PURPOSE:Acute radiation dermatitis (ARD) is a common debilitating toxicity in patients with head and neck cancer receiving radiotherapy. Current evidence-based strategies for preventing ARD remain limited, and alternative approaches are needed to optimize care. METHODS:In this double-blind, randomized, controlled phase II trial, eligible patients with head and neck cancer undergoing radiotherapy were randomly assigned in a 1:1 ratio to receive either fullerene or trolamine at West China Hospital, Sichuan University, from August 2024 to March 2025. Participants were instructed to apply the assigned cream three times daily starting from the 3 days before radiotherapy and continuing for 14 days after completion of radiotherapy. ARD was evaluated weekly during radiotherapy and for 4 weeks after radiotherapy. The primary end point was the incidence of grade ≥2 ARD, assessed in the intention-to-treat population. RESULTS:A total of 132 patients were randomly assigned, with 66 allocated to the fullerene group and 66 to the trolamine group. The patients had a mean age of 58.0 years (standard deviation, 11.1), and 39 (29.5%) were female. The incidence of grade ≥2 ARD was significantly lower in the fullerene group than in the trolamine group. In the fullerene group, 34.8% of patients (95% CI, 24.5 to 46.9) developed grade ≥2 ARD, compared with 83.3% of patients in the trolamine group (95% CI, 72.6 to 90.4). CONCLUSION:In this prospective, randomized clinical trial, fullerene significantly reduced the incidence of ARD compared with trolamine.

Radiation-induced skin injury (RISI) affects over 95% of radiotherapy patients. Current clinical management remains confined to passive supportive care, lacking mechanistic precision for RISI's unique pathophysiology. This review adopts a function-centric perspective, classifying hydrogel systems across three generations: first-generation passive moisture barriers; second-generation bioactive platforms incorporating antioxidants, growth factors, stem cells and exosomes; and third-generation stimuli-responsive systems integrating autonomous drug release, self-healing capabilities and biosensor monitoring. We establish quantitative design thresholds by correlating RISI microenvironment parameters (pH 6.5-7.0, ROS 100-500 μM, MMP-9 elevation 5-10×) with responsive polymer specifications. Single-cell transcriptomic analysis has identified pro-inflammatory IL-17+ secretory fibroblasts and dysfunctional lymphatic endothelial cells as key dysregulated populations, thereby defining precise cellular targets amenable to hydrogel-based intervention. However, randomized trials demonstrate that certain hydrogel formulations unexpectedly prolonged healing, underscoring the need for design strategies based on quantitative pathophysiological insights rather than passive empiricism. We systematically examine enabling technologies-AI-guided materials optimization, 3D bioprinting and wearable biosensor integration-while addressing translational barriers including regulatory complexity, manufacturing scalability and standardized preclinical models. This framework provides actionable design principles to accelerate clinical deployment of next-generation hydrogels for millions of cancer survivors.

12145 Background: Radiation-induced oral mucositis (RIOM) is common during head and neck radiotherapy ( > 90% incidence), and 40–70% of patients develop severe oral mucositis (SOM; WHO grade 3–4), which markedly impairs quality of life and may lead to radiotherapy interruptions. Given the limited effective therapies and the lack of evidence-based standard of care, we assessed the efficacy and safety of MeiLianFuXin Liquid ( Periplaneta americana extract) for reducing SOM incidence. Methods: This multicenter, randomized, double-blind, placebo-controlled phase II trial was conducted across 7 hospitals in China from June 12, 2024, through October 31, 2025. Eligible patients (18–80 years) had non-metastatic head and neck cancer planned for radiotherapy (planned total dose ≥60 Gy), with cisplatin as the only allowed concurrent agent. Following investigator-confirmed WHO grade 1 oral mucositis, patients were randomized (1:1:1) via a centralized interactive web response system (IWRS) using a dynamic minimization algorithm to receive low-dose MeiLianFuXin Liquid, high-dose MeiLianFuXin Liquid, or a matched placebo. The study drug was administered three times daily until 14 days post-radiotherapy. The primary endpoint was SOM incidence. Adjusted proportion differences were estimated using logistic regression. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: In the full analysis set (FAS), 215 patients received treatment (low-dose, n = 72; high-dose, n = 72; placebo, n = 71). The incidence of SOM was 22.2% (95% CI, 13.3 to 33.6) in the low-dose group, 29.2% (95% CI, 19.0 to 41.1) in the high-dose group, and 43.7% (95% CI, 31.9 to 56.0) in the placebo group. Compared with placebo, adjusted proportion differences were −22.5% (95% CI, −37.3 to −7.8; P = .0042) for the low-dose group and −16.4% (95% CI, −32.2 to −0.5; P = .0463) for the high-dose group. Adverse events and serious adverse events were generally similar across groups. Conclusions: To our knowledge, this is the first randomized, double-blind, placebo-controlled trial of a traditional Chinese medicine for RIOM showing that MeiLianFuXin Liquid reduces SOM incidence versus placebo with a favorable safety profile. These findings support MeiLianFuXin Liquid as a promising treatment strategy to mitigate RIOM. Clinical trial information: ChiCTR2400084288.

Purpose Fan-beam CT–guided adaptive radiotherapy (FBCTgART) enables treatment adaptation based on pre-fraction CT. However, only non-contrast CT is usually available during FBCTgART, making primary nasopharyngeal gross tumor volume (GTVp) delineation challenging. We proposed a dual-registration decision-guided method to improve GTVp auto-delineation during FBCTgART. Methods and materials We retrospectively collected 1023 multicenter offline adaptive radiotherapy cases of nasopharyngeal carcinoma, including 622 internal cases and 401 external cases. Two online FBCTgART cases were additionally evaluated for clinical validation. Rigid and deformable registration were performed between the previous and current CT scans to propagate the prior GTVp and generate two registration-derived priors. An intersection-based decision rule was used to exclude evidently unreliable deformable priors. The selected priors were then integrated into nnU-Net for current-fraction GTVp delineation. Performance was assessed using anatomical metrics and radiomics-based analysis. Results In five-fold internal cross-validation, the proposed model achieved a mean DSC > 0.87 and a mean IoU > 0.77. In the external validation cohort, the model achieved a DSC of 0.8236 ± 0.1169, IoU of 0.7123 ± 0.1265, HD95 of 2.6056 ± 3.6291 mm, and ASSD of 0.9956 ± 2.1110 mm, outperforming registration-only and single-prompt models. Radiomics analysis showed comparable Radscore performance between auto-delineated and manual GTVp, with C-index values of 0.679 (95% CI: 0.633–0.726) in the internal cohort and 0.608 (95% CI: 0.453–0.763) in the external cohort. Conclusion The proposed method improved GTVp auto-delineation for nasopharyngeal carcinoma during FBCTgART. It provides a practical strategy for accurate target delineation on non-contrast CT when multimodal imaging is unavailable.

For sinonasal intestinal-type adenocarcinoma (ITAC), no standardized treatment exists, particularly for cases with advanced-stage disease with intracranial invasion or recurrence. The present study describes the case of a 60-year-old male patient with ITAC and intracranial invasion who underwent surgery followed by radiotherapy; however, this was terminated early after 25 of 30 sessions [equivalent dose in 2-Gy fractions (EQD2), 54.72 Gy] due to the risk of damaging the optic nerve. The tumor recurred in the same place 12 months after the surgery. A biopsy revealed a combined positive score (CPS) of 5, indicating that the tumor was programmed death-ligand 1-positive (PD-L1-positive), leading to treatment with albumin-bound paclitaxel, cisplatin and camrelizumab for 4 cycles, followed by 12 cycles of maintenance therapy with camrelizumab. The patient maintained progression-free survival for 11 months. On the whole, the present case report highlights the need for sufficient radiotherapy (≥66 Gy EQD2) for ITAC in complex anatomical areas, highlighting the role of advanced techniques to overcome dose limitations. Moreover, the 'chemo-immuno induction plus immuno-maintenance' approach in PD-L1-positive patients exhibits potential for long-term disease control, providing a novel treatment model for advanced-stage ITAC.

Background This study sought to characterize distinct regional lymph node metastasis (LNM) patterns of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) using PET-CT imaging and postoperative pathology, and to provide evidence-based guidance for precise radiotherapy target volume delineation in NSCLC. Methods We retrospectively analyzed 422 PET-CT scans (281 LUAD, 141 LUSC) and 305 surgical pathology reports (236 LUAD, 69 LUSC) from our institution. Inter-group comparisons were performed using chi-square or Fisher’s exact tests. Binary logistic regression models were utilized for multivariate analyses. Results PET-CT and pathological data exhibited high concordance in LNM distribution. Compared with LUSC, LUAD displayed more aggressive LNM behavior, with significantly higher metastasis rates to supraclavicular, contralateral mediastinal, and contralateral hilar nodes. In contrast, LUSC showed increased level 8 LNM, especially in left inferior lobe origin. Multivariate analysis revealed: LUAD with mediastinal invasion, ipsilateral multi-lobar nodules, or LNM at levels 2L/2R/3a/6 had higher 1L/1R metastasis risk; left inferior lobe origin or larger tumor diameter in LUSC hinted level 8 metastasis. Significant inter-nodal metastatic correlations were identified across different levels. Conclusion LUAD and LUSC exhibit distinct histology- and subsite-specific LNM patterns and inter-nodal metastatic correlations. Two optimized CTVn delineation recommendations for definitive concurrent chemoradiotherapy of LUAD and LUSC were proposed to enhance targeting precision.

Radiation-induced skin injury (RISI) is a common side effect of radiotherapy, but existing preventive approaches show less-than-ideal effectiveness. Thus, developing functional patches that combine strong reactive oxygen species (ROS) scavenging capacity with good biosafety is essential for repairing RISI. In this study, we propose a nanocomposite hydrogel patch made from naturally sourced materials. This patch has two key functions: chemically eliminating ROS and physically absorbing radiation, which together help reduce radiation-induced harm.Ginsenoside-Rh2@tannic acid (Rh2@TA) nanoparticles were prepared via the spontaneous coordination between tannic acid (TA) and iron ions (Fe3+), a process that allows for the encapsulation of Rh2. These nanoparticles were subsequently integrated into gelatin methacryloyl (GelMA) hydrogel patches. The GelMA matrix not only gives the hydrogel the ability to adhere to tissues but also imparts photothermal properties to it. At the same time, the patch demonstrates robust ROS scavenging ability and facilitates the polarization of macrophages toward the M2 phenotype. Moreover, the high water content of the GelMA hydrogel enables it to physically absorb low-energy X-rays, offering a radiation shielding effect.Leveraging these features, we confirmed that the GelMA hydrogel patch loaded with Rh2@TA nanoparticles has enhanced therapeutic effects in a cellular model of RISI. The results of this research provide important references for the use of ROS-scavenging hydrogels in RISI prevention.

PURPOSE:Nasopharyngeal carcinoma (NPC) features uncertain and complex gross tumor volume (GTV) distributions in terms of location, size, and shape. A novel deep learning model with adaptability was proposed to improve the accuracy of automatic GTV delineation for NPC primary and metastatic lesions. METHODS AND MATERIALS:This study comprised 529 retrospective cases and 4 prospective cases from multiple centers, all with CT and MRI modalities. GTV adaptive delineation was achieved via a conditional denoising diffusion model (DDPM) with "inter-modal and intra-modal" attention aware mechanism. During one training epoch, the inter-modal aware mechanism linked the frequency of potentially effective features at identical coordinates across multimodal images to tumor locations. The model progressively focused on high-frequency GTV-related features. Across multiple trainings, the intra-modal aware mechanism established the repeatability of feature extraction within each modality at identical coordinates, enhancing stable feature extraction. By leveraging both mechanisms, the model dynamically calibrated fusion weights for multimodal features, ascertaining each feature's significance in GTV identification based on its positional frequency. The GTV delineation accuracy was assessed using Dice Similarity Coefficient (DSC) ( %), 95 % Hausdorff Distance (HD95 %) (mm), and Mean Surface Distance (MSD) (mm) metrics. RESULTS:For the internal test set, the adaptive delineation model yielded mean (SD) results of 81.36 ± 2.14 % for DSC, 4.30 ± 2.14 mm for HD95 %, and 3.70 ± 1.84 mm for MSD. The external test set showed corresponding values of 77.43 ± 3.41 %, 6.07 ± 3.10 mm, and 4.31 ± 2.64 mm. Paired T-tests confirmed statistically significant differences between our model and the current SOTA models for automatic GTV delineation. The adaptive delineation model attained DSC accuracies of 83.45 ± 1.75 % for primary tumor and 73.43 ± 5.32 % for metastatic lesions, while achieving HD95 precisions of 4.28 ± 2.08 mm and 7.33 ± 3.45 mm, respectively. The MSD measurements were 2.73 ± 1.70 mm and 5.90 ± 3.18 mm, respectively. These results highlighted better delineation accuracy for primary tumors. In prospective dosimetry validation, the average dose difference within primary tumors, comparing automatically and manually delineated GTVs, was 0.36 Gy-less than the 0.52 Gy difference in lymph node metastases. This aligned with retrospective validation patterns. CONCLUSION:The novel deep learning model demonstrated high accuracy and stability GTV automatic delineation for NPC cases, indicating its potential for clinical application in NPC radiotherapy at different centers.

Radiation-induced oral mucositis (RIOM) is the most common oral complication faced by patients with head and neck cancer undergoing radiotherapy or chemotherapy, significantly diminishing their quality of life. While previous studies have investigated single K12 probiotics for RIOM, they often lacked stability, free radical scavenging activity, and precise oral targeting. To overcome these challenges, we developed K12@Lip@GSH, an innovative oral probiotic that encapsulates K12 within liposomes to enhance stability and scavenging efficacy, while utilizing a glutathione (GSH) transporter-mediated targeting mechanism that exploits the favorable the overexpression of GSH transporters in RIOM. Evaluations conducted in RIOM mouse models subjects demonstrated favorable outcomes, including a reduction in ulcer size, increased epithelial cellularity and mucosal thickness, enhanced epithelial proliferation, and decreased apoptosis. Genomic analysis further indicated improvements in mRNA pathways associated with the recovery from RIOM. Additionally, K12@Lip@GSH was shown to restore the balance of oral microbiota and reduce the abundance of oral anaerobes in RIOM mice. Subsequently, the safety and efficacy of K12@Lip@GSH were confirmed through further single-arm, single-center prospective clinical trials. The clinical trial data demonstrated a manageable safety profile in the cohort of 22 enrolled patients. Treatment-related adverse events (TRAEs) were infrequent, occurring in only 4.5 % of participants, with reported symptoms including flatulence and dyspepsia. Although 59.1 % of patients experienced oral mucositis (OM), the incidence of severe OM (grade 4) was 0.0 %, and no interruptions in radiotherapy treatment occurred due to OM. Overall, K12@Lip@GSH shows promise as an adjuvant strategy for improving radiation-induced oral mucositis (RIOM) in cancer patients undergoing radiotherapy.

Chemotherapy‐induced nausea and vomiting (CINV) remains a prevalent treatment complication, often significantly impairing patients' quality of life and reducing adherence to chemotherapy regimens. The standard triplet antiemetic regimen, including either a neurokinin‐1 (NK1) receptor antagonist (RA) or olanzapine, combined with a 5‐hydroxytryptamine type 3 (5‐HT3) RA and dexamethasone (DEX), faces challenges primarily due to DEX‐related adverse effects and its potential to compromise the efficacy of antitumor agents. This study assessed whether omitting DEX (F‐Group: olanzapine + 5‐HT3 RA) is non‐inferior to the standard D‐Group (olanzapine + 5‐HT3 RA + DEX). In this multi‐center, double‐blind, randomized phase III trial, 254 adults with malignant solid tumors (Eastern Cooperative Oncology Group [ECOG] 0–2) scheduled for highly emetogenic chemotherapy (HEC) were randomized 1:1 to the F‐Group or D‐Group. The primary endpoint was the complete response (CR; no emesis/rescue medication) rate over 0–120 h, with a non‐inferiority margin of −15%. Secondary endpoints included CR and complete control (CC; no vomiting/nausea/rescue therapy) rates in acute (0–24 h) and delayed (25–120 h) phases, safety, and quality of life. Overall CR rates were 68.6% (D‐Group) and 69.7% (F‐Group; p = .9658), demonstrating non‐inferiority. Acute phase CR rates were 88.4% versus 86.9% ( p = .8643), and delayed phase CR rates were 69.4% versus 69.7% ( p > .9999). CC rates were comparable across phases, with no new adverse reactions. The combination of a 5‐HT3 RA and olanzapine is as non‐inferior as the standard triplet regimen, providing an alternative option for patients receiving HEC. The trial was registered at ClinicalTrials.gov , number NCT05805800.

Radiation-induced skin injury (RISI) is a frequent complication of radiotherapy, yet current preventive strategies exhibit suboptimal efficacy. Our previous publications have consistently demonstrated the effectiveness of biomaterials and hydrogels in preventing RISI. Based on comprehensive literature reviews, we speculate that NLRP3 overexpression plays a central role in the development of RISI. Therefore, designing DNAzyme (DZ)-hydrogels with targeted inhibition of NLRP3 overexpression is crucial for preventing RISI.To achieve this, we designed and screened the optimal NLRP3-DZ using bioinformatics, molecular dynamics, and gel electrophoresis methods. We encapsulated the NLRP3-DZ within ZIF-8 to enhance its stability, controlled release, and safety. To enhance the material’s transdermal penetration and practicality, we attached the TAT transmembrane peptide. The final preparation and characterization of NLRP3-DZ@ZIF-8/TAT was achieved.In vitro cell models revealed that DZ-hydrogels exhibit high biosafety, effectively inhibit NLRP3 expression, promote cell migration, inhibit cell apoptosis, and possess antibacterial properties. Genomics analysis suggested that DZ-hydrogels may exert these functions by regulating changes in relevant mRNA pathways.Furthermore, we established a mouse model of RISI and found that the material can promote wound healing by regulating proteins associated with apoptosis, oxidative stress, and the inflammatory response. These research findings provide valuable insights for the prevention of RISI using DZ-hydrogels.

The lymph node involvement in the posterior to level V (PLV) region is mainly observed in nasopharyngeal carcinoma (NPC). Recently, we have reported the distribution of metastatic lymph nodes in the PLV region and there are correlations between the neck node levels (NNL) of NPC, but what is the boundary of the PLV region and how to delineate it remains unclear, and we further to elaborate whether the bilateral level Va should be covered as intermediate-risk nodal regions (CTVn2, about 60 Gy equivalent) for all T and N categories based on these correlations. A total of 1021 consecutive NPC patients with N1-3 stage from January 2012 to December 2020 were reviewed. The lymph node metastasis level of each patient was evaluated according to the updated guidelines proposed in 2013. According to the distribution pattern of lymph node metastasis and the anatomical structure in the PLV region, the boundaries of PLV region was delineated, and whether it is appropriate to cover the bilateral level Va as CTVn2 for all the NPC patients was further discussed. The correlations of level Va with other NNL were studied using logistic regression model. The cranial boundary of PLV region is the caudal border of cricoid cartilage, the caudal boundary is the plane serratus anterior muscle begins to appear, the anterior boundary is the anterior border of trapezius, and the posterior boundary is the convergence of levator scapulae and trapezius. Laterally, the PLV region is limited by the medial edge of trapezius and medially by the lateral surface of levator scapulae. The nodal spread in level Va is based on the lymph node metastasis of level IIb in NPC. The PLV region is a missing NNL of head and neck tumors, especially in NPC. The proposed boundaries of the PLV region can provide a preliminary proposal for the further revision of NNL in head and neck tumors. It is theoretically feasible to reduce the prophylactic irradiation dose of the bilateral level Va in patients with N0 stage or with isolated metastases in level VIIa.

6046 Background: The relationship between sarcopenia and adverse outcomes among patients with recurrent and metastatic nasopharyngeal carcinoma (R/M NPC) undergoing immunotherapy remains underexplored. This secondary analysis of the KL-A167 clinical trial data aims to elucidate the impact of sarcopenia on treatment efficacy and prognosis in this cohort, while also identifying potential mediating hematological biomarkers. Methods: A cohort of 148 patients enrolled in the KL-A167 clinical trial was analyzed. Logistic and Cox regression models were applied to assess the association between sarcopenia and treatment response, overall survival (OS), and progression-free survival (PFS), with adjustment for clinical prognostic factors. Counterfactual causal mediation analysis was conducted to identify hematological biomarkers potentially mediating the relationship between sarcopenia and prognosis in R/M NPC patients. Results: The presence of sarcopenia was significantly associated with reduced objective response rate (ORR: OR = 0.25, 95% CI = 0.08–0.81, p = 0.020) and disease control rate (DCR: OR = 0.23, 95% CI = 0.07–0.70, p = 0.010). Furthermore, sarcopenia was linked to inferior OS (HR = 2.07, 95% CI = 1.12–3.81, p = 0.020) and PFS (HR = 2.59, 95% CI = 1.48–4.54, p = 0.001). Notably, sarcopenia was characterized by elevated levels of neutrophil count, fibrinogen, and white blood cell count, alongside decreased creatine kinase levels. Fibrinogen emerged as the sole elevated biomarker significantly associated with both OS and PFS. Causal mediation analysis indicated that fibrinogen accounted for 23.5% of the association between sarcopenia and OS and 15.7% of PFS. Conclusions: Sarcopenia significantly correlates with poor treatment response and survival outcomes in patients with R/M NPC receiving immunotherapy. Targeting fibrinogen may offer a novel strategy to mitigate the negative impact of sarcopenia on patient survival.

Exosomes are nanoscale vesicles of cellular origin. One of the main characteristics of exosomes is their ability to carry a wide range of biomolecules from their parental cells, which are important mediators of intercellular communication and play an important role in physiological and pathological processes. Exosomes have the advantages of biocompatibility, low immunogenicity, and wide biodistribution. As researchers' understanding of exosomes has increased, various strategies have been proposed for their use in diagnosing and treating diseases. Here, we provide an overview of the biogenesis and composition of exosomes, describe the relationship between exosomes and disease progression, and focus on the use of exosomes as biomarkers for early screening, disease monitoring, and guiding therapy in refractory diseases such as tumors and neurodegenerative diseases. We also summarize the current applications of exosomes, especially engineered exosomes, for efficient drug delivery, targeted therapies, gene therapies, and immune vaccines. Finally, the current challenges and potential research directions for the clinical application of exosomes are also discussed. In conclusion, exosomes, as an emerging molecule that can be used in the diagnosis and treatment of diseases, combined with multidisciplinary innovative solutions, will play an important role in clinical applications.

BACKGROUND:The chemotherapy resistance often leads to chemotherapy failure. This study aims to explore the molecular mechanism by which MUC1 regulates paclitaxel resistance in lung adenocarcinoma (LUAD), providing scientific basis for future target selection. METHODS:The bioinformatics method was used to analyse the mRNA and protein expression characteristics of MUC1 in LUAD. RT-qPCR and ELISA were used to detect the mRNA and protein expression, flow cytometry was used to detect CD133+ cells, and cell viability was detected by CCK-8 assay. The mRNA-seq was performed to analyse the changes in expression profile, GO and KEGG analysis were used to explore the potential biological functions. RESULTS:MUC1 is highly expressed in LUAD patients and is associated with a higher tumour infiltration. In paclitaxel resistance LUAD cells (A549/TAX cells), the expression of MUC1, EGFR/p-EGFR and IL-6 were higher than that of A549 cells, the proportion of CD133+ cells was significantly increased, and the expression of cancer stem cell (CSCs) transcription factors (NANOG, OCT4 and SOX2) were significantly up-regulated. After knocking down MUC1 in A549/Tax cells, the activity of A549/Tax cells was significantly decreased. Correspondingly, the expression of EGFR, IL-6, OCT4, NANOG, and SOX2 were significantly down-regulated. The mRNA-seq showed that knocking down MUC1 affected the gene expression, DEGs mainly enriched in NF-κB and MAPK signalling pathway. CONCLUSION:MUC1 was highly expressed in A549/TAX cells, and MUC1-EGFR crosstalk with IL-6 may be due to the activation of NF-κB and MAPK pathways, which promote the enrichment of CSCs and lead to paclitaxel resistance.

In patients with abdominal or pelvic tumors, radiotherapy can result in radiation-induced intestinal injury (RIII), a potentially severe complication for which there are few effective therapeutic options. Sitagliptin (SI) is an oral hypoglycemic drug that exhibits antiapoptotic, antioxidant, and anti-inflammatory activity, but how it influences RIII-associated outcomes has yet to be established. In this study, a pH-responsive metal-organic framework-based nanoparticle platform was developed for the delivery of SI (SI@ZIF-8@MS NP). These NPs incorporated mPEG-b-PLLA (MS) as an agent capable of resisting the effects of gastric acid, and are capable of releasing Zn2+ ions. MS was able to effectively shield these SI@ZIF-8 NPs from rapid degradation when exposed to an acidic environment, enabling the subsequent release of SI and Zn2+ within the intestinal fluid. Notably, SI@ZIF-8@MS treatment was able to mitigate radiation-induced intestinal dysbiosis in these mice. restored radiation-induced changes in bacterial composition. In summary, these data demonstrate the ability of SI@ZIF-8@MS to protect against WAI-induced intestinal damage in mice, suggesting that these NPs represent a multimodal targeted therapy that can effectively be used in the prevention or treatment of RIII.

BACKGROUND:Definitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images. METHODS:Overall, 358 patients with N1-N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model. RESULTS:The lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels. CONCLUSIONS:This study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

4511 Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with dismal prognosis. Therapeutic options for patients with advanced ACC after failure of standard treatments are limited. The clinical benefit of single-agent immunotherapy as second-line therapy was still unsatisfactory. Methods: This was an investigator-initiated, prospective, single-arm, open-label, phase 2 trial and conducted at a single medical center. Patients were eligible for inclusion if they were aged at least 18 years; were pathologically diagnosed as unresectable or metastatic ACC; had failed first-line therapy; had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; had at least one measurable lesion; and had adequate organ function. The key exclusion criteria included a history of treatment with immunotherapy, anti-angiogenic small molecule TKIs, or anti-angiogenic monoclonal antibodies; a history of uncontrolled hypertension; and a history of an autoimmune condition requiring systemic therapy. All study participants received camrelizumab 200 mg intravenously on the first day of each 3 week cycle, combined with apatinib 250 mg orally once per day until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR) per RECIST (version 1.1). Results: A total of 21 patients with advanced ACC received at least one dose of camrelizumab and apatinib. ORR was 52% (95% CI, 30 to 74), and the disease control rate was 95% (95% CI, 84 to 100), superior to PD-1 inhibitor monotherapy and first-line standard therapy. The median PFS was 12.6 months (95% CI, 8.4 to 20.9), and the median OS was 20.9 months (95% CI, 11.0 to 20.9). The most common grade 3—4 treatment-related adverse events were alanine aminotransferase elevation (28.6%), aspartate aminotransferase elevation (23.8%) and lymphopenia (23.8%). Our exploratory analysis showed higher peripheral blood CXCR3+CD8+ T cell abundance, lower immunosuppressive CD4+ T cell abundance, and higher overlap of clonotypes between tumor-infiltrating T cells and circulating T cells, likely related to preferable response to camrelizumab plus apatinib therapy. Conclusions: In conclusion, the combination of camrelizumab with apatinib showed promising activity and acceptable toxicity in advanced ACC patients who failed previous lines of therapy. Pre-treatment peripheral blood immune cell subsets could be regarded as potential predictors of efficacy. Given the promising clinical activity, the potential of camrelizumab with apatinib as first-line therapy for advanced ACC need further evaluated. Clinical trial information: NCT04318730 .

Radiation-induced skin injury (RISI) represents a prevalent issue following radiotherapy. The main factors influencing RISI wound recovery include ROS and NLRP3 inflammasome activation as well as wound infection, amongst others. Herein, a biomaterial for the healing of radio-induced injury was designed using multiple strategies. A gallic acid (GA)-assisted isolation process was first applied to prepare gallic acid-grafted soy protein (SPI-GA) from spherical soy protein. The SPI-GA was then modified with simultaneously-grafted phenol and thiol cohorts (SH) (SPI-GA-SH). Due to the antibacterial properties of graphene oxide (GO), SPI-SH-GA@PGO biogels was finally self-assembled into an adhesive biogel in a binary solvent system (dopamine-glycerol/water). Characterization for adhesive and paintable SPI-based biogels indicated that the material was successfully synthesized. Cytological studies further highlighted the antibacterial properties of SPI-SH-GA@PGO, its non -toxicity to HaCaT cultures as well as its ability to promote vascularization and cell migrative while inhibiting apoptotic. Genomics assessment also demonstrated that the material could effectively improve the abnormal expression of skin cultures induced by radiation. Finally, a murine model suggested that SPI-SH-GA@PGO could reduce ROS and NLRP3 expression while promoting wound recovery. This work pioneered SPI-based biogel deployment as material for RISI recovery.

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.