Fractionated Stereotactic Radiotherapy Combines With Bevacizumab for the Treatment of Multiple Brain Metastases in Lung Adenocarcinoma: a Prospective Controlled Phase III Study
For non-small cell lung cancer brain metastases, stereotactic radiotherapy is gradually replacing whole brain radiotherapy as the standard treatment. When patients have multiple brain metastases or larger tumors (diameter\>2cm), single session stereotactic radiotherapy (SRS) may cause significant neurological damage, so fractionated stereotactic radiotherapy (FSRT) is often used. The recent objective remission rate of FSRT is about 50%, and the 1-year intracranial control rate is about 45%, but intracranial progression remains the main factor affecting long-term survival of patients. Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor, which can improve the efficacy of cranial radiotherapy by normalizing neovascularization and improving the hypoxic state of tumor cells. In addition, bevacizumab can improve the abnormal permeability of neovascularization, reduce exudation and extracellular brain edema, thereby further alleviating the toxic side effects associated with brain radiotherapy. Based on this, this prospective, controlled phase III study will explore the efficacy and safety of the combined use of fractionated stereotactic radiotherapy and bevacizumab in multiple brain metastases of lung adenocarcinoma.
• Age ≥ 18 years old;
• Cellular or histopathological confirmation of lung adenocarcinoma;
• Prior to enrollment, brain enhanced magnetic resonance imaging showed (1) 1-2 brain metastases, with at least one diameter ≥ 3cm; or (2) ≥ 3 brain metastases, with at least one diameter ≥ 2cm; or (3) tumors located in or adjacent to the brainstem (distance\<1cm);
• At the time of enrollment, the extracranial disease status is stable;
• Eastern Cooperative Oncology Group (ECOG) physical fitness status score 0-2 points
• Normal liver, kidney, and bone marrow function within 14 days prior to enrollment: peripheral blood white blood cell count ≥ 4 × 10\^9/L; neutrophil count ≥ 1.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, hemoglobin ≥ 100g/L, serum creatinine\<1.5 times the upper limit of normal values; Bilirubin\<1.5 times the upper limit of normal value; Transaminase\<2 times the upper limit of normal value
• The patient and their family agree and sign an informed consent form.