Brief Title
CNG Staging Compared With 8th UICC of NPC for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy
Official Title
CNG Staging Compared With UICC Eighth Staging of Nasopharyngeal Carcinoma for Treatment Decision-marking and Selection of Chemotherapy and Radiotherapy： a Multicenter, Open Label, Randomized Controlled, Non-inferiority Clinical Trial
Brief Summary
Due to the increase of tumor control rate and survival rate in era of IMRT, the role of the
seventh edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and
inaccurate.
Therefore, we put forward a new staging for the clinical staging of NPC in the era of IMRT
without changing the current T, N, M staging definition of the 7th of the UICC/AJCC staging
system. We call this new stage "Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG
stage. In CNG stage, the clinical stages were reduced to three stages, namely, CNG I stage
includes T1-3N0-1M0 and T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG
III stage includes TanyNanyM1. For CNG I stage, the IMRT alone is sufficient. If EBV-DNA
copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given. For CNG II stage,
patients can benefit from combined radiotherapy and chemotherapy. For CNG III stage, patients
are recommended for systemic chemotherapy plus local radiotherapy (primary focus, neck
drainage area and distant metastasis).
This year, UICC/AJCC has proposed an eighth edition of NPC staging system. The eighth version
is mainly changed in the definition and refinement of the anatomic location compared with the
seventh edition. This is different from our new CNG staging concept.
Therefore, CNG staging and its treatment strategy was used as the experimental group, and the
eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control
group. The open and randomized controlled clinical study was conducted. The purpose of this
study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth
clinical staging for treatment decision-marking and selection of chemotherapy and
radiotherapy, and differentiating differences in prognosis in each clinical stage. The
survival results based on CNG staging and its treatment are not inferior to the survival
results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid
chemotherapy for some of the patients, and to improve the outcome of metastatic patients.
Detailed Description
The seventh edition of the UICC/AJCC staging system, which is widely used in recent years, is
based on survival data in the traditional era of radiotherapy. However, the survival of
nasopharyngeal cancer patients has been greatly improved in the era of modern radiation
therapy, which IMRT (Intension Modulated Radiotherapy) is widely used. Even with radiotherapy
alone, the 5 year disease specific survival rate of nasopharyngeal carcinoma with stage I-II
is more than 95%, the 3 year overall survival rate of non metastatic III-IV patients is about
75%, and the 5 year overall survival rate is about 80%. The 5 year survival rate of
metastatic nasopharyngeal carcinoma can reach more than 20% with systemic treatment. Due to
the increase of tumor control rate and survival rate in era of IMRT, the role of the seventh
edition of UICC/AJCC staging system in predicting prognosis is becoming weaker and
inaccurate.
Therefore, in the previous study, we put forward a new staging for the clinical staging of
nasopharyngeal carcinoma in the era of IMRT without changing the current T, N, M staging
definition of the seventh edition of the UICC/AJCC staging system. We call this new stage
"Cooperative Nasopharyngeal Carcinoma Group" stage, namely CNG stage. In CNG stage, the
clinical stages were reduced to three stages, namely, CNG I stage includes T1-3N0-1M0 and
T1-2N2M0, CNG II stage includes T3N2M0, T4N0-2M0 and TanyN3M0, CNG III stage includes
TanyNanyM1, and the 5 year DSS (Disease specific survival) is 93.3%, 72.7%, and 24%,
respectively, with a significant difference.
This year, UICC/AJCC has proposed an eighth edition of nasopharyngeal carcinoma staging
system based on the revision of the seventh edition. The main updates are: (1) add the
definition of the T0 phase, that is, the EBV positive cervical lymph node metastases with
uncertain primary foci, and (2) the invasion of the adjacent muscles (including the pterygus,
the extradypterygus, and the anterior vertebroid muscle) into T2; (3) replace the
"masticatory muscle space" and "subtemporal fossa" in the previous T4 definition with a
specific description of soft tissue invasion; (4) change the supraclavicular fossa to the
lower neck (defined as the lymph node metastases below the subchondral edge); (5) N3a and N3b
are combined called N3, and it is defined as a single / double neck lymph node with long
diameter > 6cm, and/or below the subchondral subchondral edge; (6) the IVA stage (T4 N0-2 M0)
and the IVB stage (anyT N3 M0) are combined called IVA stage; (7) the IVC stage (anyT anyN)
is changed to IVB stage. The eighth version is mainly changed in the definition and
refinement of the anatomic location compared with the seventh edition. Except for the
migration of the adjacent muscle invasion, and the other changes are not significant. The
upper bound of N3 is moved from the supraclavicular fossa to the subchondral edge in N
staging. This is different from our new CNG staging concept.
CNG staging of nasopharyngeal carcinoma is related to the unique biological behavior of
nasopharyngeal carcinoma, which is consistent with the three clinical patterns of
nasopharyngeal carcinoma, namely, non metastasis, tendency to metastasis and metastasis. The
pattern of tendency to metastasis was related to the late T and N staging. Based on the
biological behavior and clinical survival data of NPC, we further proposed the treatment
strategy of nasopharyngeal carcinoma under the guidance of CNG staging, that is, the CNG I
stage is consistent with the non metastasis model, and the IMRT alone is sufficient. The CNG
II stage is consistent with the tendency to metastasis mode, which can benefit from combined
radiotherapy and chemotherapy. The CNG III stage is metastatic mode, which is recommended for
systemic chemotherapy plus local radiotherapy (primary focus, neck drainage area and distant
metastasis). In clinical practice, we suggest that for patients with CNG I stage, if EBV-DNA
copies is more than 0 copy/ml, concurrent chemoradiotherapy will be given.
Therefore, CNG staging and its treatment strategy was used as the experimental group, and the
eighth edition of UICC/AJCC staging with NCCN guiding treatment was used as the control
group. The open and randomized controlled clinical study was conducted. The purpose of this
study was to evaluate in the era of IMRT, CNG staging can be better than UICC/AJCC eighth
clinical staging for treatment decision-marking and selection of chemotherapy and
radiotherapy, and differentiating differences in prognosis in each clinical stage. The
survival results based on CNG staging and its treatment are not inferior to the survival
results of the NCCN guide therapy based on the eighth edition UICC/AJCC staging, to avoid
chemotherapy for some of the patients, and to improve the outcome of metastatic patients.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Overall Survival (OS)
Secondary Outcome
Quality of life
Condition
Nasopharyngeal Carcinoma
Intervention
CNG Chemotherapy
Study Arms / Comparison Groups
Experimental Group
Description: The patients in the Experimental Group are allocated to receive CNG staging and CNG chemotherapy strategy and CNG radiation strategy
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1324
Start Date
June 12, 2018
Completion Date
June 12, 2026
Primary Completion Date
June 12, 2026
Eligibility Criteria
Inclusion Criteria:
- Pathologically confirmed and previously untreated nasopharyngeal carcinoma
- Non T1N0M0 patient according to UICC/AJCC seventh edition staging system
- Age ≥ 18 years and < 65 years
- Karnofsky performance status (KPS) score ≥ 70
- Adequate normal organ function
- No history of other malignant tumors
- No serious mental disorder (schizophrenia, delusion of victimization, manic
depression, and drug induced anxiety)
- No AIDS, active pulmonary tuberculosis and other serious immunodeficiency diseases
- No communication barrier, can answer the question
- Sign informed consent under voluntary circumstances, complete treatment and follow up
as required
Exclusion Criteria:
- Poor compliance
- Investigators consider as inappropriate for enrolling into this study
Gender
All
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
Yun-fei Xia, M.D, 86-13602805461, [email protected]
Administrative Informations
NCT ID
NCT03529279
Organization ID
B2018-030-01
Responsible Party
Principal Investigator
Study Sponsor
Sun Yat-sen University
Study Sponsor
Yun-fei Xia, M.D, Principal Investigator, Sun Yat-sen University
Verification Date
May 2018