RAIRI-Guided Adjuvant Therapy Benefit in Nasopharyngeal Cancer

A Prospective, Multicenter, Real-World Observational Study to Evaluate RAIRI-Guided Risk Stratification for Identifying Adjuvant Therapy Benefit After Standard Chemoradiotherapy in Nasopharyngeal Carcinoma

This prospective, multicenter, real-world observational study aims to evaluate whether a response-adaptive individualized risk index, the RAIRI model, can identify patients with non-metastatic nasopharyngeal carcinoma who may or may not benefit from adjuvant therapy after standard chemoradiotherapy. Patients will receive standard treatment according to routine clinical practice. After completion of chemoradiotherapy and assessment at approximately 1 month after radiotherapy, longitudinal multimodal response data, including plasma cfEBV DNA dynamics and MRI-based tumor response, will be incorporated into the RAIRI model to estimate the predicted 5-year progression-free survival. Patients will be stratified into a RAIRI low-risk group, defined as predicted 5-year PFS ≥85%, and a RAIRI high-risk group, defined as predicted 5-year PFS <85%.

Within each RAIRI risk stratum, outcomes will be compared between patients who receive adjuvant systemic therapy, mainly PD-1 inhibitor-based adjuvant immunotherapy, and those who undergo routine surveillance without adjuvant systemic therapy. The primary endpoint is 3-year failure-free survival. Secondary endpoints include overall survival, locoregional relapse-free survival, distant metastasis-free survival, complete response rate after chemoradiotherapy, distribution of RAIRI risk groups, adverse events, late toxicities, and longitudinal health-related quality of life.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Cancinoma (NPC)
• Intervention / Treatment: Drug: PD-1 inhibitor; Drug: Capecitabine

Detailed Description

Nasopharyngeal carcinoma is commonly treated with intensity-modulated radiotherapy combined with platinum-based chemotherapy, with or without induction therapy. However, the optimal selection of patients for adjuvant systemic therapy after definitive chemoradiotherapy remains uncertain in routine clinical practice. Some patients may have a sufficiently favorable prognosis after chemoradiotherapy and may be safely observed, whereas others may remain at high risk of recurrence or metastasis and may benefit from treatment intensification.

This study will prospectively collect real-world clinical, imaging, laboratory, treatment exposure, toxicity, and survival data from patients with non-metastatic nasopharyngeal carcinoma treated at multiple tertiary cancer centers. The RAIRI dynamic prognostic model will be applied after completion of standard chemoradiotherapy, using baseline clinical variables and longitudinal response indicators including cfEBV DNA kinetics and MRI-based tumor regression. The model will generate an individualized predicted 5-year PFS probability. Patients with predicted 5-year PFS ≥85% will be classified as RAIRI low-risk, whereas those with predicted 5-year PFS <85% will be classified as RAIRI high-risk.

Because this is an observational study, adjuvant treatment will not be assigned by the study protocol. After chemoradiotherapy, patients may either receive adjuvant systemic therapy, mainly PD-1 monoclonal antibody therapy, or undergo routine surveillance, according to treating physician judgment and patient preference. The main analysis will compare 3-year failure-free survival between adjuvant therapy and routine surveillance within each RAIRI risk group. Propensity score matching, multivariable Cox proportional hazards models, and sensitivity analyses will be used to adjust for baseline and treatment-related confounders.

• Study Type: Observational
• Enrollment (Estimated): 900

Contacts and Locations

• Study Contact: Name: Yang Liu; Phone Number: +86 18801342502; Email: 530669421@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Contact: Junlin Yi; Phone Number: +86-010-87788792; Email: yijunlin1969@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 18 to 75 years with histologically or cytologically confirmed EBER-positive, non-keratinizing, non-metastatic nasopharyngeal carcinoma who are scheduled to receive standard chemoradiotherapy with or without induction therapy in routine clinical practice. Eligible patients must have pretreatment contrast-enhanced MRI of the nasopharynx and neck, pretreatment quantitative plasma cfEBV DNA measurement, ECOG performance status of 0-1, adequate baseline organ function, and reliable follow-up conditions. After completion of chemoradiotherapy, patients may either receive adjuvant systemic therapy, mainly PD-1 inhibitor-based immunotherapy, or undergo routine surveillance according to treating physician judgment and patient preference.

Description

Inclusion Criteria

1. Age 18 to 75 years, male or female.
2. Histologically or cytologically confirmed EBER-positive non-keratinizing nasopharyngeal carcinoma, including differentiated or undifferentiated subtype.
3. Non-metastatic nasopharyngeal carcinoma confirmed by multimodal staging, corresponding to stage I-III according to the AJCC 9th edition staging system, or stage I-IVA according to the AJCC 8th edition staging system.
4. Eastern Cooperative Oncology Group performance status of 0-1.
5. Availability of complete pretreatment high-quality contrast-enhanced MRI of the nasopharynx and neck, including functional MRI sequences such as diffusion-weighted imaging, and at least one measurable tumor lesion according to RECIST version 1.1.
6. Availability of pretreatment quantitative plasma cfEBV DNA measurement.
7. Adequate baseline laboratory function, defined as hemoglobin >120 g/L, white blood cell count ≥4 × 10⁹/L, platelet count ≥100 × 10⁹/L, and liver and renal function parameters, including ALT, AST, total bilirubin, and serum creatinine, within 1.25 times the upper limit of normal; no severe clinically significant hearing impairment.
8. Ability to fully understand the nature and follow-up procedures of this observational study, and voluntary provision of written informed consent by the patient or the patient's legally authorized representative.
9. Agreement to allow the research team to use the patient's clinical data, routine diagnostic imaging data, and residual biospecimens, such as peripheral blood samples and pathological slides, for scientific research analyses.
10. Adequate major organ function, except for local compression or functional impairment directly attributable to nasopharyngeal carcinoma.
11. Good expected compliance with follow-up and reliable communication conditions, allowing completion of long-term survival follow-up.

Exclusion Criteria

1. Absence of pretreatment plasma cfEBV DNA measurement, or missing key baseline clinical variables required for RAIRI model calculation, such as age, AJCC stage, lactate dehydrogenase level, or central liquefactive necrosis status.
2. Presence of distant metastatic disease, M1.
3. History of previous or concurrent malignancy, except for non-melanoma skin cancer or cervical carcinoma in situ that has been successfully treated and has remained disease-free for more than 5 years.
4. Pregnant or breastfeeding women, or participants of reproductive potential who are unwilling to use effective contraception during the study observation period.
5. Current participation in another interventional clinical trial involving an investigational drug or medical device.
6. Severe or uncontrolled comorbidities, including myocardial infarction within the past 6 months, severe unstable arrhythmia, severe cerebrovascular accident, active gastrointestinal ulcer, uncontrolled psychiatric illness, uncontrolled diabetes mellitus, active autoimmune disease, long-term systemic immunosuppressive therapy, active severe infection requiring systemic anti-infective treatment, known history of human immunodeficiency virus infection, hepatitis B surface antigen positivity with HBV DNA >1 × 10³ copies/mL or >200 IU/mL, or hepatitis C virus antibody positivity with abnormal viral load.
7. Any personal, social, geographic, or psychiatric condition that, in the investigator's judgment, would make it impossible for the participant to complete regular follow-up visits and assessments.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Routine Surveillance Group; Patients who do not receive adjuvant systemic therapy after completion of standard chemoradiotherapy and enter routine post-treatment surveillance according to standard clinical practice. Treatment decisions are made by treating physicians and patients, not assigned by the study protocol.
Adjuvant Therapy Group; Patients who receive adjuvant systemic therapy after completion of standard chemoradiotherapy in routine clinical practice, mainly PD-1 inhibitor-based adjuvant immunotherapy. The specific agent, dose, duration, treatment interruption, and discontinuation are determined by treating physicians and prospectively recorded.	Drug: PD-1 inhibitor; Administered intravenously every 3 weeks for up to 12 cycles as adjuvant therapy.; Drug: Capecitabine; Metronomic capecitabine administered orally at a dose of 650 mg/m2 twice daily for one year as adjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Failure-Free Survival (FFS)	FFS is defined as the time from randomization to locoregional recurrence, distant metastasis, or death from any cause.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-year Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to 3 years
3-year Locoregional Relapse-Free Survival (LRRFS)	LRRFS is defined as the time from randomization to the first locoregional recurrence or death from any cause.	Up to 3 years
3-year Distant Metastasis-Free Survival (DMFS)	DMFS is defined as the time from randomization to the first distant metastasis or death from any cause.	Up to 3 years
Incidence of Acute and Late Toxicities and Adverse Events	Adverse events will be evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	From the start of treatment up to 3 years
Quality of Life (QoL) and its changes	Quality of life and its changes will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) version 3.0.	From baseline up to 36 months after randomization
Complete Response (CR) Rate after Chemoradiotherapy	Proportion of patients achieving a complete response after the completion of concurrent chemoradiotherapy.	1 month after the completion of radiotherapy

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Collaborators: Xiangya Hospital of Central South University; Fujian Cancer Hospital; Hunan Cancer Hospital; Peking University Cancer Hospital & Institute; Cancer Hospital of Guizhou Province; The First Affiliated Hospital of Air Force Medicial University; Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center; Sun Yat-Sen University Cancer Center
• Investigators: Principal Investigator: Junlin Yi, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: May 25, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Risk Stratification; Adjuvant Therapy; RAIRI; EBV-DNA; response-adapted
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 26/007-5732

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Data will be available beginning 6 months following article publication.
• IPD Sharing Access Criteria: Data will be shared with researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose. Proposals should be directed to the corresponding author's email.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No