Objective: Ultrahigh-dose-rate radiotherapy (FLASH-RT) has been shown to reduce radiation-induced normal tissue injury in preclinical studies. Here, we describe the first patient worldwide to receive fractionated FLASH-RT.

Methods: An elderly male patient was diagnosed with extramammary Paget disease of the scrotum along with multiple lymph node and bone metastases. After 6 cycles of chemotherapy, the disease progressed in the scrotum. The scrotal lesions were evaluated for FLASH-RT. 9 MeV electron FLASH-RT was performed at a dose rate of 120 Gy/s. The field size was 5 cm × 5 cm, and the prescribed dose was 40 Gy in five fractions. Dosimetric verification was performed daily. Treatment response was evaluated at 3-month post FLASH-RT, and normal tissue toxicity was assessed from the beginning of FLASH-RT to 12-month post-irradiation.

Results: A 1-year follow-up was achieved for scrotal lesions treated with electron FLASH-RT in patients with extramammary Paget disease. Electron FLASH-RT was safe, and treatment-related adverse events were mild. Transient skin toxicity occurred 2–5 weeks post FLASH-RT, and exudation and burning pain were significantly alleviated. A complete response was achieved 2–3 months post FLASH-RT, and the tumor lesions were covered by the normal epithelium of the scrotum. At the end of the one-year follow-up, the tumor lesions continued to respond, and one-year survival was achieved without additional injury to the irradiated areas after FLASH-RT.

Conclusion: Fractionated electron FLASH-RT is feasible and safe for the treatment of extramammary Paget disease of the scrotum. Our findings support further exploration of electron FLASH-RT in patients with skin tumors.

Background: This study aimed to compare the dosimetric characteristics of lattice radiotherapy across different linear accelerator platforms (Versa HD, Halcyon, and NeuRT Aurora) and to evaluate the feasibility of its clinical application.

Methods: This study included ten patients with bulky tumors who were eligible for spatially fractionated radiotherapy, including five pelvic cases and five abdominal cases. For each patient, high-dose vertices were contoured within the gross tumor volume using a standardized method, followed by three independently designed treatment plans on the Versa HD, Halcyon, and NeuRT Aurora platforms. The prescribed dose was 2400 cGy in three fractions. Dosimetric evaluation of the target volume included vertex coverage, maximum dose, and the peak-to-valley dose ratio. In addition, a vertex-specific dose analysis was performed to quantify the number of vertices with a D95 of less than 2400 cGy. For organs at risk, the following dosimetric parameters were evaluated: the mean dose to the intra-lattice margin volume, the maximum dose to tissues located more than 2 cm from the vertices, and standard dosimetric parameters for the spinal cord, small bowel, colon, liver, stomach, lungs, and kidneys.

Results: All plans demonstrated the characteristic dosimetric features of lattice radiotherapy by establishing alternating high-dose peaks and low-dose valleys within the target volume, while achieving effective protection of surrounding normal tissues without compromising target coverage. Among the three platforms, NeuRT Aurora demonstrated superior performance in dose gradient control and normal tissue protection. The mean peak-to-valley ratios were 6.4, 6.9, and 8.9 for the Versa HD, Halcyon, and NeuRT Aurora platforms, respectively. The maximum dose to tissues located more than 2 cm from the vertices was significantly lower in the NeuRT Aurora plans (1158.6 cGy) than in the Versa HD plans (1280.6 cGy) and Halcyon plans (1257.8 cGy). Consistent with this trend, the NeuRT Aurora plans were also associated with a lower mean dose to the intra-lattice margin volume (792.4 cGy) than the Versa HD (831.4 cGy) and Halcyon (845.7 cGy) plans. For all specific organs at risk, the evaluated dosimetric parameters remained within clinical tolerance limits across the three treatment platforms.

Conclusions: This study systematically evaluated lattice radiotherapy plans across three accelerator platforms. Although differences were observed in peak-to-valley ratios and organ-at-risk sparing, all plans met clinical requirements, confirming the overall feasibility of each platform.

Purpose: To develop and validate a fully automated quality assurance method for high-dose rate (HDR) brachytherapy, enabling the precise evaluation of source dwell-position accuracy and dwell-time linearity using radiochromic film analysis and advanced image processing algorithms.

Methods: A novel analytical framework was established to verify HDR source positional precision and dwell-time linearity. Radiochromic films were irradiated under predefined treatment plans. Image preprocessing involved grayscale conversion, median filtering, rotation correction, and absolute coordinate calibration. The centroid of each dwell position was determined using two-dimensional Gaussian fitting. Temporal linearity analysis employed radial grayscale summation within the radii of 250–400 pixels. Linearity was quantified using the coefficient of determination (R²), with R² approaching 1 indicating optimal performance.

Results: Automated Gaussian fitting achieved sub-millimeter positional accuracy (maximum error ≤ 0.6 mm), eliminating manual intervention. Rotation correction algorithms effectively mitigated positional errors caused by film misalignment. Comparative analysis with commercial software yielded nearly identical results, validating the reliability of the method. Dwell-time analysis demonstrated excellent linearity (R²≥0.999) over summation radii ranging from 150 to 400 dpi.

Conclusions: This study presents a robust and fully automated quality assurance (QA) solution for HDR brachytherapy that simultaneously verifies sub-millimeter-level dwell-position accuracy and temporal linearity. The integration of radiochromic film dosimetry with algorithmic image processing eliminates manual intervention and standardizes QA workflows, representing a substantial advancement in treatment safety and efficiency.

Objective: This study aimed to investigate whether baseline skeletal muscle status and malnutrition in patients with locally advanced head and neck cancer (HNC) are associated with short-term treatment outcomes and acute radiation oral mucositis (OM).

Methods: We retrospectively analyzed data from 68 patients with stage III–IV HNC treated at a single center with definitive radiotherapy (66–70 Gy) with or without chemotherapy (induction and/or concurrent) between July 2021 and July 2023. Malnutrition was diagnosed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Patient-Generated Subjective Global Assessment (PG-SGA). Short-term response was assessed at first post-treatment imaging after radiotherapy according to RECIST 1.1, and OM severity was graded using World Health Organization criteria. Univariate and multivariate logistic regression analyses evaluated the correlation between short-term response and grades III–IV OM.

Results: Of the 68 patients, 32.4% had a lower skeletal muscle index (SMI), 26.5% had lower hand grip strength (HGS), 20.6% (GLIM) and 58.8% (PG-SGA) had malnutrition. At the end of treatment, 64.7% of the patients achieved partial remission, and 35.3% achieved a stable condition. Low HGS was associated with low short-term efficacy (OR = 0.31, 95% CI = 0.10–0.95, p = 0.040); however, this difference did not reach statistical significance in the multivariate model. A total of 41.2% of patients had Grade III–IV OM; however, OM was not significantly associated with low SMI, HGS, or malnutrition.

Conclusion: Baseline skeletal muscle status and malnutrition did not consistently predict short-term treatment outcomes or severe radiation-induced OM in patients with locally advanced HNC. However, these results suggest a potential relationship between low HGS and treatment response. Further research with larger sample sizes and longitudinal evaluations is needed to clarify muscle and nutritional status impact on multidimensional outcomes in this patient population.

Background: The optimal management of locally advanced resectable esophageal squamous cell carcinoma (ESCC), particularly for cT3-4a disease, remains debated. This study aimed to compare the survival outcomes and toxicity profiles of neoadjuvant chemoradiotherapy (NCRT) and adjuvant chemoradiotherapy (ACRT) in this patient population.

Methods: We retrospectively analyzed 223 patients with resectable cT3-4a ESCC who underwent radical surgery combined with NCRT or ACRT. Propensity score matching (PSM) was used to generate 59 balanced pairs for comparative analysis.

Results: After matching, the NCRT group demonstrated significantly improved overall survival (OS) compared with the ACRT group, with a median OS of 62 versus 46 months and 5-year OS rates of 66.6% versus 47.5%, respectively (p = 0.023). Despite the longer median progression-free survival (PFS) observed in the NCRT group (53 vs. 42 months), the difference in the 5-year PFS rate was not statistically significant (56.7% vs. 44.4%; p = 0.113). Furthermore, the two groups exhibited similar profiles of treatment-related adverse events (all p > 0.05). Multivariable analysis identified treatment strategy, body mass index (BMI), and clinical nodal (cN) status as independent predictors of OS (all p < 0.01). A novel prognostic score (PS) integrating BMI and cN status effectively stratified patients into distinct risk categories, with higher scores predicting poorer prognosis but not in the neoadjuvant subgroup.

Conclusions: For patients with resectable cT3-4a ESCC, NCRT provides superior OS compared to ACRT, with similar PFS and toxicity. These findings support the prioritization of NCRT for this disease stage; however, larger randomized trials are warranted to optimize patient selection.

Radiotherapy (RT) has become an indispensable part of modern cancer treatment owing to its efficacy, precision, and safety. With continuous advances in clinical practice, the role of RT in comprehensive cancer treatment has been repositioned. Through a combination of chemotherapy, targeted therapy, and immunotherapy, RT can achieve multiple therapeutic goals, including disease cure, symptom relief, improved quality of life, and prolonged survival. Therefore, understanding the development of RT, its mechanisms, technological innovations, combined therapeutic strategies, and prospects is essential for advancing tumor treatment and improving patient survival.

The interaction between immune checkpoint inhibitors (ICIs) and radiotherapy has significantly improved the treatment outcomes for patients with cancer. ICIs activate the immune system by blocking the programmed death-1 (PD-1), programmed cell death-Ligand 1(PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling pathways, thereby killing tumor cells. Radiotherapy activates local and abscopal effects by killing tumor cells, inducing immunogenic death, and releasing antigens and damage-related molecules. The combination of the two methods forms a closed-loop process of “antigen release-immune activation,” which significantly improves the therapeutic effect of patients with cancer. Clinical studies have shown that ICIs combined with radiotherapy can significantly improve the objective response rate (ORR) and progression-free survival (PFS) in patients with solid tumors, such as Non-Small Cell Lung Cancer (NSCLC) and melanoma. However, heterogeneous responses, immune-related adverse events (irAEs), and drug resistance are still common clinical problems. Optimizing the fractionation of radiotherapy dose, timing of synchronous intervention, and biomarkers, such as tumor mutation burden, are key to improving tumor treatment efficacy. In the future, precise tumor treatment is expected to improve patient prognosis through the interaction between ICIs and radiotherapy.

Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in treating hematological malignancies. However, compared to its efficacy against hematologic cancers, the application of CAR-T cell therapy for solid tumors still faces several challenges. Radiotherapy, an important component in the treatment of solid tumors, has recently attracted widespread attention because of its immunomodulatory effects. Combined radiotherapy may overcome the limitations of CAR-T cell therapy for solid tumors. This review discusses the theoretical foundations of combined radiation therapy and CAR-T cell therapy, along with preclinical and clinical research progress. Additionally, this study provides an innovative exploration of key factors to be considered when combining these two therapies. These factors include radiation dose, mode, radiation type, and timing and scheduling of the combined treatment. This review offers new perspectives on future research directions and highlights critical issues that remain to be addressed.

Boron neutron capture therapy (BNCT) has emerged as a promising therapeutic modality in cancer treatment, demonstrating the ability to selectively eliminate cancer cells through the ¹⁰B(n,α)⁷Li nuclear reaction with minimal side effects on normal tissues. As a binary, target-specific therapeutic modality for malignancies, BNCT critically depends on novel boron delivery carriers that exhibit high tumor affinity and prolonged intratumoral retention. Although several boron carriers have received Food and Drug Administration approval for clinical investigation, leading carriers such as L-p-boronophenylalanine (BPA) and sodium borocaptate (BSH) continue to require high infusion doses and exhibit limited tumor selectivity and affinity, short systemic half-lives, and limited in vivo stability. These challenges have stimulated extensive global research into novel boron-10 carriers and innovative carrier platforms, including amino acids, sugars, porphyrin derivatives, nucleotides, and a variety of nanocarrier systems. This review provides a systematic classification of high-abundance boron-10 carriers, critically examines radio-boron research, and evaluates the potential integration of BNCT into clinical diagnostics and advanced cancer treatment protocols. By detailing the current status of novel boron-10 carriers, this review further aims to elucidate critical challenges and opportunities in BNCT drug development, ultimately providing a theoretical foundation for next-generation BNCT interventions.

Radiotherapy has emerged as a cornerstone modality in the management of malignant tumors. Its evolution from a localized intervention to a radical curative strategy has been particularly pronounced in lung cancer, where its role has shifted from symptom palliation to survival prolongation. Radiation esophagitis (RE) is one of the most common acute adverse effects of thoracic radiotherapy, particularly in patients with lung cancer. In the early phase of RE, the predominant features include reactive oxygen species-mediated DNA damage and disruption of the epithelial barrier. The inflammatory phase is characterized by nuclear factor kappa B activation, edema, and pain. During the dysregulated repair phase, impaired regeneration of the esophageal mucosal epithelium, compounded by microbiota imbalance, further exacerbates tissue injury. In the late phase, transforming growth factor beta-driven fibrosis may culminate in stricture or fistula formation. Clinically, the condition primarily manifests as dysphagia and odynophagia. The prevention and management of RE remain significant clinical challenges. This review examines key issues related to RE within the context of precision radiotherapy, with particular emphasis on its incidence and current management strategies.

Boron neutron capture therapy (BNCT) is an emerging targeted radiotherapy technology that enables precise eradication of tumor cells. The development of efficient boron carriers is crucial for the advancement of BNCT technology. Notably, biomolecular carriers currently represent the only class of drug carriers that has achieved market approval (e.g., boronophenylalanine [BPA] in Japan), underscoring their pivotal role in clinical applications. Their outstanding biocompatibility, high payload capacity, and tumor-targeting capabilities align closely with the stringent requirements of BNCT drug delivery. For instance, amino acid-based carriers (such as BPA) utilize L-type amino acid transporter 1 (LAT1) for tumor-specific accumulation; nucleoside prodrugs are activated by thymidine kinase 1 (TK1) and incorporated into tumor DNA; carbohydrate-based carriers improve solubility and targeting through glucose transporters (GLUTs); peptide carriers facilitate cellular uptake via receptor-mediated endocytosis or cell-penetrating peptides; and liposomes leverage the enhanced permeability and retention (EPR) effect together with active-targeting modifications for enhanced tumor delivery. Nevertheless, delivering ultrahigh doses of boron remains a major challenge. Biomacromolecules, particularly albumin-based systems, have garnered increasing attention because of their excellent biosafety and high boron-loading potential, offering promising avenues for overcoming dose delivery barriers in BNCT. This review systematically summarizes the recent advances in biomolecular carriers for BNCT and highlights emerging applications of protein-based boron carriers, addressing a notable gap in the comprehensive review of biomolecular strategies within the BNCT drug delivery field.