**Brief Summary**

The goal of this clinical trial is to learn whether intensified adjuvant treatment is safe and may help delay disease progression in adults with high-risk newly diagnosed glioblastoma. High-risk newly diagnosed glioblastoma in this study includes glioblastoma that has been partially removed by surgery or glioblastoma that shows early progression or recurrence before postoperative radiotherapy.

The main questions this study aims to answer are:

• Does intensified adjuvant treatment improve median progression-free survival in participants with high-risk newly diagnosed glioblastoma?
• How long do participants survive after receiving this treatment?
• What medical problems do participants have during or after intensified adjuvant treatment?
• How often do participants develop radiation necrosis?
• How does this treatment affect participants' quality of life?

Participants will:

• Receive postoperative concurrent radiotherapy and temozolomide chemotherapy.
• Receive a higher radiation dose to the residual tumor or early recurrent/progressive lesion, while standard radiation doses are given to the tumor bed and surrounding high-risk and low-risk areas.
• Receive adjuvant temozolomide after concurrent chemoradiotherapy.
• Receive sintilimab and bevacizumab by intravenous infusion once every 21 days for up to 1 year.
• Have regular blood tests, biochemical tests, thyroid function tests, myocardial enzyme tests, electrocardiograms, and other safety assessments.
• Have enhanced brain MRI scans regularly to evaluate disease status.
• Be followed by clinic visits and/or telephone calls to collect information about disease progression, survival, side effects, later cancer treatments, and quality of life.

Inclusion Criteria:

• Voluntary participation in the clinical study: fully understands and is informed about the study and has signed the informed consent form in writing; willing to comply with and able to complete all trial procedures.

• Age: >=18 years; male or female.

• Pathologically confirmed Glioblastoma.

• Subtotal resection or recurrent/progressive disease 4-6 weeks after surgery (before radiotherapy).

• Adequate organ and bone marrow function, with no severe hematopoietic dysfunction or cardiac, pulmonary, hepatic, renal dysfunction, or immunodeficiency:

  1. Complete blood count: absolute neutrophil count (ANC) >=1.5*10^9/L (1500/mm3), platelets >=75*10^9/L, hemoglobin >=9 g/dL (if there is bone marrow involvement, platelets >=50*10^9/L, ANC >=1.0*10^9/L, hemoglobin >=8 g/dL).
  2. Liver function: serum bilirubin <=1.5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=1.5 times ULN (if there is liver involvement, AST and ALT <=5 times ULN are allowed).
  3. Renal function: serum creatinine <=1.5 times ULN.
  4. Coagulation function: INR <=1.5 times ULN; PT and APTT <=1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT at screening are within the expected range for anticoagulant therapy).

• Left ventricular ejection fraction (LVEF) >=50% on cardiac function examination.

• Negative serum pregnancy test, and effective contraceptive measures from signing the informed consent form until 6 months after the last chemotherapy.

• Thyroid-stimulating hormone (TSH), free thyroxine (FT4), or free triiodothyronine (FT3) within the normal range ±10%.

• Ophthalmologic examination: including dilated fundus examination, slit-lamp examination, and color fundus photography.

Exclusion Criteria:

• Currently participating in another clinical study, or less than 4 weeks since completion of treatment in a previous clinical study.
• History of malignancy other than Glioblastoma within the past 3 years, or another uncured primary malignancy.
• Prior history of brain radiotherapy.
• Pregnant or lactating women.
• Patients assessed as having contraindications to radiotherapy.
• Severe active comorbidity that would affect the study treatment.
• Active infection requiring systemic anti-infective treatment, including but not limited to bacterial, fungal, or viral infection.
• Within 6 months before screening, New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe poorly controlled ventricular arrhythmia, or electrocardiographic evidence of acute ischemia or myocardial infarction.
• QTcF interval >480 msec, unless secondary to bundle branch block.
• Uncontrolled concomitant disease, including but not limited to uncontrolled hypertension, active peptic ulcer disease, or hemorrhagic disease.
• Prior history of mental illness; lack of capacity for civil conduct or limited capacity for civil conduct.
• Any medical history or disease evidence, treatment, or abnormal laboratory value that may interfere with trial results or prevent the subject from fully participating in the study, or any other condition that the investigator considers unsuitable for enrollment.