Since 2011, immune checkpoint inhibitors (ICI) have transformed the treatment of various cancers. However, our understanding of the autoimmune adverse events, particularly those affecting the nervous system, remains limited. These adverse events can cause significant disability or even death, yet there are currently no established guidelines or biomarkers to aid diagnosis and treatment. With this study, we aim to gain a deeper understanding of neurological adverse events and investigate potential predictive biomarkers.

Between 19 December 2019 and 21 August 2021, 150 out of 543 ICI-treated cancer patients were eligible for our prospective monocentric cohort study. Neurological assessments, clinical scores and the severity of side effects were analysed. Blood samples were taken before, during and after therapy. Patients with neurological AEs (the nAE group) and those without (the non-nAE group) were compared to identify potential predictive markers.

Of the 150 patients, 55 (36.7%) experienced nAE of any kind or severity, ranging from non-specific neurological symptoms to severe events. Severe nAE (Grade ≥ 3) was observed in 3.3% of patients and included cases of encephalitis and cerebral vasculitis. Regarding potential biomarkers, an increase in C-reactive protein (CRP) within the first 3-4 weeks was statistically associated with an increased likelihood of nAE in this study. As for patient- and treatment-related parameters, concurrent chemotherapy was found to be significantly associated with the occurrence of nAE.

This study observed a relatively high rate of nAE under ICI therapy, partly due to the intentionally broad case definition. CRP elevation emerged as a potential predictive biomarker, warranting further investigation. However, other statistically significant markers did not consistently demonstrate clinical relevance.

Cancer-associated thrombosis (CAT) is a leading cause of morbidity and mortality among cancer patients. While venous thromboembolic events have been extensively studied due to their higher incidence, arterial thrombosis in cancer patients-referred to as cancer-associated arterial thromboembolism (CA-ATE)-is less well understood but may pose a greater danger. The pathophysiology of CA-ATE involves complex interactions between the tumor microenvironment, cancer cells, patient-related factors, and cancer therapies. Some chemotherapeutic agents, particularly platinum-based compounds (cisplatin, oxaliplatin), gemcitabine, taxanes, and targeted therapies such as tyrosine kinase inhibitors (TKIs), have been associated with an increased risk of arterial thrombosis. In certain patient populations, hormonal therapy and selective estrogen receptor modulators may also contribute to this risk. Additionally, factors such as patient age, cancer type, and stage contribute to an increased risk of arterial thrombosis in this population. Key mechanisms driving CA-ATE include endothelial injury, hypercoagulability, and platelet activation. Certain malignancies, notably lung and pancreatic cancers, are associated with a higher incidence of arterial thrombotic events. The aim of this review is to enhance understanding of the underlying mechanisms of cancer-related arterial thromboembolism and to highlight the various therapeutic, cancer-related, and patient-related factors that contribute to the occurrence of cancer-associated arterial thrombotic events.

Immunotherapy has markedly reshaped the therapeutic landscape for patients with postoperative progression and metastasis. As a programmed death-1 (PD-1) inhibitor, camrelizumab has been proven to exhibit both efficacy and safety in the treatment of advanced dMMR solid tumors.

A 58-year-old female patient with neuroendocrine carcinoma of the endometrium (NECE) who was treated with camrelizumab coupled with chemotherapy, subsequent maintenance monotherapy with camrelizumab, and adjuvant pelvic local radiotherapy. Up to December 2024, the patient has survived 28 months since treatment, with 26 months free from disease progression, and the assessment indicated a status of clinical complete response (cCR).

The combined regimen achieves notable efficacy and is free of unexpected adverse effects, with only a radiotherapy-related pelvic insufficiency fracture (PIF) report.

The optimal sequencing of surgery and chemotherapy in advanced epithelial ovarian cancer remains debated. While primary debulking surgery (PDS) has been considered the standard approach, recent randomized trials have questioned its survival advantage over neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). The study aimed to systematically evaluate phase III randomized controlled trials comparing PDS and NACT.

Following PRISMA guidelines (PROSPERO ID 1169057), PubMed and Scopus were systematically searched in October 2025 for phase III randomized clinical trials evaluating cytoreductive strategies in ovarian carcinoma. Only full-text English studies reporting overall survival (OS) or disease-free survival (DFS) were included. Risk ratios (RR) with 95% confidence intervals (CI) were calculated.

Five phase III trials (EORTC 55971, CHORUS, JCOG0602, SCORPION, TRUST) comprising 2296 patients met the inclusion criteria. PDS (n = 1139) and NACT (n = 1157) showed comparable OS (RR 0.99, 95% CI 0.94-1.03, p = 0.55, I ² = 0%) and DFS (PDS RR 0.98, 95% CI 0.95-1.02, p = 0.27, I ² = 0%). Subgroup analyses confirmed the absence of significant differences for patients with CC0 (RR 0.96, 95% CI 0.87-1.05, p = 0.35, I ² = 0%), FIGO stage III disease (RR 0.97, 95% CI 0.92-1.03, p = 0.34, I ² = 0%), or age under 70 years (RR 1.03, 95% CI 0.97-1.09, p = 0.38, I ² = 0%).

PDS and NACT provide no significant survival outcomes in advanced ovarian cancer. No clear survival benefit for PDS was observed. Refinement of patient selection, integration of predictive biomarkers, and re-evaluation of PDS in the context of HIPEC and Poly-ADP-Ribose Polymerase (PARP) inhibitor use are warranted to guide individualized treatment strategies.

The incidence of renal cell carcinoma (RCC) and its associated economic burden have risen significantly in Taiwan. While targeted therapy has become a standard treatment, its real-world effectiveness and cost-effectiveness remain to be fully evaluated.

This population-based cohort study utilized the Taiwan National Health Insurance Research Database and Cancer Registry to analyze 14,131 RCC cases diagnosed between 1998 and 2016. Key outcomes included life expectancy (LE), loss of LE, and lifetime medical costs.

The cumulative incidence rate of RCC increased from 0.37 to 0.73% in men and from 0.23 to 0.36% in women. Significant LE loss was observed, particularly in patients under 50 years of age (14.38 years in men; 12.89 years in women). In advanced cases, targeted therapy yielded a slightly higher LE (4.43 years) compared to non-targeted therapy (3.63 years); however, the loss of LE was similar between groups.

The real-world relationship between survival outcomes and lifetime medical costs of targeted therapy in Taiwan suggests suboptimal efficiency under current clinical practice. These findings suggest a need to re-evaluate reimbursement strategies by considering pharmacogenomic heterogeneity, implementing genomic profiling for precision medicine, and transitioning toward more effective combination therapy paradigms.

Testicular microlithiasis (TM) is common in infertile men, but its management is controversial due to an unclear link to testicular germ cell tumor (TGCT) risk. This scoping review synthesizes evidence to clarify the basis for personalized management of TM, focusing on infertile men.

Following PRISMA-ScR guidelines, we systematically searched PubMed, Embase, and Web of Science (2015-2025) for studies on TM pathogenesis, imaging, molecular mechanisms, management, and TGCT association. Data were charted and narratively synthesized.

TM and TGCT share molecular pathways (e.g., KIT/KITLG, BMP7) within testicular dysgenesis syndrome. Isolated TM carries minimal risk, while coexisting with factors like cryptorchidism, infertility, or family history significantly elevates TGCT risk. Advanced imaging and liquid biopsy markers (e.g., miR-371a-3p) may refine risk assessment. Intermediate-risk patients (TM plus one established risk factor) may be considered for periodic ultrasound within shared decision-making; routine biomarker testing is not supported and should be individualized to selected high-risk contexts.

The available evidence remains heterogeneous, and routine imaging surveillance for isolated testicular microlithiasis is not supported. We propose an evidence-informed, hypothesis-generating risk-stratification framework to support shared decision-making and highlight priorities for prospective validation.

Postoperative pulmonary complications (PPCs) remain a major source of morbidity after McKeown esophagectomy for esophageal squamous cell carcinoma (ESCC), particularly in patients receiving neoadjuvant chemoimmunotherapy (nICT). Readily available preoperative biomarkers may improve risk stratification. This study evaluated the predictive value of the aggregate index of systemic inflammation (AISI), the C-reactive protein-albumin-lymphocyte (CALLY) index, and their combined use for PPCs after McKeown esophagectomy following nICT.

We retrospectively analyzed 412 consecutive ESCC patients who underwent McKeown esophagectomy after nICT between January 2019 and December 2025. The primary endpoint was PPCs within 30 days after surgery. Univariable and multivariable logistic regression analyses were used to examine associations between preoperative biomarkers and PPCs. A combined AISI-CALLY model was constructed using binary logistic regression, and its predictive performance was assessed by receiver operating characteristic (ROC) analysis, DeLong testing, calibration analysis, and decision curve analysis. Propensity score matching (PSM) was performed as a sensitivity analysis.

PPCs occurred in 157 of 412 patients (38.1%). In the fully adjusted model, both AISI and CALLY remained independently associated with PPCs. Higher AISI was associated with increased PPC risk (adjusted odds ratio [aOR] 1.195 per 100-unit increase, 95% CI 1.081-1.321, P < 0.001), whereas higher CALLY was associated with lower risk (aOR 0.926 per 1-unit increase, 95% CI 0.884-0.970, P = 0.001). The biomarker-only AISI-CALLY model achieved an AUC of 0.689, compared with 0.650 for AISI alone and 0.665 for CALLY alone. The final integrated model incorporating clinical variables, AISI, and CALLY showed the best discrimination (AUC 0.712, 95% CI 0.658-0.762) and provided greater net benefit on decision curve analysis. In the matched cohort, both biomarkers remained independently associated with PPCs, although discrimination was attenuated.

Preoperative AISI and CALLY were independently and complementarily associated with PPCs after McKeown esophagectomy following nICT. Their combined use provided only modest incremental predictive value and may serve as an accessible adjunct, rather than a stand-alone tool, for preoperative PPC risk stratification.

The clinical translation of prostate-specific membrane antigen (PSMA)-directed chimeric antigen receptor (CAR) T-cell therapy for metastatic castration-resistant prostate cancer (mCRPC) has reached a critical impasse. Despite compelling preclinical rationale and early biological activity, durable clinical responses remain scarce, constrained by three core solid tumor challenges: a profoundly immunosuppressive/metabolically hostile tumor microenvironment (TME), pervasive antigen heterogeneity driving immune escape, and intrinsic limitations in T-cell fitness and in vivo persistence. This review synthesizes the current translational landscape (updated to February 2026), and posits a tripartite synergistic framework to systematically deconstruct these barriers: (1) advances in CAR synthetic biology; (2) active TME reprogramming via armored CAR-T cells, stromal-targeting agents, and rational combinations; (3) next-generation cellular product paradigms, with a focus on stem cell-derived immune effectors. Emerging platforms, including induced pluripotent stem cell (iPSC)-derived CAR-T, CAR-natural killer (NK) cells, and CAR-macrophages, offer unprecedented opportunities to overcome autologous product limitations via off-the-shelf availability, enhanced persistence, and intrinsic TME resistance. We further delineate a translational roadmap emphasizing biomarker-driven adaptive trials, predictive humanized preclinical models, and accessibility strategies. All core claims are graded using the 2011 Oxford Centre for Evidence-Based Medicine (OCEBM) Levels of Evidence to ensure academic rigor. This work provides a strategic blueprint to advance PSMA-CAR-T therapy toward curative-intent mCRPC treatment, with insights broadly applicable to next-generation stem cell-derived immunotherapies.

Chimeric antigen receptor (CAR) T cells represent an exciting therapeutic strategy with improved survival outcomes for patients with hematological malignancies. However, the efficacy of CAR T-cell therapy in the treatment of solid tumors remains suboptimal due to therapeutic barriers associated with the solid tumor microenvironment. We investigated whether ionizing radiation could improve vascular perfusion and CAR T-cell delivery in an EGFRvIII-expressing B16F10 melanoma model. Tumors received radiation doses of 2-12 Gy, and perfusion was evaluated at multiple time points using immunofluorescence detection of intravenously administered fluorescent dyes. We found that a single 8-Gy dose of ionizing radiation produced the most significant increase in B16F10 tumor perfusion 4 h after irradiation. Consistently, the irradiation of tumors 4 h prior to a systemic administration of EGFRvIII-targeting CAR T cells led to higher intratumoral CAR T-cell accumulation than in non-irradiated tumors. This approach also resulted in a significantly delayed tumor growth and improved survival relative to radiation or CAR T cells alone. Interestingly, the CD28ζ EGFRvIII-CAR T-cell levels substantially increased in irradiated tumors over time relative to 4-1BBζ EGFRvIII-CAR T cells and produced greater tumor growth delays and survival improvements in comparison to 4-1BBζ EGFRvIII-CAR T cells administered at a 10-fold higher concentration. Taken together, these data highlight the importance of co-stimulatory domains in CAR T-cell function in vivo and demonstrate that irradiating tumors prior to systemic CAR T-cell infusion can increase CAR T-cell infiltration and efficacy in solid tumors.

Accumulating evidence underscores the significance of inflammation and nutrition in tumor progression. Although low albumin-lymphocyte score (ALS) and skeletal muscle index (SMI) are known to be associated with negative outcomes in patients with ovarian cancer (OC) undergoing primary debulking surgery, the usefulness for predicting prognosis remains unclear. We aimed to assess the relevant preoperative prognostic variables and their combined impact on patients with OC.

This retrospective study included 347 patients with primary OC from multiple medical centers. The patients were divided into discovery (237 patients) and validation (110 patients) cohorts. Serological tests and plain computed tomography were performed to quantify the ALS and SMI. We investigated the preoperative prognostic ability of a unique index based on a combination of ALS and SMI, the CAS grade.

Patients with a lower ALS and a higher SMI showed improved overall survival (OS) and recurrence-free survival (RFS). Upon stratification by CAS grade, grade 1 patients demonstrated the highest body mass index and the most favorable survival prognosis, whereas grade 3 patients demonstrated the poorest OS and RFS. The independent variables for OS and RFS included residual disease and elevated CAS grade. These findings were validated in an independent cohort study.

The CAS grade, a combination of ALS and SMI, is a meaningful and independent predictor of prognosis in patients with OC.