This prospective, multicenter, real-world observational study aims to evaluate whether a response-adapted 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.
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
900
Administered intravenously every 3 weeks for up to 12 cycles as adjuvant therapy.
Metronomic capecitabine administered orally at a dose of 650 mg/m2 twice daily for one year as adjuvant therapy.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITING3-year Failure-Free Survival (FFS)
FFS is defined as the time from enrollment to locoregional recurrence, distant metastasis, or death from any cause.
Time frame: Up to 3 years
3-year Overall Survival (OS)
OS is defined as the time from enrollment to death from any cause.
Time frame: Up to 3 years
3-year Locoregional Relapse-Free Survival (LRRFS)
LRRFS is defined as the time from enrollment to the first locoregional recurrence or death from any cause.
Time frame: Up to 3 years
3-year Distant Metastasis-Free Survival (DMFS)
DMFS is defined as the time from enrollment to the first distant metastasis or death from any cause.
Time frame: Up to 3 years
Complete Response (CR) Rate after Chemoradiotherapy
Proportion of patients achieving a complete response after the completion of concurrent chemoradiotherapy.
Time frame: 1 month after the completion of radiotherapy
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.
Time frame: From the start of treatment up to 3 years
Longitudinal Changes in EORTC QLQ-C30 Scores
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, version 3.0. All scale and single-item scores are linearly transformed to a 0 to 100 scale. For the global health status/quality-of-life scale and functional scales, higher scores indicate better global health status, quality of life, or functioning. For symptom scales and single-item symptom measures, higher scores indicate worse symptoms or greater problems.
Time frame: From baseline to 36 months after enrollment
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