This article was published by WuXi AppTec's content team "New Perspectives on Medicine" with the permission of the team of study authors
The geographical characteristics of nasopharyngeal carcinoma are obvious, especially in southern China and Southeast Asia. The incidence of nasopharyngeal carcinoma in China accounts for about 50% of the new cases in the world, and the incidence of nasopharyngeal cancer in some parts of South China is more than 20 times the global average.
Radiation therapy is the root cause of nasopharyngeal cancer. The incidence of cervical lymphatic metastases in nasopharyngeal carcinoma is high, with about 70% of patients having cervical lymph node metastases upon diagnosis. To eradicate micrometastatic tumor foci, traditional radiation therapy usually includes bilateral total neck when selecting lymph node targets. However, total cervical preventive irradiation often leads to significant late toxic effects, with an incidence of hypothyroidism as high as 40% within 2 years, a soft tissue damage rate of 30%, and about 40% of patients affected by late esophageal toxic effects. These toxic side effects affect the patient's quality of life to varying degrees.
Professor Ma Jun and Professor Tang Linglong of the Department of Radiotherapy of the Cancer Prevention and Treatment Center of Sun Yat-sen University are concerned about the individualized neck irradiation technology of patients with nasopharyngeal carcinoma, and a multi-center Phase 3 clinical study led by the team is expected to improve this situation.
The study showed that for patients with newly diagnosed nasopharyngeal cancer with non-distant metastases (M0) and N0-N1, selective upper and cervical irradiation was used on the negative side of the cervical lymph nodes of nasopharyngeal cancer, and the survival rate was similar to that of standard total neck irradiation, radiation therapy was less toxic, and the quality of life was better.
The trial was conducted in three medical centers in China (Cancer Prevention and Control Center of Sun Yat-sen University, The First People's Hospital of Foshan, and Affiliated Hospital of Guilin Medical College). The results were recently published in The Lancet Oncology.
Professor Ma Jun of the Cancer Prevention and Control Center of Sun Yat-sen University is the corresponding author, Professor Tang Linglong, Dr. Zhou Guanqun and Dr. Chen Lei are the co-corresponding authors, and Professor Tang Linglong, Dr. Huang Chenglong, Professor Zhang Ning (Foshan First People's Hospital), Professor Jiang Wei (Affiliated Hospital of Guilin Medical College), and Dr. Wu Yishan are the co-first authors.
In order to introduce this cutting-edge research result and its clinical significance in more detail, the author team brings readers an interpretation of the article.
About the author
Prof. Jun Ma (Corresponding Author)
Academic positions: Doctor of Medicine, Chief Physician, Professor, Doctoral Supervisor, the first chairman of the Nasopharyngeal Cancer Committee of the Chinese Clinical Oncology Association, and the convener of the Special Medicine Review Group of the Degree Committee of the State Council
Administrative position: Executive Vice President of cancer prevention and control center of Sun Yat-sen University
Research Areas: Committed to the research of clinical staging, comprehensive treatment and precise intensity-modulated radiation therapy for nasopharyngeal carcinoma.
Prof Tang Linglong (First Author and Co-Corresponding Author)
Academic position: Chief Physician, Doctoral Supervisor
Administrative position: District Chief of Radiotherapy District 1 of Cancer Prevention and Control Center of Sun Yat-sen University
Research areas: Committed to the clinical staging of nasopharyngeal carcinoma and the study of precise intensity-modulated radiation therapy.
Article interpretation
Research background
The team's previous research found that lymph node metastasis in nasopharyngeal cancer follows certain rules:
Transfer to the upper neck drainage area first, and then to the lower neck drainage area, and the jump jump transfer is rare;
In addition, lymph node metastasis follows a hysteretic metastasis pattern, with one neck shift rarely occurring to the contralateral neck.
On this basis, retrospective studies have found that selective upper neck irradiation on the negative side of the cervical lymph nodes of NASOPHARY can also achieve survival rates similar to full-neck irradiation.
In order to provide higher quality evidence of prospective randomized controlled clinical trials, the Center for Cancer Prevention and Control of Sun Yat-sen University led this large-scale prospective, multicenter, randomized controlled, non-inferior Phase 3 clinical trial.
Image credit: 123RF
Research methodology
The trial included patients with nasopharyngeal carcinoma aged 18 to 65 years with a KPS score of 70-1 under the uiccum/AJCCTNM staging system of the seventh edition of the UICC/AJCCTNM staging system, who received no treatment and whose pathology type was nonkeratotic and had no distant metastases. 1:1 randomly assigned to the cervical lymph node-negative upper cervical irradiation group and the total cervical irradiation group.
▲Schematic diagram of the scope of nasopharyngeal carcinoma prevention (image source: reference [7])
A: Control group: full cervical preventive irradiation is performed regardless of lymph node metastases;
B: Experimental group: no cervical lymph node metastasis, bilateral neck irradiation of the upper half of the neck;
C: Test group: unilateral lymph node metastases (red area), lymph node-negative lateral upper neck irradiation
Specific treatment options are:
Irradiation 30-33 times a total of 5 times a week. The total dose varies by target:
Primary foci and enlarged retropharyngeal lymph nodes: 70 Gy total dose,
Invaded cervical lymph nodes: 66-70 Gy total dose,
High-risk tumor target: 60-62Gy total dose,
Low-risk tumor target: 54-56Gy total dose;
For patients with stage II-IVA, cisplatin-based intravenous chemotherapy is recommended, including induction chemotherapy plus concurrent chemotherapy, or concurrent chemotherapy alone.
The primary endpoint was Regional relapse-free survival (RRFS) in intentionally treated populations. Toxicity side effects analysis was performed in all patients initiated to receive randomly assigned therapy.
Research results
After a preliminary screening, 446 patients were enrolled and randomly assigned to the upper neck irradiation group (224 cases) and the full neck irradiation group (222 cases) on a 1:1 basis.
(1) The survival rate of the upper neck irradiation group and the full neck irradiation group was similar
The median follow-up time was 53 months (46-59 months in interlump intervals), and survival analysis found that 3-year RRFS was similar between the upper neck irradiation group and the full neck irradiation group (97.7% vs 96.3%; Difference - 1.4%, non-inferior p-value
Non-inferiority is defined: the upper limit of the 95% confidence interval for the 3-year RRFS difference between the total neck irradiation group and the upper neck irradiation group does not exceed 8%.
Similarly, the 3-year overall survival rate (99.1% vs 96.4%; HR 0.39, p=0.10), survival without distant metastases (94.6% vs 93.5%; HR 0.85, p=0.15), local recurrence-free survival (97.3% vs 95.4%); HR 0.88, p=0.67) is similar between the two groups.
RRFS (A), overall survival (B), survival without distant metastases (C), and survival without local recurrence (D) in the upper neck irradiation group compared to the total neck irradiation group (Image source: Reference [7])
(2) The radiation therapy-related late toxicity side effects in the upper neck irradiation group were lower and the quality of life was good
Acute radiotherapy-related toxicities were similar between the two groups, but the incidence of late toxicity was lower in the upper and neck irradiation group than in the total cervical irradiation group, including any level of hypothyroidism (30% vs 39%), skin toxicity (14% vs 25%), dysphagia (17% vs 32%), and neck tissue injury (23% vs 40%). No patients died during treatment, and one patient in the total neck irradiation group after treatment died of dermatomyositis (non-cancer-related causes).
Acute and advanced toxicity associated with radiotherapy in both groups of patients (table source: reference [7])
The long-term quality of life in the upper neck irradiation group, including swallowing function, overall health, and fatigue, was better than that in the total neck irradiation group.
conclusion
The study proposed an individualized neck irradiation technique for nasopharyngeal carcinoma: that is, for patients without cervical lymph node metastases, the range of cervical prophylaxis only needs to include bilateral upper neck (above annular cartilage), avoiding irradiation of the lower neck; for patients with unilateral cervical lymph node metastases, the negative side of cervical lymph node prophylaxis only needs to include this lateral upper neck.
This irradiation technology reduces the volume of radiation to important organs such as skin, trachea, esophagus, and thyroid in the lower neck, significantly reduces the sequelae of radiotherapy such as hypothyroidism, dysphagia, and neck tissue damage, and improves the quality of life of patients.
With the continuous advancement of diagnosis and treatment technology, the current 5-year survival rate of nasopharyngeal cancer exceeds 80%, and the quality of life of long-term survival patients has become an urgent problem that needs our attention. The results are expected to rewrite the treatment guidelines for clinical NASOPHARY and benefit 70% of patients with nasopharyngeal cancer who have just treated it.