Search Results (1,631)

Background/Objectives: Multiple myeloma (MM) is a complex hematologic malignancy characterized by abnormal plasma cell proliferation in the bone marrow. [¹⁸F]FDG PET/CT has emerged as a key imaging modality, demonstrating high sensitivity and specificity for the detection of metabolically active disease compared with conventional imaging techniques. This review examines the role of PET/CT imaging in evaluating therapeutic response in symptomatic myeloma, including minimal residual disease (MRD) assessment. Methods: We surveyed the literature published between 2014 and 2024 across PubMed, Scopus, Web of Science, and the Cochrane Library for peer-reviewed articles evaluating PET imaging in the assessment of treatment response in multiple myeloma. Results: [¹⁸F]FDG PET/CT provides a whole-body assessment of disease burden, extramedullary involvement detection, and early metabolic response evaluation. Standardized response assessment criteria (Deauville, IMPeTUs, IMWG) have enhanced the reproducibility and accuracy of treatment monitoring. Semiquantitative parameters including SUVmax and metabolic tumor volume (MTV) provide useful prognostic information with PET negativity correlating with improved progression-free and overall survival. The integration of PET/CT with bone marrow assessment techniques (next-generation flow cytometry and sequencing) optimizes MRD evaluation and patient stratification. Conclusions: PET/CT represents a valuable imaging tool for improving therapeutic decision making and risk stratification in MM management. Emerging radiotracers beyond FDG, including [¹¹C]choline, [¹¹C]methionine, and targeted agents like [⁶⁸Ga]pentixafor and CD38-targeted immunoPET tracers, hold promise for enhanced diagnostic capabilities in specific clinical contexts. Full article

Background/Objectives: Acromegaly is a chronic endocrine disorder caused mainly by GH-secreting pituitary adenomas, leading to excess GH and elevated IGF-1. Although surgery is first-line therapy, many patients require medical treatment, and remission is often not achieved with first-generation somatostatin receptor ligands (SRLs). Pasireotide, a second-generation SRL, offers superior biochemical and tumor control but is associated with hyperglycemia. This study aimed to evaluate real-world outcomes associated with pasireotide treatment in patients with acromegaly inadequately controlled on first-generation SRLs, with IGF-1 normalization as the primary endpoint. Secondary outcomes included GH control, tumor response, and glycemic safety. Methods: We conducted a historical cohort study of adults with acromegaly treated at Clínica Imbanaco (Cali, Colombia) between 2017 and 2024. Eligible patients had residual tumors and persistently elevated GH and/or IGF-1 levels above the age-adjusted upper limit of normal despite treatment with clinically adequate doses of first-generation SRLs, as well as 12 months of continuous pasireotide treatment and follow-up after pasireotide initiation. Demographic, biochemical, imaging, and glycemic data were collected. Statistical analysis included paired and independent Student’s t-tests, Wilcoxon signed-rank tests, McNemar’s test, and Fisher’s exact test, with significance set at p < 0.05. Results: Fourteen patients (50% female; mean age 52.1 ± 14.5 years) were included. After 12 months, mean IGF-1 decreased from 2.73 ± 0.73 to 0.99 ± 0.56 × ULN, and 50% achieved IGF-1 normalization. Additionally, 35.7% achieved GH <1 ng/mL, and 14.3% achieved combined control. Mean tumor diameter decreased by −3.26 mm (95% CI −4.56 to −1.95; p < 0.001). HbA1c increased from 5.56% to 6.05%, while type 2 diabetes mellitus prevalence rose from 14.3% to 35.7%. No patient discontinued pasireotide due to metabolic adverse events. Conclusions: Pasireotide was associated with favorable biochemical and tumor responses in patients with acromegaly inadequately controlled on first-generation SRLs under real-world conditions. Although treatment was associated with higher HbA1c and increased diabetes incidence, proactive monitoring and early management of hyperglycemia may have supported treatment persistence. Full article

The new therapeutic options now available for patients with hepatocellular carcinoma (HCC) have made their assessment more complex, especially due to the different stages of liver cirrhosis typically associated with this tumor. The management of the disease therefore requires an interdisciplinary approach aimed at identifying the most appropriate treatment based on the risk–benefit profile and residual liver function, as well as in relation to the patient’s age and potential for a full or partial recovery, risk of complications, and cancer recurrence. Another factor to be carefully considered in patients with hepatocellular carcinoma is the frequent comorbidities and the associated socio-health variables (substance abuse, addictions, unfavorable economic or family circumstances), which can impact patient management or the possibilities for long-term monitoring, thus influencing the choice of the most appropriate therapeutic pathway. The healthcare services offered in the Province of Salerno (Campania Region, Southern Italy) to ensure all possible diagnostic and therapeutic options for these patients can be difficult to access due to the territorial extension of the Local Health Authority, characterized by clinics and hospitals located in distant locations, as well as the potential fragmentation of expertise between the University Hospital and ambulatorial facilities or small hospitals. An interdisciplinary consensus conference on the management of patients with HCC has been set with the aim of involving clinicians and surgeons working in healthcare facilities located in Salerno and its Province for the optimal care and effective management of these patients, taking into account all the clinical characteristics of the disease and individual health needs or expectations, from the perspective of personalized medicine. Full article

Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article

Circulating tumor DNA (ctDNA) was initially conceived as a minimally invasive surrogate for interrogating cancer biology; however, three decades of evidence have demonstrated that plasma is not a passive reservoir of tumor-derived material, but rather a dynamic and biologically heterogeneous milieu in which multiple competing genomic signals coexist. This review explores the level of interpretive rigor required to translate ctDNA detection into clinically actionable precision oncology. Clonal hematopoiesis of indeterminate potential (CHIP) is discussed not as an occasional confounder, but as an intrinsic source of biological background noise, underscoring the critical importance of matched leukocyte sequencing to discriminate tumor-derived alterations from hematopoietic variants, particularly in older individuals and in patients previously exposed to cytotoxic therapies. The widespread assumption that variant allele frequency (VAF) directly reflects tumor burden is critically re-evaluated through the mathematical relationships linking VAF to tumor fraction, local copy-number architecture, and mutation multiplicity. Within this framework, estimation of cancer cell fraction (CCF) and probabilistic discrimination between clonal and subclonal events are examined, including the emergence of reversion mutations as molecular evidence of therapy-driven evolutionary adaptation. The review also addresses the central paradox of ultra-sensitive sequencing technologies: although unique molecular identifiers and duplex sequencing can extend analytical sensitivity below 0.01% VAF, sensitivity in the absence of contextual specificity risks conflating technical artifacts and biologically insignificant alterations with clinically meaningful disease. Equal emphasis is placed on pre-analytical variables, highlighting how sample collection, stabilization, and processing protocols define the upper limit of downstream analytical reliability. Beyond single-nucleotide variants, fragmentomic and methylation-based approaches are presented as complementary orthogonal dimensions capable of revealing tumor-associated signals even when mutational evidence is limited or absent. Longitudinal ctDNA assessment is argued to provide substantially greater biological and clinical insight than isolated static measurements, while robust clinical reporting is shown to depend on transparent disclosure of assay limitations, residual uncertainty related to CHIP, and structured bidirectional communication between molecular laboratories and treating clinicians. Ultimately, the transition from a biomarker-centered model toward an integrated systems-based framework, combining genomics, epigenomics, fragmentomics, and evolutionary modeling, emerges as the defining challenge for the next generation of liquid biopsy in precision oncology. Full article

Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous mature B-cell neoplasm whose classification, prognosis, and therapy have been reshaped by advances in genomic, transcriptomic, epigenomic, single-cell, and spatial profiling technologies. This review focuses on how these approaches have refined the molecular landscape of DLBCL, including recurrent chromosomal translocations, tumor-suppressor alterations, oncogenic signaling pathways, and tumor-microenvironment programs. Cell-of-origin (COO) frameworks remain clinically useful. However, contemporary models extend beyond conventional germinal center categories by incorporating probabilistic genetic subtypes, expression-defined high-risk states, and spatially resolved lymphoma-cell and immune-cell ecosystems. These high-resolution methods clarify intratumoral heterogeneity, identify biologically distinct subgroups, and inform prognosis and therapeutic selection. The review also summarizes how tumor-intrinsic biology and the tumor-microenvironment (TME) shape responses to frontline therapy, targeted agents, antibody-drug conjugates, bispecific antibodies, and CD19-directed CAR T-cell therapy. Particular emphasis is placed on product-specific evidence in relapsed/refractory disease, rational sequencing of immunotherapies, and emerging biomarkers such as circulating tumor DNA-based measurable residual disease (ctDNA-MRD). Together, these developments support a shift from COO-centric classification toward dynamic, biology-driven models that incorporate tumor-intrinsic and microenvironmental determinants to guide personalized therapy in DLBCL. Full article

Transformer, with its unique self-attention mechanism, naturally excels in modeling global features. Convolutional Neural Networks (CNNs), on the other hand, leverage strong spatial inductive biases to effectively capture local features with fewer parameters. In 3D brain tumor segmentation, both local and global features are critical. Moreover, balancing high accuracy with computational cost in 3D segmentation models remains a key challenge. To address this, we propose TransLiteUNet, a lightweight 3D solution that combines CNN and Transformer architectures for accurate brain tumor segmentation without pretraining. To enhance parameter efficiency, we introduce a 3D axial depthwise separable convolution residual structure (3DRes-ADS block) and a lightweight LiteViT module, which improves global feature modeling at a lower computational cost. Specifically, TransLiteUNet (0.43 M parameters, 14.98 GFLOPs) and its simplified version, TransLiteUNet-S (0.31 M parameters, 7.68 G FLOPs), offer significantly lower model complexity compared to current state-of-the-art models. Tested on two publicly available datasets, our models outperform leading models under identical conditions. The parameter and computational costs are reduced by orders of magnitude, with optimized inference and training costs. Full article

Accurate, automated delineation of adult diffuse gliomas from multi-parametric magnetic resonance imaging (mpMRI) is central to quantitative neuro-oncology. Volumetric 3D networks dominate the BraTS leaderboard but require expensive GPUs, long training cycles, and provide diminishing returns relative to their compute budget. Slice-wise 2D models, by contrast, discard inter-slice context that is informative for thin tumor rims and small enhancing foci. We introduce GDNet, a 2.5D multimodal MRI segmentation framework for adult glioma evaluated on the BraTS 2024 cohort. GDNet consumes a stack of three adjacent axial slices from the four standard BraTS modalities (T1, T1ce, T2, FLAIR) as a 12-channel input to a compact U-shaped encoder–decoder with Group Normalization and predicts whole tumor (WT), tumor core (TC), and enhancing tumor (ET) masks for the central slice. The training pipeline pairs the 2.5D backbone with: (i) Exponential Moving Average (EMA) of model weights with decay 0.999, (ii) mixed tumor-aware slice sampling (p_tumor = 0.50), (iii) a compound Cross-Entropy + Soft-Dice loss, and (iv) AdamW with warm-up plus cosine annealing under Automatic Mixed Precision. We performed a systematic, step-by-step ablation covering a 2D baseline, EMA + mixed sampling, tumor-centered crop fine-tuning, a GDNet-inspired architectural integration, a region-aware loss, 3-slice and 5-slice 2.5D inputs, and connected-component post-processing, and we report multi-seed results to quantify reproducibility. On the held-out BraTS 2024 test partition, the final 3-slice 2.5D GDNet achieved positive-only Dice scores of 0.791 ± 0.000 (WT), 0.736 ± 0.003 (TC), 0.654 ± 0.004 (ET), and a mean foreground positive-only Dice of 0.820 ± 0.000 across seeds; the all-slice mean foreground Dice exceeded 0.927 ± 0.000. Validation positive-only scores were 0.805 ± 0.002 (WT), 0.757 ± 0.004 (TC), 0.683 ± 0.009 (ET). The inter-seed standard deviation was small for every region (≤0.01 Dice points), indicating low inter-seed variance across the two seeds evaluated; with only two seeds, we regard this as preliminary evidence of training stability rather than a strong reproducibility claim. The ablation isolated EMA + mixed tumor sampling and the 2.5D context window as the dominant sources of improvement; notably, a GDNet-style architectural integration with a region-aware loss did not outperform the simpler 2.5D U-Net on positive-only WT/TC/ET, and light post-processing improved only all-slice Dice. A failure-mode audit found that the residual catastrophic predictions are concentrated on a small minority of diffuse, infiltrative tumors with mass effect. Conclusions: Carefully engineered training strategies, tumor-aware sampling, EMA stabilization, and a modest 2.5D context window recover a substantial fraction of the accuracy of much heavier 3D networks at a fraction of the compute, are reproducible across seeds, and outperform a heavier GDNet-inspired architectural variant on the same data. GDNet is therefore a practical and, pending external validation, potentially clinically deployable framework for multimodal glioma segmentation on workstation-class GPU hardware. Full article

For decades, peritoneal metastases (PM) have been regarded as a terminal manifestation of advanced malignancies and managed primarily with palliative intent because of limited sensitivity to systemic therapies. Accumulating clinical, molecular, and immunological evidence now supports the view that PM is not merely an anatomic pattern of spread but a distinct metastatic niche with characteristic biological, microenvironmental, and therapeutic features. This review summarizes the major routes of PM development—transcoelomic, lymphatic, and hematologic dissemination—and emphasizes how these pathways converge through shared biological programs. Core mechanisms include epithelial–mesenchymal transition (EMT), adhesion signaling, extracellular matrix remodeling, and tumor–immune cell interactions. A central focus is the peritoneal tumor microenvironment: mesothelial-to-mesenchymal transition, cancer-associated fibroblast activity, adipocyte-derived metabolic support, macrophage polarization, and regulatory T-cell enrichment collectively shape an immunotolerant and treatment-resistant niche on the peritoneal surface. In addition, evidence from pre-metastatic niche biology suggests that primary tumor-derived exosomes and epitranscriptomic regulation can prime the peritoneal environment before overt implantation. These features provide a biological rationale for locoregional strategies such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, as well as emerging intraperitoneal modalities and microenvironment-targeted approaches. Finally, organoid platforms, liquid biopsy-based minimal residual disease monitoring, and theranostic technologies may enable more personalized, biology-driven management of PM. Full article

Background/Objectives: Low skeletal muscle index (SMI) has been linked to adverse outcomes in colorectal cancer, but its association with local pathological tumor extent is less clear. This study examined whether preoperative CT-derived SMI was associated with pathological T4 disease in patients undergoing colorectal cancer resection. Methods: This retrospective single-center observational study included 147 consecutive adults who underwent colorectal resection for histologically confirmed adenocarcinoma between January 2022 and November 2025 and had suitable preoperative abdominal or abdomino-pelvic CT imaging within 90 days before surgery. Skeletal muscle area was measured on a single axial CT image at the L3 level, and SMI was calculated as muscle area/height². Patients were classified as having pathological T1–3 or T4 disease. Logistic regression assessed the association between SMI, expressed per 5 cm²/m² increase, and pathological T4 stage. Results: Patients with pathological T4 tumors had lower SMI than those with T1–3 disease (37.22 vs. 42.85 cm²/m², p = 0.016). Higher SMI was associated with lower odds of T4 disease in univariable analysis (OR 0.79, 95% CI 0.66–0.94; p = 0.008) and after adjustment for age and sex (OR 0.77, 95% CI 0.63–0.94; p = 0.009). Conclusions: Lower preoperative SMI was associated with pathological T4 colorectal cancer in this cohort. Because of the retrospective observational design, causality cannot be inferred. The association should be interpreted as hypothesis-generating and may reflect reverse causality, shared inflammatory–nutritional pathways, or residual confounding. Full article

Background: Predicting tumor regression following neoadjuvant chemoradiotherapy (nCRT) remains a major challenge in the management of locally advanced rectal cancer (LARC). Readily available inflammatory biomarkers may provide useful information regarding treatment response. Methods: This retrospective single-center study included 88 patients with stage II–III rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by curative-intent surgery between 2017 and 2025. Patients were classified according to the College of American Pathologists tumor regression grading system as CAP 0 (pathological complete response, n = 22), CAP 2 (partial response, n = 50), or CAP 3 (poor/no response, n = 16). Pretreatment C-reactive protein, carcinoembryonic antigen (CEA), neutrophil, platelet, monocyte, and lymphocyte counts, together with NLR, PLR, and PIV, were compared across groups. Receiver operating characteristic and logistic regression analyses were performed for pathological complete response (pCR). Results: None of the evaluated biomarkers differed significantly across CAP groups. The smallest omnibus p-values were observed for neutrophil count (p = 0.052), monocyte count (p = 0.075), and CEA (p = 0.088). Monocyte count showed the highest discriminatory performance for pathological complete response (AUC = 0.663), followed by CEA (AUC = 0.640). In sensitivity analyses adjusted for baseline clinical T stage and receipt of total neoadjuvant therapy, CEA, neutrophil count, and monocyte count were not independently associated with pathological complete response. More favorable tumor regression was associated with lower residual tumor burden and reduced nodal involvement. Conclusions: Pretreatment inflammatory biomarkers showed biologically plausible numerical patterns across tumor regression groups, but their discriminatory and independent predictive performance was limited. These markers should not be considered stand-alone clinical prediction tools and should be validated within larger, multimodal prospective models. Full article

The laminin-derived nonapeptide CDPGYIGSR contains the bioactive YIGSR motif, historically associated with inhibition of tumor cell adhesion, invasion, angiogenesis, and laminin-receptor-mediated cell responses. Although these activities have often been attributed to the 37/67 kDa laminin receptor/RPSA axis, the molecular identity and organization of the laminin-binding receptor system remain debated. This uncertainty makes it essential to define the intrinsic conformational preferences of CDPGYIGSR in solution before assigning a unique receptor-bound structure. In this study, temperature replica-exchange molecular dynamics (T-REMD) simulations in explicit solvent are employed to characterize the solution conformational ensemble of CDPGYIGSR. Free energy landscape analysis, clustering, and structural descriptors reveal a predominant compact bend-like backbone arrangement, together with alternative low-lying conformational states within a heterogeneous ensemble. Rather than assuming a single bioactive conformation, the conformational ensemble is analyzed in terms of structural features that are consistent with available NMR observations and reported structure–activity relationships. Importantly, the most populated conformations in solution do not necessarily correspond to the bioactive state upon receptor binding. Instead, a subset of conformations sharing common structural motifs, including a central backbone bend and specific residue exposure patterns, may represent states compatible with receptor recognition. These results provide an ensemble-based structural framework that connects simulation-derived conformational motifs with available NMR observations and structure–activity data, supporting a recognition-compatible ensemble model in which compact preorganized states may contribute to receptor binding. Full article

KRAS is one of the most frequently mutated oncogenes in human cancer and has long been considered an “undruggable” therapeutic target because of its high affinity for guanine nucleotides and limited druggable binding pockets. Recent advances in structural biology and molecular pharmacology have transformed this paradigm, leading to the successful development of KRAS G12C inhibitors such as sotorasib and adagrasib. These agents established proof-of-concept for direct KRAS inhibition and marked an important advance in precision oncology. However, intrinsic and acquired resistance mechanisms, adaptive signaling reactivation, and tumor heterogeneity continue to limit the durability of clinical responses. Therapeutic development has rapidly expanded beyond KRAS G12C toward broader strategies including KRAS G12D inhibitors, pan-RAS and RAS(ON) inhibitors, degraders, and biomarker-guided combination approaches. In parallel, circulating tumor DNA (ctDNA) and other biomarker-driven strategies are increasingly enabling dynamic monitoring of treatment response, minimal residual disease, and resistance evolution. In this review, we summarize the molecular biology and conformational regulation of KRAS signaling, recent advances in allele-specific and pan-RAS therapeutic strategies, mechanisms of resistance, and emerging precision oncology frameworks for KRAS-mutant cancers. Full article

Glioblastoma multiforme (GBM) remains one of the most aggressive primary brain tumors with poor prognosis despite multimodal therapy. Photodynamic therapy (PDT) using indocyanine green (ICG) is an emerging adjuvant approach aimed at eliminating residual tumor cells after resection. While ICG-PDT exerts cytotoxic effects, its impact on molecular pathways regulating programmed cell death in glioma cells is not fully understood. In this study, T98G and U-118MG glioblastoma cells were divided into four groups: untreated control, light-only (10 min broadband irradiation), ICG-only (15 min incubation), and ICG-PDT (15 min ICG + 10 min broadband irradiation). Relative mRNA expression of apoptosis-related genes (BAX, BCL2, CASP3, FAS) and ferroptosis-related genes (GPX4, ACSL4, SLC7A11, GCH1) was quantified 24 h post-treatment by RT-qPCR using the 2^−ΔΔCt method. ICG-PDT significantly reduced cell viability to 67.79% ± 3.39% (vs. 86.66% ± 4.33% in control), confirming effective phototoxicity. No statistically significant differences in mRNA levels were observed for any of the investigated genes across the groups (one-way ANOVA and Kruskal–Wallis, all p > 0.05). The largest non-significant deviation was a mild decrease in GPX4 (fold change 0.87) in the ICG-PDT group. Fluctuations in GCH1 were accompanied by high variance, likely reflecting technical noise rather than a true biological trend. The mRNA BAX/BCL2 ratio remained stable (~30) across all conditions. In contrast, the U-118MG line showed greater transcriptional sensitivity, with statistically significant decreases in CASP3 (p = 0.012) and ACSL4 (p = 0.031) expression, along with downward trends in BCL2 and GPX4 following ICG-PDT. ICG-PDT does not induce significant transcriptional changes in the analyzed genes T98G at the 24 h time point under the applied experimental conditions. In U-118MG cells, moderate transcriptional engagement of both apoptotic and ferroptotic routes was observed. Further studies at the protein and functional levels, across multiple time points and models, are warranted to fully elucidate the mechanisms of ICG-PDT in glioblastoma. Full article

Background: Pancreatic resection (Pancreatoduodenectomy, PD, distal pancreatectomy, DP, or total pancreatectomy, TP) is the standard of care for resectable pancreatic adenocarcinoma (PDAC). Despite advances in multimodal therapy, recurrence rates remain high, approaching 80%, and continue to drive poor overall survival. Objective: This review evaluates the burden and clinical significance of localized recurrence in PDAC and critically examines the potential role of intraoperative radiation therapy (IORT) in improving locoregional disease control. Results: Distant recurrence remains the predominant pattern of failure, occurring in 55–75% of patients, most commonly involving the liver, lungs, and peritoneum. However, isolated local recurrence, observed in approximately 17–32% of patients, represents a clinically meaningful subset associated with significant morbidity and potential for subsequent metastatic progression. IORT, delivered as a single high-dose radiation treatment to the tumor bed at the time of surgery, enables precise targeting of areas at highest risk for residual microscopic disease while minimizing radiation exposure to adjacent radiosensitive structures. Retrospective and meta-analytic data, while limited, suggest that IORT is associated with improved local control and modest survival benefit without a significant increase in perioperative morbidity, though interpretation is limited by study heterogeneity and lack of randomized control trials. Conclusion: IORT represents a rational adjunct in the multimodal management of PDAC, particularly for patients at high risk of locoregional failure, including those with borderline resectable or locally advanced disease, nodal involvement, perineural invasion, or concern for margin positivity. Prospective studies are needed to better define optimal patient selection and to clarify the role of IORT in the modern treatment paradigm. Full article