Importance:It remains uncertain which Epstein-Barr virus (EBV)-related biomarkers provide the most reliable diagnostic performance for suspected nasopharyngeal carcinoma (NPC) in outpatient settings, especially regarding the novel anti-EBV BNLF2b total antibody (P85-Ab) assay. Clarifying their accuracy is critical to improving early detection and reducing misdiagnosis. Objective:To evaluate the diagnostic performance of the P85-Ab assay in suspected NPC in outpatient settings and compare it head-to-head with EBV viral capsid antigen (VCA)-immunoglobulin A (IgA), EBV early antigen (EA)-IgA, and EBV nuclear antigen 1 (EBNA1)-IgA. Design, Setting, and Participants:A prospective, multicenter cohort study was conducted between April 2021 and March 2024, with a median follow-up of 27.2 months in outpatient clinics across 5 medical centers in China. Key inclusion criteria comprised clinically suspected NPC. Data were analyzed from June 2025 to July 2025. Exposures:P85-Ab was tested using chemiluminescent immunoassay. VCA-IgA, EA-IgA, and EBNA1-IgA were tested via enzyme-linked immunosorbent assays. Main Outcomes and Measure:Primary outcomes included sensitivity and specificity of P85-Ab. Results:A total of 3795 eligible participants were consecutively recruited. After excluding individuals with low-quality samples or lost to follow-up, 3777 participants were included in the final analysis (1680 with NPC and 2097 without NPC). Among the 3777 evaluated participants (median [IQR] age, 49.0 [37.0-58.0] years; 65 % male), P85-Ab demonstrated superior diagnostic performance, with a sensitivity of 93.0% (95% CI, 91.6-94.0) and specificity of 97.3% (95% CI, 96.5-97.9). Other biomarkers showed lower sensitivity (ranging from 60.4% to 93.0%) and specificity (<90%). P85-Ab maintained high sensitivity among asymptomatic individuals (92.0%; 95% CI, 85.9-95.6) and those presenting with NPC-nonspecific symptoms (88.4%; 95% CI, 75.5-94.9), with no additional diagnostic benefit observed from the triplet-antibody strategy combining P85-Ab, VCA-IgA, and EBNA1-IgA. However, among participants with NPC-specific symptoms, the triplet-antibody strategy improved sensitivity compared with P85-Ab alone (95.9%; 95% CI, 94.8-96.8 vs 93.1%; 95% CI, 91.7-94.3; P < .001). Conclusions and Relevance:In this cohort study, P85-Ab was a robust and accurate biomarker for suspected NPC in outpatient settings. P85-Ab alone may be suggested for populations with asymptomatic or NPC-nonspecific symptoms, and combining P85-Ab with VCA-IgA and EBNA1-IgA may be suggested for populations with NPC-specific symptoms.

PURPOSE:We previously reported that reduced-dose (60 Gy) radiation was associated with favorable survival outcomes and limited toxicities in patients with low-risk stage III nasopharyngeal carcinoma (NPC) sensitive to induction chemotherapy (IC). However, the consistency of long-term outcomes remains unclear. METHODS AND MATERIALS:This 5-year follow-up secondary analysis of a single-arm phase II trial enrolled patients with nonkeratinizing stage III NPC with pretreatment Epstein-Barr virus (EBV) DNA <4000 copies/mL. All 215 eligible patients received 2 cycles of IC. After IC, 116 patients achieved complete response/partial response and undetectable EBV DNA, and they were assigned to receive intensity-modulated radiation therapy (IMRT) at 60 Gy in 30 fractions. The remaining 99 patients were assigned to receive standard IMRT at 70 Gy in 33 fractions. The primary endpoint was progression-free survival. RESULTS:At a median follow-up of 68.1 months, the 5-year progression-free survival was 90.5% (95% CI, 85.3%-96.0%) in the 60 Gy cohort and 79.8% (72.3%-88.1%) in the 70 Gy cohort, whereas the 5-year overall survival was 96.6% (93.3%-99.9%) and 94.9% (90.7%-99.4%), respectively. The 5-year locoregional relapse-free survival was 93.1% in the 60 Gy cohort and 82.8% in the 70 Gy cohort; the 5-year distant metastasis-free survival was 93.1% in the 60 Gy cohort and 89.9% in the 70 Gy cohort. No grade 3-4 late toxicity was observed in the 60 Gy group. In the 70 Gy cohort, 10.1% of patients experienced grade 3-4 late toxicities, with dry mouth and deafness/otitis being the most frequently reported. CONCLUSIONS:Long-term analysis showed that in patients with low-risk stage III NPC selected by EBV DNA and IC response, reduced-dose IMRT (60 Gy) achieved favorable survival outcomes with limited late toxicities.

LBA6005 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the current standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC remain at high risk of disease progression. Although adjuvant capecitabine has demonstrated efficacy in high-risk LA-NPC, whether intensifying adjuvant therapy by adding sintilimab, a highly selective, fully humanized monoclonal PD-1 inhibitor to capecitabine, can further improve survival outcomes remains unclear. Methods: This open-label, randomized, phase 2 trial enrolled patients aged 18–70 years with untreated, non-keratinising, stage II–IVA LA-NPC according to the eighth edition of the American Joint Committee on Cancer classification system with suboptimal response to IC, defined as detectable EBV DNA and/or stable or progressive disease after platinum-based IC. After CCRT, all patients were randomly assigned (1:1) to receive either adjuvant sintilimab plus capecitabine or capecitabine alone. Sintilimab (200 mg intravenously) was administered on days 1 and 14 after randomization as a lead-in phase, and then every 3 weeks starting 28 days after CCRT, combined with capecitabine (1000 mg/m² twice daily, days 1–14) for eight cycles; the control group received capecitabine alone on the same schedule starting 28 days after CCRT for eight cycles. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. The study was registered at ClinicalTrials.gov (NCT05201859), and patients are under follow-up. Results: One hundred fifty patients were randomised (76 to sintilimab–capecitabine group; 74 to capecitabine group). At a median follow-up of 41 (IQR 35-44) months, the 2-year PFS was 88.2 % in the sintilimab–capecitabine group and 87.8% in the capecitabine group (stratified HR 0.85; 90% CI 0.43–1.70; p=0.77). Grade 3-4 adverse events were reported in 25 (34%) patients in the sintilimab–capecitabine group and in 22 (31%) patients in the capecitabine group; hand-foot syndrome was the most common adverse event in both groups (8% vs. 10%). Immune-related grade 3 myocarditis were occurred in 2 (3%) patients in the sintilimab–capecitabine group. No treatment-related deaths occurred. Conclusion: In patients with LA-NPC who had a suboptimal response to IC, intensification of adjuvant therapy with the addition of sintilimab to capecitabine did not result in a significant improvement in progression-free survival. Future studies are warranted to focus on biomarker-driven patient selection and optimization of immunotherapy sequencing with conventional treatments. Clinical trial information: NCT05201859 .

2622 Background: First-line chemotherapy combined with immunotherapy (CT-IO), followed by selective locoregional radiotherapy (LRRT), has emerged as the mainstay treatment for de novo metastatic nasopharyngeal carcinoma (dmNPC). However, the efficacy of adding concurrent immunotherapy to LRRT remains controversial. Methods: This study enrolled patients with dmNPC who received platinum-based chemotherapy, anti–PD-1 immunotherapy, and definitive LRRT. Survival outcomes were assessed using a 12-month landmark analysis to minimize immortal time bias. Inverse probability of treatment weighting (IPTW) was employed to balance baseline characteristics between the CCRT+IO (LRRT with concurrent immunotherapy) and CCRT-IO (LRRT without concurrent immunotherapy) groups. Recursive partitioning analysis (RPA) utilizing baseline and post-CT-IO factors was applied to stratify patients into low- or high-risk groups to evaluate the benefit of concurrent IO. Absolute lymphocyte count (ALC) was monitored during and up to 6 months post-LRRT. Results: A total of 238 patients were included (185 receiving concurrent IO and 53 without). In the IPTW-adjusted Kaplan-Meier analysis at the 12-month landmark, the addition of concurrent IO was associated with significantly inferior progression-free survival (PFS) (Hazard Ratio [HR]: 3.189; 95% CI, 1.352–7.524; p = 0.008). The "Sandwich" mode—comprising 4-6 cycles of induction CT-IO, followed by LRRT, and subsequent IO maintenance—yielded the optimal survival outcomes (HR: 0.288; 95% CI, 0.106–0.786; p = 0.015). An RPA model incorporating five prognostic factors (the number of metastatic lesions, pretreatment LDH level, post-CT-IO Epstein-Barr virus DNA, and radiological response post-CT-IO) stratified patients into two risk subgroups. Low-risk patients derived no clinical benefit from concurrent IO (p = 0.134), whereas high-risk patients exhibited significantly worse 12-month landmark adjusted PFS (p = 0.031). Notably, subgroup analysis showed that patients with persistent radiation-induced lymphocytopenia at 3 months post-RT demonstrated the most unfavorable survival outcomes after concurrent immunotherapy (p < 0.001). Conclusions: DmNPC patients receiving first-line CT-IO followed by LRRT did not benefit from concurrent immunotherapy during RT, particularly those identified as high-risk by the prognostic model and those with persistent lymphocytopenia at 3 months post-RT.

Background Patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) who progress after immune checkpoint inhibitor (ICI) therapy have limited treatment options and poor outcomes. We evaluated the efficacy and safety of liposomal irinotecan plus nimotuzumab in patients with epidermal growth factor receptor (EGFR)-positive, ICI-refractory R/M NPC. Methods In this single-arm, open-label, phase II trial (NCT06414577) conducted in China, patients with EGFR-positive, ICI-refractory R/M NPC were enrolled between May 27, 2024, and January 9, 2025. Patients received intravenous liposomal irinotecan (70 mg/m2) plus nimotuzumab (400 mg) every 2 weeks for up to eight cycles. The primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Findings Thirty-six heavily pretreated patients were enrolled, of whom 12 (33.3%) had received three or more prior lines of therapy for advanced disease. In the intention-to-treat population, 13 of 36 patients achieved an objective response (ORR 36.1%; 95% CI 20.8–53.8), and 22 of 36 patients achieved disease control (61.1%). Median progression-free survival was 3.0 months (95% CI, 2.2–4.1), and median duration of response was 2.3 months (95% CI 1.5–3.1). After a median follow-up of 22.0 months, the median overall survival was 14.1 months (95% CI, 8.7-not estimable). Grade 3 or higher treatment-related adverse events occurred in eight of 36 patients (22.2%), and no treatment-related deaths were observed. In a post-hoc exploratory analysis, an early decline of at least 50% in plasma Epstein–Barr virus DNA was associated with a higher ORR. Interpretation Liposomal irinotecan plus nimotuzumab showed preliminary antitumor activity and manageable safety in heavily pretreated patients with ICI-refractory R/M NPC. However, response durability was limited, and further comparative studies are needed to evaluate its clinical value and identify patients most likely to derive durable benefit. Funding Supported by grants from the National Natural Science Foundation of China, Science and Technology Program of Guangdong Esophageal Cancer Institute, and China Postdoctoral Science Foundation.

Background:Neuroblastoma is characterized by multiple immune evasion strategies, making it critical to explore the use of immunotherapy. CDK1 is known for its role in regulating cell cycle progression and is aberrantly expressed in various tumors, yet its role in NB and immunogenic cell death remains unclear. Methods:We investigated the association between the expression of CDK1 and the outcome of neuroblastoma according to the TCGA database and confirmed the results by tissue arrays. Furthermore, we evaluated the correlation between CDK1 expression and immune cell infiltration as well as cytokine effectiveness. Finally, in vitro and in vivo experiments were used to confirm the effects of a CDK1 inhibitor. Results:CDK1 was overexpressed in advanced neuroblastoma and was associated with poor prognosis. High CDK1 expression correlated with reduced immune cell infiltration and decreased levels of effector cytokines including IL-12, IFN-γ, and IRF1. Furthermore, the inhibition of CDK1 slowed the growth of neuroblastoma cells and promoted immunogenic cell death in neuroblastoma. CDK1 inhibition via RO-3306 suppressed tumor growth and induced hallmark features of ICD, including CRT exposure, HSP70 expression, and HMGB1 release. Conclusion:CDK1 inhibition not only slows neuroblastoma progression but also triggers DAMP release consistent with ICD and immune activation. CDK1 may be a potential prognostic marker and effective treatment target for improving immunotherapy efficacy in neuroblastoma patients.

BACKGROUND:Recent clinical trials have suggested that incorporating immunotherapy into the treatment of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) may improve survival outcomes. However, for patients who experience disease progression despite immunotherapy, the clinical value of immunotherapy rechallenge as a first-line treatment for recurrent or metastatic disease remains unclear. METHODS:In this real-world study, patients with LA-NPC who received immunotherapy during the initial treatment and subsequently experienced disease progression were retrospectively analyzed. All patients received first-line treatment with or without immunotherapy rechallenge after progression. The primary endpoint was progression-free survival after the first relapse (PFS-r). FINDINGS:From a total of 24,183 consecutive patients screened between 2018 and 2023, 160 met the eligibility criteria and were included, with 117 receiving immunotherapy rechallenge and 43 receiving non-immunotherapy treatment after progression. The median follow-up time was 39.3 months (interquartile range, 26.0-48.4). After inverse probability of treatment weighting adjustment, immunotherapy rechallenge did not confer a significant survival advantage in the overall cohort (2-year PFS-r, 40.8% vs. 26.2%; hazard ratio [HR] = 0.677, 95% confidence interval [CI] 0.419-1.094, p = 0.111). Subgroup analyses showed that, in patients with an immunotherapy-free interval >1 year, immunotherapy rechallenge was associated with a significantly improved prognosis (2-year PFS-r, 65.4% vs. 15.5%; HR = 0.210, 95% CI 0.093-0.474, p < 0.001). CONCLUSIONS:Immunotherapy rechallenge may not provide a significant survival benefit following initial immunotherapy failure in LA-NPC, except in patients with an immunotherapy-free interval exceeding 1 year. FUNDING:National Natural Science Foundation of China and Science and Technology Program of Guangzhou.

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC, defined as detectable Epstein-Barr virus DNA and/or stable or progressive disease after IC, remain at high risk of treatment failure. Here we report an open-label, randomised, phase 2 trial evaluating whether adding nimotuzumab, a humanised anti-epidermal growth factor receptor antibody, to CCRT improves outcomes in this high-risk population. A total of 246 patients with untreated, non-keratinising, stage II-IVA LA-NPC were randomly assigned (1:1) to receive CCRT with or without nimotuzumab. The primary endpoint was 2-year progression-free survival (PFS); secondary endpoints included overall survival, distant metastasis-free survival, locoregional relapse-free survival, short-term response rate, and safety. At a median follow-up of 47 months, the 2-year PFS was 81.0% (90% confidence interval [CI], 74.3-86.1) in the nimotuzumab plus CCRT group and 80.8% (90% CI, 74.2-85.7) in the CCRT-alone group (hazard ratio, 0.93 [90% CI, 0.63-1.37]; p = 0.70). Survival outcomes were similar between groups, while low-grade rash occurred more frequently with nimotuzumab. These findings indicate that adding nimotuzumab to CCRT does not improve survival in patients with LA-NPC with a suboptimal response to IC, underscoring the need for predictive biomarkers and alternative therapeutic strategies. Trial registration: NCT04223024.

In this retrospective case-control study involving 424 pediatric patients diagnosed with Pediatric Acute Lymphoblastic Leukemia (ALL), the investigation focused on analyzing the clinical characteristics and prognosis associated with the Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) gene. Treatment and evaluation followed the South China Children's Leukemia Group-ALL-2016 protocol (SCCLG-ALL-2016). Among the cohort, 92 patients (21.7%) exhibited CDKN2A/2B gene deletions, with 11.1% homozygous and 10.6% heterozygous deletions. Notably, ALL patients that do have CDKN2A/2B gene deletions tended to present at an older age (P = 0.001), demonstrate hepatosplenomegaly on palpation (P < 0.001), and exhibit a higher incidence of Central nervous system leukemia (CNSL) (P = 0.037) and T-ALL (P = 0.007). A significant correlation was observed between ALL that does have CDKN2A/2B gene deletions and ETV6::RUNX1-positive (8.7% vs. 19.3%, P = 0.017) and IKZF1 gene deletions (20.7% vs. 8.4%, P = 0.001). Survival analysis of 392 patients revealed no significant differences in 5-year relapse, Overall survival (OS), or Event-free survival (EFS) between ALL that does/ does not have CDKN2A/2B gene deletions. Subgroup analysis highlighted poorer prognosis among hepatosplenomegaly patients in the CDKN2A/2B gene deletion group, with a 5-year EFS of 81.8%, 95%CI (0.695-0.963), P = 0.05. Hepatosplenomegaly emerged as the most significant prognostic factor for EFS [HR = 2.306, 95%CI (1.192-4.461), P = 0.013]. Cox regression analyses identified covariates influencing prognosis, ALL with the CDKN2A/2B gene showing no significant impact on outcomes. In conclusion, while ALL that does have CDKN2A/2B gene deletions is associated with certain clinical characteristics and genetic aberrations, they did not significantly impact OS or EFS. Furthermore, subgroup analysis revealed a potential prognostic role of ALL that does have CDKN2A/2B deletions presenting with hepatosplenomegaly on palpation, emphasizing the importance of comprehensive risk stratification in treatment decision-making for this subgroup.

Purpose: GFH018 is a novel TGFβRI inhibitor, which has been shown to potentiate the antitumor effect of anti-PD-1/PD-L1 blockade. This study aimed to evaluate the safety and efficacy of GFH018 plus toripalimab in recurrent/metastatic (R/M) NPC patients. Patients & Methods: This phase Ib/II study included patients with R/M NPC who had failed at least one prior line of standard therapy. Patients received GFH018 (40 or 80 mg) BID for 14 days on/14 days off, combined with toripalimab (3 mg/kg) intravenously every two weeks on a 28-day cycle. Treatment continued until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DoR), and safety. Results: Forty-six patients were were accrued. The ORR was 26.1% (90% CI: 15.8–38.8%), and the disease control rate (DCR) was 43.5% (90% CI: 31.0–56.6%). The median PFS was 2.0 months (90% CI: 1.8–8.9), and the median DoR was 7.6 months (90% CI: 5.6–not reached). In patients without prior immune checkpoint inhibitor (ICI) treatment, the ORR was 40% (90% CI: 23.6–58.3%), and the DCR was 60% (90% CI: 41.7–76.4%). The median PFS was 9.0 months (90% CI: 1.9–not reached), and the median DoR was not reached. High parenchymal CD8+ T cell density correlated with better PFS in these patients. Conclusions: The combination of GFH018 and toripalimab showed a manageable toxicity profile and durable antitumor activity in R/M NPC patients, especially those without prior ICI exposure.

BackgroundPredicting the intracranial efficacy of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains challenging. The objective of this study was to construct a habitat-peritumoral radiomics framework for immunotherapy response prediction, concurrently identifying the optimal peritumoral extent.MethodsThis retrospective multicenter study analyzed 378 NSCLC-BM patients receiving PD-1/PD-L1 inhibitors. Participants were stratified into training (n=146), internal validation (n=63), and two external test cohorts (test 1: n=57; test 2: n=112). Logistic regression was conducted to determine significant clinical predictors. Habitat subregion segmentation was performed using K-means clustering with peritumoral extensions at incremental distances (1, 2, and 3 mm). Predictive models were developed using radiomic features extracted from intratumoral cores, habitat subregions, and peritumoral zones through machine learning approaches. A combined model integrated habitat signatures, peritumoral features, and clinical predictors. Model performance assessment employed the area under the curves (AUCs), calibration curves, and decision curve analyses (DCA).ResultsThe habitat-based XGBoost model demonstrated superior predictive performance across all cohorts compared to alternative models, achieving AUCs of 0.900 (training), 0.886 (internal validation), 0.820 (test 1), and 0.804 (test 2). For peritumoral analysis, the peri-1 mm RandomForest model exceeded other regional configurations. Integrating peri-1 mm features and clinical factors yielded a marginal performance enhancement in the combined model, with corresponding AUCs of 0.898, 0.894, 0.837, and 0.814. The combined model demonstrated optimal calibration and significant clinical utility, as evidenced by calibration curves and DCA.ConclusionThe validated habitat-peritumoral radiomics framework, optimized at a 1-mm peritumoral extent, demonstrates robust predictive accuracy for intracranial immunotherapy response in NSCLC-BM patients and offers significant clinical utility.

BACKGROUND:Concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy (AC) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, the optimal duration of oral AC remains poorly defined. METHODS:This study examined newly diagnosed patients between April 2017 and December 2020. The primary endpoint was overall survival (OS). Restricted cubic splines (RCS) and Kaplan-Meier method were used to evaluate the relationship between AC maintenance and survival. Inverse probability of treatment weighting (IPTW) was used to control for confounding factors. RESULTS:The RCS demonstrated an L-shaped association between oral AC maintenance and OS. The risk of mortality was relatively flat after 12 months. Patients with oral AC duration >186 days (defined by RCS) had a significantly better OS (HR 0.23 [95% CI 0.10-0.55], log-rank p < 0.001), with a higher 3-year OS rate (98.7% [95% CI 96.8-100.0] vs 88.3% [95% CI 82.5-94.5]). For patients with pretreatment Epstein-Barr virus (EBV) DNA level >4000 copies/mL, mortality risk decreased to 1 at 194 days of AC duration. CONCLUSIONS:The optimal duration of oral AC after CCRT was >186 days (6 months) for LA-NPC. And the maintenance beyond 12 months may not bring additional benefits.

Nasopharyngeal carcinoma (NPC) is often diagnosed at an advanced stage due to its hidden location, with 70–80

Importance:It remains uncertain which chemotherapy sequence is more effective for locoregionally advanced nasopharyngeal carcinoma. Objective:To compare the efficacy and safety of induction-concurrent with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma. Design, Setting, and Participants:In this open-label, randomized, phase 3 clinical trial conducted at Sun Yat-sen University Cancer Center (China) from November 20, 2017, to March 19, 2021, patients aged 18 to 65 years with stage T1-4N2-3M0 and a pretreatment Epstein-Barr virus DNA level of 1500 or more copies/mL were enrolled. The data were analyzed from December 2024 to March 2025. Intervention:The patients were randomly assigned to receive 3 cycles of paclitaxel-cisplatin-fluorouracil induction chemotherapy followed by concurrent chemoradiotherapy or concurrent chemoradiotherapy followed by 3 cycles of cisplatin-fluorouracil adjuvant chemotherapy. Main Outcome and Measure:The primary end point was 3-year progression-free survival, assessed locally by the investigator and defined as the time from random assignment to documented local or regional relapse, distant metastasis, or death of any cause, whichever occurred first. Results:A total of 162 patients (median [IQR] age, 44 [34-53] years; 40 female individuals [24.7%]) were assigned to the induction-concurrent group and 162 (median [IQR] age, 45 [37-52] years; 36 female individuals [22.2%]) to the concurrent-adjuvant group. Regarding the data cutoff (October 8, 2024), the median (IQR) follow-up period was 60.4 (58.2-62.6) months. The 3-year progression-free survival rates were 73.5% (95% CI, 65.9%-79.6%) in the induction-concurrent group and 70.4% (95% CI, 62.7%-76.8%) in the concurrent-adjuvant group (stratified hazard ratio, 0.86; 95% CI, 0.58-1.27; P = .45). The most common short-term grade 3 or worse adverse events were leukopenia (53 of 160 [33.1%] in the induction-concurrent group vs 47 of 142 [33.1%] in the concurrent-adjuvant group), neutropenia (52 [32.5%] vs 32 [22.5%], respectively), and mucositis (47 [29.4%] vs 42 [29.6%], respectively). The most common grade 3 or worse late adverse event was auditory or hearing loss (10 [6.3%] vs 12 [8.5%], respectively). Two patients in the induction-concurrent group died of treatment-related toxic effects. No treatment-related death occurred in the concurrent-adjuvant group. Conclusions and Relevance:This randomized clinical trial found that induction-concurrent chemotherapy did not significantly improve progression-free survival compared with concurrent-adjuvant chemotherapy in high-risk N2 to N3 nasopharyngeal carcinoma. Both treatment strategies were effective, and clinicians should discuss with the patients about the potential risks and benefits of the induction chemotherapy or adjuvant chemotherapy to provide the most appropriate treatment for patients with high-risk features. Trial Registration:ClinicalTrials.gov Identifier: NCT03306121.

Adolescent and childhood nasopharyngeal carcinoma (NPC) is a rare malignancy with unique biological and genetic characteristics, often associated with Epstein-Barr virus (EBV). This CACA guideline provides an integrative approach to the management of adolescent and childhood NPC, focusing on biology, diagnosis, staging, and treatment strategies. The incidence of NPC is higher in adolescent boys and is more frequently diagnosed at an advanced stage in adolescent and childhood population compared to adults. However, adolescent and childhood NPC generally have a better prognosis. The primary treatment is radiotherapy (RT), with intensity-modulated radiation therapy (IMRT) being the preferred technique due to its reduced damage to normal tissues. Chemotherapy, particularly induction chemotherapy, plays a significant role, especially in locally advanced disease. Personalized treatment strategies, including adjusting RT dosage based on chemotherapy outcomes, may reduce long-term adverse effects. The role of adjuvant therapy post-RT remains unclear and requires further research. The main objective of this guideline is to standardize the clinical diagnosis and treatment process of adolescent and childhood nasopharyngeal carcinoma, with a multidisciplinary approach to optimize therapeutic outcomes and quality of life for this disease.

6078 Background: Patients with low-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC) have high survival when treated with radiotherapy (RT) plus cisplatin after induction chemotherapy (IC). Whether replacement of cisplatin with nimotuzumab—a humanized antibody against the epidermal growth factor receptor (EGFR)—can preserve high survival and reduce treatment toxicity is unknown for patients with good response to IC. Therefore, we assessed whether nimotuzumab plus RT was non-inferior to cisplatin plus RT in low-risk LA-NPC with favorable response to IC. Methods: The study was a randomised, non-inferiority, phase 3 trial at Sun Yat-sen University Cancer Centre, China. Adult patients (aged 18–70 years) with non-keratinizing stage II-IVA (except N3 category; the eighth edition of the American Joint Committee on Cancer classification system) NPC, with pre-treatment plasma EBV DNA<1500 copies/mL, positive EGFR expression and an Eastern Cooperative Oncology Group performance status of 0–1, were treated with 2 cycles of paclitaxel-cisplatin-fluorouracil IC, those achieved CR/PR with undetectable EBV DNA were randomly assigned (1:1) to receive either intravenous nimotuzumab at a dose of 200 mg weekly or cisplatin 100 mg/m² on days 1, 22 and 43 of intensity-modulated radiotherapy. Randomization was done using a computer-generated code random number code with a block size of six, stratified by overall stage. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, number NCT 04456322. Results: Of the 381 patients who underwent randomization, 191 were assigned to RT plus nimotuzumab and 190 to RT plus cisplatin. After median follow-up duration of 39.5 months, in the evaluation of 2-year PFS, RT plus nimotuzumab was noninferior to RT plus cisplatin (94.2% and 95.8%, respectively; absolute difference, 1.6 percentage points; 95% CI, –2.8 to 6.0, [noninferiority margin, -10 percentage points], P noninferiority =0.0001). The most common grade 3-4 acute toxicities were leucopenia (37 [19.5%] of 190 patients in the cisplatin group vs. 2 [1.1%] of 189 patients in the nimotuzumab group), mucositis (36 [18.9%] vs. 28 [14.8%]), and vomiting (21 [11.1%] vs. 0). No patients died during treatment. Patients in the cisplatin group also showed more grade 1-2 auditory or hearing loss and peripheral neuropathy in late adverse events, and impaired long-term quality of life. Conclusions: Our findings show that nimotuzumab plus RT represents an alternative concurrent treatment strategy for patients with low-risk LA-NPC with a favorable response to IC. Clinical trial information: NCT04456322 .

BACKGROUND:The use of maintenance therapy for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) following first-line treatment with gemcitabine, cisplatin, and anti-PD-1 antibody remains controversial. Therefore, an effective and low-toxicity maintenance treatment option is urgently needed. METHODS:This retrospective study included 301 patients who received either combined maintenance therapy (anti-PD-1 antibody plus capecitabine) or anti-PD-1 antibody alone. Patients were matched in a 1:3 ratio using propensity score matching (PSM). Progression-free survival (PFS) was the primary outcome, and its association with maintenance therapy was assessed using the log-rank test and Cox proportional hazards model. RESULTS:Fifty-eight patients were included in the combined maintenance therapy group. After PSM, 174 patients were included in the anti-PD-1 antibody maintenance therapy group. In the matched cohort, the 2-year PFS rate was significantly higher in the combined maintenance therapy group than in the anti-PD-1 antibody monotherapy group (66.8% vs. 51.3%, P = .0063). Subgroup analysis showed that patients with pre-treatment Epstein-Barr virus (EBV) DNA > 12 400 copies/mL and undetectable post-treatment levels had significantly improved PFS with combined maintenance therapy (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.20-0.96, P = .033). In contrast, no statistically significant PFS improvement from the combined maintenance therapy was observed among patients with low pre-treatment EBV DNA (≤12 400 copies/mL) and undetectable post-treatment levels (HR = 0.59, 95% CI = 0.27-1.27, P = .17), or those with detectable post-treatment EBV DNA levels regardless of pre-treatment levels (HR = 0.73, 95% CI = 0.31-1.70, P = .46). Combined maintenance therapy was associated with higher rates of grade 3-4 hand-foot syndrome (P < .001) and leukopenia (P = .0487). CONCLUSIONS:Anti-PD-1 antibody plus capecitabine maintenance therapy improved PFS with manageable toxicities in patients with RM-MPC following first-line immunochemotherapy, particularly in those with pre-treatment EBV DNA >12 400 copies/mL and undetectable post-treatment levels.

CD155 is a crucial factor in the regulation of T cell function and contributes to immune escape. CD155 upregulation has been found in several types of cancer. However, the mechanism by which CD155 regulates CD8+ T cell function in colorectal cancer remains unclear. Here we investigated the role and mechanism of CD155 in the regulation of CD8+ T cell function. We studied the expression of CD155 in colorectal cancer tissues through western blot, immunohistochemistry, and the TCGA database. We verified the effects of CD155 on the functions of colorectal cancer cells and CD8+ T cells through in vitro experiments. We demonstrated that CD155 affects CD8+ T cell migration and thus promotes tumor growth in a mouse subcutaneous tumor model. We then tested the changes in the PI3K/AKT/NF-κB pathway in CD8+ T cells by flow cytometry. We demonstrated that stable CD155 expression was negatively correlated with prognosis in colorectal cancer patients. In vitro experiments confirmed that CD155 does not affect tumor cell proliferation, migration, or invasion. We also revealed that CD155 downregulated the function and migration of CD8+ T cells in vivo and in vitro. Furthermore, CD155 might regulate CD8+ T cells function via the PI3K/AKT/NF-κB pathway. This study revealed that CD155 can promote the progression of colorectal cancer by regulating the PI3K / AKT-NF-κB pathway to promote the depletion of CD8+ T cells and reduce their migration to the tumor microenvironment. CD155 may become an important prognostic biomarker and an effective target for colorectal cancer immunotherapy.

Background:Intensity-modulated radiation therapy (IMRT) with two cycles of concurrent 100 mg/m2 cisplatin (DDP) presents a potential alternative for low-risk, locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This study assessed its long-term survival outcomes and late toxicities. Methods:This is a secondary analysis of an open-label, randomised, controlled, phase 2 non-inferiority trial, which enrolled patients with low-risk LA-NPC (pretreatment plasma Epstein-Barr virus DNA < 4000 copies/mL) at Sun Yat-sen University Cancer Center. Eligible participants were randomly assigned (1:1) to receive either two cycles or three cycles of concurrent cisplatin (100 mg/m2 every 3 weeks) with intensity-modulated radiation therapy. The primary endpoint was 5-year progression-free survival (PFS); secondary endpoints were 5-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and late toxic effects. The non-inferiority margin was 10%. This secondary analysis of long-term follow-up was prespecified in the study protocol. Analyses of primary and secondary endpoints included intention-to-treat and per-protocol populations. The trial is registered with ClinicalTrials.gov, NCT02871518. Findings:Between Sept 28, 2016, to Oct 18, 2018, 332 patients were enrolled and randomly assigned to the two-cycle group (n = 166) or three-cycle group (n = 166). The final follow-up date was Oct 11, 2024. Data were analysed from Oct 11, 2024, to June 5, 2025. At median follow-up of 79.7 months (IQR, 75.4-88.3 months), 5-year PFS rates were 85.0% (95% CI, 79.4-90.4) for the two-cycle group vs. 87.3% (95% CI, 82.2-92.4) for the three-cycle group (difference 2.4%; 95% CI, -5.0%-9.8%; noninferiority P = 0.016). No significant differences were observed in 5-year OS (95.2% [91.9-98.5] vs. 97.6% [95.3-100], HR, 2.02 (95% CI: 0.61-6.72), P log-rank = 0.240) and the cumulative incidences of locoregional relapse (6.1% [2.4-9.8] vs. 6.0% [2.3-9.7], HR, 1.00 (95% CI: 0.42-2.41), P Fine-Gray = 0.993) and distant metastasis (6.8% [2.9-10.7] vs. 7.3% [3.4-11.2], HR, 1.08 (95% CI: 0.48-2.44), P Fine-Gray = 0.855). The three-cycle regimen demonstrated higher incidences of late toxicities: trismus (22.4% [37/165] vs. 12.7% [21/166], P = 0.028), xerostomia (83.0% [137/165] vs. 72.9% [121/166], P = 0.036), and hearing impairment/otitis (55.8% [92/165] vs. 44.0% [73/166], P = 0.042). Interpretation:Five-year outcomes support the viability of two cycles of concurrent DDP with IMRT as an alternative to the standard three-cycle regimen, offering comparable survival outcomes with fewer late toxicities in patients with low-risk LA-NPC. However, as the study was conducted at a single center, the generalisability of these findings to non-endemic regions warrants further validation. Funding:National Key Research and Development Program of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, and China Postdoctoral Science Foundation.