Optimization of Cervical Nodal Clinical Tumor Volume for Early and Medium Stage Nasopharyngeal Carcinoma: a Multicenter Non-inferior Randomized Controlled Phase III Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 414
- 试验地点
- 2
- 主要终点
- Regional-recurrence-free survival
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 75 years;
- •Karnofsky performance status (KPS) score ≥ 70;
- •Pathologically confirmed World Health Organization (WHO) type II-III NPC;
- •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;
- •Available baseline nasopharynx and neck computed tomography (CT) or magnetic resonance imaging (MRI) (strongly advocated) data (including functional MRI sequences) and measurable tumor lesions;
- •All procedures for defining the tumor burden completed within 4 weeks of registration;
- •Survival expectancy of at least 6 months;
- •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;
- •Patient willingness to comply with the protocol;
- •Patient willingness and ability to provide an informed consent form.
排除标准
- 未提供
研究组 & 干预措施
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)
干预措施: intensity-modulated radiotherapy (IMRT) with reduced-volume (Radiation)
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)
干预措施: Chemotherapy (Drug)
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
干预措施: intensity-modulated radiotherapy (IMRT) with reduced-volume (Radiation)
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
干预措施: Chemotherapy (Drug)
结局指标
主要结局
Regional-recurrence-free survival
时间窗: 3-year
measured from the registration to the documented regional recurrence
次要结局
- Overall survival(3-year)
- Progression-free survival(3-year)
- Number of Participants with acute and late radiation-related toxicities(8-year)
- Distant metastasis-free survival(3-year)
研究者
Yi Junlin
Radiotherapy director
Cancer Institute and Hospital, Chinese Academy of Medical Sciences