A Randomized, Open, Controlled, Multi-center Clinical Trial of Hypofractionated Postoperative Radiotherapy for Adult Glioblastoma
This study was a multicenter, open-label, randomized, controlled, phase Ⅲ clinical trial to evaluate the efficacy and safety of hypofractionated concurrent radiotherapy followed by sequential temozolomide after surgery in patients with newly diagnosed glioblastoma. A total of 420 subjects were enrolled in this study, randomized 1:1. According to the changes in overall survival time after postoperative concurrent chemoradiotherapy with different radiation doses, the stratification factors included the extent of surgical resection (total resection vs subtotal resection); The time of postoperative concurrent chemoradiotherapy (less than 28 days or more than 28 days); MGMT promoter methylation expression (positive or negative). The study design was as follows: Participants were required to undergo a screening period within 14 days before randomization to determine eligibility. Subjects who met the inclusion criteria were randomly divided into two groups at a 1:1 ratio: trial group, hypofractionated concurrent chemoradiotherapy followed by at least 6 cycles of adjuvant temozolomide; The control group was treated with the existing standardized treatment (standard dose of concurrent chemoradiotherapy and at least 6 cycles of temozolomide adjuvant chemotherapy). Experimental group: subjects randomly assigned to the experimental group were required to start treatment within 7 working days. The experimental group received hypofractionated radiotherapy with a total dose of 52.5Gy, 3.5 Gy/ fraction, 15 fractions, 5 fractions per week, and temozolomide was given for 21 days. Sequential temozolomide chemotherapy was started 4 weeks after the end of chemoradiotherapy. Sequential chemotherapy was given 5 days before each 28-day cycle. During the study period, the experimental group was required to complete the vital signs, physical examination, laboratory examination and other examinations within the specified period. After randomization, the experimental group underwent radiologic response assessments (or as deemed necessary by the investigator based on clinical symptoms) and QOLs at the end of radiotherapy, 3-4 weeks after the end of radiotherapy, and every 12 weeks (±7 days). Radiologic response assessments required plain and contrast-enhanced magnetic resonance imaging. If there were residual lesions after surgery, measurable lesions were evaluated according to RANO standard case criteria. Control group: subjects randomly assigned to the experimental group were treated within 7 working days. The control group received conventional fractionated radiotherapy with a dose of 60Gy, 2Gy per fraction, 30 fractions, 5 fractions per week, and temozolomide was given for a total of 42 days. Sequential temozolomide chemotherapy was started 4 weeks after the end of chemoradiotherapy. Sequential chemotherapy was given 5 days before each 28-day cycle. During the study period, the experimental group was required to complete the vital signs, physical examination, laboratory examination and other examinations within the specified period. After randomization, the experimental group underwent radiologic response assessments (or as deemed necessary by the investigator based on clinical symptoms) and QOLs at the end of radiotherapy, 3-4 weeks after the end of radiotherapy, and every 12 weeks (±7 days). Radiologic response assessments required plain and contrast-enhanced magnetic resonance imaging. Measurable lesions assessed according to RANO criteria were required if residual lesions were present after surgery.
• Newly diagnosed glioblastoma confirmed by histopathology or molecular pathology;
• Complete or partial tumor resection or biopsy via neurosurgery;
• The age of signing the informed consent form was 18-70 years old, male or female; (4) KPS score ≥60; (5) expected survival time ≥6 months;
⁃ 6\. Radiotherapy should be started within 6 weeks after surgery; 7. Vital organ function meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days) : Normal bone marrow reserve: white blood cell (WBC) ≥3.0×109/L, neutrophil count (NEUT) ≥1.5×109/L, platelet count (PLT) ≥80×109/L, hemoglobin (Hb) ≥90 g/L Normal renal function or serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥50 ml/ minute (Cockcroft-Gault equation) Normal liver function or total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN); 8. Able and willing to follow the study and follow-up procedures; 9. Men and women of childbearing potential must agree to use adequate contraception throughout the study and for 6 months after the end of treatment. Female subjects of childbearing potential were required to have a negative blood pregnancy test within 72 hours before the first dose.
⁃ 10\. The subjects voluntarily participated in this clinical study and signed the informed consent form. The compliance was good and the subjects could cooperate with the follow-up.