Optimization of Cervical Nodal CTV for Early and Medium Stage NPC

Optimization of Cervical Nodal Clinical Tumor Volume for Early and Medium Stage Nasopharyngeal Carcinoma: a Multicenter Non-inferior Randomized Controlled Phase III Clinical Trial

Current radiotherapy guidelines and consensus statements uniformly recommend elective region irradiation (ERI) as the standard strategy for nasopharyngeal carcinoma (NPC). However, given the scarcity of skip-metastasis, the improved assessment accuracy of nodal involvement, and the striking advancements in chemotherapy for NPC, a one-fits-all delineation scheme for clinical target volumes for the nodal region (CTVn) may not be appropriate anymore, and modifications of the CTVn delineation strategy may be warranted. Involved site irradiation (ISI) covering merely the initially involved nodal site and potential extranodal extension has been confirmed to be as effective as ERI with decreased radiation-related toxicities in some malignancies, but has not yet been investigated in NPC. This study aims to compare the regional control, survival outcomes, radiation-related toxicities, and quality of life (QoL) of ISI with conventional ERI in NPC patients with a limited nodal burden.

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: intensity-modulated radiotherapy (IMRT) with reduced-volume; Drug: Chemotherapy

Detailed Description

ISRT-NPC is a prospective, multicenter, open-label, noninferiority, phase III randomized controlled trial. A total of 488 patients will be randomly assigned in a 1:1 ratio to receive ISI or ERI. Randomization will be stratified by institution and N stage. Generally, in the ISI group, the high-risk CTV1 (dose: 60 Gy) includes a 1-cm expansion of the positive LN as well as the VIIa and the retrostyloid space above the bilateral transverse process of the atlantoaxial spine (C1), regardless of N status. The low-risk CTV2 (Dose: 50 Gy) covers the cervical nodal region with a 3-cm caudal expansion below the transverse process of C1 for N0 disease and a 3-cm expansion below the positive LN for positive LNs (at least covering the level II).

• Study Type: Interventional
• Enrollment (Estimated): 414
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100021
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

1. Age between 18 and 75 years;
2. Karnofsky performance status (KPS) score ≥ 70;
3. Pathologically confirmed World Health Organization (WHO) type II-III NPC;
4. TNM stage I-III (T1-3N0-2M0) according to the 8th American Joint Committee on Cancer / Union for International Cancer Control (AJCC/UICC) staging system with a maximum diameter (MAD) of cervical involved LNs ≤ 3 cm, namely LB-LN;
5. Available baseline nasopharynx and neck computed tomography (CT) or magnetic resonance imaging (MRI) (strongly advocated) data (including functional MRI sequences) and measurable tumor lesions;
6. All procedures for defining the tumor burden completed within 4 weeks of registration;
7. Survival expectancy of at least 6 months;
8. Normal marrow and organ function: hemoglobin ≥ 120 g/L, WBCs ≥ 4 × 109 /L, platelets ≥ 100 × 109 /L; liver and kidney function-related indicators within 1.25*the normal upper limit;
9. Patient willingness to comply with the protocol;
10. Patient willingness and ability to provide an informed consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Involved site irradiation; High-risk CTV1 : GTVnx plus a 10-mm margin to encompass the microscopic extension of the gross tumor, the whole nasopharynx, the high-risk structures recommended for CTVp2 by the contouring consensus* (such as parapharyngeal space, skull base, pterygopalatine fossa and the inferior part of the nasal cavity and maxillary sinus), the VIIa, and the retrostyloid space above the bilateral transverse process of C1. Low-risk CTV2: N0/positive RPLN only: Bilateral cervical nodal region with the 3-cm caudal expansion below transverse process of C1, and at least covering the level II. N1-2 (positive cervical LNs): Ipilateral cervical nodal region with the 3-cm expansion below the positive LN (GTVnd), and at least covering the level II; contralateral cervical nodal region with the 3-cm caudal expansion below the transverse process of C1, and at least covering the level II. Suspicious LN: 1-cm expansion below the suspicious LN (GTVnd-suspicious)	Radiation: intensity-modulated radiotherapy (IMRT) with reduced-volume; PGTVnx: 69.9Gy/2.12Gy/33f GTVrpn: 69.9Gy/2.12Gy/33f GTVnd: 69.9Gy/2.12Gy/33f GTVnd-suspicious: 60.06Gy/1.82Gy/33f PTV1: 60.06Gy/1.82Gy/33f PTV2: 50.96Gy/1.82Gy/28f; Other Names: intensity-modulated radiotherapy; Drug: Chemotherapy; Concurrent cisplatin (100 mg/m², d1-3, Q3w, maximum to three cycles); The application of induction chemotherapy and consolidation chemotherapy is dependent on the physician's discretion.
Active Comparator: Elective region irradiation; High-risk CTV1 : GTVnx plus a 10-mm margin to encompass the microscopic extension of the gross tumor, the whole nasopharynx, the high-risk structures recommended for CTVp2 by the contouring consensus* (such as parapharyngeal space, skull base, pterygopalatine fossa and the inferior part of the nasal cavity and maxillary sinus), the VIIa, and the retrostyloid space above the bilateral transverse process of C1. Low-risk CTV2: N0/positive RPLN only: Bilateral level III + Va N1-2 (positive cervical LNs): At least one subsequent level below CTV1	Radiation: intensity-modulated radiotherapy (IMRT) with reduced-volume; PGTVnx: 69.9Gy/2.12Gy/33f GTVrpn: 69.9Gy/2.12Gy/33f GTVnd: 69.9Gy/2.12Gy/33f GTVnd-suspicious: 60.06Gy/1.82Gy/33f PTV1: 60.06Gy/1.82Gy/33f PTV2: 50.96Gy/1.82Gy/28f; Other Names: intensity-modulated radiotherapy; Drug: Chemotherapy; Concurrent cisplatin (100 mg/m², d1-3, Q3w, maximum to three cycles); The application of induction chemotherapy and consolidation chemotherapy is dependent on the physician's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional-recurrence-free survival	measured from the registration to the documented regional recurrence	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	measured from registration to documented death from any cause or last follow-up	3-year
Distant metastasis-free survival	measured from registration to documented distant metastasis or death from any cause	3-year
Progression-free survival	measured from registration to documented locoregional recurrence or distant metastasis or death from any cause	3-year
Number of Participants with acute and late radiation-related toxicities	Acute radiation-related toxicities are assessed using the National Cancer Institute Common Toxicity Criteria version 4.0 scale. Acute radiation-related toxicities include dermatitis, mucositis, dry mouth, dysphagia, trismus, and subcutaneous soft tissue. Late radiation toxicities are assessed according to the Radiation Therapy Oncology Group (RTOG) and European Organisation for Research and Treatment of Cancer (EORTC) late radiation morbidity scoring scheme, including skin, neck tissue damage, hypothyroidism, dry mouth, dysphagia, trismus, and other adverse events.	8-year

Collaborators and Investigators

• Sponsor: Yi Junlin
• Investigators: Principal Investigator: Junlin Yi, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Liu Y, Han Y, Liu F, Hu D, Chen Z, Wang P, Li J, Qin J, Jin F, Li Y, Wang J, Yi J. Involved site radiation therapy in stage I-III nasopharyngeal carcinoma with limited lymph node burden (ISRT-NPC) or elective region irradiation: a study protocol for a multicenter non-inferiority randomized controlled phase III clinical trial. BMC Cancer. 2023 Aug 3;23(1):724. doi: 10.1186/s12885-023-11212-7.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 25, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Drug Therapy; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: NCC-2021C-257

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No