Despite promising data showing that circulating tumour DNA (ctDNA) dynamics during treatment can inform real-time tumour response and recurrence risk1, how best to translate these insights into actionable clinical decision-making remains unclear. Here we report results from the EP-STAR trial-a multi-centre, ctDNA-driven, risk-adapted, non-randomized phase II study ( NCT04072107 ; ClinicalTrials.gov) testing whether a risk-adaptive treatment (RAT) strategy guided by on-treatment ctDNA dynamics can meaningfully improve survival, using nasopharyngeal carcinoma as a model. Eligible patients were enrolled and began treatment with standard-of-care gemcitabine-cisplatin neoadjuvant chemotherapy (GP-NAC; the P in this abbreviation stands for platinum)2, followed by RAT or standard-of-care chemoradiotherapy guided by ctDNA clearance trajectory during GP-NAC. Protocol-eligible patients who did not receive RAT, drawn from a prospectively registered ctDNA biomarker cohort ( NCT03855020 )3, served as a non-randomized, contemporaneous no-RAT external cohort. The primary end-point was failure-free survival (FFS) in the RAT group. After a median follow-up of 47.3 months, the 3-year FFS was 89.1% (83.2-95.0%) in the RAT group (n = 110). Patients who received RAT showed significantly improved FFS (P = 0.003, log-rank test) compared with the no-RAT external cohort (hazard ratio = 0.41 [0.23-0.75]; P = 0.004, Cox regression model). The RAT strategy was well-tolerated with no treatment-related deaths. Collectively, these data show that a ctDNA-driven RAT paradigm could be a promising strategy to improve survival, challenging the conventional fixed-course, static treatment approach.

Anthropogenic activities in Daya Bay (DYB), a prominent aquaculture region and also a petrochemical industrial estate in Guangdong Province, China, may pose potential hazardous to environmental safety. The present study investigated the distribution of 16 polycyclic aromatic hydrocarbons (PAHs) listed by the USEPA (EPA 16 PAHs) and 18 alkylated PAHs (18 APAHs) in seawater and surface sediments of DYB in dry, wet, and normal seasons. The results indicated that the average concentrations of E34 PAHs in seawater ranged from 584.02 f 107.54-961.07 f 621.61 ng/L across different seasons, while the average concentrations of the EPA E16 PAHs in seawater varied between 265.63 f 55.66 and 424.16 f 267.55 ng/L. In surface sediments, the concentrations of E34 PAHs ranged from 350.52 f 33.33-571.33 f 98.76 ng/g, E16 PAHs from 185.21 f 34.24-270.04 f 55.78 ng/g, which were three orders of magnitude higher than in the aqueous phase. No significant seasonal variation was found in sediments PAHs. APAH accounted for a significant proportion of E34 PAHs. Low-and medium-molecular-weight PAHs were predominant in both seawater and sediments. Molecular ratios diagnose and PCA analysis suggested that the primary sources of PAHs in seawater were inputs from petroleum products and pyrolysis products related to transportation, the PAHs in sediments were mainly from fossil fuel combustion and diagenesis. Incremental lifetime cancer risk values suggested that the health risks associated with PAHs in DYB seawater were below USEPA risk levels. Compared with previous reports, the concentration of E16 PAHs in both seawater and surface sediments of DYB has shown a gradual decline over the past 20 years. The results of this study provided valuable insights into PAHs contamination and trends in marine environment protection within this region, which has undergone more than 30 years of rapid economic development.

Purpose : To characterize the lymph node (LN) distribution difference in the supraclavicular region across five cancers—nasopharyngeal carcinoma (NPC), head and neck squamous cell carcinoma (HNSCC), esophageal cancer (EC), lung cancer (LC), and breast cancer (BC), thereby guiding clinical target volume (CTV) optimization.Materials and Methods : We conducted a retrospective analysis of 1,900 patients with supraclavicular LN metastasis, including 700 with NPC and 300 each with HNSCC, EC, LC, and BC. LNs with short-axis diameter ³4 mm were marked on a template computed tomography scan. LN distribution probability maps and distribution curves were established for visualization and were analyzed against the 2013 consensus guidelines to propose CTV modifications.Result s : A total of 2533 (NPC), 727 (HNSCC), 932 (EC), 705 (LC), and 1091 (BC) supraclavicular LNs were marked, enabling constrution of distribution probability maps and distribution curves. Overall, most LNs fell within the guidelines-defined levels. Level Ⅳa was the most common site across all cancers, level Ⅵb being particularly frequent in EC and LC, while BC-derived LNs often existed caudally in levels Ⅳb and Ⅴc. No LNs emerged in level Ⅵa. Crucially, subregions within levels Ⅳ and Ⅴc showed minimal LN involvement, whereas LNs exceeded the posterior boundaries of levels Ⅴb and Ⅴc in 28.6% (200 of 700) of NPC, 5.3% (16 of 300) of HNSCC, 0.7% (2 of 300) of EC, 2.7% (8 of 300) of LC, and 20.9% (62 of 300) of BC patients. These findings support cancer-specific and risk-adapted reduction of the boundaries in levels Ⅳ and Ⅴc and posterior extension in levels Ⅴb and Ⅴc.Conclusion s : This study demonstrates LN distribution patterns in the supraclavicular region. We propose CTV optimization in levels Ⅳ, Ⅴb and Ⅴc.

ABSTRACT The year 2025 marked significant advances in precision medicine for nasopharyngeal carcinoma (NPC). This review summarizes recent advances in treatment strategies aimed at addressing longstanding challenges in NPC management, including treatment‐related toxicity, therapeutic resistance, and the limited precision of risk stratification. For locoregionally advanced NPC, a novel efficacy‐enhancing and toxicity‐minimizing strategy has emerged: toxicity minimizing involves replacing toxic concurrent cisplatin chemotherapy with PD‐1 blockade, achieving superior safety while maintaining non‐inferior 3‐year failure‐free survival; meanwhile efficacy‐enhancing employs adjuvant immunotherapy to improve survival specifically in high‐risk patients, supporting the transition toward risk‐adapted strategies. In radiotherapy, international consensus guidelines recommend reducing target volumes and sparing normal tissues to minimize side effects. For recurrent or metastatic NPC, antibody–drug conjugates(ADCs) and novel immunotherapeutic combinations show promise in overcoming treatment resistance and expanding therapeutic options. Furthermore, advances in artificial intelligence and deeper understanding of resistance mechanisms are accelerating clinical innovation. Collectively, these advances underscore the ongoing shift toward reduced toxicity, improved efficacy, and greater precision in the management of NPC.

The nasopharynx constitutes a critical niche in the upper respiratory tract, harboring a diverse microbiota linked to nasopharyngeal carcinoma (NPC), the mechanistic roles of which remain poorly understood. Here, we established the Nasopharyngeal Mucosal and Tumor-resident Bacterial Catalog (NMTBC) that comprises 5311 bacterial isolates representing 127 species, with 1006 of them being fully sequenced and annotated, providing a comprehensive culturable resource facilitating mechanistic dissection of the microbiome-tumor interactions. With NMTBC, we uncovered a Fusobacterium-Prevotella mutualism and revealed heterotypic bacterium-bacterium interactions involving transcriptional reprogramming and metabolic cross-talk. Using single-bacterial transcriptomics, we mapped a high-resolution transcriptomic trajectory, showing the ability of a single strain to differentiate into functionally distinct subpopulations that cooperate to sustain mutualism. By analyzing a multicenter NPC cohort, we showed that Fusobacterium and Prevotella co-colonization in NPC tumors correlated with unfavorable clinical outcomes after conventional radiochemotherapy. Analysis of RNA-seq data from two previous phase 3 clinical trials showed that coenrichment of Fusobacterium-Prevotella predicted better response to anti-PD-1 immunotherapy, highlighting their important role in microbiota-mediated immunomodulation. Overall, this study establishes a comprehensive nasopharyngeal bacterial catalog through culturomics, which offers valuable insights into microbiome-derived biomarker discovery and immunotherapy patient stratification in clinical practice.

OBJECTIVE:To determine the pre-specified long term efficacy (survival and swallowing function) and safety of medial retropharyngeal lymph node (MRLN) region sparing radiotherapy for non-metastatic nasopharyngeal carcinoma. DESIGN:Pre-specified five year analysis of an open label, non-inferiority, multicentre, randomised phase 3 trial. SETTING:Three Chinese medical centres between 20 November 2017 and 3 December 2018. PARTICIPANTS:Adults (18-65 years) with untreated, non-keratinising, non-metastatic nasopharyngeal carcinoma without MRLN involvement. INTERVENTIONS:Eligible patients were randomised (1:1; block size of four) to MRLN sparing radiotherapy or standard radiotherapy. Randomisation was stratified by institution and treatment modality (radiotherapy alone, concurrent chemoradiotherapy, or induction chemotherapy plus radiotherapy or concurrent chemoradiotherapy). MAIN OUTCOME MEASURES:The primary outcome was local relapse-free survival. The three year local relapse-free survival to assess the non-inferiority, with a margin of 8%, of MRLN sparing radiotherapy compared with standard radiotherapy has been reported previously. This updated report focuses on five year survival, toxicity, and quality of life. Additionally, a videofluoroscopic swallowing study and magnetic resonance imaging (MRI) measurements of pharyngeal contractors were used as objective measures of dysphagia RESULTS: This trial enrolled 285 patients in the MRLN sparing group and 283 patients in the standard group. At a median follow-up of 70 months, the MRLN sparing and standard groups had similar five year local relapse-free survival (89.2% (95% confidence interval (CI) 85% to 92%) versus 90.6% (87% to 94%); stratified hazard ratio 1.03 (95% CI 0.61 to 1.74); P=0.90) and overall survival (89.2% (85% to 93%) versus 90.3% (87% to 94%); stratified hazard ratio 1.06 (0.68 to 1.68); P=0.79). Updated safety profiles of the MRLN sparing group showed a lower rate of grade ≥1 dysphagia (45/206 (22%) v 70/216 (32%); P=0.01) and grade ≥2 dry mouth (33/206 (16%) v 55/216 (25%); P=0.02) and enhanced swallowing related quality of life (mean difference -11.9; P<0.001). Videofluoroscopy showed a lower prevalence of vallecular residue (49/66 (74%) v 62/62 (100%); P<0.001), pyriform sinus residue (32/66 (48%) v 45/62 (73%); P=0.01), coating of pharyngeal wall (7/66 (11%) v 17/62 (27%); P=0.01), pharyngeal transit time >1.0 s (1/66 (2%) v 7/62 (11%); P=0.03), and aspiration (8/66 (12%) v 18/62 (29%); P=0.03) in the MRLN sparing group. Additionally, MRI detectable late atrophy in the superior pharyngeal constrictor (mean thickness: 1.80 v 1.65 mm; P=0.005) and middle pharyngeal constrictor (2.34 v 2.15 mm; P=0.01) was less severe after MRLN sparing radiotherapy. CONCLUSIONS:MRLN sparing radiotherapy maintained uncompromised efficacy and better long term swallowing function by reducing radiation damage to pharyngeal contractors, supporting its use as a standard of care for non-metastatic nasopharyngeal carcinoma. TRIAL REGISTRATION:ClinicalTrials.gov NCT03346109.

Accurate tumor-node-metastasis (TNM) staging is essential for treatment decision-making, prognostic stratification, and outcomes modeling in oncology. However, real-world clinical databases often extend over decades and inherently encompass multiple successive staging systems, introducing substantial heterogeneity that undermines the stability and interpretability of survival analyses, prognostic modeling, and staging system evaluation. To address this challenge, we developed an automated framework that combines TNM staging criteria and staging-relevant anatomical knowledge with a large language model (LLM) and a second-stage reflection step to convert narrative radiology reports into unified AJCC/UICC 9th edition TNM staging. In an expert-annotated cohort of 340 NPC patients, we evaluated multiple LLMs and found that the GLM4.5-based framework achieved the highest accuracy for T (0.95), N (0.86), and M (0.99) classification. Based on this optimal performance, the framework was applied to a real-world cohort of 51,242 NPC patients between 2010 and 2025. A stratified random validation subset of 200 cases showed high concordance with the expert reference standard. In downstream utility analyses, the unified staging was associated with a higher C-index and more distinct survival-curve separation than existing electronic health record staging. Collectively, this study provides a scalable framework for unifying heterogeneous historical cancer staging data, supporting longitudinal analyses in large real-world oncology cohorts.

Habitat analysis enables spatial characterization of intratumoral heterogeneity; however, its application in nasopharyngeal carcinoma (NPC), particularly regarding metastatic lymph node (MLN), remains limited. This study aims to systematically compare the prognostic performance of various models using different sequences and spatial region combinations for predicting overall survival in NPC. The study retrospectively included 725 NPC patients (543 training, 182 testing). Habitat analysis was conducted based on T1, T1C, and T2 sequences in three regional strategies: primary gross tumor volume (GTVp), metastatic lymph nodes (MLNs), and the combined region of GTVp-MLN. The tumor area was divided into six subregions, and a multi-region spatial interaction (MSI) matrix was constructed to extract MSI features. On this basis, a radiomics model (R Model) and a clinical-radiomics model (CR Model) were established, and the model performance was evaluated using C-index and Kaplan-Meier survival analysis. The results show that the combined GTVp-MLN model based on the T1 sequence achieved the best overall predictive performance (R Model: C-index = 0.693; CR Model: C-index = 0.722). Significant survival differences were observed between the high- and low-risk groups. These findings suggest that habitat analysis incorporating the combined GTVp-MLN region may improve prognostic prediction and risk stratification in patients with NPC.

Despite the alarming prevalence of loneliness in adolescents, few studies addressed its impact on health-related quality of life (HRQOL). This study aimed to investigate the association between loneliness and HRQOL in adolescents, as well as the mediating role of depressive symptoms and the moderating role of age in this association. A cross-sectional study surveyed 6743 middle school adolescents, assessing loneliness with the 6-item UCLA Loneliness Scale and HRQOL through the Pediatric Quality of Life Inventory Version 4.0. Depressive symptoms were assessed by the Patient Health Questionnaire-9. Pearson correlation analysis was performed to determine the correlation among the main variables. A moderated mediation analysis was established to evaluate the mediating role of depressive symptoms and the moderating role of age in the association between loneliness and HRQOL. Of the participating adolescents, 25.0

OBJECTIVES:This study aimed to investigate the incidence of post radiation nasopharyngeal necrosis (PRNN) in primary NPC after intensity modulated radiation therapy (IMRT) and identify the predictors of risk. METHODS:Data of 5798 NPC patients who received IMRT-based treatment between April 2009 and December 2015 were retrospectively reviewed. PRNN was diagnosed by MRI or nasopharyngoscopy. Dosimetric factors were selected by the least absolute shrinkage and selection operator logistic regression and applied to Cox proportional hazards modeling with clinical predictors. RESULTS:Among the 5798 patients, 53 developed PRNN-an incidence rate of 0.89%. Age > 55 years, diabetes, LDH > 170 U/L, and tumor volume of nasopharynx > 60.5 cm3,were independently associated with risk of PRNN(all p < 0.05. Dosimetric analysis showed that D0.5ccEQD2 of 80.20 Gy might be the dose constraint for nasopharynx (sensitivity = 62.3%, 33 out of 53; specificity = 84.2%, 4897 out of 5925). Besides, the RTOG dose constraints of V110% (V77.0) should be less than 0.2% in case of increasing risk of PRNN(HR = 2.28, 95% CI: 1.26-4.41, p = 0. 01). CONCLUSION:Nasopharyngeal necrosis is rare after primary IMRT. The independent risk factors for this rare complication include age > 55 years, diabetes mellitus, LDH > 170 U/L, tumor volume of nasopharynx > 60.5 cm3, D0.5ccEQD2 > 80.20 Gy, and V77.0 < 0.2% to the planning treatment volume of nasopharynx. KEYPOINTS:High radiation dose may lead to devastating nasopharyngeal necrosis after primary IMRT. Real world analysis will provide valuable information for prevention. FINDINGS:The aged, diabetes mellitus, large tumor volume, D0.5ccEQD2 > 80.20 Gy and V77.0 < 0.2% to planning treatment volume increased the risk of nasopharyngeal necrosis. CLINICAL RELEVANCE:This real-world study provided valuable information for prevention of PRNN. Compared with RTOG protocol, D0.5ccEQD2 > 80.20 Gy is a reliable evidence-based new complement to dose constraint, especially for T3-4 disease, who received high prescribe dose in China.

Dual-receptor targeting strategies hold promise for improving nanocarrier specificity in complex tumor microenvironments. Herein, we engineered lipid nanoparticles (LNPs) functionalized with GPR77 and CD10 antibodies to exploit receptor co-expression as a mechanism for enhanced targeting. To rigorously validate this approach, we developed a GPR77+CD10+ overexpressing CHO cell model, which served as a controlled system to dissect ligand-receptor interactions. The dual-targeting LNPs (DOPE(GPR77/CD10)) exhibited significantly higher cellular uptake in receptor-positive CHO cells compared to single-targeted or non-targeted formulations, demonstrating synergistic binding efficacy. These LNPs also showed excellent drug encapsulation and prolonged circulation. In a CHO xenograft model, dual-targeting LNPs achieved higher tumor accumulation than non-targeted controls, with minimal off-target organ retention. Biosafety assessments confirmed negligible hemolysis and no hepatorenal toxicity. While this study focused on mechanistic validation in a simplified model, our findings establish a generalizable platform for dual-receptor targeting, with potential applications in stromal or tumor cell-specific drug delivery.

Contrastive vision-language pre-training models have achieved significant success on large-scale general multi-modality datasets. However, in the medical domain, the high costs of data collection and expert annotation are likely to result in small-sized and noisy datasets, which can severely limit model performance due to overfitting unreliable data and misrepresenting patterns. To address this challenge, we present MIRAGE, a novel framework designed to handle mismatched false positives and semantically related false negatives during medical image-text pre-training. Cross-entropy-based optimization proves inadequate for noisy contrastive settings, as it tends to fail in distinguishing noisy samples and ends up fitting them, leading to suboptimal representations. To overcome this limitation, we introduce an optimal transport-based contrastive loss that effectively identifies noisy samples leveraging the nearest cross-modality neighbor prior, thereby reducing noisy samples’ adverse impact. Additionally, we propose an adaptive gradient balancing strategy that mitigates the influence of gradients from noisy samples. Extensive experiments demonstrate that MIRAGE achieves superior performance across six tasks and 14 datasets, largely outperforming representative state-of-the-art methods. Furthermore, comprehensive analyses on synthetic noisy data are performed, clearly demonstrating the contribution of each component in MIRAGE.

Extracellular regulated protein kinases (ERK) signaling is aberrantly activated in oral squamous cell carcinoma (OSCC), and targeting ERK signaling with ERK1/2 inhibitors is a potential strategy for OSCC treatment. However, methods for the more efficient delivery of ERK inhibitors to improve drug utilization remains a pressing challenge. Notably, the application of antiangiogenic therapies to treat OSCC has received increasing attention, yet single therapies often have very limited efficacy. The combination of antiangiogenic therapies with strategies targeting ERK1/2 signaling for the treatment of OSCC is very promising. In this study, we utilized bioactive phospholipids (dipalmitoyl phosphatidic acid, DPPA) with antiangiogenic functions to encapsulate a small-molecule ERK inhibitor (called NP-AE) and constructed an intrinsically biotherapeutically active nanomedicine delivery platform with dual therapeutic efficacy. NP-AE effectively inhibited the proliferation and promoted the apoptosis of OSCC cell lines. A tongue orthotopic xenograft model and a patient-derived xenograft (PDX) model of OSCC were subsequently used to investigate its therapeutic effect. The nanoplatform was able to accumulate in tumor tissues and was internalized by tumor cells after intravenous administration. NP-AE effectively inhibited ERK1/2 phosphorylation and Angptl2 and VEGFA expression in OSCC in vitro and in vivo and significantly inhibited the growth of xenografts. Taken together, these findings suggest that targeting ERK1/2 signaling in combination with antiangiogenic therapy by NP-AE may be a promising strategy for the treatment of OSCC.

Insects are critical indicators of environmental health, providing a valuable insight into pollutant dynamics within mangrove ecosystems. Despite the recognized use of fatty acids (FAs) as biomarkers in various organisms, the effects of organohalogen contaminants (OHCs) on FA profiles in insects have not been extensively investigated. This study analyzed 54 OHCs and 36 FAs across 16 insect species from the Pearl River Estuary to assess the viability of FAs as biomarkers for OHC exposure. Results indicated that insects from Shenzhen (160 ± 5.1 ng/g lw) exhibited significantly higher concentrations of OHCs than those from Zhuhai (100 ± 4.9 ng/g lw). Carnivorous insects (190 ± 6.1 ng/g lw) accumulated higher OHC levels but had lower proportions of polyunsaturated fatty acids than herbivores (80 ± 4.2 ng/g lw), with OHCs exerting stronger effects on lipid metabolism among carnivores. Significant correlations were observed between OHC levels and desaturase activity/lipogenesis indices in both regions, indicating potential lipid metabolism disruptions. While correlations between OHCs and FAs in insects from Shenzhen and Zhuhai suggest the potential of FAs as biomarkers of OHC exposure, the limited overlap in OHC-FA correlations (5 out of 279) between the regions highlights the influence of spatial heterogeneity. These findings underscore the promise of FAs as biomarkers for OHC exposure but emphasize the need to account for species- and habitat-specific factors.

Mangrove-settled spiders play a crucial role in maintaining the ecological balance of mangrove wetlands, yet organohalogen contaminants (OHCs) pose a significant threat to these species. This study evaluated the dietary composition (including 15 insect species) and OHC accumulation in Nephila pilipes, a dominant spider species, across two mangrove habitats, using data from 80 OHCs and quantitative fatty acid signature analysis (QFASA). Dichlorodiphenyltrichloroethane (DDT) accounted for over 50 % of the total OHCs in both spiders and insects, followed by polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), alternative halogenated flame retardants (AHFRs), and hexachlorocyclohexane (HCHs). Biomagnification and trophic magnification patterns of OHCs were consistent across both mangroves, suggesting that spatial variability did not significantly influence overall biomagnification. Carnivorous insects exhibited lower proportions of tetra- and penta-BDEs compared to phytophagous insects but had significantly higher total OHC concentrations. The presence of carnivorous insects, such as the ditch jewel, in the spider diet was negatively correlated with phytophagous insects, such as the common emigrant and tobacco cutworm, suggesting potential niche exclusivity. Spiders from more polluted mangroves accumulated higher OHC concentrations, with carnivorous insects contributing 64.9 ± 3.90 % and 67.9 ± 5.79 % to the total OHC load in Zhuhai and Shenzhen, respectively. The regional differences in OHC concentrations were primarily attributed to higher background pollution levels in Shenzhen rather than dietary composition alone. This study highlights the influence of regional pollution on OHC accumulation in mangrove spiders and underscores the importance of region-specific dietary assessments for accurate pollutant bioaccumulation evaluations.

6049 Background: Published risk prediction tools have focused on pretreatment factors, whereas the accuracy remains challenging in cancer care. Emerging evidences emphasize the dynamic rather than static recurrence risks during treatment course, and non-invasive diagnostics tools have advanced opportunities for serial tumor assessments. Here, we present an effective dynamic risk individualized prediction model (NPC-DRIM) incorporating serial ctDNA data, using the endemic EBV-related NPC as a model. Methods: This study included 1000 patients (pts) enrolled from a prospective biomarker study EP-SEASON, with complete longitudinal ctDNA data at 11 timepoints across treatment: after each neoadjuvant chemotherapy (NAC) circle (T1-3), every week during radiotherapy (T4-T9), within 1 week after radiotherapy (T10), and 1-3 months after radiotherapy (T11). Pts were divided into subcohort NAC (n=752) and subcohort no-NAC (n=248) according to receiving NAC or not, and randomly 70/30% split into training and validation cohort. Time-series and statistical features characterizing the dynamic change of ctDNA at each timepoint were extracted. The NPC-DRIM at T3-T11 were developed using the features selected via Cox univariate analysis in training cohort and then validated. The performance of NPC-DRIM was determined by C-index, time-dependent AUC, calibration curves, and decision curves, and compared with existing models. Results: The NPC-DRIM incorporated 4 clinical variables, 8 time-series features and 10 statistical features of ctDNA data. The C-index for predicting recurrence increased with time: 0.64 at T2, 0.69 at T3-T4, 0.70 at T5, 0.71 at T6, 0.73 at T7-T9, 0.77 at T10, and 0.76 at T11 in subcohort NAC ; 0.70 at T5, 0.68 at T6, 0.82 at T7, 0.78 at T8, 0.73 at T9, 0.74 at T10, and 0.83 at T11 in subcohort no-NAC . The NPC-DRIM at T11 had statistically improved outcome prediction compared to other dynamic models (Landmark Cox and Joint Model), and static models (AHR_Chen, RPA_Guo, RPA_Lee, and AJCC_8th staging system) (Table). For individualized dynamic risk prediction, we developed a web-based calculator to visualized the estimated changing recurrence risks. In addition, we showed that the high-risk pts identified by NPC-DRIM benefit from immune checkpoint inhibitors (ICI), while the low-risk pts did not. Conclusions: We introduce for the first time that the dynamic risk prediction model NPC-DRIM outperformed the conventional models, facilitating personalized therapeutic paradigms. Clinical trial information: NCT03855020 . Subcohort NAC Subcohort no-NAC C-index p value C-index p value NPC-DRIM 0.76 0.83 Landmark Cox 0.65 0.01 0.63 <0.01 Joint Model 0.63 <0.01 0.61 0.01 AHR Model (Chen et al. 2021) 0.61 <0.01 0.57 <0.01 RPA Model (Guo et al. 2019) 0.59 <0.01 0.59 <0.01 RPA Model (Lee et al. 2019) 0.59 <0.01 0.66 0.02 AJCC_8th 0.56 <0.01 0.57 <0.01

Approximately 20% to 30% of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) experience disease relapse despite definitive chemoradiotherapy. The programmed cell death 1 (PD-1) blockade camrelizumab has demonstrated considerable value in recurrent or metastatic NPC, while its role in locoregionally advanced NPC is unclear. To evaluate the efficacy and safety of adjuvant camrelizumab for patients with locoregionally advanced NPC. Randomized, open-label, multicenter, phase 3 clinical trial conducted from August 2018 to November 2021 at 11 centers in China and enrolling 450 patients with T4N1M0 or T1-4N2-3M0 NPC who had completed induction-concurrent chemoradiotherapy. The final date of follow-up was March 20, 2024. Patients were randomized (1:1) to receive adjuvant camrelizumab (200 mg intravenously once every 3 weeks for 12 cycles; n = 226) or observation (standard therapy group; n = 224). The primary end point was event-free survival (freedom from distant metastasis, locoregional relapse, or death due to any cause). Secondary end points included distant metastasis–free survival, locoregional relapse–free survival, overall survival, safety, and health-related quality of life. Among the 450 participants (mean age, 45 [SD, 10] years; 24% women), after a median follow-up of 39 (IQR, 33-50) months, the camrelizumab group had a 3-year event-free survival rate of 86.9%, whereas the standard therapy group had a rate of 77.3% (stratified hazard ratio, 0.56; 95% CI, 0.36-0.89; P = .01). Grade 3 or 4 adverse events were reported in 23 patients (11.2%) in the camrelizumab and 7 (3.2%) in the standard therapy group. Reactive capillary endothelial proliferation was the most common adverse event related to camrelizumab, occurring in 85.8% of patients at grade 1 or 2, while 2% of patients had grade 3 or 4 events. There was no significant deterioration in quality of life associated with camrelizumab treatment. Adjuvant PD-1 blockade with camrelizumab significantly improved event-free survival with manageable toxicities, highlighting its potential role in the management of locoregionally advanced NPC. ClinicalTrials.gov Identifier: NCT03427827