Induction Chemotherapy Response-Guided Reduced-Dose Radiotherapy for Nasopharyngeal Carcinoma

Induction Chemotherapy Response-Guided Reduced-Dose Radiotherapy for Nasopharyngeal Carcinoma: A Prospective Single-center Randomized Phase II Study

To evaluate whether the 2-year local failure-free survival (LRFFS) in Cohort 1 patients with AJCC/UICC 8th edition stage IB-II nasopharyngeal carcinoma who achieved EBV-DNA = 0 after induction chemotherapy and had MRI assessment of complete response (CR) or partial response (PR) ≥50% is non-inferior when treated with reduced-dose IMRT (59.4 Gy/27 fractions) compared to standard-dose IMRT (66.0 Gy/30 fractions).

This study focused on patients with AJCC/UICC 9th edition stage IB-II（The participants were required to have no extensive skull base invasion and lymph nodes < 4 cm before treatment）. It aimed to adaptively guide the reduction of radiation dose for nasopharyngeal carcinoma based on the response to induction chemotherapy, thereby minimizing radiation-related toxicity while ensuring local control. Cohort 1 was randomly assigned 1:1 to the 59.4 Gy/27 fractions group and the 66.0 Gy/30 fractions group and compared their LRFFS. The participants were required to have EBV-DNA = 0 and CR or PR > 50% after 2 courses of induction therapy. Those who did not meet the criteria were assigned to Cohort 2 to receive standard-dose radiotherapy combined with concurrent cisplatin to avoid excessive reduction of intensity for potentially high-risk patients.

Inclusion Criteria:

• Age: 18 - 65 years old.
• Pathologically confirmed nasopharyngeal carcinoma, WHO type II or III non-keratinizing cancer.
• AJCC/UICC 9th edition stage IB-II untreated non-metastatic nasopharyngeal carcinoma (T3 requires no extensive cranial base invasion and the invasion volume should be < 22 mL; N1-2 requires baseline lymph nodes < 4 cm).
• Before treatment, plasma EBV-DNA needs to be tested and dynamic monitoring of EBV-DNA can be completed.
• ECOG performance status 0 - 1 points.
• Main organ functions meet the following requirements: neutrophils ≥ 1.5 × 10^9/L, platelets ≥ 100 × 10^9/L, hemoglobin ≥ 90 g/L; ALT/AST ≤ 2.5 × ULN, total bilirubin ≤ 1.5 × ULN; creatinine clearance rate ≥ 60 mL/min.
• Sign a written informed consent form and be willing to complete the treatment, follow-up and quality of life assessment according to the protocol.

Exclusion Criteria:

• Metastasis to T4, N3 or distant sites; AJCC/UICC 9th edition stage III-IV.
• Had received chemotherapy, targeted therapy, or immunotherapy before the diagnosis of nasopharyngeal carcinoma, and had a history of radiotherapy or surgery for head and neck tumors (except for diagnostic biopsies).
• Pregnant or lactating; non-pregnant and non-lactating subjects who do not agree to take effective contraceptive measures.
• Had severe and uncontrollable heart, lung, liver, kidney, neurological or mental diseases, and the investigator judged that they were not suitable for radical treatment or affected compliance.
• Had a history of other malignant tumors within the past 5 years, except for the following situations: cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, breast carcinoma in situ, papillary thyroid carcinoma, etc.
• Could not complete the imaging examinations, EBV-DNA tests, follow-up or quality of life assessment as required by the protocol.