Symptomatic radiation necrosis after radiotherapy for primary and metastatic brain tumors, and tumors of the adjacent tissues to the brain
Conditions
Interventions
Bevacizumab of 5mg/kg is administered intravenously every other week (day 1, day 15, day 29, day 43, day 57, and day 71), 6 cycles in total. MRI is examined after 3 cycles. Then the rest of 3 cycles a
Sponsors
Department of Neurosurgery, Osaka Medical College
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Radiation necrosis occurring 3 months after radiotherapy for primary and metastatic brain tumors, and tumors of the adjacent tissues to the brain; Patients with symptomatic radiation necrosis; A lesion was enhanced by contrast medium accompanying to peri-lesional edema on MRI; Radiation necrosis is diagnosed with F-BPA-PET or C-MET-PET and tumor recurrence is denied; With regard to F-BPA-PET, lesion/normal ratios of less than 2.0 and 2.5 were absolute and relative indications for bevacizumab treatment, respectively. With regard to C-MET-PET, L/N ratios of less than 1.25 and 1.8 were absolute and relative indications for bevacizumab treatment, respectively; Karnofsky performance status more than 60% or equal; Patients are refractory to medical treatments including corticosteroids, anticoagulants, and vitamin E; Patients cannot undertake necrotomy because of lesions in the eloquent area or poor general status; Adequate hematologic, hepatic, and renal function (absolute neutrophil count more than 1500mm3 or equal; platelet count more than 100000mm3 or equal; hemoglobin more than 9.5 g/dl or equal; GOT and GPT less than 2.5 folds; total bilirubin less than 2.0 mg/dl or equal; serum creatinine less than 1.2 mg/dl or equal; urine protein less than 1+ or equal; PT-INR more than 1.5 folds or equal or 1.5 to 2.5 when warfarinization); Life expectancy greater than 3 months; Able to provide written informed consent by patients or legally authorized representative; In cases of radiation necrosis with metastatic brain tumors, no active lesion is systemically detected by PET or other radiographical examinations and values of tumor marker are within normal limit if they are examined.
Exclusion criteria
Exclusion criteria: Patients are able to undertake necrotomy; Intracranial tumors are active and recurrent (L/N ratio on F-BPA-PET is greater than 2.5, or L/N ration on C-MET-PET is greater than 1.8; Patients require intravenous administration of antibiotics, antiviral drugs, and antifugal drugs for infection; Febrile patients more than 38 degree Celsius of body temperature or equal; Patients having severe comorbidities such as heart diseases, pulmonary fibrosis, interstitial pneumonia, hemorrhagic diathesis, uncontrollable hypertension or diabetes; *Comorbidity or history of unstable angina and myocardiac infarction within 6 months *Uncontrollable peptic ulcer *Uncontrollable hypertension *Unhealed advanced wound or fracture *Comorbidity or history of gastrointestinal perforation and fistula, and abdominal abscess within 6 months *Comorbidity or history of emoptysis and pulmonary hemorrhage greater than Grade 1 *Comorbidity or history of vascular diseases (venous and arterial thrombosis and embolism, aortic aneurysms) required interventions within 6 months *Congestive heart failure more than NYHA class I *Patients with a schedule of an operation during this study or patients having had an operation within 4 weeks; Patients with hemorrhage (intracranial hemorrhage, gastrointestinal hemorrhage, urinary hemorrhage, hemoptysis); PT-INR is greater than 2.5 or unstable when warfarinization; History of severe hypersensitivity or allergy to bevacizumab; Pregnant patients, patients with a possibility of pregnancy, or patients breastfeeding; Investigators judge patients who are inappropriate to include this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Peri-lesional edema is decreased by more than 30% or equal on MRI after bevacizumab treatment and this reduction has been maintained for 4 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety of bevacizumab treatment; The amount of corticosteroids used; The improvement of patient's performance status after bevacizumab; The recurrence rate of radiation necrosis within one year from bevacizumab treatment; The improvement of enhanced area by contrast medium on MRI | — |
Countries
Japan
Contacts
Public ContactShin-Ichi Miyatake
Osaka Medical College Neurosurgery
Outcome results
None listed