Clinical trial NCT04127760: Efficacy of Postoperative Radiotherapy for Atypical Meningioma Without Venous Sinus Invasion After Gross-total Resection
Official title: A Multicenter Randomized Controlled Trial of the Efficacy of Postoperative Radiotherapy for Atypical Meningioma Without Venous Sinus Invasion After Gross-total Resection
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Meningioma Atypical
Radiotherapy
Progression-Free Survival
Adverse Effect of Radiation Therapy
Keywords: Meningioma Atypical
radiotherapy
Lead sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sponsor class: OTHER
Collaborators: name: Sir Run Run Shaw Hospital
name: Zhejiang Provincial People's Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Jinhua Central Hospital
name: Taizhou Hospital
name: Shaoxing Hospital of Zhejiang University
name: People's Hospital of Quzhou
name: Huzhou Central Hospital
First posted: 2019-10-16
Enrollment: 140
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: Postoperative adjuvant radiotherapy is a key component of comprehensive treatment of meningioma. However, for atypical meningioma after total resection, there is still a huge controversy in patients who need adjuvant radiotherapy after surgery.

Many scholars have focused on this problem and carried out some small-scale retrospective studies, but they have contradictory results. Some of the studies found that postoperative adjuvant radiotherapy could not improve the prognosis of patients, but was questioned because the sample size was too small, resulting in insignificant results, while other studies found that postoperative adjuvant radiotherapy can improve progression free survival. A study based on the National Cancer Database found that postoperative adjuvant radiotherapy and gross tumor resection are associated with a good prognosis. A recent meta-analysis enrolled a total of 757 patients and found that postoperative adjuvant radiotherapy reduced the risk of tumor recurrence but did not improve survival time. Our team reviewed the meningioma data in the SEER database and conducted a study previously. The study found that postoperative adjuvant radiotherapy did not improve the overall survival of these patients. The relevant research results were recently published in Frontiers in oncology. We further reviewed and summarized the single-center data of our hospital and found that postoperative adjuvant radiotherapy could not improve the progression free survival and overall survival of patients. Besides, we also performed a meta-analysis and found that postoperative adjuvant radiotherapy had a trend to improve progression-free survival, but there was no statistical difference.

Because there are many deficiencies in previous researches, and the research results are also contradictory, it is still unclear whether patients with atypical meningioma who have undergone gross total resection can benefit from postoperative adjuvant radiotherapy. Further high quality clinical trials is still needed to be conducted in order to guide the postoperative care of patients. Therefore, we intend to conduct this multicenter randomized controlled trial to determine the value of postoperative adjuvant radiotherapy in patients with atypical meningioma who underwent gross total resection.

Detailed description: The study aims to enroll a total of 140 participants. Subjects would be enrolled with the following information: name, age, gender, contact, KPS score, preoperative ASA score, current ECOG score, tumor location, date of surgery, degree of tumor resection (modified Simpson grade), pathology type, Ki-67 Proliferation index, etc. The preoperative magnetic resonance image of the subject is stored. Tissue specimens are genetically examined.

Using a simple randomization method and random assignment in a 1:1 ratio, a random sequence was first generated, and SAS version 9.1 statistical software was used to generate an allocation sequence table including subject numbers, 140 random numbers, and random groupings. 140 Subjects would be assigned to the test group (n=70) and the control group (n=70) in a 1:1 ratio. The table of the assignment sequence is duplicated and saved by the neurosurgical secretary and the trial designer of the Second Affiliated Hospital of Zhejiang University. The secretary puts the group mark into the 140 opaque kraft envelopes with the serial number 1 to 140 according to the order of the allocation sequence table, and submits them to the test designer. Zhige Guo is responsible for enrolling the participants according to the inclusion criteria, assigning the subjects numbers according to the order of the treatment, and Qiang Zeng is responsible for disassembling the corresponding opaque envelopes according to the number of the subjects, and exerting interventions according to the group marks. Chenhan Ling is responsible for follow-up and regular measurement of various indicators, and Fei Dong is responsible for the images reports. Until the end of the trial, Zhige Guo, Chenhan Ling and Fei Dong would not know the grouping of the subjects.

The test level of the study was α=0.05, and the two-sided test was used. All statistical analysis was performed by SPSS 16.0 statistical software.

1. For PFS, OS, and DSS data, the COX proportional hazards model was used to calculate the hazard ratio (HR) of radiotherapy and to assess the statistical difference between the corresponding prognostic data between the two groups.
2. For the 3-year progression-free survival, 3-year survival rate, and 5-year progression-free survival, 5-year survival rate data, the chi-square test was used to compare the differences between the two groups.

Eligibility criteria: Inclusion Criteria:

* Patients who underwent gross total resection at each center and were diagnosed as atypical meningioma (WHO class II) according to the WHO 2016 diagnostic criteria.
* Gross total resection was defined as modified Simpson 1-3 and confirmed by postoperative magnetic resonance imaging.

Exclusion Criteria:

* age less than 18 years old or older than 70 years
* meningioma recurrence
* patients had previous radiotherapy
* multiple meningioma
* optic nerve sheath meningioma or other extracranial meningioma
* tumor involving venous sinus
* ECOG score ≥ 2 points
* preoperative ASA grade ≥ 3
* previous or current malignant tumors
* pregnant or lactating women
* Patients with Gd-DTPA allergies, spatial claustrophobia or pacemaker implantation that can not be conducted constract-enhanced head magnetic resonance examination
* patients who were unable to obtain informed consent or refused to participate in the study.

Primary outcomes:
measure: Progression-free survival
timeFrame: 60months
Secondary outcomes:
measure: 3-year survival rate
timeFrame: 36months
measure: 3-year progression-free survival
timeFrame: 36months
measure: 5-year survival rate
timeFrame: 60months
measure: 10-year progression-free survival
timeFrame: 120 months
measure: 10-year survival rate
timeFrame: 120 months
measure: Disease-specific survival
timeFrame: from diagnosis up to 10 years
measure: overall survival
timeFrame: from diagnosis up to 10 years
Other outcomes:
Locations:
Study officials:
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