Proton therapy has been criticized due to its relatively low biological effectiveness compared with heavy particle therapy, for example, C-12 ion therapy. Recently, we proposed a new strategy for proton therapy to improve biological effectiveness, termed as nitrogen-targeting-Proton-Carbon-Alpha-Therapy (Proton-CAT). The previous work has demonstrated its feasibility to enhance the yield of high-linear energy transfer (LET) particles with a monoenergetic proton beam. To assess the feasibility of Proton-CAT for spread-out Bragg peak (SOBP) beams, we employed Monte Carlo simulations at both macroscopic and microscopic levels. For macroscopic calculations, an SOBP of 24-32 MeV protons with a modulation width of 3.0 mm was constructed and irradiated into a tissue-equivalent phantom with and without N-15 material (10% and 30% N-15 concentration). Dose deposition by protons, alpha particles, and C-12 ions was scored along the beam path. For microscopic evaluation, a cell model was used to assess the damage inflicted by energetic particles (C-12 ions and alpha-particles). The results demonstrated the advantages of the Proton-CAT. Within the SOBP (0.6-0.82 cm depth), the average dose amplification for C-12 ions exceeded 15.8% (10% N-15) and 38.5% (30% N-15), while for alpha-particles, it surpassed 68.5% (10% N-15) and 203.8% (30% N-15). Moreover, the energy deposition of C-12 ions and alpha-particles in cell nucleus reached up to 3.50 keV mu m(-3) (10% and 30% N-15 concentration). These findings support the hypothesis that the Proton-CAT has the feasibility to yield short-range, high-LET C-12 ions and alpha-particles within the SOBP region.

Background The reliability of contrast-enhanced CT (CHCT) as a reference image for MR-based dose calculation in lung stereotactic body radiation therapy (SBRT) with MR-Linac remains uncertain due to contrast-induced electron density (ED) discrepancy. Whether CHCT can be used as a reference image for dose calculation for patients with lung tumors treated with MR-Linac still needs to be explored in further works. Methods This retrospective study included 30 patients with lung metastases treated with SBRT (50 Gy in 5 fractions) on a 1.5 T MR-Linac. Non-contrast CT (pCT) and corresponding CHCT acquired in the same respiratory phase were used to extract mean electron density for targets and organs at risk (OARs). The treatment plans (TP csCT and TP psCT ) based on synthetic CT (sCT) generated by assigning mean ED derived from pCT and CHCT were recalculated without altering parameters. Dosimetric discrepancy were evaluated using dose-volume histogram metrics, conformity indices, gradient indices and gamma analysis. Results Significant differences in mean ED between pCT and CHCT were observed for several structures, most notably the lungs (mean differences > 12%), heart, aorta, and bronchial tree ( p < 0.05), whereas minimal changes were found in bone and spinal cord. Despite these ED variations, dosimetric differences in target coverage were modest, with average discrepancy of 2.21% and 2.31% for TP csCT and TP psCT , respectively. The other dosimetric parameters (D max , D 2% , D 95% , D 98% , D mean , CI and GI) differences for target were generally below 3%. Although statistically significant differences were detected in some OARs dose metrics, all values remained well within clinical tolerance limits (3%). Conclusion Despite significant contrast-induced variations in ED, the using of CHCT as a reference image result in minor dosimetric differences in lung SBRT. Considering the patient's financial capacity and the radiation dose from repeated CT scans, CHCT may be used as a reference image for lung tumor SBRT with MR-Linac when clinical risks are appropriately managed.

Stereotactic re-irradiation (re-SRT) is a promising salvage treatment for locally recurrent brain metastases (BMs) after prior stereotactic radiotherapy (SRT), but its feasibility and safety remain insufficiently validated. A systematic search was conducted for studies involving patients who received re-SRT, following PRISMA guidelines. Pooled local control rate (LCR), overall survival (OS), and radiation necrosis (RN) rates were calculated using a random-effects model. Meta-regression analyses were conducted to evaluate the relationship between variables and outcomes. Logistic dose–response models were hypothetically constructed for tumor control probability (TCP) in terms of the biological effective dose using an α/β of 10 Gy (BED10). Fourteen studies (687 patients, 896 BMs) were included, with a median BED10 of 50.4 Gy. Pooled 1-year LCR and OS rate were 76

Background The application of guidance template in interstitial brachytherapy (ISBT) was expected to improve target coverage and sparing organs at risk for locally advanced cervical cancer (LACC). The purpose of this study was to compare dosimetric and procedural outcomes of template-guided ISBT against free-handed ISBT. Methods Consecutive patients with LACC were prospectively enrolled at Sichuan Cancer Hospital from February to September 2025. A novel 3D-printed free-assembled interstitial template (FAIT), featuring a tandem with optimized non-coplanar needle channels, was invented and utilized for ISBT. Each patient underwent both FAIT-guided and free-handed high-dose-rate ISBT within 3 days with a random sequence. Treatment plans were generated in the Oncentra planning system with a 600 cGy prescription, and dosimetric parameters including high-risk clinical target volume (HRCTV) D 90 , dose of organs at risk (OARs) (D 1cc and D 2cc for bladder, rectum, sigmoid and bowel) were extracted. The number of interstitial needles and implantation time were also recorded. Data were presented as mean ± standard deviation and compared using paired Student’s t -tests. Statistical significance was defined as P < 0.05. Results 55 patients received both FAIT-guided and free-handed ISBT procedures after pelvic external beam radiotherapy (EBRT) of 45-50.4 Gy with 25–28 fractions. Most patients were stage ⅡB (n = 34, 61.8%) and squamous cell carcinoma (n = 49, 89.1%), and mean post-EBRT HRCTV volume was 61.8 ± 21.3 cm 3 . There was no significant difference on the number of needles used in FAIT-guided and free-handed ISBTs (4.88 ± 0.90 vs. 4.76 ± 1.24, P = 0.30). FAIT guidance shortened implantation time (5.83 ± 1.93 vs 8.03 ± 2.71 min, P < 0.0001) and achieved higher HRCTV D90 (611.38 ± 35.12 vs 580.86 ± 64.65 cGy, P < 0.01), with similar OAR doses (P > 0.05). Conclusions Improved target volume dose coverage and shortened needle implantation time were achieved with the application of the novel 3D-printed FAIT in ISBT. This novel template had high clinical utility and was worthy of further promotion and application.

Objective To identify risk factors for post-radiation xerostomia and to evaluate the tolerance to doses administered to the parotid gland in patients with nasopharyngeal carcinoma (NPC). Methods A total of 462 patients with NPC who received radiotherapy at Nanfang Hospital of Southern Medical University and Sichuan Cancer Hospital from 2012 to 2016 were retrospectively analyzed. Xerostomia was diagnosed according to the Radiation Therapy and Oncology Group (RTOG) grade. Medcalc software and SPSS software were used for statistical analysis, and MATLAB and R software was used for modeling. Results The cut-off values for Dmean (the average dose of parotid), Dmean-L (the average dose of left parotid) and D50-R (dose received at 50% volume of right parotid) were 26.00, 28.30 and 23.93 Gy, above which the risk of long-time xerostomia occurs is increased (P < 0.05). D50, D50-L, D50-R, Dmean, Dmean-L and Dmean-R were 28.66, 23.12, 29.04, 28.00, 28.30 and 35.55 Gy, respectively, but the results showed that this dose was not associated with highest xerostomia grade (HXG) (P > 0.05). The relevant factors were independent risk factors for the development of xerostomia, the same was true for age, T stage, and D-PTV (dose of PTV). Using patient's gender, radiation treatment, number of radiotherapy sessions, T stage, TNM stage, Dmean and D50 (dose received at 50% volume of the parotid glands) to established a prediction model to predict HXG and long-term xerostomia grading (LTG), the results indicated that Training showed R = 0.82. The independent risk factors were included to establish the nomogram prediction model. The results showed that the C-index was 0.671. Conclusion It is feasible to establish a neural network model or a nomogram prediction model using parotid dose parameters to predict the incidence of radiation-induced xerostomia.

Proton therapy has been rapidly advancing due to its excellent conformal index, but its relatively low relative biological effect (RBE) has somewhat limited its therapeutic efficacy for certain tumors. To address this, we previously proposed a nitrogen-targeting Proton-Carbon-Alpha-Therapy (Proton-CAT) enhancement method. In this letter, we present combined multi-scale DNA damage simulations and in vitro cell experiments, further investigating the mechanism of the Proton-CAT. It has been show that ^15N enrichment significantly enhances complex DNA damage induced by high linear energy transfer(LET) particles within tumor regions. Under 30% ^15N conditions, α and ^12C particle induced DSB++ increased by 175.19% and 52.94%, respectively. Furthermore, in vitro cell experiments using ^15N-glutamine (^15N-Glu) as the ^15N carrier indicated that high concentrations of ^15N-Glu did not bring about significant cytotoxicity. Following 2 Gy irradiation, the cell viability in the 500 μg/mL ^15N-Glu treated group exhibited a net reduction of about 15.41% compared to the control group.This indicates that the enhanced effect of Proton-CAT primarily stems from increased complex DNA damage. This work provides a theoretical basis and multi-scale research framework for the development of the Proton-CAT.

Ultra-high dose rate radiotherapy (FLASH-RT) has emerged as a promising technology in recent years. Unlike conventional radiotherapy (CONV-RT), FLASH-RT delivers radiation at an ultra-high dose rate over a very short duration. This approach not only greatly shortens the treatment time, but also exhibits the “FLASH effect”, which significantly spares healthy tissues while maintaining antitumor efficacy comparable to that of CONV-RT. Radiotherapy ignites immunity, fueling the radioimmunotherapy boom. However, even the most advanced radiotherapy techniques inevitably expose healthy tissue, immune organs, vasculature, and circulating or infiltrated lymphocytes to radiation-induced toxicity, limiting the synergistic effect of radioimmunotherapy. Notably, FLASH-RT offers a considerable alternative by protecting the immune system, converting the immunosuppressive tumor microenvironment (TME) into a moderately immune-infiltrated TME, and reducing immunosuppressive responses, thereby enhancing antitumor immunity. A growing number of studies have demonstrated that this combination shows synergistic antitumor effects even in drug-resistant tumor models. Despite these encouraging findings, the combination of FLASH-RT with immunotherapy remains in its early stages and has yet to reach clinical implementation. In this review, we present the current status, underlying mechanisms, and future prospects of FLASH-RT, with a particular focus on its immunomodulatory abilities and potential as a future platform for cancer radioimmunotherapy.

AbstractBackground: Lattice spatially fractionated radiotherapy (Lattice SFRT) is a promising modality for advanced solid tumors, but optimal treatment parameters (e.g., fractionation schedule, dose contrast) and patient stratification criteria remain unclear. This study aimed to systematically investigate these parameters and identify the patient population most likely to benefit.Methods: A retrospective cohort of 135 patients with pathologically confirmed solid tumors who received Lattice SFRT at Sichuan Cancer Hospital (2021–2024) was analyzed. Relationships between tumor characteristics (size, location, histology), treatment parameters (dose contrast, fractionation schedule), and clinical outcomes (objective response rate [ORR], disease control rate [DCR]) were evaluated. Subgroup analyses stratified by tumor burden were performed to explore interactions with fractionation regimens.Results: The overall DCR was 93.3% and ORR was 20.7%. Tumor burden was the only factor significantly associated with DCR (P=0.044), with higher DCR in larger tumors. In medium-sized tumors (3–6 cm), once-daily (qd) and once-weekly (qw) fractionation yielded 100% DCR, significantly superior to every-other-day (qod) regimens (P=0.021). Dose contrast (>4 vs. 2–4) was not associated with DCR (P=0.678). No variables were significantly associated with ORR.Conclusions: Lattice SFRT achieves high disease control in advanced solid tumors. Optimal application requires stratification by tumor burden; qd/qw fractionation is superior to qod for medium-sized tumors. Moderate dose contrast (2–4-fold) is sufficient for efficacy, lowering technical barriers to clinical implementation, providing evidence for individualized treatment planning.

Background:Epstein-Barr virus (EBV) DNA is a well-established biomarker in nasopharyngeal carcinoma (NPC), but its integration into artificial intelligence (AI)-based prognostic tools remains limited. This study aimed to develop and validate AI models incorporating EBV DNA load levels to predict progression-free survival (PFS) in patients with advanced NPC treated with concurrent chemoradiotherapy (CRT). Methods:A retrospective multicenter cohort of 503 patients was divided into training (n = 301) and validation (n = 202) sets. Four machine learning algorithms-Cox regression, LASSO, RSF, and GBM-were applied to predict 1- and 1.5-year PFS in patients with advanced NPC. Model performance was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC), decision curve analysis (DCA), and interpretability tools such as SHAP values and partial dependence plots (PDP). Results:The 1-, 3-, and 5-year PFS rates were 100.0%, 91.5%, and 88.6% in the EBV = 0 group; 99.4%, 91.2%, and 88.5% in the > 0 and < 1500 group; and 92.3%, 81.0%, and 75.7% in the ≥ 1500 group, respectively, with statistically significant differences among the three groups (P = 0.0024). The RSF model outperformed other models with the highest C-index (0.778) and area under the ROC curve of 0.810 and 0.634 at 1 and 1.5 years, respectively. EBV DNA emerged as the most influential predictor across all interpretability analyses. Patients with EBV DNA ≥1500 copies/ml had the poorest predicted survival, showing a distinct threshold effect in the PDP. Conclusions:High EBV DNA levels were associated with poorer PFS in advanced NPC. Among the models evaluated, the RSF model demonstrated the best predictive performance and interpretability. EBV-informed AI modeling represents a promising approach for enhancing individualized risk prediction and clinical decision-making in NPC.

Table S4 shows reagents and antibodies.

Figure S7 shows fecal microbial transplantation (FMT) influenced the immune microenvironment of subcutaneous xenograft tumor tissues.

PURPOSE:Lattice radiation therapy (LRT) is a promising approach for treating bulky tumors; however, current methods do not consider patient-specific tumor heterogeneity. Low apparent diffusion coefficient (ADC) regions, identified via diffusion-weighted magnetic resonance imaging, correspond to areas of high cellular density and radioresistance. Targeted dose escalation in these regions may enhance tumor control. Thus, we propose biologically guided lattice radiation therapy (BG-LRT), which optimizes lattice positioning based on the ADC map. METHODS AND MATERIALS:We retrospectively analyzed 20 patients with bulky tumors (>6 cm) who underwent diffusion-weighted magnetic resonance imaging and simulation computed tomography within 3 days. BG-LRT plans were created by aligning high-dose lattice regions with low-ADC areas and comparing them with hexagonal close-packed-LRT (HCP-LRT). Both techniques prescribed 60 Gy in lattice regions and 20 Gy to the gross tumor volume (GTV) over 5 fractions. The dosimetric evaluation included the peak-valley dose ratio (PVDR) and ablation dose ratio (ADR) within the GTV as well as dose distribution in ADC-defined tumor subregions (R_ADC10 to R_ADC50) and organs at risk (OARs). RESULTS:BG-LRT achieved a higher PVDR (2.7 vs 2.4) and ADR (2.6% vs 1.7%) than HCP-LRT. ADR values across all ADC-defined tumor subregions (R_ADC10 to R_ADC50) were significantly higher for BG-LRT. OAR doses were comparable between methods, with no significant differences in mean dose (Dmean) to the heart, stomach, esophagus, kidneys, liver, and duodenum as well as the maximum doses (Dmax) to the lens, eye, optic nerve, brainstem, and optic chiasm. Planning time, delivery time, monitor units, and gamma pass rates were similar between techniques. CONCLUSIONS:BG-LRT improves PVDR and ADR in the GTV while focusing on dose escalation in biologically relevant tumor regions. This technique maintains low OAR doses and represents a promising step toward personalized LRT treatment planning.

Table S3 shows clinical characteristics of feces providers for fecal microbiota transplantation.

Figure S1 shows detection of intra-tumoral microbiota in the ESCC tissues.

Table S2 shows clinical characteristics of patients with esophageal squamous cell carcinoma (ESCC) who underwent NACI1 treatment.

Figure S8 shows intra-tumoral bacterial contents were stable during tumor growth.

Immunotherapy combined with chemotherapy is currently the first-line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). This study aims to evaluate whether adding metastasis-directed radiotherapy (MDRT) to immunotherapy and chemotherapy could improve the survival rate of patients with metastatic HNSCC. A retrospective analysis was conducted on patients with HNSCC who developed distant metastases after curative treatment. Systemic treatment was determined by the multidisciplinary team, with a programmed cell death-1 (PD-1) inhibitor combined with chemotherapy as the primary approach. The feasibility of radiotherapy was evaluated by clinical and imaging examinations. Stereotactic body radiotherapy (SBRT) was used to deliver different doses according to the number and location of metastatic lesions. Kaplan–Meier method was used to estimate survival, and Cox regression analysis was performed to evaluate the association between clinical factors and survival outcomes. From January 2018 to June 2023, a total of 94 patients with 164 metastatic sites were included for the analysis. The most common primary tumor was the nasopharynx (77.7