Search Results (12,527)

Background: MGMT-methylated glioblastomas respond well to temozolomide-based standard of care (Stupp protocol), demonstrate longer survival as compared to unmethylated tumors, and carry an increased risk of pseudo-progression. Establishing time to first true progression can serve as a non-invasive clinical reference point to distinguish true from pseudo-progression. Objective: To define the time to first true progression in patients with MGMT-methylated glioblastoma who were treated with the standard of care/Stupp protocol. Methods: We conducted a retrospective analysis from our institutional database of MGMT-methylated glioblastoma patients from 2018–2024. Time to first progression was measured from initial surgery to first true progression, as determined by a multidisciplinary team based on radiographic imaging review and/or pathology. Results: Fifteen patients met eligibility criteria. Median time to first progression of MGMT-methylated glioblastoma patients who received standard of care was twenty-one months. 40% of patients remained progression-free beyond thirty-six months after their initial surgery. Conclusions: Most patients with MGMT-methylated glioblastomas do not develop true progression within the first year and a half post-operatively. Therefore, MRI changes on surveillance scans should be carefully interpreted within this time frame. Expected timeline for true progression, alongside advanced radiographic imaging techniques and knowledge of treatment-specific pseudo-progression risk, may improve diagnostic accuracy. Full article

Does mandatory sustainability disclosure improve the quality of corporate financial reporting immediately, gradually, or with delay? We address this question using Saudi Arabia’s January 2021 Tadawul ESG Disclosure Guidelines—the first comprehensive sustainability disclosure framework in the Gulf Cooperation Council and a uniform, accurately dated regulatory shock affecting all listed firms. Using a balanced panel of 135 non-financial firms over 2017–2024 (1080 firm-year observations), we estimate absolute discretionary accruals from the Modified Jones Model and employ event-time fixed-effects regressions with Driscoll–Kraay standard errors robust to heteroskedasticity, autocorrelation, and cross-sectional dependence. We document a temporal paradox: reporting quality did not change in the announcement year (2021), deteriorated significantly in 2022 (+28%) and 2023 (+38%) relative to the pre-reform baseline, and then improved significantly in 2024 (−17%). The pattern survives performance-matched discretionary accruals, exclusion of the 2020 COVID-19 year, a placebo test, sectoral disaggregation across nine Tadawul-aligned industry groups, and a battery of pre-reform firm characteristics. Heterogeneity analysis identifies the underlying mechanism: voluntary pre-2021 ESG disclosers and firms with stronger pre-reform governance exhibit amplified short-run deterioration, while larger firms with pre-existing reporting infrastructure show a substantially attenuated paradox. These patterns are jointly consistent with the adjustment-cost mechanism we develop: the reform redirected scarce reporting governance toward the new disclosure margin during a three-year compliance buildout, after which the constraining effect on accrual-based earnings management emerged. The findings carry direct implications for the design and evaluation of mandatory sustainability disclosure reforms currently advancing across emerging and developed markets. Full article

Background/Objectives: Minimally invasive (MIS) mitral valve surgery has been proven to be a safe and effective alternative to median sternotomy (ST), with advantages in postoperative recovery and morbidity. However, its role in the setting of infective endocarditis (IE) remains uncertain. This meta-analysis aims to evaluate the outcomes of MIS in mitral valve surgery for infective endocarditis. Methods: A PRISMA-compliant search for studies including patients undergoing MIS for mitral valve IE was performed through 14 January 2026, in PubMed, Scopus and Cochrane. Time-to-event data were reconstructed from published Kaplan–Meier curves. A secondary comparative analysis focusing on MIS versus ST techniques was conducted. Results: Fourteen retrospective studies comprising 949 patients were analyzed. In the MIS cohort, early mortality was 4.2% (95%CI: 1.8%, 7.4%). Overall survival was 86.7% at 1 year, 75.2% at 5 years and 56.2% at 10 years. Freedom from IE-related reoperation remained high at 97.5%, 95.9%, and 90.7% at 1, 5, and 10 years, respectively. Mitral valve repair was performed in 52.5% of patients. In secondary comparative analyses, overall survival at 4-year follow-up was not different between MIS and ST [HR: 0.82 (95%CI: 0.43, 1.57), p = 0.55]. MIS was associated with a significantly shorter intensive care unit (ICU) stay [MD: −1.52 days (95%CI: −2.08, −0.97), p < 0.01]. Conclusions: MIS for mitral valve IE is associated with favorable early and long-term outcomes, comparable survival with sternotomy, and reduced ICU stay. These findings suggest that MIS may be considered as a feasible and potentially effective alternative for the management of mitral valve IE in carefully selected patients. Further prospective comparative studies are warranted. Full article

Background: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) is a potential strategy for glioma treatment, but effective intracranial delivery remains a major obstacle. Convection-enhanced delivery (CED) may improve local parenchymal coverage by bypassing the blood–brain barrier and using pressure-driven interstitial transport. Methods: We evaluated whether CED could improve the early intracerebral distribution and antitumor activity of ex vivo-expanded TILs in an orthotopic rat C6 glioma model. Expanded TILs were characterized as a CD3-enriched lymphocyte product with inducible effector function against C6 glioma cells in vitro. TILs were administered as either Control-TILs by Hamilton syringe-based conventional intratumoral injection or CED-TILs by catheter-based CED infusion using matched cell dose, volume, infusion rate, target coordinates, and dwell time. Intracerebral CD3⁺ T-cell coverage, tumor progression, and overall survival were assessed. Short-term safety was evaluated in a separate cohort of naïve rats receiving CED-PBS or CED-TILs. Results: CED-TILs produced broader early intraparenchymal CD3⁺ T-cell coverage than Control-TILs, particularly at distal sampling sites from the infusion tract. Under this single-dose regimen, CED-TILs were associated with reduced tumor progression, decreased Ki67 expression, increased apoptosis-associated signaling, and prolonged survival. In the short-term naïve safety cohort, CED-TILs did not produce overt neurologic, histologic, hematologic, or systemic toxicity within the observation window. Conclusions: These findings support CED-TILs as an early proof-of-concept locoregional delivery strategy that improves early spatial CD3⁺ T-cell coverage and is associated with antitumor activity in a rat glioma model. Full article

Background/Objectives: Older adults often experience difficulties in smartphone use, especially when digital tasks require goal maintenance, visual search, sequential action, and response verification. Working memory and parietal theta-band activity may support these cognitively demanding operations, but it remains unclear whether a single session of theta-frequency high-definition transcranial alternating current stimulation (HD-tACS), centered over CP5 as a parietal scalp location intended to approximate the left inferior parietal region, is associated with short-term changes in smartphone-task performance in aging. Methods: This study examined performance in a controlled smartphone-based shopping task and exploratory post-stimulation EEG correlates. In Experiment 1, 40 older adults were randomly assigned to active HD-tACS or sham stimulation. In Experiment 2, 28 older adults completed a reduced-trial EEG extension of the same task with electroencephalography (EEG) recording before and after stimulation. Results: Active stimulation improved smartphone-task performance, including faster completion under high cognitive load, higher target selection accuracy, and reduced difficulty–time slope. Working-memory performance on a two-back task was also improved, and individual differences in working-memory gains were associated with improvements in smartphone-task efficiency. Active HD-tACS most strongly improved target selection accuracy, and exploratory post-stimulation theta-power changes in posterior/parietal regions may have accompanied high-demand target-selection-accuracy improvement. These neural findings should be interpreted cautiously because the omnibus EEG effects were trend-level, EEG–behavior correlations were based on a small active-stimulation subgroup, data-quality sensitivity analyses indicated artifact-related instability in theta-power estimates, and the full exploratory EEG–behavior correlation matrix did not survive FDR correction. Conclusions: These findings provide short-term behavioral evidence that CP5-centered parietal HD-tACS may support performance in a cognitively demanding smartphone-based task and motivate further work at the intersection of neuromodulation, cognitive aging, and human–technology interaction. Full article

Antimicrobial resistance is increasing, necessitating the development of novel and efficacious therapies. Plants contain phytochemicals, some of which may possess antibacterial properties. This research employed broth dilution experiments to investigate the antibacterial efficacy of fifteen phytochemicals identified in medicinal plant extracts. The sum of fractional inhibitory concentration of phytochemicals in conjunction with reference antibiotics were also analysed. The inhibitory effects of phytochemicals against β-lactamase were evaluated to explore their potential mechanisms of action. The phytochemicals were evaluated for toxicity on human dermal fibroblast cells. Gallic acid and luteolin significantly inhibited Staphylococcus aureus and the methicillin-resistant S. aureus (MRSA) strain, with minimum inhibitory concentration (MICs) of 62.5 µg/mL. Gallic acid also demonstrated restricted efficacy against Gram-negative species, with MICs ranging from 312.5 to 1250 µg/mL. Gram-negative bacteria exhibited no response to luteolin. Ellagic acid, catechin, naringenin, and quercetin exhibited moderate antibacterial efficacy against the tested pathogens (625–2500 µg/mL MIC). Corilagin exhibited significant antibacterial activity against S. aureus and MRSA, with a MIC of 7.81 µg/mL. Corilagin also exhibited notable efficacy against Bacillus. cereus, Shigella flexneri, and Klebsiella pneumoniae, with MICs ranging from 62.5 to 250 µg/mL. Fractional inhibitory concentration studies revealed a synergistic effect between amoxicillin and corilagin against B. cereus. Additionally, catechin, luteolin, and quercetin synergised penicillin G against S. aureus. Quercetin potentiated the activity of β-lactams (amoxicillin, penicillin G, and oxacillin) against MRSA. Notably, these antibiotics were ineffective against MRSA alone. Isobologram analysis revealed potentiation between penicillin G and quercetin against MRSA at all tested ratios. The β-lactamase inhibitory activity of the phytochemicals was evaluated using a commercial screening kit, and the percentage of relative inhibition was determined. Quercetin and luteolin both inhibited β-lactamase, achieving relative inhibition rates of 77–100% across two-time intervals. All phytochemicals were nontoxic against human dermal fibroblasts. Indeed, quercetin enhanced cell survival by 200%. Full article

Background: Metastasis and poor chemotherapy response have stagnated therapeutic progress in osteosarcoma (OS) for the past three decades. Defining the transition from localized to metastatic OS before overt dissemination is fundamental for improving survival. However, effective early diagnostic tools remain scarce, largely due to limited exploitation of the metastasis-associated tumor microenvironment’s own record of prior environmental and stress exposures encoded in cell-intrinsic transcriptional states. Here, we employed a supervised machine learning framework with iterative resampling and multi-stage model selection to identify molecular markers associated with metastasis in osteosarcoma and to develop a computational signature, Auto-RS. Methods: Transcriptomic and clinical data from 139 OS patients with ≥5 years of follow-up were analyzed. A LASSO–Cox framework was applied to derive a gene expression-based risk score, Auto-RS, from which a nomogram integrating age and sex was generated for individualized prognosis. Model interpretability was assessed across six independent single-cell OS patient datasets, and drug sensitivity predictions were inferred by integrating Auto-RS with the Precily algorithm to uncover actionable therapeutic vulnerabilities. Results: Auto-RS, constructed from the expression of four autophagy genes (BNIP3, MYC, PEA15, and SAR1A), served as an independent prognostic factor for overall survival (HR = 1.091; 95% CI, 1.047–1.136; p < 0.001). Time-dependent ROC analysis showed that Auto-RS was the most accurate single predictor (AUC = 0.88), exceeding metastasis (0.83), sex (0.45), and age (0.39). A basic prognostic model (BpM) incorporating metastasis status yielded a C-index of 0.741 (95% CI, 0.679–0.803). The addition of Auto-RS (CpM) improved discrimination (C-index = 0.788; 95% CI, 0.731–0.845), whereas a model without metastasis information (ApM) retained predictive ability (C-index = 0.709; 95% CI, 0.640–0.778). Single-cell analysis confirmed that Auto-RS features aligned with known metastatic trajectories, reflecting the transition from proliferative to invasive tumor states and highlighting coordinated programs among cancer-associated fibroblasts and immune cells. Drug sensitivity integration through Precily identified gemcitabine and cytarabine as FDA-approved agents predicted in silico to show greater sensitivity in the high-risk subgroup. Conclusions: We identified autophagy-mediated transcriptional ‘stress fingerprints’ that are tightly associated with OS metastasis. The Auto-RS signature, composed of BNIP3, MYC, PEA15, and SAR1A, enables early therapeutic stratification of patients independent of overt metastatic status. Moreover, Auto-RS delineates key molecular underpinnings of OS metastasis at single-cell resolution. As a practical laboratory tool, Auto-RS may represent a step toward improved risk stratification, where advances in metastasis prediction and therapeutic guidance converge to improve outcomes in OS. Full article

The long-term reliability of stay cables is essential to the structural integrity of cable-stayed bridges, particularly under the coupled effects of high stress ratios, progressive corrosion, and local stress concentrations. Conventional fatigue formulations—such as S–N curves or static Weibull models—are inadequate for representing the nonlinear and stochastic nature of corrosion-fatigue deterioration. This study develops a time-dependent reliability model formulated within a four-parameter Weibull framework, where the shape and scale parameters evolve as functions of the corrosion rate and stress ratio. The corrosion evolution is modeled by an exponential function of exposure time, establishing a temporal coupling between mechanical loading and environmental degradation. Analytical derivations yield closed-form expressions for the time-dependent hazard function ℎ(t) and survival function R(t), providing explicit reliability evaluation without iterative computation. At the system level, a series–parallel reliability model is constructed by integrating wire-level degradation with a load redistribution function that captures sequential wire failures. Model parameters are estimated using a maximum-likelihood method based on 99 experimental datasets, and Monte Carlo simulations are performed to assess stochastic reliability evolution under varying corrosion intensities. The findings show that models incorporating corrosion evolution and stress-amplification effects consistently predict earlier fatigue failure than those based on the conventional assumption of constant corrosion, thereby offering a more conservative and realistic representation of structural degradation. The proposed framework is mathematically tractable and broadly applicable, enabling rigorous corrosion–fatigue reliability assessment for cable-stayed structures and other complex multi-component systems. Full article

Background: Antibiotics are commonly prescribed to patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy; however, peri-treatment antibiotic use may adversely affect patients’ outcomes. Methods: A retrospective cohort study was conducted. The association between antibiotic use and patients’ survival time was analyzed using Kaplan–Meier and Cox proportional hazards regression models. Results: Among 455 NPC patients, 42.0% received antibiotics around primary treatment. Patients who had an advanced tumor stage (p = 0.019) or had received neoadjuvant chemotherapy (p = 0.008) or concurrent chemoradiotherapy (p = 0.002) were more likely to be prescribed antibiotics. Univariate analysis showed that antibiotic use around primary treatment was associated with worse disease-specific survival (DSS) at both 5 years (p = 0.043) and 10 years (p = 0.019). Subgroup analysis showed that 5-year and 10-year DSS were significantly shortened in patients receiving RT only and Abx within 2 w or 1 w around RT (5-year: 2 w p = 0.001, 1 w p < 0.001; 10-year 2 w p < 0.001, 1 w p = 0.005). Conclusions: In NPC, antibiotic use around primary treatment was associated with poorer disease-specific survival. Further prospective studies are warranted to clarify the causality and underlying mechanisms. Full article

Background/Objectives: The Mini-Mental State Examination (MMSE) often shows ceiling effects in community-dwelling older adults, limiting the detection of subtle functional vulnerability. We examined whether an age-adjusted score derived from the Color Kanji Pick-Out Test (CKPT) app could identify functional heterogeneity among older adults with near-ceiling MMSE scores. Methods: In this cross-sectional study, 155 community-dwelling older adults aged ≥65 years underwent CKPT app assessment. An age-adjusted score (ΔINDEX1) was calculated as the residual from a linear regression of INDEX1 on age, and participants were classified into two groups using a median split. Group differences in cognitive, physical, psychological, and lifestyle variables were examined across 70 indicators retained after consolidation (Spearman’s |r| ≥ 0.75). Effect sizes (rank-biserial r and Cramer’s V) were reported, and false discovery rate (FDR) correction was applied (Benjamini–Hochberg). Results: MMSE scores were uniformly high in both the ΔINDEX1 groups (median 29–30, p = 0.138). Of the 70 indicators, 10 reached uncorrected significance (p < 0.05). After FDR correction, both Timed Up and Go (TUG) time (p < 0.001, r = 0.33, q = 0.029) and maximum walking speed (p = 0.001, r = 0.30, q = 0.044) remained statistically significant. Other uncorrected associations (single-leg stance, step length, usual walking speed, sarcopenia, bodily pain, and BMI) did not survive FDR correction and should be regarded as exploratory. Conclusions: Age-adjusted CKPT app profiling was associated with mobility-related differences in TUG and maximum walking speed, both significant after FDR correction, despite uniformly high MMSE scores. Psychosocial and lifestyle associations were preliminary and require confirmation in future studies. Because ΔINDEX1 was both derived and tested within the same predominantly female sample (86.5% women), these cross-sectional findings require external validation before generalization, particularly in older men. Full article

Background/Objectives: Early allograft dysfunction (EAD) is a common complication after liver transplantation and is associated with inferior graft survival. While normothermic machine perfusion (NMP) has reduced EAD incidence, the prediction of early graft performance prior to implantation remains elusive. We aimed to correlate the peri-transplant energetic and metabolic profile of liver grafts with post-transplant outcome in a cohort that included grafts preserved with NMP. Methods: Sequential biopsies were taken from 20 transplanted livers (10 immediate graft function [IGF] and 10 EAD), preserved by either static cold storage or NMP. Samples were collected immediately prior to implantation and 30 min after hepatic arterial reperfusion. Untargeted liquid chromatography-mass spectrometry was performed, and energy charge was calculated as (ATP + 1/2 ADP)/(ATP + ADP + AMP). Univariate and receiver operating characteristic analysis identified metabolites correlated with EAD and assessed predictive accuracy. Results: Hepatic concentrations of adenine nucleotides and calculated energy charge did not differ between outcome groups either before implantation or after reperfusion. In contrast, trans-urocanate was significantly enriched in IGF livers across both time points, and additional histidine catabolism pathway metabolites were preferentially increased in IGF grafts. Trans-urocanate demonstrated discriminatory performance for EAD with 80% sensitivity and 80% specificity, confirmed as the single strongest predictive feature among >1600 detected metabolites. Conclusions: These data identify histidine catabolism as a novel metabolic pathway associated with early graft function and a potential indicator of allograft resilience to ischemia-reperfusion injury. Integration of histidine pathway metabolites into perfusion-era viability assessment may serve as a discriminative biomarker of EAD and support future metabolite-guided graft optimization strategies. Full article

Background: Current cardiopulmonary resuscitation (CPR) guidelines recommend a uniform chest compression depth (5–6 cm) for all adults, disregarding anatomical variability. The primary objective was to determine whether thoracic anthropometric parameters are associated with 28-day mortality after in-hospital cardiac arrest (IHCA); the secondary objective was whether these associations vary with CPR duration. Methods: In this retrospective single-center cohort, 431 adults with IHCA and available chest computed tomography (CT) were analyzed. Body mass index (BMI), internal anteroposterior diameter (IAPD), and external anteroposterior diameter (EAPD) were measured. Patients were stratified by CPR duration (≤5, 5–10, >10 min), and multivariable logistic regression with interaction terms tested time-dependent effects on 28-day mortality. Results: Overall 28-day survival was 40.8% (176/431). During the early phase (≤5 min), higher BMI, IAPD, and EAPD were each associated with increased mortality, and underweight patients had lower mortality than normal-weight and overweight patients. These anatomical associations attenuated and lost significance during prolonged resuscitation (>10 min), when CPR duration dominated outcomes. Conclusions: The prognostic value of body composition after IHCA is time-dependent, being greatest during the first five minutes, supporting individualized, body composition-guided chest compression—particularly using readily available BMI—during early resuscitation. Full article

Background/Objectives: Nivolumab monotherapy is a standard of care in previously treated advanced renal cell carcinoma (aRCC) and was approved based on the results of the randomized clinical trial Checkmate-025. The non-interventional study (NIS) NORA collected data on the effectiveness and safety of nivolumab monotherapy in real-world clinical routine. Its final, long-term follow-up data are presented here. Methods: NORA was a prospective, multicentre NIS recruiting at 54 German sites, evaluating the effectiveness and safety of nivolumab monotherapy in pre-treated patients with aRCC. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), safety, and patient-reported outcomes (PROs). Results: A total of 232 patients were eligible. Of the patients, 15% had favourable, 58% had intermediate, and 15% had poor risk according to the International Metastatic RCC Database Consortium. Of the patients, 77% received nivolumab as second-line, 15% as third-line, and 8% as ≥fourth-line therapy. With a median long-term follow-up of 76 months (minimum 62 months), median OS was 22.2 months (95% confidence interval [CI] 16.5–25.9) and median PFS was 4.1 months (95% CI 3.2–5.4). The ORR was 21% with a median DOR of 27.9 months (95% CI 15.9—not evaluable). Of the patients, 47% and 16% had treatment-related adverse events of all grades and of grades 3–4, respectively. One patient died from autoimmune hepatitis related to treatment. PROs did not reveal any new signals. Conclusions: The long-term follow-up of NORA confirms that nivolumab monotherapy is an effective and safe therapy in patients with aRCC after prior therapy. With comparable follow-up times, our real-world data were not substantially different from the final long-term results of the pivotal Checkmate-025 study. Full article

Background/Objectives: Identifying aggressive tumor biology within early-stage hepatocellular carcinoma (HCC) remains challenging. Scores based on liver function, systemic inflammation, and HCC biomarkers have been linked to overall survival prognosis; however, the combined ability of these scores to assess tumor-specific prognosis in early-stage disease is unclear. In this single-center, prospective study, biomarker profiling with AFP, AFP-L3, and DCP, along with modified albumin–bilirubin (mALBI), and neutrophil–lymphocyte ratio (NLR)/platelet–lymphocyte ratios (PLRs) were evaluated to determine their prognostic role in assessing clinical manifestations of aggressive biology by stratifying HCC progression risk. Methods: Indices and biomarkers were assessed at BCLC-A-stage HCC diagnosis and prior to liver-directed therapy (LDT). The primary prospective study endpoint was time-to-advanced-stage tumor progression (TTP). Results: The cohort included 232 patients diagnosed with early-stage HCC who underwent treatment with LDT. A multivariate model revealed that mALBI grade (p = 0.021), cumulative lesion size (p = 0.005), and elevations in HCC biomarkers (p < 0.001) were associated with TTP. Biomarker profile stratified TTP (p < 0.001) in which patients with complex profiles (3+) had 1-year progression risks of 69%. The biomarker system retained the ability to stratify TTP within small (≤3 cm) and large (>3 cm) cumulative tumor burden (p < 0.001, p = 0.005). While PLR was not prognostic for TTP, NLR disappeared from the multivariate model and mALBI stratified long-term progression risk (p = 0.003). In low-complex biomarker patients (0–1+), mALBI stratified progression risk (p = 0.001). Conclusions: Multi-positive biomarker profiling in early-stage HCC identifies a population with clinical manifestations of aggressive tumor biology at high risk of rapid post-treatment disease progression that may benefit from more aggressive treatment approaches. In patients with low-risk biomarker profiles (0–1+), mALBI can assess longer-term (>1-year) post-treatment disease progression risk, while scores based on systemic inflammation were not associated with tumor-restricted outcomes. 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