Validation of the 9th AJCC Staging System for NPC in Non-High-Incidence Areas in China

NCT07088861 | Active Not Recruiting DMC

• 1 other identifier: KM-2025-123
• Study Type: observational
• Target: 1,401
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Nasopharyngeal carcinoma (NPC) is a malignancy with marked geographic variation, with over 80% of global cases found in Southeast and East Asia. However, the characteristics of NPC in non-high-incidence areas in China (such as Jiangsu, Zhejiang, and Anhui provinces) remain understudied. These regions show different EBV prevalence, environmental exposures, and socioeconomic factors compared to endemic regions, which may affect tumor biology and treatment response. The 9th edition AJCC/UICC TNM staging system (TNM-9) introduces critical revisions to improve risk stratification-particularly in N classification-based on new imaging and biological insights like radiologic extranodal extension (rENE). However, its applicability to non-high-incidence populations remains unclear and requires validation. Objectives: To validate the prognostic performance of TNM-9 compared to TNM-8 in non-high-incidence NPC populations, assessing survival outcomes (OS, PFS, DMFS, LRFS) and model performance (C-index, AUC, etc.). To explore subtypes among locally advanced NPC (LA-NPC) under TNM-9 for potential treatment intensification or de-escalation strategies. To assess the clinical significance of ENE among N3 patients and its impact on survival and treatment response. To develop risk models based on anatomic features of advanced nodal involvement to enhance personalized treatment planning. Design and Methods: Study Type: Multicenter retrospective cohort study. Sites: Tertiary cancer centers in Jiangsu, Zhejiang, and Anhui. Sample Size: Approximately 1,401 patients diagnosed between 2011 and 2023. Inclusion Criteria: Adults aged 18-75 with newly diagnosed, untreated NPC from non-high-incidence regions who underwent complete MRI and standard chemoradiotherapy. Exclusion Criteria: Prior treatment, severe comorbidities, pregnancy, or incomplete data. Treatment: Patients received standard radiotherapy-based treatment according to CSCO guidelines, including IMRT with or without induction/adjuvant chemotherapy or targeted/immunotherapy. Endpoints: Primary: Overall Survival (OS) Secondary: Progression-Free Survival (PFS), Distant Metastasis-Free Survival (DMFS), and Local Recurrence-Free Survival (LRFS) Model Metrics: Harrell's C-index, time-dependent ROC, Brier score Statistical Analysis: Kaplan-Meier survival curves, log-rank tests, univariable and multivariable Cox regression. Prognostic models compared via performance metrics. Bootstrap used for internal validation. Subgroup analyses explore survival differences under TNM-9 stratification. Safety Evaluation: Though retrospective, adverse events are extracted from clinical records, including grade ≥3 toxicities from radiotherapy, chemotherapy, and immunotherapy. Particular attention is given to immune-related adverse events (irAEs) and treatment discontinuations. Ethics and Data Handling: The study complies with the Declaration of Helsinki. No experimental interventions are involved. All data are anonymized and securely stored; informed consent is obtained as per GCP guidelines. Significance: This study addresses the gap in NPC staging validation in non-high-incidence populations. It aims to confirm the utility of TNM-9 in real-world Chinese cohorts outside high-incidence areas and explore refined treatment strategies for LA-NPC. The findings could impact staging policy, risk stratification, and clinical decision-making, supporting more personalized NPC management across diverse regions.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

Nasopharyngeal carcinoma; The 9th Edition AJCC/UICC Staging System; long-term follow-up; Multicentre

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time from initiation of treatment to death from any cause or the date of last follow-up.

  10 years

Secondary Outcomes (3)

• Progression-Free Survival

  10 year

• Locoregional Recurrence-Free Survival

  10 year

• Distant Metastasis-Free Survival

  10 year

Study Arms (3)

Overall Cohort

All eligible patients from three centers in Jiangsu, Zhejiang, and Anhui provinces. Used for overall staging validation and prognostic analysis.

Internal Validation Cohort

Patients from Jiangsu Cancer Hospital. Used for model training and internal validation.

External Validation Cohort

Patients from Zhejiang Cancer Hospital and Anhui Cancer Hospital. Used for external validation of staging performance.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 to 75 years, any sex, newly diagnosed with histologically confirmed nasopharyngeal carcinoma (NPC) from non-high-incidence areas in China (Jiangsu, Zhejiang, Anhui). All patients were treatment-naïve, completed high-quality MRI of the nasopharynx and neck, and received standard radiotherapy-based treatment. Eligible patients had adequate organ function, ECOG 0-1, Karnofsky score ≥70, and expected survival \>3 months. Exclusion criteria included prior treatment (radiotherapy, chemotherapy, or surgery), severe comorbidities, uncontrolled infections, active autoimmune diseases needing immunosuppression, pregnancy or lactation, and incomplete or non-standard radiotherapy data.

You may qualify if:

• Age 18-75 years old and gender
• Long-term residence in a non-high prevalence area for nasopharyngeal cancer
• Histologically confirmed primary nasopharyngeal cancer (without any treatment)
• Completed MRI examination of nasopharynx and neck with image quality meeting the needs of imaging analysis
• All receiving a standard comprehensive treatment plan with radiotherapy as the core
• Adequate bone marrow, liver, and kidney function (meeting laboratory index thresholds)
• ECOG 0-1, KPS ≥ 70 points, and life expectancy \> 3 months
• No previous history of immune disorders

You may not qualify if:

• Received radiotherapy, chemotherapy, or surgery to the primary site or lymph nodes
• Severe underlying disease (heart failure, renal failure, etc.), uncontrolled active infection, active autoimmune disease, or history of autoimmune disease requiring immunosuppressive therapy
• Pregnant or breastfeeding females
• Irregular radiotherapy or missing treatment data

Sponsors & Collaborators

• Lirong Wu: lead

Related Publications (14)

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MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Xia He, Professor, MD

  Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: associate professor, Department of Radiotherapy, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: July 28, 2025
• Study Start: January 26, 2011
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share