Clinical trial NCT05228093: A Randomized Controlled Clinical Trial of Surgery Versus Conservative Treatment for Mild and Moderate-grade Nasopharyngeal Necrosis
Official title: A Randomized Controlled Clinical Trial of Curative-intent Endoscopic Necrectomy Followed by Construction Using the Posterior Pedicle Nasal Septum and Floor Mucoperiosteum Flap Versus the Best Conservative Treatment for Mild and Moderate-grade Nasopharyngeal Necrosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Nasopharyngeal Carcinoma, Postradiation, Necrosis, Endoscopy Surgery, Conservative Treatment
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2022-02-08
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Post radiation nasopharyngeal necrosis is a relatively special radiotherapy sequelae after radiotherapy for nasopharyngeal carcinoma. According to the degree of its development, it can be roughly divided into three stages: mild, moderate and severe stages, corresponding to the pre-nasopharyngeal necrosis stage, the soft tissue necrosis stage and the bone necrosis stage respectively. In the past, treatment methods were limited, including anti-infection, topical nasopharyngeal drugs, etc., the efficacy was not good, the nasopharyngeal necrosis lesions progressed, and a series of serious complications occurred, such as: intracranial infection secondary to osteonecrosis, massive nasopharyngeal hemorrhage, etc. It seriously endanger the life of the patient. With the continuous development of medical technology, the means of treatment are also constantly updated, such as repeated debridement guided by nasal endoscope, modified nasopharyngeal irrigation and hyperbaric oxygen therapy, the healing rate of nasopharyngeal necrosis has improved, especially the cure rate of patients in the mild and moderate-stages can reach 54.1%-54.8%. However, there are still some patients with poor healing of nasopharyngeal wounds after treatment.

Since 2004, our team has carried out a series of studies such as transnasal endoscopic nasopharyngeal resection combined with posterior pedicle nasal septum and floor mucoperiosteum flap(NSFF), and successfully achieved minimally invasive and en bloc resection of localized recurrent nasopharyngeal carcinoma. This method basically solved the problem of surgical wound healing of recurrent nasopharyngeal carcinoma. On this basis, we further applied it to the treatment of nasopharyngeal necrosis to further improve the cure rate and improve the prognosis. In addition, our retrospective study showed that compared with conservative treatment, curative-intent endoscopic necrectomy followed by reconstruction using the posterior pedicle nasal septum and floor mucoperiosteum flap can effectively prolong the overall survival time of patients and significantly improve the symptoms, but it still needs to be further confirmed by prospective clinical trials.

In addition, some patients (22.2%) had necrosis of the mucosal flap after receiving surgery, which affected the healing of surgical wounds. Besides, the development of nasopharyngeal necrosis is a slow process. If nasopharyngeal necrosis removal combined with pedicled mucosal flap repair is performed prematurely, the area outside the operation area may be necrotic again. Theoretically, each patient only has the nasal septum-nasal septum mucosal flaps on both sides of the nasal septum, which means that each patient only has 2 chances of repairing the nasal septum-nasal floor mucosal flaps. Premature surgical intervention may not only lead to incomplete debridement, but also lose a valuable opportunity for mucosal flap repair.

Therefore, based on the above problems, this study intends to compare the endoscopic nasopharyngeal necrosis debridement combined with pedicled mucosal flap repair versus the best conservative regimen for the treatment of early and mid-stage nasopharyngeal necrosis, to explore the prognosis of patients with nasopharyngeal necrosis. The preferred regimen, if confirmed by this study, is expected to standardize the treatment of nasopharyngeal necrosis after radiotherapy and further promote it, effectively increasing the cure rate of nasopharyngeal necrosis and improving the prognosis of patients.


Eligibility criteria: Inclusion Criteria:

1. Received radical radiotherapy for the nasopharynx;
2. For patients with early-stage and mid-stage nasopharyngeal necrosis diagnosed for the first time by clinical symptoms, imaging examinations and pathology. The lesions are limited to the superficial tissue of the nasopharynx and the deep tissue of each wall of the nasopharynx, regardless of the exposure of internal carotid artery invasion(ICA). For those patients with ICA exposure, vascular pretreatment (vascular embolization or bypass surgery) would be performed and reassess after 2-4 weeks of vascular treatment.
3. The patient has signed the informed notice and is willing and able to comply with the study plan visits, treatment plans, laboratory tests and other study procedures.

Exclusion Criteria:

1. Karnofsky score ≤ 70 points or Zubrod score \> 2 points;
2. Patients with severe medical complications, insufficiency of important organs (heart, lung, liver, kidney) or neuropsychiatric disorders at the time of diagnosis.
3. Patients with pathologically confirmed local recurrence.
4. Cases who have received local nasal cavity and nasopharyngeal surgery in the past.
5. Patients who cannot cooperate with regular follow-up due to psychological, social, family and geographical reasons.
6. Other patients who are considered unsuitable for inclusion by the treating physician.

Primary outcomes:
measure: The cure rate of nasopharyngeal necrosis at 3 months after enrollment
timeFrame: 3 months
Secondary outcomes:
measure: The Numeric Rating Scales (NRS) of pain
timeFrame: 3 months
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) overall
timeFrame: up to 1 year
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: up to 1 year
measure: The cure rate of nasopharyngeal necrosis at 6 months after enrollment
timeFrame: 6 months
measure: Overall survival
timeFrame: up to 1 year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: The Fifth Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Nanchang
country: China
facility: The First Hospital of Nanchang
state: Jiangxi
Study officials:
affiliation: Sun Yat-sen University
name: Mingyuan Chen, MD
role: PRINCIPAL_INVESTIGATOR
References: