stratified by IT, with a median OS of 40 months (95% CI 22.1-NR) in the IT maintenance cohort compared with 19.4 months (95% CI 7.1–58.1) in the non-IT cohort. Differences were also noted in progression-free survival (PFS), with a median PFS of 20.8 months (95% CI 9.6-NR) in the IT cohort versus 8.4 months (95% CI 3.1–25.1) in the non-IT cohort. These differences remained significant according to the multivariate model (OS: HR 0.45 [95% CI 0.36–0.56], p < 0.001; PFS: HR 0.5 [95% CI 0.42–0.59], p < 0.001). Conclusions: The management of NSCLC-SIII patients can vary, leading to differences in treatment outcomes. The treatment of lung cancer in NSCLC-SIII patients in RTDs across Spain aligns with international guidelines and expert recommendations. Full article

Background/Objectives: Hepatocellular carcinoma (HCC) ranks as the third most prevalent cancer and is the second leading cause of cancer-related deaths globally. This study sought to evaluate microwave ablation (MWA), radiofrequency ablation (RFA), and percutaneous ethanol injection (PEI)—whether used separately or together (RFA+PEI, MWA+PEI)—for treating single HCC lesions ≤5 cm, focusing on outcomes, survival rates, complications, costs, and recurrence rates. Methods: This retrospective–prospective research study involved 250 patients with solitary HCC lesions measuring ≤5 cm, recruited from the National Liver Institute at Menoufia University. Patients were evenly divided into five groups, each containing (n = 50): RFA, MWA, PEI, combined RFA+PEI, and combined MWA+PEI. Indications and contraindications adhered to the Barcelona Clinic Liver Cancer (BCLC) guidelines. Results: Three patients were administered antiviral therapy 1–2 years after ablation. Average intervention costs were 17,340 ± 700, 31,200 ± 900, 1140 ± 300, 17,500 ± 0.0, and 33,800 ± 0.0 EGP for groups 1 through 5, respectively. Short-term advancement rates were 12%, 8%, 18%, 4%, and 2%. After 36 months, all patients survived six months after ablation. Average survival durations were 2.44 ± 1.17, 2.59 ± 1.02, 2.69 ± 0.99, 2.83 ± 1.06,and 2.91 ± 1.04 years, respectively. Complications were mainly minor (pain, nausea, and low-grade fever); one patient experienced an abscess and biloma post-MWA, one experienced minimal pleural effusion, and two combined-therapy cases had abdominal wall hematoma. Conclusions: RFA, MWA, and PEI—whether used individually or together—are successful treatment choices for early-stage HCC. The combination of MWA and PEI demonstrated the most favorable results, minimal recurrence rates, and the longest duration of progression-free survival. Full article

Background: Conventional prognostic factors are typically assessed at diagnosis in metastatic hormone-sensitive prostate cancer (mHSPC). However, variations in vital signs and laboratory parameters occur during systemic treatment and may predict patients’ prognosis and anticipate organ-specific toxicity development. Methods: This single-center retrospective study included 363 patients with de novo mHSPC treated between 2014 and 2023. Clinical and laboratory data were systematically collected from the hospital data warehouse, from treatment initiation through the following seven months. Variations in vital parameters and blood test results were graded using CTCAE V5.0 (dynamic variables). Cox regression analyses were performed to explore the impact of dynamic variables on progression-free survival (PFS) and overall survival (OS). Machine learning (ML) models (Support Vector Classifier, Random Forest, and LGBM Classifier) were developed to predict single organ-specific toxicities and to identify good and poor responders based on 7-month PSA levels, PFS and OS. We compared ML model performance when trained only on baseline factors (static models) with those integrating variables generated by vital sign and blood test monitoring within 3 and 7 months from treatment start (dynamic models). Results: Dynamic model failed to improve the prediction of single organ-specific toxicities. Univariable Cox analysis revealed that the development of hematological, liver, and kidney-related toxicity, as well as the development of electrolyte disturbances within 3 or 7 months, was associated with shorter PFS (p = 0.011, 0.007, 0.174, and 0.02, respectively) and/or OS (p = 0.001, 0.099, 0.012, and 0.001, respectively). In multivariable Cox analysis, increasing alkaline phosphatase levels (HR = 1.93, p = 0.009), decreasing albumin (HR = 1.92, p = 0.008) and development of hyponatremia (HR = 1.79, p = 0.033) were associated with a shorter OS. The combination of static and dynamic variables significantly improved the ability of ML models to identify poor responders (shorter PFS: AUC range 0.91–0.94 vs. 0.79–0.89). Conclusions: The integration of conventional prognostic factors with the detection of significant changes in vital signs and blood tests occurring early during systemic treatment in patients with de novo mHSPC may enhance patient stratification and improve prediction of survival outcomes. Multicenter validation studies are needed to confirm these results. Full article

Background: Immune checkpoint inhibitors (ICIs) targeting PD-1 have significantly improved outcomes in patients with advanced melanoma. However, the optimal treatment duration remains undefined. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for treatment response monitoring and surveillance and can predict long-term clinical outcomes. Methods: Clinical and ctDNA data from prospectively enrolled patients with stage IV melanoma treated with anti–PD-1-based therapy at a single academic center were retrospectively analyzed. Of the 56 patients eligible, 28 underwent serial ctDNA testing during ICI treatment and follow-up (median 31 months) using a personalized, tumor-informed assay. Landmark analysis at 6 and 9 months was performed to assess progression-free survival (PFS) based on ctDNA status. Multivariable Cox regression was used to identify independent predictors of long-term outcomes. Results: Pre-ICI treatment, 91.7% (11/12) of evaluable patients were ctDNA-positive. At 6 months, ctDNA negativity or clearance was observed in 47.4% (9/19), and was strongly associated with improved PFS in the landmark analysis (HR: 10.0, p = 0.03; 2-year PFS: 89% in ctDNA-negative versus 30% in ctDNA-positive groups). At 9 months, persistent ctDNA positivity trended toward worse PFS. Multivariate analysis confirmed ctDNA status at the 6-month landmark timepoint to be an independent predictor of long-term benefit. Conclusions: Tumor-informed ctDNA testing is a robust, non-invasive tool to predict long-term benefit from anti–PD-1-based therapy in advanced melanoma. ctDNA clearance or sustained negativity at 6 months may serve as a surrogate for durable response and could inform individualized treatment discontinuation strategies, and minimize toxicity and cost while maintaining efficacy. These findings, derived from a limited single-center cohort, warrant further exploration and validation in larger studies. Full article

Background/Objectives: MET overexpression is common in non-small cell lung cancer (NSCLC). The correlation between MET overexpression and immune checkpoint inhibitor (ICI) efficacy in NSCLC is underexplored. Methods: In this retrospective observational cohort study, we curated a dataset of 279 stage IV NSCLC patients who received ICI treatment and had MET expression assessed by CLIA-certified immunohistochemistry (IHC) assay. MET expression was graded on a scale from 0 to 3+, with overexpression defined as 2+ or 3+. Clinicopathological features associated with MET expression were assessed using logistic regression. Overall survival (OS) and progression-free survival (PFS) were evaluated via Kaplan–Meier analysis and the multivariate Cox proportional hazards model. To derive the most parsimonious and statistically robust models, stepwise refinement based on the Akaike Information Criterion (AIC) was applied. Results: MET overexpression was observed in 220 of 279 patients (78.9%). Adenocarcinoma histology (p = 0.003) and PD-L1 expression (p < 0.001) were independently associated with MET overexpression. Kaplan–Meier analysis showed patients with MET overexpression had significantly superior OS (p = 0.012) and PFS (p = 0.033). Full Cox regression analysis revealed that MET overexpression was associated with longer OS (p = 0.040), independent of PD-L1 levels. Patients with MET overexpression had numerically longer PFS (p = 0.145). Following adjustment for metastatic burden, the AIC-selected OS and PFS models both demonstrated that MET overexpression remained a significant prognostic factor (OS: p = 0.010; PFS: p = 0.026). Conclusions: This real-world study suggests that MET overexpression, as assessed by IHC, is associated with better survival in advanced NSCLC patients treated with ICIs, independent of PD-L1 level. These results suggest the potential of MET expression as a predictive marker for ICI efficacy in advanced NSCLC patients and support the combination of MET-targeted agents with anti-PD1/PD-L1 ICIs as a promising strategy for NSCLC patients with MET overexpression. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with limited therapeutic options despite rapid progress in the immunotherapy era. The balance among CD4⁺ helper T cells (Th), CD8⁺ cytotoxic T cells (Tc), and regulatory T cells (Tregs) is a central determinant of tumor immune dynamics and clinical outcomes. The profound immune suppression in PDAC, driven largely by regulatory T cells (Tregs), remains a major barrier to successful immunotherapy response. Tregs enforce tolerance, shape fibroblasts’ immunosuppressive effect, and reprogram the tumor metabolic niche. This study describes the effect of the relative abundance of effector T cell subtypes and Tregs on survival outcomes in metastatic pancreatic cancer patients and reviews how Tregs and other effector T cell subtypes regulate PDAC immunobiology and influence clinical outcomes. Methods: This retrospective study provides immunohistochemical profiling of 62 metastatic PDAC patients, revealing differential prognostic associations among intratumoral and peritumoral subsets of Th, Tc, and Tregs. For each immunostaining, the immune cell infiltrates were evaluated by counting the number of positive cells under the objective of X20 magnification per 0.125 mm². Results: While high intratumoral Th (>16.8) and Tc (>19.6) abundances correlated with improved overall survival and progression-free survival, Treg infiltration (both IT and PT) showed no significant prognostic effect. Conclusions: The effector Th and Tc are the dominant prognostic T cell subsets in PDAC, whereas Treg abundance alone is an incomplete surrogate of immunosuppression. These findings describe the immunobiological landscape of PDAC. Full article