Nasopharyngeal Carcinoma (NPC), Osteoradionecrosis of the Jaw
Conditions
Keywords
Nasopharyngeal carcinoma, Jaw osteoradionecrosis, Impacted tooth, Prophylactic tooth extraction, Intensity-modulated radiotherapy
Brief summary
This multicenter, randomized controlled trial is designed to determine whether omitting prophylactic extraction of impacted teeth before radiotherapy leads to an unacceptably higher risk of jaw osteoradionecrosis (JORN) compared with conventional prophylactic extraction in patients with non-metastatic nasopharyngeal carcinoma (NPC). JORN is a condition in which jawbone tissue is damaged and fails to heal properly after radiotherapy. A total of 536 eligible participants with at least one impacted tooth will be randomly assigned to either omit prophylactic extraction of impacted teeth before radiotherapy or undergo conventional prophylactic extraction before radiotherapy. All participants will receive standard curative-intent intensity-modulated radiotherapy (IMRT), with chemotherapy administered when indicated according to the study protocol. Participants will be followed for up to 5 years. The primary outcome is the incidence of JORN within 2 years after completion of radiotherapy. Secondary outcomes include longer-term incidence of JORN, overall survival, locoregional relapse-free survival, distant metastasis-free survival, quality of life, and treatment-related toxicities.
Detailed description
Prophylactic extraction of impacted teeth before radiotherapy is performed to reduce the potential risk of dental complications and jaw osteoradionecrosis after treatment. However, whether prophylactic extraction is necessary for impacted teeth without indications for therapeutic extraction remains uncertain. This study is designed to evaluate whether omission of prophylactic impacted tooth extraction is noninferior to conventional prophylactic extraction with respect to the risk of jaw osteoradionecrosis in patients with non-metastatic nasopharyngeal carcinoma undergoing curative-intent radiotherapy. The study will also assess the long-term clinical outcomes and safety of this tooth-management strategy.
Interventions
OTHEROmission of Prophylactic Impacted Tooth Extraction
Participants will not undergo prophylactic extraction of eligible impacted teeth before radiotherapy.
PROCEDUREProphylactic Impacted Tooth Extraction
Participants will undergo prophylactic extraction of eligible impacted teeth before radiotherapy according to the study protocol.
Sponsors
First Affiliated Hospital of Guangxi Medical University
People's Hospital of Guangxi Zhuang Autonomous Region
LiuZhou People's Hospital
Liuzhou Workers' Hospital
Wuzhou Red Cross Hospital
Guigang People's Hospital
First People's Hospital of Yulin
Affiliated Hospital of Guilin University
Youjiang Medical College for Nationalities
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Age 18-75 years, regardless of sex. * Histologically confirmed non-keratinizing nasopharyngeal carcinoma, including differentiated or undifferentiated subtype (WHO type II or III). * Newly diagnosed, previously untreated nasopharyngeal carcinoma with stage T1-4N0-3M0 according to the 9th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system. * Presence of permanent dentition with at least one impacted third molar. * Adequate bone marrow function, defined as white blood cell count ≥4.0 × 10⁹/L, platelet count ≥100 × 10⁹/L, and hemoglobin ≥90 g/L. * Adequate hepatic function, defined as alanine aminotransferase and aspartate aminotransferase ≤2.5 × the upper limit of normal (ULN), and total bilirubin ≤1.5 × ULN. * Adequate renal function, defined as blood urea nitrogen and serum creatinine ≤1.5 × ULN, or creatinine clearance ≥60 mL/min. * Coagulation function within normal limits. * Written informed consent provided, with willingness and ability to comply with study visits, treatment plans, laboratory assessments, and other study procedures.
Exclusion criteria
* Histopathological diagnosis other than WHO type II or III nasopharyngeal carcinoma. * Impacted third molars with recurrent pericoronitis or inflammation due to incomplete eruption. * Fully erupted third molars with dental caries involving the pulp. * Impacted third molars with radiographic evidence of periapical or periodontal inflammation. * Third molars completely impacted within the jawbone. * History of active malignancy or other malignant tumors diagnosed within the previous 5 years, except for adequately treated non-melanoma skin cancer or carcinoma in situ. * Previous chemotherapy, surgery (except diagnostic procedures), radiotherapy, or other antitumor treatment for nasopharyngeal carcinoma or cervical lesions. * Patients receiving palliative treatment. * Pregnant or breastfeeding women. * Severe uncontrolled cardiovascular or cerebrovascular diseases. * Severe hepatic or renal dysfunction. * Uncontrolled diabetes mellitus. * Severe osteoporosis, medication-related osteonecrosis/osteomyelitis, or chronic diseases requiring long-term systemic corticosteroid therapy. * Other severe chronic debilitating diseases that may increase study risk or affect study compliance. * History of drug abuse or alcohol dependence. * Uncontrolled psychiatric disorders or inability to provide legally valid informed consent. * Positive hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \>1,000 copies/mL. * Active hepatitis C virus infection (positive HCV RNA). * Human immunodeficiency virus (HIV) infection or diagnosis of acquired immunodeficiency syndrome (AIDS). * Active tuberculosis within the previous 1 year. * History of active tuberculosis more than 1 year previously without documented completion of standard anti-tuberculosis treatment. * Any other medical, psychological, social, or laboratory condition that, in the investigator's judgment, may compromise participant safety, interfere with study procedures, affect protocol compliance, or result in premature withdrawal from the study. * Refusal or inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Cumulative Incidence of Jaw Osteoradionecrosis | Within 24 months after completion of radiotherapy | The cumulative incidence of jaw osteoradionecrosis (JORN) within 24 months after completion of radiotherapy will be estimated and compared between the two treatment groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-Year Overall Survival | 24 months after randomization | The 2-year overall survival rate will be estimated as the probability of remaining alive at 24 months after randomization and compared between the two treatment groups. |
| 2-Year Event-Free Survival | 24 months after randomization | The 2-year event-free survival rate will be estimated as the probability of remaining free from local recurrence, regional recurrence, distant metastasis, or death from any cause at 24 months after randomization and compared between the two treatment groups. |
| 2-Year Local Relapse-Free Survival | 24 months after randomization | The 2-year local relapse-free survival rate will be estimated as the probability of remaining free from local recurrence or death at 24 months after randomization and compared between the two treatment groups. |
| 2-Year Regional Relapse-Free Survival | 24 months after randomization | The 2-year regional relapse-free survival rate will be estimated as the probability of remaining free from regional recurrence or death at 24 months after randomization and compared between the two treatment groups. |
| 2-Year Distant Metastasis-Free Survival | 24 months after randomization | The 2-year distant metastasis-free survival rate will be estimated as the probability of remaining free from distant metastasis or death from any cause at 24 months after randomization and compared between the two treatment groups. |
| Quality of Life Assessed by the EORTC QLQ-C30 | Baseline and 3, 6, 12, and 24 months after completion of radiotherapy | Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Scores are transformed to a 0-100 scale. Higher scores on the functional scales and global health status/quality-of-life scale indicate better functioning or quality of life, whereas higher scores on the symptom scales indicate greater symptom burden. |
| Head and Neck Cancer-Specific Quality of Life Assessed by the EORTC QLQ-H&N35 | Baseline and 3, 6, 12, and 24 months after completion of radiotherapy | Head and neck cancer-specific symptoms and quality-of-life problems will be assessed using the EORTC QLQ-H\&N35 questionnaire. Scores are transformed to a 0-100 scale, with higher scores indicating greater symptom burden or more severe problems. |
| Acute Treatment-Related Toxicities | From initiation of treatment through 90 days after completion of radiotherapy | The incidence and severity of acute treatment-related toxicities will be assessed and compared between the two treatment groups. Toxicities will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, as applicable. |
| 5-Year Cumulative Incidence of Jaw Osteoradionecrosis | Within 60 months after completion of radiotherapy | The cumulative incidence of jaw osteoradionecrosis (JORN) within 60 months after completion of radiotherapy will be estimated and compared between the two treatment groups. |
| 5-Year Overall Survival | 60 months after randomization | The 5-year overall survival rate will be estimated as the probability of remaining alive at 60 months after randomization and compared between the two treatment groups. |
| 5-Year Event-Free Survival | 60 months after randomization | The 5-year event-free survival rate will be estimated as the probability of remaining free from local recurrence, regional recurrence, distant metastasis, or death from any cause at 60 months after randomization and compared between the two treatment groups. |
| 5-Year Local Relapse-Free Survival | 60 months after randomization | The 5-year local relapse-free survival rate will be estimated as the probability of remaining free from local recurrence or death from any cause at 60 months after randomization and compared between the two treatment groups. |
| 5-Year Regional Relapse-Free Survival | 60 months after randomization | The 5-year regional relapse-free survival rate will be estimated as the probability of remaining free from regional recurrence or death from any cause at 60 months after randomization and compared between the two treatment groups. |
| 5-Year Distant Metastasis-Free Survival | 60 months after randomization | The 5-year distant metastasis-free survival rate will be estimated as the probability of remaining free from distant metastasis or death from any cause at 60 months after randomization and compared between the two treatment groups. |
| Late Treatment-Related Toxicities | From more than 90 days through 60 months after completion of radiotherapy | The incidence and severity of late treatment-related toxicities will be assessed and compared between the two treatment groups using the RTOG/EORTC late radiation morbidity scoring criteria and CTCAE version 5.0, as applicable. |
Countries
China
Contacts
CONTACTLi Jiang, MD
CONTACTZhen Meng, MD
PRINCIPAL_INVESTIGATORMin Kang, MD
First Affiliated Hospital of Guangxi Medical University
Outcome results
None listed