Spatially fractionated radiation therapy (SFRT) can enhance tumor control by delivering high-dose subvolumes while sparing normal tissue and stimulating antitumor immunity. However, its application to superficial disease through electron beam radiation therapy remains limited. Electron SFRT (eSFRT) could serve as a strategy for initial tumor downsizing of ulcerated cutaneous and subcutaneous tumors by delivering a superficial, spatially heterogeneous dose, enabling subsequent conventional electron therapy to enhance local control.

To evaluate the dosimetric feasibility of eSFRT using a novel 3D-printed tungsten-filament GRID (TS) and compare it to lead sheet (LS) references.

The TS GRID collimators were 3D-printed from a tungsten alloy filament (91%-93% tungsten by weight, PLA-based), with a hexagonal array of 27 apertures (1.5 cm diameter, 2.0 cm spacing, 1 mm thickness) in a 10 × 10 cm² sheet. LS GRIDs (1.5 and 3.0 mm thick) were used as reference. GRIDs were placed directly on water and anthropomorphic phantoms. Dosimetric measurements for GRID field properties, including percent depth dose (PDD) and crossbeam plane dose profiles at various depths, were performed in a water tank phantom for 6, 9, and 12 MeV electron beams. Key parameters, such as depths of maximum dose (d_max) and doses at 90% (d90) and 50% (d50), were determined. Peak-to-valley dose ratios (PVDRs) were also evaluated and compared with data from an anthropomorphic phantom.

The TS GRID collimator produced highly heterogeneous superficial dose distributions with PVDR > 2.0 at depths > 10 mm for 6-9 MeV, supporting spatially fractionated dose delivery. PVDR reductions on curved phantom surfaces were minimal (<3%). TS demonstrated reproducible geometry, mechanical stability, and biocompatibility, enabling direct placement on superficial tumors. Compared to previously reported tungsten-based composite GRID collimators, including tungsten functional paper (TFP) and tungsten-containing rubber (TCR), TS achieved higher PVDR at clinically relevant depths. LS GRID collimators achieved slightly higher PVDR but are not suitable for clinical use directly on skin.

This study demonstrates the feasibility of eSFRT using a 3D-printed TS GRID collimator to deliver superficial, spatially heterogeneous doses. TS provides reproducible geometry, mechanical stability, and biocompatibility, making it a clinically translatable alternative to lead, TFP, and TCR GRID collimators warranting further preclinical and clinical investigation.

This White Paper by the European Association for Palliative Care addresses the imperative to integrate spiritual care into the support of individuals living with neuro-oncological and neurodegenerative conditions. These diseases present complex biomedical, social, psychological, and existential challenges that demand a whole-person approach to care. Various initiatives have progressed the understanding of spirituality as a dimension of well-being, yet the systemic delivery of spiritual care remains inconsistent and inequitable.

This study adopts a narrative umbrella review approach. We provide a synthesized framework highlighting current knowledge and models of care, educational needs, and future priorities for research, while advocating for the formal integration of spiritual care into all stages of illness.

Our exploration highlights the importance of early integration of dynamic and multidimensional spiritual care for people with neuro-oncological or neurodegenerative diseases. The implementation of spiritual care in this context should address the unique challenges that arise with these diseases, such as changes in spiritual needs and in the ability to communicate spiritual needs across disease progression. Spiritual care should be carried out by the whole care team, offering regular spiritual screenings and referring care to specialists when needed, and it should be offered across all stages of care. Spiritual care should be culturally safe, offering multilingual access, and multi-faith chaplaincy services.

Spiritual care is not a luxury or an optional extra; it is a fundamental aspect of palliative care. There is a need to implement spiritual care across all stages of care, taking into consideration the patient's evolving needs. Sufficient time should be allocated to spiritual care education for social and healthcare professionals. More research is needed to develop validated screening tools and effective interventions.

Fibroblast activation protein inhibitor (FAPI) has demonstrated promising oncological diagnostic performance. Although no adverse events (AEs) have been previously reported, a formal safety evaluation of FAPI PET/CT is lacking. This study aimed to assess the safety and tolerability of [⁶⁸Ga]Ga-FAPI-46 PET/CT, with a focus on hemodynamic parameters, AEs, and patient-reported discomfort.

Participants were included from two ongoing prospective diagnostic trials: (1) FAPI PET/CT in ovarian cancer (EU CTIS no. 2023-505938-98-00) and (2) FAPI PET/CT in gastric and gastroesophageal junction cancer (EU CTIS no. 2023-505916-40-01). A dose of 150-250 MBq [⁶⁸Ga]Ga-FAPI-46 was administered, and low-dose, non-contrast CT was performed. Hemodynamic parameters, including systolic and diastolic blood pressure (BP) and heart rate (HR), were measured at baseline, 1-min post-injection (p.i.), 10 min p.i., and post-scan. Additionally, potential AEs and discomfort were assessed at these timepoints and 1 day p.i., and participants were instructed to report events. AEs were graded according to the Common Terminology Criteria for Adverse Events version 5.0.

Thirty participants were included. No patient reported AEs or discomfort attributable to [⁶⁸Ga]Ga-FAPI-46, and no significant changes in mean systolic or diastolic BP were observed; however, three patients experienced increases in systolic BP classified as AEs. A clinically non-relevant but statistically significant (p < 0.01) decrease in HR (from 77 bpm at baseline to 73 bpm at post-scan) was observed.

[⁶⁸Ga]Ga-FAPI-46 PET/CT is well tolerated with no immediate patient-reported discomfort or clinically relevant hemodynamic AEs. The observed decrease in HR from baseline to post-scan likely reflects prescan nervousness.

In glioblastoma, first-line treatment can influence subsequent treatment lines. Therefore, progression-free survival 2 (PFS2), the time from initial randomization to progression on subsequent treatment or death, may better predict overall survival (OS) compared to PFS. However, this association needs validation in glioblastoma, particularly with novel targeted agents in early clinical trials.

Medical records of glioblastoma patients from a multicentric Spanish cohort with genomic profiling treated between 2018 to 2023 were analyzed. Correlations between OS and PFS or PFS2 were calculated using an iterative multiple imputation approach and time-to-event endpoints with Kaplan-Meier methods.

We analyzed 405 patients. Median OS, PFS, and PFS2 were 25.4, 8.7 and 16.4 months, respectively. Correlation between OS-PFS was 0.69 (95% CI, 0.62-0.75), whilst for OS-PFS2 it was 0.83 (95% CI, 0.78-0.87). In patients who received targeted therapy, OS-PFS correlation was 0.51 (95% CI, 0.02-0.81), whilst for OS-PFS2, it was 0.72 (95% CI, 0.30-0.91). For patients with ESCAT tier I-II molecular targets, OS-PFS correlation was 0.69 (95% CI, 0.26-0.89), weaker than OS-PFS2 (0.83 [95% CI, 0.29-0.97]). PFS2 also performed better than PFS in ESCAT III-IV patients (0.80 [95% CI, 0.75-0.85] vs. 0.69 [95% CI, 0.61-0.75]) and in those without targetable alterations (0.86 [95% CI, 0.74-0.92] vs. 0.68 [95% CI, 0.51-0.80]).

Progression-free survival 2 (PFS2) is a more robust surrogate for OS than PFS in glioblastoma, including patients receiving targeted therapies or without actionable targets. These findings support adoption of PFS2 as a candidate surrogate endpoint in glioblastoma, offering a balance between trial feasibility and meaningful survival outcomes.

IntroductionPancreatic neuroendocrine tumors (PanNETs) have shown an increasing incidence, yet population-based studies examining the clinical characteristics and cancer-specific survival (CSS) specifically in adolescents and young adults (AYA) (aged 13-39 years) remain scarce.MethodsThis population-based, retrospective cohort study identified all patients diagnosed with PanNETs through the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was adopted to reduce selection bias. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate the impact of demographic and clinical variables on CSS. Temporal trends in incidence by age group were also assessed over the study period.ResultsA total of 4408 patients were included, with 338 in the AYA group and 4,070 in the older adult (OA) group (aged ≥ 40 years). Compared to the OA group, the AYA group had more female patients, earlier clinical staging, lower distant metastasis rates, and higher surgical treatment rates (P < 0.05). The AYA group exhibited better CSS (P=0.005). After PSM, the AYA group and the OA group had comparable CSS (P=0.261). Multivariate Cox regression analysis identified N stage and surgery as independent risk factors for CSS in the AYA group.ConclusionsIn this study, distinct clinical characteristics of AYA patients with PanNETs were identified compared with older adults. In this observational analysis, after PSM, CSS rates were similar between the two age groups, despite baseline differences before matching. The rising incidence of PanNETs in AYA individuals suggests a need for continued surveillance and personalized management in this young population.

Submandibular gland oncocytoma is a rare benign epithelial tumor accounting for less than 1% of all salivary gland neoplasms. It is composed of oncocytes-large polygonal epithelial cells with abundant eosinophilic granular cytoplasm resulting from mitochondrial accumulation-and typically affects adults between the fifth and seventh decades of life, without a clear gender predilection. Radiation exposure has been reported as a possible predisposing factor. Clinically, oncocytomas usually present as painless, slow-growing masses. Imaging modalities, particularly ultrasound and contrast-enhanced computed tomography, typically demonstrate well-circumscribed and homogeneous lesions suggestive of a benign process. Fine-needle aspiration cytology may contribute to the preoperative assessment by suggesting an oncocytic lesion; however, definitive diagnosis relies on histopathological examination of the excised specimen, which remains essential to reliably differentiate oncocytoma from malignant oncocytic neoplasms. The main differential diagnoses include Warthin's tumor, pleomorphic adenoma, and oncocytic carcinoma. Surgical excision of the tumor along with the affected gland is the treatment of choice. Recurrence and malignant transformation are exceedingly rare, and prognosis is excellent following complete resection. We report the case of a 52-year-old male patient with no significant medical history who presented with a slowly enlarging submandibular mass. Imaging findings were consistent with a benign salivary gland tumor, and the diagnosis of oncocytoma was subsequently confirmed by histopathological analysis after surgical excision. Given its rarity and potential diagnostic overlap with other oncocytic lesions, an integrated clinical, radiological, and pathological approach is essential for accurate diagnosis and optimal management.

Magnesium transporter 1 (MAGT1) plays a crucial role in magnesium homeostasis and immune regulation, yet its clinical significance and functional role in breast cancer remain largely unexplored.

The expression pattern and prognostic value of MAGT1 in breast cancer were analyzed using data from The Cancer Genome Atlas (TCGA) and validated by immunohistochemistry on a tissue microarray comprising 60 patient samples. Genomic alteration analysis of MAGT1 with BRCA clinical implications was performed. The biological functions of MAGT1 were investigated in vitro using MCF-7 and MDA-MB-231 cell lines. MAGT1 expression was knocked down by siRNA, and its effects on cell proliferation, colony formation, DNA synthesis, migration, and invasion abilities were inhibited through MTT assays, colony formation assays, EdU assays, wound healing assays, and Transwell assays. Immune cell infiltration associated with MAGT1 expression was analyzed using bioinformatics tools.

MAGT1 was significantly overexpressed in breast cancer tissues compared with adjacent normal tissues. High MAGT1 expression was strongly associated with advanced tumor stage, poorer histological grade, and unfavorable patient prognosis, serving as an independent risk factor for overall survival. MAGT1 mutations were not statistically significantly associated with overall survival (OS) in breast cancer, but MAGT1 mutations were closely associated with ERBB2 and CDH1. Bioinformatic analysis revealed a correlation between MAGT1 expression and altered immune cell infiltration within the tumor microenvironment. In vitro functional assays demonstrated that silencing MAGT1 markedly inhibited the proliferative capacity, clonogenicity, migration, and invasion of breast cancer cells.

Our findings indicate that MAGT1 is frequently upregulated in breast cancer and correlates with aggressive tumor behavior and poor clinical outcomes. MAGT1 promotes key oncogenic phenotypes in breast cancer cells and may influence the immune landscape, highlighting its potential as both a prognostic biomarker and a promising therapeutic target.

To address the therapeutic challenges associated with triple-negative breast cancer (TNBC), we developed a folic acid-polyethylene glycol-modified ZIF8-based nanotheranostic platform (FA-PEG@ZIF8@CIP) designed to integrate synergistic sonodynamic therapy, chemotherapy, and immune activation for enhanced antitumor treatment.

FA-PEG@ZIF8@CIP was constructed as a folic acid-polyethylene glycol-functionalized ZIF8 nanoplatform for the delivery of ciprofloxacin. In this system, ciprofloxacin acted as both a sonosensitizer and a chemotherapeutic agent, while the ZIF8 carrier provided pH-responsive release behavior in the acidic tumor microenvironment. The platform was further evaluated for its physicochemical properties, cellular uptake, antitumor efficacy, immune activation, and ultrasound imaging performance through a series of in vitro and in vivo experiments.

FA-PEG@ZIF8@CIP exhibited favorable tumor-targeting capability and potent antitumor activity. Under ultrasound irradiation, the platform markedly enhanced reactive oxygen species (ROS) generation, leading to effective tumor cell killing. In addition, it induced immunogenic cell death (ICD), as evidenced by enhanced calreticulin exposure, HMGB1 translocation, and extracellular ATP release. These effects further promoted dendritic cell maturation and increased cytotoxic T-lymphocyte infiltration within tumor tissues, indicating activation of antitumor immune responses. The proportions of CD8⁺ T cells in tumor tissues and spleen increased to 18.7% and 14.6%, respectively, corresponding to approximately 3.0-fold and 2.9-fold increases over the PBS group. The antitumor efficacy of FA-PEG@ZIF8@CIP+US was 4.21-fold higher than that of PBS. Moreover, the platform demonstrated effective ultrasound imaging capability, supporting its application for imaging-guided therapy. Collectively, these findings suggest that FA-PEG@ZIF8@CIP exerts therapeutic effects through the coordinated actions of sonodynamic therapy, chemotherapy, and immune modulation.

This multifunctional nanosystem enables the integration of diagnosis and therapy and represents a promising strategy for TNBC treatment. By combining targeted delivery, pH-responsive drug release, ultrasound imaging, and synergistic therapeutic effects within a single platform, FA-PEG@ZIF8@CIP may offer a valuable approach for improving theranostic outcomes in TNBC.

The clinical application of small interfering RNA (siRNA) therapy is limited by instability, inefficient tumor targeting, and inadequate responsiveness to the hypoxic tumor microenvironment. Therefore, this study aimed to construct a hypoxia-sensitive polymer-based nanocarrier to improve siRNA delivery efficiency and enhance antitumor effects in colorectal cancer (CRC).

A hypoxia-sensitive polymer (mPEG-Azo-PEI) was synthesized and its cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The polymer was loaded with siRNA targeting the METTL3 gene to form nanoparticles, which were then optimized and characterized. Coumarin-loaded nanoparticles were also prepared to study the cellular uptake in HCT116 cells under hypoxic conditions. The Antitumor effects were evaluated via MTT and real-time polymerase chain reaction (RT-PCR) in vitro and in vivo, and a rectal cancer model was established using HCT116 cells in nude mice. Tumor size, weight, and histology (HE staining) were assessed, and RT-PCR analyzed METTL3 ex-pression.

The CMC of mPEG-Azo-PEI was 0.001687 mg/mL, indicating good self-assembly stability under dilution conditions. The optimized mPEG-Azo-PEI@siRNA2 nanoparticles exhibited a mean particle size of 141.34 ± 2.31 nm, a PDI of 0.213 ± 0.011, and a zeta potential of +21.76 ± 1.76 mV. Hypoxia-triggered release reached ~95% within 24 h, compared with ~10% under normoxic conditions. Coumarin uptake by HCT116 cells was enhanced under hypoxic conditions, indicating improved intracellular delivery. In vitro, the nanoparticles inhibited tumor cell proliferation, with IC50 values of 1.133 (normoxia) and 0.481 (hypoxia) nM. In vivo, mPEG-Azo-PEI@siRNA2 significantly suppressed tumor growth and improved body weight. RT-PCR confirmed the downregulation of METTL3, aligning with tumor suppression.

These results demonstrated that hypoxia-sensitive mPEG-Azo-PEI@siRNA2 nanoparticles effectively delivered siRNA2 and inhibited HCT116 cell proliferation, offering a promising hypoxia-activated targeting strategy for colon cancer therapy.

Liquid biopsy provides a non-invasive approach for cancer detection. It examines tumor-associated components in blood and other body fluids, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs, including exosomes). This technology is transforming cancer diagnosis, prognosis, and therapy monitoring. This review summarizes recent advancements in liquid biopsy technologies, particularly focusing on circulating tumor components such as ctDNA, CTCs, and EVs. This review emphasizes the role of liquid biopsy in the early detection of drug resistance and therapeutic response monitoring. A primary emphasis is on how liquid biopsy detects various forms of drug resistance. It evaluates treatment efficacy, monitors alterations in tumor genomics over time, and assists in customizing therapy for people. We also discuss the integration of liquid biopsy with innovative technologies such as artificial intelligence and big data. The objective is to provide practical guidance for the future development of precision oncology.