Portal vein tumor thrombus (PVTT) is a major manifestation of macrovascular invasion in hepatocellular carcinoma (HCC) and is associated with aggressive progression and heterogeneous responses to immune checkpoint inhibitor-based therapy. Current stratification relies mainly on anatomical extent, liver function, and tumor burden and does not fully capture the biology of the intravascular lesion. In this Review, we propose PVTT as an anatomically distinct, lesion-centered intravascular tumor-immune niche for hypothesis generation rather than as an established autonomous immune compartment. We distinguish PVTT-direct evidence from supportive venous-thrombus/metastatic evidence and HCC-extrapolated mechanisms. Current PVTT-direct evidence is strongest for clonal and spatial divergence and PVTT-specific stromal remodeling, including myofibroblast-like cancer-associated fibroblast accumulation, NID1-associated immune barriers, and FAP-positive fibroblast/GJA5-positive endothelial hubs. Venous-thrombus studies provide supportive evidence for macrophage-associated immune suppression, including C5aR-positive tumor-associated macrophages, whereas hypoxia-adenosine signaling, adaptive checkpoint activation, and lipid metabolic rewiring remain largely extrapolated candidate mechanisms requiring direct PVTT validation. On this basis, we organize the available evidence into literature-informed candidate resistance phenotypes and outline a translational framework integrating paired primary tumor-PVTT sampling, spatial and single-cell profiling, functional imaging, and liquid biopsy. These phenotypes are conceptual groupings rather than empirically derived or validated patient subtypes and should guide mechanistic testing and biomarker-enriched trial design rather than routine treatment assignment. Prospective PVTT-specific studies with anatomically resolved sampling, longitudinal pharmacodynamic assessment, and biomarker-by-treatment interaction analyses are required to determine whether this lesion-centered niche framework can ultimately provide clinically useful stratification.

Human papillomavirus (HPV) is the principal etiological factor in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Persistent infection with high-risk HPV types promotes immune evasion, malignant transformation, and tumor progression. Currently licensed prophylactic HPV vaccines, based on L1 virus-like particles, are highly effective at preventing new infections and HPV-associated neoplastic disease through the induction of neutralizing antibodies. However, they do not eradicate established infections or preexisting lesions. These limitations have driven the development of therapeutic HPV vaccines and adoptive T-cell strategies aimed at eliciting robust cell-mediated immunity against HPV-associated malignancies. The viral oncoproteins E6 and E7 are attractive therapeutic targets. They disrupt cell-cycle control and are consistently expressed in HPV-driven precancerous and cancerous lesions. In this review, we provide a comprehensive overview of therapeutic HPV vaccines-including viral and bacterial vectors, DNA and RNA constructs, peptide/protein vaccines, and cell-based approaches-all designed to target E6 and E7, while considering the benefits and limitations of each platform. We also present an in-depth analysis of adoptive T-cell therapies, highlighting Immuno-STAT, a peptide-HLA fusion platform for the direct expansion of HPV-specific CD8⁺ T cells. Furthermore, we discuss rational combination strategies that integrate these modalities with immune checkpoint inhibitors and other immunomodulatory agents, including the bifunctional PD-L1/TGF-β inhibitor bintrafusp alfa, to overcome key barriers and enhance clinical efficacy. Overall, this review synthesizes current evidence and outlines future directions for the development of more precisely tailored HPV-specific immunotherapies in cancer treatment.

Microvessel density (MVD) is an inconsistent prognostic factor in colorectal cancer (CRC). We evaluated the vascular proliferation index (VPI), a qualitative marker of proliferating endothelial cells, as an alternative biomarker. This study aimed to comprehensively compare the prognostic performance of MVD and VPI in Stage II/III CRC patients.

MVD and VPI were examined using dual immunohistochemistry (IHC) for CD31/Ki-67 in 85 patients with Stage II/III CRC. Single-cell flow cytometry (FCM) was performed in 72 patients whose samples were suitable for single-cell evaluation among the 85 patients.

High VPI (>16.5%) via IHC correlated with a significantly shorter disease-free survival (DFS) (p=0.020), whereas MVD showed no prognostic correlation. Consistently, a high Ki-67/CD31 ratio via single-cell FCM predicted a poorer DFS (p=0.002). In the multivariate analysis, high VPI was an independent poor prognostic factor for the DFS (p=0.011). Neither marker was correlated with overall survival.

VPI via single-cell analysis is a superior, independent prognostic biomarker to MVD for the DFS in Stage II/III CRC, offering an objective platform for postoperative recurrence risk stratification.

Ramucirumab (RAM) plus taxane is the standard second-line treatment for unresectable advanced gastric cancer (AGC). However, the clinical outcomes of this regimen after immune checkpoint inhibitor (ICI)-based first-line therapy remain unclear, particularly in patients who exhibit progressive disease (PD) as the best overall response to prior treatment.

We analyzed the data of 31 patients with HER2-negative AGC who received RAM plus taxane as a second-line therapy after ICI-based treatment in our institution between November 2021 and March 2025. Survival and response rates were compared between the PD and non-PD groups in the first-line treatment setting.

The median progression-free survival (PFS) and overall survival (OS) were 3.26 months and 5.83 months, respectively. The Eastern Cooperative Oncology Group performance status ≥2 was the only independent poor prognostic factor for both PFS and OS. Among the 23 patients with measurable disease, the objective response rate (ORR) was 30.4%. When stratified according to response to first-line therapy, no significant differences in PFS or OS were observed between patients with PD (n=11) and without PD (n=20). However, the ORR was significantly higher in the PD group than in the non-PD group (54.5% vs. 8.3%, p=0.027).

Although poor performance status was associated with worse survival, RAM plus taxane demonstrated meaningful antitumor activity, regardless of response to prior ICI-based treatment. These findings suggest that RAM plus taxane may warrant consideration as a treatment option in this setting.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer shows consistently low pathological complete response (pCR) rates after neoadjuvant chemotherapy (NAC), yet no preoperative tool exists to identify non-responders for whom alternative strategies - including upfront surgery or early trastuzumab deruxtecan (T-DXd) - may be considered. We investigated whether a three-factor model using routinely available pretreatment data could identify this chemoresistant subgroup.

We retrospectively analyzed 124 patients who underwent surgery after neoadjuvant chemotherapy (2020-2024). Multivariable logistic regression was performed in the overall cohort and HER2-low subgroup. A three-factor scoring model (non-mass enhancement, histologic grade 1-2, and clinical T stage ≥3; 1 point each; total 0-3) was evaluated by receiver operating characteristic curve analysis.

HER2-low tumors showed low pCR rates regardless of hormone receptor (HR) status (HR+: 10.0%; HR-: 10.3%). In multivariable analysis, HER2-low status [odds ratio (OR)=0.176, p=0.002], histologic grade (OR=2.55, p=0.046), and clinical T stage (OR=0.38, p=0.017) were independently associated with pCR; among HER2-low patients, histologic grade was the only independent predictor (OR=8.40, p=0.023). The scoring model yielded pCR rates of 36.4%, 7.7%, 0%, and 0% for scores 0-3 [p for trend=0.005; area under the curve (AUC)=0.836, 95% confidence interval (CI)=0.701-0.953]. No pCR occurred in the 22 patients with a score ≥2 [positive predictive value (PPV)=100%, 95%CI=84.6-100%].

A three-factor scoring model identified a HER2-low subgroup (score ≥2, n=22) in whom no patient achieved pCR (PPV=100%, 95%CI=84.6-100%). If validated externally, this score may inform preoperative decisions regarding upfront surgery or early-line trastuzumab deruxtecan. These findings are hypothesis-generating and require prospective multicenter validation.

Adjuvant chemotherapy is the standard of care for stage II-III gastric cancer; however, treatment discontinuation is frequently observed in elderly patients. This study aimed to evaluate the association between the G8 screening tool and the continuation of adjuvant chemotherapy in elderly patients with gastric cancer.

We retrospectively reviewed 40 patients (age ≥70 years) who underwent curative gastrectomy followed by adjuvant chemotherapy. The G8 score was assessed preoperatively. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value, and logistic regression was used to identify predictors of treatment discontinuation.

The optimal G8 cut-off was 12 (area under the curve 0.72). Adjuvant chemotherapy was discontinued owing to adverse events in 37.5% of patients. Patients with G8 <12 had a significantly higher discontinuation rate than those with G8 ≥12 (85.7% vs. 27.3%; p=0.001). Multivariable analysis identified G8 <12 as a significant predictor of treatment discontinuation (odds ratio 9.5; 95% confidence interval=1.1-205; p=0.04). Furthermore, G8 <12 was significantly associated with shorter treatment duration (p=0.0032).

A low preoperative G8 score was associated with early discontinuation of adjuvant chemotherapy in elderly patients with gastric cancer. Preoperative G8 screening may help identify vulnerable patients who may require careful perioperative management and individualized treatment strategies.

Matrix metalloproteinase-13 (MMP-13) plays an important role in extracellular matrix remodeling and has been implicated in the susceptibility and progression of several malignancies. However, the contribution of MMP-13 genetic polymorphisms to childhood acute lymphoblastic leukemia (ALL) remains unknown. This study aimed to investigate the associations of MMP-13 rs2252070 and rs478927 polymorphisms with childhood ALL susceptibility in a Taiwanese population.

A hospital-based case-control study was conducted involving 266 pediatric ALL patients and 266 age- and sex-matched healthy controls. Genomic DNA was isolated from peripheral blood leukocytes, and MMP-13 rs2252070 and rs478927 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis.

The genotype distributions of rs2252070 and rs478927 among controls were consistent with Hardy-Weinberg equilibrium (p=0.1481 and 0.1843, respectively). No significant association was observed between rs2252070 genotypes and childhood ALL risk. Compared with the AA genotype, the AG genotype exhibited an OR of 0.83 (95% CI=0.56-1.23, p=0.4071), while the GG genotype showed an OR of 0.86 (95% CI=0.54-1.36, p=0.5961). Similarly, no significant association was identified for rs478927, with ORs of 0.81 (95% CI=0.54-1.20, p=0.3436) and 0.81 (95% CI=0.51-1.29, p=0.4454) for CT and TT genotypes, respectively. Allelic analyses further demonstrated no association between rs2252070 (OR=0.91, 95% CI=0.72-1.16, p=0.4991) or rs478927 (OR=0.89, 95% CI=0.70-1.13, p=0.3566) and childhood ALL susceptibility.

This is the first study to evaluate MMP-13 polymorphisms in childhood ALL. Our findings indicate that no statistically significant association between MMP-13 rs2252070 or rs478927 polymorphisms and childhood ALL susceptibility was detected in this Taiwanese cohort. Larger multi-center and functional studies are warranted to validate these observations and further clarify the role of MMP-13 in leukemogenesis.

Evidence regarding first-line enfortumab vedotin plus pembrolizumab (EVP) in elderly patients with advanced urothelial carcinoma (UC), particularly those aged ≥80 years, remains limited. This study evaluated the real-world effectiveness, safety, and treatment feasibility of EVP stratified by age.

We retrospectively analyzed 40 consecutive patients with unresectable locally advanced or metastatic UC who received first-line EVP at a single institution between December 2024 and April 2026. Outcomes were assessed using predefined age cutoffs of 75 and 80 years. Tumor response was evaluated according to RECIST version 1.1 and adverse events according to CTCAE version 5.0.

The median age was 76.2 years, 22 patients (55.0%) were aged ≥75 years and 11 (27.5%) were aged ≥80 years. Patients in the older group were more likely to have lymph node-only disease and lower creatinine clearance. Objective response rates were 52.9% and 77.3% in patients aged <75 and ≥75 years and 64.3% and 72.7% in those aged <80 and ≥80 years, respectively. Grade ≥3 treatment-related adverse events occurred in nine patients (22.5%) overall. Median treatment duration was 2.7 months. At a median follow-up of 7.7 months, no significant differences in progression-free or overall survival were observed according to either age cutoff. Several elderly responders had no documented disease progression at their most recent post-discontinuation assessment; however, treatment duration and follow-up after discontinuation were limited.

In this small, selected real-world cohort, first-line EVP showed preliminary antitumor activity and feasible treatment delivery in elderly patients with advanced UC, including very elderly patients. These findings should be considered hypothesis-generating and require validation in larger studies with longer follow-up and standardized geriatric assessment.

Hepatocellular carcinoma (HCC) >3 cm often recurs after resection, indicating a need for better risk stratification. The ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUV_max) reflects tumor aggressiveness. We evaluated the prognostic significance of preoperative FDG-PET SUV_max in patients with resectable initial HCC >3 cm.

This retrospective analysis included 136 patients who underwent curative resection for HCC >3 cm between 2012 and 2021 with preoperative FDG-PET imaging. Patients were classified into low- and high-uptake groups based on tumor SUV_max. Associations between FDG-PET findings and clinicopathological factors were analyzed.

Patients with high SUV_max had significantly worse overall survival than those with low SUV_max (49.2% vs. 90.0%, p<0.0001). Multivariate analysis identified high SUV_max as an independent predictor of poor overall survival (hazard ratio=3.16, 95% confidence interval=1.42-7.03, p=0.0048). Furthermore, recurrence-free survival was significantly worse in the high SUV_max group (33.4% vs. 60.4%, p=0.0006). High SUV_max was strongly associated with microscopic vascular invasion (MVI). Combining SUV_max with alpha-fetoprotein improved preoperative prediction of MVI.

Preoperative FDG-PET SUV_max is an independent prognostic biomarker in HCC >3 cm and, when combined with serum alpha-fetoprotein, may enhance prediction of MVI. These findings support incorporating metabolic imaging into preoperative risk models to guide management.

Hippocampal brain metastases are uncommon, and evidence regarding their management and outcomes remains limited. This study evaluated the efficacy and safety of whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for hippocampal brain metastases at a single institution.

We retrospectively reviewed 21 patients treated for hippocampal brain metastases over a 20-year period. Clinical characteristics, treatment approaches, intracranial tumor control, treatment-related toxicity, and survival were analyzed. Eleven patients received WBRT and 10 received SRS.

The mean patient age was 60.7 years. Most patients were symptomatic (86%), had multiple brain metastases (71%), and had extracranial metastatic disease (76%). Memory impairment was documented in one patient. Among patients receiving WBRT, contralateral hippocampal avoidance was not feasible in five (45%) because of multiple brain metastases. The mean follow-up was 17.2 months. Intracranial tumor control was achieved in 18 patients (86%), and radionecrosis occurred in one patient (5%). The overall median survival was four months, and the estimated one-year survival rate was 42%. Intracranial tumor control rates were 91% after WBRT and 80% after SRS (p=0.49); the corresponding median survival times were one and five months, respectively (p=0.29). No acute or chronic treatment-related toxicity was documented, although post-treatment neurocognitive function was not systematically assessed.

WBRT and SRS provided high rates of intracranial tumor control with limited observed toxicity in this small cohort of patients with hippocampal brain metastases. However, overall survival remained poor. Larger studies incorporating standardized neurocognitive assessment are needed to clarify the comparative benefits and long-term safety of these treatment approaches.