Purpose The clinical and pathological characteristics of nasopharyngeal neuroendocrine carcinoma (NNEC) remain poorly defined, and its association with Epstein-Barr virus (EBV) remains not well established. Methods We conducted a retrospective analysis of patients with pathologically confirmed NNEC treated between 2013 and 2024. Clinical, pathological, and treatment data were collected, including histology, immunophenotyping, plasma EBV DNA levels, and imaging features. Survival endpoints were overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Results Among 15 patients (12 males, 3 females; median age 51 years), 12 were EBV-positive. Lymph node metastasis was frequently observed at baseline (15/15, 100%), characterized by involvement of the retropharyngeal lymph node (RPN) (10/15, 66.7%) and at level II (14/15, 93.3%) and followed by an orderly caudal progression without skip metastasis. Following treatment, 14 patients (93.3%) achieved a complete response. After a median follow-up of 44 months, the 3-year OS, PFS, and DMFS rates were 77.4%, 50.5%, and 50.5%, respectively; the median OS and PFS were both 72 months, whereas DMFS was not reached. Distant metastases developed in 7 patients (46.7%), most commonly in the liver, bone, and brain. Among patients with detectable EBV DNA at baseline, complete EBV DNA clearance was achieved in 11 of these 12 patients (91.7%), and 6 of 7 patients with disease progression exhibited a concomitant exponential rise in EBV DNA levels. Conclusion NNEC exhibits an orderly pattern of cervical lymph node metastasis. Plasma EBV DNA level is a promising dynamic biomarker for treatment response and disease surveillance in EBV-positive NNEC. Despite the high initial complete response rate, the considerable risk of distant metastasis contributes to compromised long-term survival, underscoring the need for novel therapeutic strategies.

IMPORTANCE:Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. OBJECTIVE:To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. DESIGN, SETTING, AND PARTICIPANTS:The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. INTERVENTIONS:Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. MAIN OUTCOME:The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. RESULTS:Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided P = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; P = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; P = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; P < .001). CONCLUSIONS AND RELEVANCE:In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the benefit of PD-1-based chemoimmunotherapy in this setting. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03707509.

ABSTRACT Background TNM‐9 Stage IB nasopharyngeal carcinoma (NPC) encompasses markedly heterogeneous risk profiles, yet lacks reliable biomarkers to guide the choice between de‐escalation and intensification strategies. This study aimed to explore the prognostic significance of upper‐ and middle‐neck nodal involvement (UNI and MNI) in this population and how it affects treatment outcomes and prognosis. Methods Patients with Stage IB NPC treated between June 2016 and December 2019 at our institution were included. Nodal levels were classified into UNI and MNI. Survival outcomes, including overall survival (OS), progression‐free survival (PFS), distant control (DC), and regional control (RC), were analyzed. Results A total of 370 patients were analyzed, with 257 (69.5%) classified in the UNI group and 113 (30.5%) in the MNI group, respectively. MNI was found to be associated with significantly worse prognosis compared to UNI. Specifically, the MNI group had lower 5‐year OS (91.1% vs. 98.8%, p < 0.001), PFS (78.6% vs. 95.6%, p < 0.001), DC (90.2% vs. 98.8%, p < 0.001), and RC (93.3% vs. 98.4%, p = 0.005) than the UNI group. Association analysis revealed that nodal level was significantly associated with other known adverse prognostic factors, including the maximum diameter of positive lymph nodes, matted nodes, and high EBV‐DNA levels (all p < 0.001). Crucially, after multivariate adjustment, nodal level is the only independent prognostic factor. Conclusion The nodal level was a critical factor in predicting patient outcomes in Stage IB NPC. These findings are hypothesis‐generating: UNI patients may represent a candidate population for prospective de‐escalation trials, whereas MNI patients may warrant evaluation of intensified or novel strategies in future studies. Prospective validation is required before any change in clinical management.

Abstract Background: SYS6010 is a novel EGFR-targeted ADC, consisting of a humanized anti-EGFR mAb linked to a topoisomerase I inhibitor (JS-1) via a glycine̶̶-glycine-phenylalanine-glycine tetrapeptide linker (DAR = 8). This phase I study (ChiCTR2300072141) evaluated SYS6010 in advanced solid tumors, with NPC cohort results reported here following prior NSCLC data oral presentation on AACR 2025 (25-LB-9831-AACR). Methods: Patients with advanced NPC progressing after ≥1L prior therapy (including PD1 inhibitor and platinum-based chemotherapy) received SYS6010 at 4.2 or 4.8 mg/kg IV every 3 weeks (Q3W) until progression or intolerable toxicity. Primary endpoints were safety and tolerability; secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Subgroup analyses were conducted by prior EGFR monoclonal antibody treatment and therapy lines. Results: As of September 15, 2025 (data cutoff), 56 patients were enrolled in the safety population (4.2 mg/kg, n=34; 4.8 mg/kg, n=22). Median age was 49.5 years (range, 27-70); 83.9% were male; 19.6% had ECOG PS 0 and 80.4% PS 1; mean BMI was 22.7 ± 3.34; 30.4% had prior EGFR mAb therapy. All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs occurred in 64.3% (37/56) of patients, with a comparable incidence between the 4.2 mg/kg (64.7%) and 4.8 mg/kg (63.6%) groups. Most common Grade ≥3 TEAEs were hematological toxicities: white blood cell count decreased (33.9%), neutrophil count decreased (32.1%), and platelet count decreased (28.6%), and their median time of recovering to baseline or grade 1 was 5 days(d), 4 d and 10 d respectively. Non-hematological Grade ≥3 TEAEs were infrequent. As hematological toxicities are well manageable in clinical practice, so the TEAEs led to permanent drug withdrawal in only 7.1% (4/56) of patients, with dose reductions (39.3%) and interruptions (31.6%). In efficacy population (N=54), ORR was 31.5% (17/54), with rates of 28.1% (9/32) in 4.2 mg/kg group and 36.4% (8/22) in 4.8 mg/kg group, including 1 complete response in 4.2 mg/kg group, and DCR was 87.0% (47/54). Median PFS was 7.5 months (mo) (95% CI: 5.49, 8.38) and was consistent across dose groups (4.2 mg/kg: 7.4 mo; 4.8 mg/kg: 7.7 mo). Median OS was not reached, and the 12-mo OS rate was 66.4% (95% CI: 45.01, 81.00). Notably, in EGFR mAb-naive patients receiving ≥2nd line therapy, the ORR was 42.9% (6/14) for the 4.2 mg/kg dose and 50.0% (5/10) for the 4.8 mg/kg dose. The relationship between efficacy and biomarkers (Epstein-Barr virus status, EGFR expression level and so on) will be reported in future conference. Conclusions: SYS6010 demonstrated encouraging antitumor activity and manageable safety profile in advanced NPC patients, supporting further pivotal clinical development. Citation Format: Haiqiang Mai, Linquan Tang, Xicheng Wang, Shaojun Lin, Lei Liu, Runxiang Yang, Song Qu, Kunyu Yang, Yi Gong, Feng Liu, Yanhong Shang, Jinsheng Wu, Shaozhang Zhou, Mengxia Li, Jinheng Hao, Xiugao Yang, Xuechao Wan, Changming Xie, Ying Chen, Jiaxing Hao, Jing Yuan, Kai Zou, Chao Liu, Shun Lu. A first-in-human study result of a novel EGFR-targeted antibody drug conjugate (ADC) in patients with advanced nasopharyngeal carcinoma (NPC) (SYS6010-001-NPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT036.

Programmed cell death 1 protein (PD-1) or programmed cell death 1 ligand 1 inhibitors plus chemotherapy is the current standard first-line treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the long-term survival benefits at the 5-year benchmark remain uncertain. To determine whether adding camrelizumab to chemotherapy significantly improved 5-year overall survival (OS) as first-line treatment for RM-NPC, compared with chemotherapy alone. The CAPTAIN-1st trial was a randomized, double-blind, phase 3 trial conducted at 28 hospitals in China. Between November 13, 2018, and November 29, 2019, patients with treatment-naive RM-NPC were enrolled. This secondary analysis of the CAPTAIN-1st trial was prespecified. Data analysis was conducted on June 1, 2025. Patients were randomized (1:1) to receive camrelizumab or placebo in combination with gemcitabine and cisplatin for 4 to 6 cycles, followed by maintenance therapy with camrelizumab or placebo until disease progression, unacceptable toxic effects, or completion of 2 years of treatment. The primary end point, progression-free survival per independent review committee, has been reported previously. Herein, the secondary end point of OS is reported as prespecified in the protocol. Among 263 randomized patients (134 in randomized to camrelizumab, 129 to placebo), baseline characteristics were generally balanced between groups, except for age. The mean (SD) age was 49 (11.25) years, and 218 patients (82.9%) were male individuals, 45 (17.1%) were female individuals. With a median survival follow-up of 63.5 (95% CI, 61.2-64.6) months for the camrelizumab group and 63.0 (95% CI, 60.8-64.6) months for the placebo group, 85 (63.4%) and 95 (73.6%) deaths occurred, respectively. Median OS was 34.5 months (95% CI, 29.4-45.7) with camrelizumab vs 26.6 months (95% CI, 19.8-33.5) with placebo (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99; 2-sided P = .047). After adjusting for age imbalance, the HR was 0.65 (95% CI, 0.48-0.89; P = .01). The 5-year OS rates were 37.8% vs 24.2%, reflecting an absolute difference of 13.6% (95% CI, 2.4%-24.8%; P = .02) in favor of camrelizumab. The OS benefits were generally consistent across subgroups. In the camrelizumab group, patients who achieved rapid clearance of Epstein-Barr virus (EBV) DNA had significantly longer OS compared with those without EBV DNA clearance (HR, 0.32; 95% CI, 0.18-0.58; P < .001). In this secondary analysis of a randomized clinical trial, the addition of camrelizumab to chemotherapy produced statistically significant and clinically meaningful 5-year OS benefits compared with chemotherapy alone in the first-line treatment of RM-NPC. These findings provided the first 5-year evidence supporting the benefit of PD-1–based chemoimmunotherapy in this setting. ClinicalTrials.gov Identifier: NCT03707509

BACKGROUND:Circulating cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) is a promising epigenetic biomarker in cancer. Its prognostic role in nasopharyngeal carcinoma (NPC), however, remains unclear. METHODS:Genome-wide 5hmC profiling was conducted using 5hmC-Seal sequencing on cfDNA from 174 newly diagnosed NPC patients. Patients were randomly assigned to training (n = 105) and test (n = 69) sets. Differential analysis was performed by survival outcome, EBV status, and tumor stage. The primary endpoint was overall survival (OS); the secondary endpoint was event-free survival (EFS). A prognostic score based on a seven-gene 5hmC signature was developed using LASSO-Cox regression in the training set and validated in the test cohort. A nomogram integrating the 5hmC score, tumor stage, and EBV status was constructed. Model performance was assessed via Kaplan-Meier survival analysis, time-dependent ROC curves, calibration plots, and decision curve analysis (DCA). RESULTS:Marked 5hmC differences were detected between survivors and non-survivors. The 5hmC score stratified OS with AUCs of 0.83 (3-year) and 0.87 (5-year) in the training set and 0.78 (3-year) and 0.80 (5-year) in the test set, and remained predictive across EBV and stage subgroups. The integrated nomogram demonstrated robust calibration and offered the greatest net clinical benefit in DCA, with a 5-year C-index of 0.796. CONCLUSIONS:cfDNA 5hmC profiling enables noninvasive prognostic risk stratification in NPC. The proposed model may support personalized treatment planning and long-term management.

BACKGROUND:Current international guidelines mandate routine skull base coverage for the nodal clinical target volume (CTVn) in nasopharyngeal carcinoma (NPC), however, this universal approach may lead to unnecessary radiation exposure. This study aimed to validate the feasibility of our optimized CTVn delineation strategy that challenges this conventional paradigm. METHODS:This retrospective study included non-metastatic NPC patients who received radical IMRT at our institution between 2014 and 2018. We employed an individualized CTVn delineation strategy: the cranial border was primarily set at the caudal edge of the lateral process of atlas (C1), with a minimal 1-cm margin above involved nodes. Skull base coverage was selectively applied only when level IIb nodes extended above the C1 landmark. RESULTS:A total of 627 patients were included. Applying this risk-adapted strategy, only 80 patients (12.8%) required skull base coverage due to nodal extension beyond C1 (Group A), while the majority (547 patients, 87.2%) were successfully treated with the C1-based border (Group B). With a median follow-up of 73 months, the 5-year regional control reached 97.2%. Notably, only one recurrence occurred in the region between the C1 border and skull base, which was an in-situ GTVn failure in Group A. Dosimetric analysis confirmed significant parotid gland sparing with this selective approach. CONCLUSION:Our optimized CTVn delineation strategy demonstrates both safe and effective, achieving excellent regional control while substantially reducing radiation exposure. This risk-adapted approach provides a superior therapeutic ratio compared to the universal skull base coverage recommended by current guidelines, offering a practical alternative for precision radiotherapy in NPC.

To establish consensus recommendations and standardized protocols for the clinical assessment and management of radiation-induced hearing loss (RIHL), a common yet potentially serious complication in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, for which effective treatments remain limited. A two-round Delphi survey was conducted with 19 Chinese experts from diverse specialties, including radiation oncology, medical oncology, radiology, and otorhinolaryngology. Utilizing a detailed items questionnaire that addressed diagnosis, prevention, and treatment aspects of RIHL, the panel formulated consensus recommendations. Additionally, the final recommendations were formulated based on the findings of the Delphi survey, in conjunction with evidence appraised using the GRADE system. During radiotherapy planning, the implementation of dose constraints for key auditory structures—namely the tympanic cavity, internal auditory canal and cochlea—was emphasized to preserve auditory function. Diagnostic evaluations were advised to comprise comprehensive assessments such as pure tone and speech audiometry, tympanometry, otoacoustic emissions, auditory evoked potentials, otoscopic examination, and CT/MRI imaging, with classification guided by the 2021 WHO grading criteria for type and severity. Therapeutic approaches should be customized based on disease stage and underlying etiology, incorporating strategies like Eustachian tube function restoration, management of otitis media with effusion, and tailored auditory rehabilitation. However, consensus on the applicability of most interventions was limited due to insufficient or conflicting evidence, underscoring the need for further research. This consensus provides a structured framework to standardize clinical assessment and management of RIHL, while laying a groundwork for future studies focused on optimizing patient outcomes.

Objectives To ascertain the prognostic value of grade 2 imaging extranodal extension (G2 iENE), also called matted nodes (MNs), in nasopharyngeal carcinoma (NPC) based on the 9th-version of AJCC/UICC TNM staging system (TNM-9) and the Head and Neck Cancer International Group (HNCIG)’s criteria for diagnosing iENE, and propose future refinement of the TNM-9 N category. Materials and methods Non-metastatic NPC patients treated between 2017 and 2018 were screened. MRI data were reviewed for re-staging according to the TNM-9 and iENE status per the HNCIG-criteria. Five-year overall survival (OS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) were analyzed. Recursive partitioning analysis (RPA) based on the ordinal N category of TNM-9 and the G2 iENE status were performed to propose a refined N category. Results Totally, 1334 patients were included, with 462 (34.6%) patients presenting with G2 iENE at baseline. Besides N Category, G2 iENE also showed independent prognostic value for OS (HR: 1.453, P = 0.042), PFS (HR: 1.293, P = 0.057) and DMFS (HR: 1.363, P = 0.042). The RPA-N category was then derived: RPA-N0 (N0), RPA-N1 (N1 without G2 iENE), RPA-N2 (N1 with G2 iENE and N2) and RPA-N3 (N3). The RPA-N classification had a lower Akaike information criterion (AIC) and higher C-index for all endpoints, and performed better in hazard consistency, hazard discrimination, sample size balance and outcome prediction when compared to TNM-9. Conclusions G2 iENE, based on the HNCIG-criteria, constitute an independent adverse prognostic factor for NPC based on the TNM-9. The RPA-N category, which integrated N category of TNM-9 and G2 iENE, demonstrated better performance than N category in TNM-9, further validation in multicenter cohorts is warranted.

N3 nasopharyngeal carcinoma (NPC) continues to demonstrate high distant metastasis rates despite aggressive treatment. This phase II trial evaluated schedule-modified oral maintenance chemotherapy with capecitabine or S-1 following definitive chemoradiotherapy in this high-risk population. In this multicenter, single-arm study, patients with non-metastatic N3 NPC received induction chemotherapy (gemcitabine/nedaplatin) followed by concurrent definitive chemoradiotherapy (nedaplatin). Within one month post-radiotherapy, patients initiated 12 cycles of oral maintenance therapy (capecitabine 1250 mg/m² twice daily or S-1 body surface area based dosing, days 1–14, every 28 days). Primary endpoint was 2-year progression-free survival (PFS). Among 115 enrolled patients, after 46.2 months median follow-up, 2-year PFS reached 92.0

Elderly patients are underrepresented in clinical studies supporting platinum-based concurrent chemoradiotherapy (CCRT) as the standard therapy (ST) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Many such patients in real-world settings cannot tolerate CCRT and instead receive individualized therapy (IT). This study aimed to compare the efficacy and safety of ST versus IT in elderly NPC patients. A retrospective analysis was conducted on 393 elderly (≥ 65 years) LA-NPC patients from two centers in China between January 2013 and December 2020. Patients were categorized into ST (platinum-based CCRT with or without induction/adjuvant therapy) or IT (radiotherapy alone, or concurrent radiotherapy with non-chemotherapy agents, with or without induction/adjuvant therapy) groups. Propensity score matching (PSM) generated 141 patient pairs. Survival outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards models. Toxicities were compared with chi-square or Fisher’s exact tests. In the PSM cohort, no significant differences were observed between the ST and IT groups in overall survival, cancer-specific survival, progression-free survival, locoregional relapse-free survival, and distant metastasis-free survival (all P > 0.05). Multivariable analysis confirmed that treatment group (ST vs. IT) was not a significant predictor for any survival endpoint. In exploratory stratified analysis, radiotherapy alone was associated with inferior OS, CSS, and PFS, whereas radiotherapy combined with systemic therapy showed survival outcomes similar to those of ST. Additionally, compared with the ST group, the IT group had significantly lower rates of grade 3 or higher hematologic toxicities, including leukopenia (8.5

To assess the prognostic utility of the M1 category in version nine of the AJCC/UICC TNM staging system (TNM-9) in metachronous metastatic nasopharyngeal carcinoma (mmNPC) and to develop a refined M1 classification for improved risk stratification. Patients with newly diagnosed mmNPC (2015–2024) were restaged per TNM-9 M1 criteria. Independent prognostic factors from multivariate Cox analysis were integrated using recursive partitioning analysis (RPA) to derive an RPA-based M1 classification (RPA-M1). Model performance was evaluated using Harrell’s C-index, time-dependent area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC), calibration, and decision curve analysis (DCA). Totally, 218 patients were included, 111 (50.9

Accurate diagnosis of cervical lymph node (CLN) metastasis is essential for staging nasopharyngeal carcinoma (NPC). Conventional size-based MRI criteria exhibit high specificity but low sensitivity, leading to underdiagnosis. This study pathologically validated the Node Reporting and Data System (Node-RADS) vs size criteria for diagnosing CLN metastasis in NPC. Patients with histologically confirmed NPC who underwent ultrasound-guided fine-needle aspiration cytology (FNAC) of CLNs between March 2014 and April 2023 were included. All patients had a pretreatment head and neck MRI within 7 days before FNAC. Two blinded radiologists independently assigned Node-RADS scores (1–5) to each biopsied node according to the standardized workflow. Diagnostic performance was compared against conventional size-based criteria using receiver operating characteristic (ROC) analysis. A total of 273 patients (202 men; median age, 51.0 years [IQR: 37–65]) with 335 CLNs were included, of which 150 (44.8

BACKGROUND:In the PLATINUM (ClinicalTrials.gov: NCT03984357) trial, nivolumab plus chemoradiotherapy sparing concurrent cisplatin demonstrated efficacy and safety in nasopharyngeal carcinoma (NPC). Herein, patient-reported outcomes (PROs) on quality of life (QoL), tolerability, and social reintegration are reported. METHODS:Patients with T4N1M0/T1-4N2-3M0 NPC were assessed for general and head-and-neck-specific QoL (using the European Organization for Research and Treatment of Cancer and the Functional Assessment of Cancer Therapy) and tolerability (using the PRO-specific Common Terminology Criteria for Adverse Events). Analyses included change over time, effect of the treatment phase on QoL, time-to-event analysis, and a comparison of PROs and clinician-reported outcomes (CROs) in toxicity. FINDINGS:Among 152 patients, 44.1% achieved social reintegration, and 51.3% were satisfied with their current life. Radiotherapy dominated QoL deterioration rather than induction chemotherapy (pooled mean difference, -18.51; 95% confidence interval [CI], -29.50 to -7.52; p = 0.001), and its removal dominated QoL improvement rather than that of nivolumab (pooled mean difference, -7.62; 95% CI, -10.05 to -5.19; p < 0.001). Patients without social reintegration had greater deterioration in speech (hazard ratio [HR], 0.60; 95% CI, 0.38 to 0.94; p = 0.027) and swallowing functions (HR, 0.59; 95% CI, 0.39 to 0.89; p = 0.011). Under-reporting of decreased appetite severity by CROs vs. by PROs in all three treatment phases was associated with poorer social reintegration (p = 0.002) and reduced failure-free survival (3 years, 86.1% vs. 95.0%; p = 0.021). CONCLUSIONS:Social reintegration is a practical composite indicator of favorable PROs in NPC. Interventions targeting speech, swallowing, and decreased appetite might promote better recovery. FUNDING:This study was funded by the Academician Workstation of Jun Ma (YSGZZ2024001), the Specific Research Fund of the Innovation Platform for Academicians of Hainan Province (YSPTZX202501), the National Natural Science Foundation of China (82573549, 82172870), the Guangdong Special Support Program for Young Top Talents (TZ09B0046), and the Guangzhou Science and Technology Program (2023A04J1786).

Severe toxicities caused by concurrent cisplatin are a critical problem in nasopharyngeal carcinoma (NPC) treatment. In this phase 2 multicenter PLATINUM trial (NCT03984357), we recruited 152 NPC patients who received 12-cycle nivolumab plus induction chemotherapy and radiotherapy without concurrent cisplatin. After a median follow-up of 43 months, the 3-year failure-free survival (FFS) was 88.5% (95% confidence interval [CI], 83.4%-93.8%) and the 3-year overall survival was 97.9%. An early clearance of Epstein-Barr virus (EBV) DNA after induction-phase treatment was associated with FFS benefit. Sixty (40.2%) and eight (5.2%) patients had acute and late grade 3-4 adverse events (AEs), respectively. Most patients had good tolerance to AE-associated frequency (68.0%-96.7%), severity (56.0%-98.6%), and interference (58.0%-98.0%); 86.7%-100.0% of quality-of-life domains showed either no clinically meaningful deterioration or a rapid recovery. Nivolumab plus induction chemotherapy and radiotherapy demonstrated efficacious anti-tumor activity, low toxicity, and favorable tolerability and quality-of-life for NPC patients.

Importance Induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) has been a standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but with high acute toxic effects in CCRT phase. Whether CCRT can be safely replaced by radiation therapy with adjuvant chemotherapy (AC) is unknown. Objective To assess if sequential chemoradiotherapy (SCRT; IC, followed by radiotherapy alone, followed by AC) is noninferior to IC plus CCRT for LA-NPC in terms of efficacy, with less acute toxic effects. Design, Setting, and Participants This multicenter, open-label, phase 3 noninferiority randomized clinical trial was conducted from January 2018 to September 2021 in 6 centers in China. Patients aged 18 to 65 years with newly diagnosed stage III/IVA NPC were enrolled. The data cutoff date was June 30, 2024. Interventions Patients were randomly assigned 1:1 to receive 2 cycles of IC with a gemcitabine and cisplatin (GP) regimen (gemcitabine, 1000 mg/m(2), on days 1 and 8 plus cisplatin, 25 mg/m(2), on days 1, 2, and 3, repeated every 3 weeks) plus radiotherapy alone, followed by 2 cycles of AC with a GP regimen (SCRT group) or 2 cycles IC (GP regimen) followed by radiotherapy concurrent with weekly cisplatin, 30 mg/m(2) (IC plus CCRT group). Main Outcomes and Measures The primary end points were 3-year failure-free survival (FFS) with a noninferiority margin of 10% (hazard ratio [HR] less than 1.6) and the incidence of grade 3 or higher acute mucositis during radiotherapy. The secondary end points included overall survival, locoregional FFS, distant FFS, response rate, and toxic effects. Results Of 420 enrolled patients, 107 (25.5%) were women, and the median (IQR) age was 48 (41-54) years. A total of 210 patients were randomized to the SCRT group and 210 to the IC plus CCRT group. The median (IQR) follow-up time was 50 (40-61) months. In the intention-to-treat population, 3-year FFS was 83.7% (95% CI, 78.6-88.8) vs 79.5% (95% CI, 74.0-85.0) in the SCRT group vs the IC plus CCRT group, respectively (HR, 0.77; 95% CI, 0.50-1.19; P = .24), with the upper bound of the 95% CI less than 1.6. Identical outcomes were reported in the per-protocol population. Compared with the IC plus CCRT group, the SCRT group had significantly lower incidences of grade 3 or higher acute nonhematological toxic effects (acute mucositis, 61 [29.0%] vs 88 [41.9%], respectively; P < .001; nausea, 20 [9.5%] vs 38[18.1%], respectively; P = .01; vomiting, 8 [3.8%] vs 20 [9.5%], respectively; P = .02). No differences were observed in late toxic effects. Conclusions and Relevance Results from this noninferiority randomized clinical trial suggest that SCRT is noninferior to IC plus CCRT in terms of 3-year FFS in LA-NPC, with less severe acute nonhematological toxic effects.

The Chinese Society for Therapeutic Radiology Oncology, the Chinese Anti-Cancer Association, the Chinese Society of Clinical Oncology, Head and Neck Cancer International Group, the European Society for Radiotherapy and Oncology, and the American Society for Radiation Oncology jointly developed evidence-based guidelines and a contouring atlas for primary target volume delineation for radiotherapy in nasopharyngeal carcinoma. The guidelines systematically address three crucial challenges: margin design of clinical target volumes; target volume delineation after induction chemotherapy; and low-risk clinical target volume delineation based on local stepwise extension patterns. Based on a comprehensive systematic review and critical appraisal by an international multidisciplinary panel of 50 nasopharyngeal carcinoma specialists from 17 countries and regions, these guidelines are in keeping with advances in nasopharyngeal carcinoma diagnosis and treatment, embodying contemporary treatment concepts, and elaborating on the differences in practice. These guidelines aim to support global clinical practice in radiotherapy target volume delineation, substantially enhancing homogeneity and reducing variability in nasopharyngeal carcinoma target delineation.

OBJECTIVE:To evaluate the applicability of the M1 category of the version-nine of AJCC/UICC TNM staging system (TNM-9) for M1 nasopharyngeal carcinoma (M1-NPC) in immunotherapy era and propose potential refinements. METHODS:M1-NPC patients who underwent palliative chemotherapy and immune checkpoint inhibitors (ICIs) between January 2019 and June 2023 across five institutions were included and re-staged according to TNM-9. Overall survival (OS) and Progression-free survival (PFS) were analyzed. A recursive partitioning analysis (RPA) model was employed to derive a new RPA-M1 category. RESULTS:Among the 472 patients included, 219 were M1a and 253 were M1b. With a median follow-up time of 27 months, the M1a subgroup exhibited significantly higher 2-year OS (90.4 % vs. 73.7 %) and PFS (69.2 % vs. 40.6 %) than M1b subgroup (all P<0.001), which was further confirmed by multivariate analysis (MVA). Additionally, number of involved organs was found to be another independent predictor. New RPA-M1 category were then developed: RPA-M1a (≤3 metastatic lesions and confined to one single organ), RPA-M1b (≤3 metastatic lesions but involving multiple organs or >3 lesions and confined to one single organ), and RPA-M1c (patients with >3 metastatic lesions and involving multiple organs), with 2-year OS rates of 91.5 %, 81.4 %, and 69.8 %, respectively (P < 0.05) and PFS rates of 72.4 %, 54.3 % and 29.1 %, respectively (P < 0.005). Compared to the M1 Category in TNM-9, RPA-M1 category had a lower Akaike Information Criterion (AIC) and a higher concordance index (C-index) for OS and PFS. CONCLUSION:The M1 category in the TNM-9 is applicable in the immunotherapy era. The RPA-M1 category offers improve depiction of survival outcomes compared to TNM-9, allowing for more refined stratification of patient outcomes and individulized decision-tailoring.

Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.