Search Results (779)

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

Background and Objectives: Conversion therapy has expanded treatment options for patients with initially unresectable hepatocellular carcinoma (HCC), but the surgical literature remains focused more often on radiologic response than on the pathological, perioperative, and postoperative outcomes of patients who actually proceed to hepatectomy. This focused systematic review aimed to synthesize the available evidence on conversion hepatectomy after contemporary combination downstaging for initially unresectable HCC. Materials and Methods: A structured PubMed/MEDLINE search with backward reference-list screening was performed and last updated on 3 February 2026. The full Boolean strategy, field tags, and eligibility framework are now reported explicitly. Because the literature was observational and clinically heterogeneous, findings were synthesized narratively and complemented by structured assessments of reporting completeness, potential cohort overlap, and study-level bias. Results: Fourteen studies were included, nearly all retrospective and predominantly from East Asia. Treatment platforms clustered into systemic doublets, systemic plus HAIC strategies, and broader locoregional–systemic triplet or multimodal approaches. Across studies reporting pathological response, pathological complete response ranged from 28.0% to 50.0%, while R0 resection ranged from 85.7% to 100%, where stated. Postoperative morbidity ranged from 14.3% to 71.4%, and major complication rates from 9.5% to 16.9%; however, extent of resection, liver reserve, post-hepatectomy liver failure, transfusion, and perioperative mortality were not uniformly reported. Most studies carried moderate-to-high overall concerns for bias because of response-based surgical selection, heterogeneous denominators, incomplete perioperative reporting, and possible partial overlap among some cohorts. Conclusions: The available literature suggests that conversion hepatectomy can be feasible and oncologically meaningful in carefully selected patients treated in experienced centers, but current evidence remains hypothesis-generating rather than practice-standardizing because it is observational, heterogeneous, and incompletely reported. Full article

Background: Locally advanced thyroid cancer is associated with a poor prognosis and high surgical morbidity. This study evaluated the feasibility and outcomes of neoadjuvant treatment including targeted therapy with locoregional interventions. Methods: We retrospectively analyzed 17 patients with locally advanced thyroid cancer who received neoadjuvant treatment, including tyrosine kinase inhibitors (TKIs), transarterial embolization (TAE), and radiofrequency ablation (RFA), either alone or in combination. The primary outcome was the proportion of patients who proceeded to R0 or R1 surgical resection following neoadjuvant treatment. Secondary outcomes included tumor response assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and changes in surgical morbidity evaluated using the MGH/MEEI–MSK–MD Anderson surgical morbidity complexity score (MMM score) and the Invasive Thyroid Class. Results: Five patients (29%) achieved R0/R1 resection, including four with R0 resection. Most patients demonstrated reduced tumor burden and surgical complexity, as reflected by improvements in the MMM score and the Invasive Thyroid Class. The objective response rate was 47% and the 12-month progression-free survival rate was 58.2%. Conclusion: Neoadjuvant treatment may improve tumor downstaging and surgical feasibility in selected patients with initially unresectable thyroid cancer. Further prospective studies are required to validate these findings. Full article

Hepatic malignancies account for a substantial portion of global cancer mortality, with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC), and metastatic liver disease representing the most common diagnoses. While surgical resection and liver transplantation remain curative options for eligible patients, most patients are diagnosed at stages unsuitable for surgery. This has shifted medical management towards locoregional therapies (LRTs) which are often catheter-directed. Of these interventions, the use of conventional end-hole catheters for therapeutic infusion has been a mainstay of treatment, but this method is constrained by retrograde particle escape and elevated tumoral interstitial fluid pressure. Together, these factors limit drug penetration into the tumor microenvironment. Pressure-enabled drug delivery (PEDD), achieved through balloon-occlusion or microvalve-based catheter platforms, has emerged as a strategy to overcome these limitations. This narrative review synthesizes current evidence regarding PEDD and contextualizes its role within the broader LRT landscape. Preclinical studies and early clinical data illustrate improved drug-delivery characteristics, acceptable safety profiles, and highlight the potential for adaptation to regional immunotherapy regimens. However, while PEDD represents a promising advance in catheter-based hepatic oncologic therapy, prospective randomized comparisons against conventional infusion remain limited, and significant investigation is needed to establish its definitive role in interventional oncology. Full article

Background and Objectives: Head and neck cancer in patients aged 40 years or younger represents a rare and heterogeneous entity with conflicting data regarding prognosis and risk factors. This study aimed to evaluate oncological outcomes and independent prognostic factors in young patients treated with radio(chemo)therapy. Materials and Methods: This retrospective multi-center analysis included patients aged ≤ 40 years with histologically confirmed HNC who received definitive or adjuvant radio(chemo)therapy between 2002 and 2023 at the University Hospital Regensburg and affiliated partner hospitals. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Independent prognostic factors were identified by Cox proportional hazard regression with backward stepwise elimination. Results: A total of 88 patients were included. The median age at diagnosis was 38.2 years (IQR 35.8–39.8). Median OS was 91.0 months in the adjuvant and 23.7 months in the definitive treatment group. In multivariate analysis, four independent predictors of OS were identified: nicotine abuse (HR 2.887; p = 0.004), pre-existing comorbidities (HR 2.871; p = 0.005), absence of complete remission 12 weeks after radiotherapy (HR 25.676; p < 0.001), and locoregional recurrence or distant metastases (HR 8.183; p < 0.001). Failure to achieve complete remission was the sole independent predictor of PFS (HR 4.479; p < 0.001). Conclusions: In young HNC patients, early treatment response and disease recurrence are the strongest determinants of survival, alongside modifiable lifestyle factors and comorbidity burden. These findings support the need for intensified response monitoring and tailored follow-up strategies in this patient population. Full article

Primary liver malignancies, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although systemic therapies have advanced substantially, intrahepatic tumor progression, liver failure, and portal hypertension continue to drive adverse outcomes in many patients. Interventional radiology plays a central and expanding role in the multidisciplinary management of these tumors by providing image-guided locoregional therapies for local tumor control, downstaging, bridging transplantation or resection, palliation, and potential survival benefit. This narrative review summarizes current evidence and technical considerations for major locoregional approaches, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization, transarterial radioembolization, endobiliary therapies, stereotactic body radiation therapy, irreversible electroporation, histotripsy, high-intensity focused ultrasound, hepatic arterial infusion, and brachytherapy. Interventional radiology also contributes to preoperative liver optimization through portal vein embolization, liver venous deprivation, lobar radioembolization to induce contralateral hypertrophy, and, in some patients, portal decompression before hepatic resection. For hepatocellular carcinoma, ablation and transarterial therapies are integrated into stage-based treatment algorithms and may provide curative-intent treatment in some patients. In intrahepatic cholangiocarcinoma, locoregional therapies provide meaningful disease control and may prolong survival, particularly when combined with systemic therapy. In combined hepatocellular cholangiocarcinoma, treatment remains individualized because of limited prospective data and heterogeneous tumor biology. Beyond cytoreduction, locoregional therapies can modulate the tumor immune microenvironment through immunogenic cell death, antigen release, cytokine signaling, and vascular remodeling, providing a rationale for combination strategies with immune checkpoint inhibitors, anti-angiogenic agents, and targeted therapies. As treatment paradigms evolve, the future of interventional radiology in primary liver cancer will depend on appropriate patient selection, optimized dosimetry and technique, integration with molecular and immunologic biomarkers, and coordinated multidisciplinary care. Full article

Background: Accurate post-treatment imaging assessment of hepatocellular carcinoma (HCC) is essential for guiding retreatment, transplantation eligibility, and prognosis. The Liver Imaging Reporting and Data System Treatment Response Algorithm (LI-RADS TRA) was updated in 2024, introducing refinements across contrast-enhanced ultrasound (CEUS), CT/MRI, and radiation-based therapies, including the TR-Nonprogressing category. We aimed to systematically review current evidence on the diagnostic performance, reproducibility, and clinical implications of LI-RADS TRA v2024 for post-treatment assessment of HCC across imaging modalities and locoregional therapies. Methods: A systematic search of PubMed, Embase, Scopus, Web of Science, and CENTRAL was conducted according to PRISMA 2020 guidelines. Original studies applying LI-RADS TRA v2024 (or comparisons with earlier versions or mRECIST) after locoregional therapies were included. Outcomes of interest comprised diagnostic accuracy metrics, inter-reader and inter-modality agreement, temporal behavior of TRA categories, and prognostic associations. Given substantial heterogeneity, results were synthesized narratively. Results: Six studies met inclusion criteria. After thermal ablation, CEUS applying the non-radiation TRA v2024 showed very high specificity (approximately 88–100%) and excellent negative predictive value (about 94–98%), with substantial-to-almost-perfect inter-reader agreement (κ up to 0.92) and excellent inter-modality agreement with CT/MRI (ICC ≈ 0.90). After transarterial chemoembolization, CEUS performance was time-dependent, with higher sensitivity at early follow-up (~15 days) and higher specificity at later assessment (~30 days). On MRI, non-radiation TRA v2024 combined with ancillary features improved sensitivity and, in some analyses, accuracy compared with v2017 and v2024 without ancillary features, while remaining more specific than mRECIST. In radiation-based therapies, the radiation TRA v2024 captured delayed-response patterns through the TR-Nonprogressing category, which demonstrated meaningful temporal evolution and prognostic separation from TR-Viable. Surgical validation confirmed preserved diagnostic performance against histology. Conclusions: Despite heterogeneous data, available evidence supports LI-RADS TRA v2024 as a clinically useful framework that improves clarity, reproducibility, and actionability of post-treatment HCC imaging. CEUS is particularly effective after ablation; timing is critical after TACE, ancillary features should be routinely applied on MRI, and TR-Nonprogressing appropriately reflects radiation biology while preserving prognostic value. Full article

Immune checkpoint inhibitors (ICIs) have improved clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), including oral squamous cell carcinoma (OSCC). However, many patients eventually develop resistance to systemic therapy, highlighting the need for novel strategies that can restore or sustain antitumor immunity. Near-infrared photoimmunotherapy (PIT) has emerged as a tumor-selective locoregional treatment that not only induces targeted tumor cell death but also promotes antitumor immune activation through immunogenic cell death. This narrative review summarizes current evidence regarding PIT for recurrent oral cancer and explores the immunological rationale for sequential ICI–PIT–ICI therapy (ICI–PIT–ICI sequence). Within this framework, PIT-induced tumor antigen release and inflammatory activation may reinitiate elements of the cancer-immunity cycle, whereas continued PD-1 blockade may help sustain newly activated tumor-reactive T-cell responses. To illustrate this concept, we present two cases of recurrent oral cancer treated with the ICI–PIT–ICI sequence. Both patients achieved durable clinical and radiological complete responses following PIT and subsequent nivolumab continuation. Longitudinal analyses of peripheral immune surrogate markers demonstrated a biphasic temporal pattern characterized by transient increases in inflammatory markers, including neutrophil-to-lymphocyte ratio, C-reactive protein, platelet-to-lymphocyte ratio, and systemic immune-inflammation index, followed by recovery trends in absolute lymphocyte count and lymphocyte-to-monocyte ratio during continued PD-1 blockade. These observations support the biological plausibility of PIT as an immune-modulating intervention with potential immune-reprogramming effects. Although hypothesis-generating, the ICI–PIT–ICI sequence may represent a promising strategy integrating locoregional tumor destruction with systemic immune modulation in recurrent oral cancer. Further prospective studies incorporating peripheral and tissue-based immune profiling are warranted. Full article

Background: High-risk (HR) prostate cancer has a propensity for local and distant progression with ultimate death, mandating aggressive locoregional and systemic treatment approaches to maximize oncologic outcomes. Although brachytherapy (BT) with supplemental therapies has demonstrated favorable biochemical and quality of life outcomes, improvements in overall survival have been hampered by an excessive incidence of non- prostate cancer deaths. In this HR study, we report on biochemical failure (BF), prostate cancer-specific mortality (PCSM), overall mortality (OM) and patterns of death with recommendations for the mitigation of non-prostate cancer deaths. Materials and Methods: From April 1995 to November 2018, 577 consecutive HR patients were treated with LDR BT (97.9% Pd-103). Patients were stratified into three age cohorts: ≤ 59, 60–69 and ≥70 years. The BT prescription dose was prescribed to the prostate gland with generous peri-prostatic margins and the proximal 10mm of the seminal vesicles. 94.6% received supplemental EBRT (45–50.4 Gy) and 63.3% received androgen deprivation therapy (ADT) (median duration 12 months). Post-implant CT-based dosimetry was performed on day 0. BF was defined as a PSA > 0.40 ng/mL after nadir. The cause of death was determined for each patient. Patients with metastatic prostate cancer or non-metastatic castrate resistant prostate cancer who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause. Multiple clinical, pathologic and treatment were evaluated for impact on patient outcomes. Results: Of the patients, 87.5% (median follow-up 8.9 years) presented with a single HR factor. The day 0 D90 was 122.5%. Overall, the 15-year BF, PCSM and OM were 12.4%, 5.6% and 51.7%. When stratified by age, there was no significant difference in BF or PCSM. The median post- treatment PSA in biochemically controlled patients was <0.01 ng/mL. In all three cohorts, OM increased linearly for the first 10 years and then approximately doubled from years 10 to 15. Moreover, 239 patients died: 10.9% due to prostate cancer, 38.1% from cardiovascular (CV) disease and 28.4% from other malignancies (to include one rectal and three bladder cancers). In MVA, BF was most closely related to percent positive biopsies (p < 0.001, SHR 1.018), PCSM to Gleason score (p = 0.004, SHR 2.884) and percent positive biopsies (p = 0.005, SHR 1.021) and OM to age (p < 0.001, HR 1.075) and tobacco (p < 0.001, HR 2.374). Conclusions: Despite high cancer control rates, overall survival was limited by a preponderance of CV and non-prostate cancer deaths, which were 6 times more likely than prostate cancer deaths. The implementation of a comprehensive multidisciplinary survivorship program will be essential to impact longevity in this patient population. Full article

Background/Objectives: Photon re-irradiation in previously treated head and neck cancer (HNC) is constrained by cumulative normal-tissue toxicity. Pencil-beam scanning intensity-modulated proton therapy (PBS-IMPT) allows for a sharper dose conformation than conventional photon techniques, which may widen the therapeutic window in previously irradiated tissue. Methods: Sixty-five patients with recurrent or second primary HNC were enrolled in a prospective single-institution registry and re-irradiated with PBS-IMPT between January 2020 and December 2025. Forty-five were treated with radical intent (69.2%), and 20 were treated postoperatively (30.8%), with a median prescribed dose of 66 Gy (RBE) in 30 fractions. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Locoregional control (LRC), adverse events and the prognostic impact of anatomical extent were secondary endpoints. Results: The median follow-up was 9.3 months. The median OS was 17.2 months (95% CI 13.9–NR), with a 12-month rate of 67.1%. The median PFS was 10.1 months and the median LRC was 28.1 months. Central/skull-base involvement was associated with a non-significant trend toward worse OS (14.3 vs. 35.2 months; p = 0.062) and with significantly worse PFS (9.1 vs. 14.7 months; p = 0.037) than peripheral disease, but LRC did not differ between the groups (p = 0.240). Grade ≥ 3 oral mucositis occurred in 7.7%, with no grade 4–5 acute events. Within a median follow-up of 9.3 months, late osteoradionecrosis affected 6.2%, but late toxicity data remain preliminary given the short follow-up. Ninety-two percent of patients completed treatment. Conclusions: PBS-IMPT re-irradiation provided adequate survival with low acute toxicity. T3–T4 stage at re-irradiation was the only variable retaining significance for PFS on multivariable analysis (HR 4.32, 95% CI 1.24–15.13; p = 0.022). The poor survival observed for central/skull-base disease on Kaplan–Meier curves disappeared after T-stage adjustment, indicating the higher concentration of advanced disease in that compartment. Multicentre prospective data and longer follow-up are needed. Full article

Colorectal cancer frequently metastasizes to the liver, and a substantial proportion of patients present with unresectable colorectal liver metastases (CRLM), which are associated with limited survival. While systemic chemotherapy remains a central component of management, advances in liver-directed therapies and transplantation have significantly expanded therapeutic possibilities in selected patients. This review provides a comprehensive and up-to-date overview of current management strategies for unresectable CRLM, with a focus on systemic chemotherapy, intra-arterial therapies, and liver transplantation. Systemic chemotherapy plays a central role, either as conversion therapy aimed at achieving secondary resectability or as palliative treatment to prolong survival and maintain quality of life. The integration of targeted agents and molecular profiling has enabled increasingly personalized therapeutic strategies. Liver-directed therapies, including hepatic arterial infusion chemotherapy, transarterial chemoembolization, and radioembolization, provide effective local disease control and may facilitate downstaging in selected patients. In parallel, liver transplantation has re-emerged as a promising option for highly selected patients with liver-only disease, demonstrating encouraging long-term survival in recent prospective studies. However, optimal patient selection, timing, and sequencing of these modalities remain key challenges. The management of unresectable CRLM is evolving toward a multidisciplinary and individualized approach that integrates systemic, locoregional, and transplant-based strategies. In selected patients, this paradigm shift may translate into meaningful survival benefit, although further prospective studies are required to refine indications and optimize treatment sequencing. Full article

Peritoneal metastasis (PM) is the most frequent and lethal pattern of dissemination in gastrointestinal malignancies. Despite advances in systemic chemotherapy, outcomes remain poor because the unique biology of PM, characterized by poor vascularization and the peritoneal–plasma barrier (PPB), limits drug penetration and contributes to treatment resistance. To address these challenges, several locoregional treatment strategies have been developed, including cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). However, their widespread adoption is constrained by invasiveness, strict patient selection, and inconsistent survival benefits. Normothermic intraperitoneal and systemic treatment (NIPS) has emerged as a practical and less invasive alternative, particularly in East Asia. Through an implanted intraperitoneal port, NIPS enables repeated drug administration, providing sustained regional exposure while imposing minimal procedural burden. Importantly, it can be readily integrated with systemic chemotherapy, making it suitable for long-term multimodal treatment. Among available agents, paclitaxel (PTX) is particularly well suited for intraperitoneal administration because of its prolonged retention within the peritoneal cavity and limited systemic absorption. These pharmacokinetic properties allow high local drug concentrations with relatively low systemic toxicity. Consequently, PTX-based NIPS represents a biologically rational and clinically feasible treatment strategy for PM. This review summarizes the pharmacological rationale, clinical evidence, and emerging innovations in drug formulation and delivery that may further enhance the efficacy of PTX-based intraperitoneal chemotherapy for this challenging disease. 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: Head and neck neuroendocrine carcinoma (HN-NEC) is exceedingly rare. Standardized treatment strategies for this malignancy remain unestablished. This study aimed to explore promising treatment modalities, and to identify prognostic factors in HN-NEC. Materials and Methods: Thirty-nine patients diagnosed with HN-NEC at West China Hospital of Sichuan University between 2006 and 2025 were enrolled. The 5-year survival rates were estimated by Kaplan–Meier analysis. The log-rank test and Firth’s penalized Cox multivariable analysis regression model were used to identify prognostic factors. Results: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates for patients who did and did not receive radiotherapy were 63.2% vs. 29.6% (p = 0.031), 75.5% vs. 48.0% (p = 0.065), and 81.4% vs. 46.9% (p = 0.039), respectively. Laryngeal NEC was associated with poorer 5-year DMFS (41.2% vs. 87.5%, p = 0.023) and 5-year OS (38.1% vs. 92.9%, p = 0.027) compared with non-laryngeal HN-NEC. Radiotherapy (HR = 0.152, 95% CI: 0.025–0.757, p = 0.022) was a potentially protective factor influencing LRRFS. Conclusions: Radiotherapy may be associated with improved LRRFS in patients with HN-NEC. HN-NEC originating in the larynx appeared to be associated with a poorer prognosis compared with other primary sites of the head and neck. 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