RT-24EXTENT OF CEREBRAL RADIONECROSIS IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA (GBM) TREATED ON A CLINICAL TRIAL WITH HYPOFRACTIONATED INTENSITY-MODULATED RADIATION THERAPY (HYPO-IMRT) COMBINED WITH TEMOZOLOMIDE (TMZ) AND BEVACIZUMAB (BEV)

摘要

BACKGROUND: Hypofractionated RT schemes may result in increased occurrence of clinically-significant radionecrosis (CSRN), but this potentially might be mitigated by bevacizumab (BEV). METHODS: 30 patients received hypo-IMRT to the surgical cavity and residual tumor with a 1cm margin (PTV1) to a total dose of 60 Gy in 10 daily fractions and to the T2 abnormality with a 1cm margin (PTV2) to 30 Gy. Concurrent TMZ (75mg/m2 daily) and BEV (10mg/kg every 2 weeks) was administered followed by adjuvant TMZ and BEV for 6 months. CSRN was defined as progressive MRI changes not attributable to tumor progression resulting in neurological deficits. Differentiation from tumor progression was based on perfusion weighted imaging showing hypoperfusion in areas of MRI change. RESULTS: 16/30 developed CSRN at a median of 12.5 months. The median PTV1 volume in these patients was 131.0 cm³(range: 37.9-241.7), and the median PTV2 volume was 337.3 cm³ (range: 130.6-519.2.0). PTV1 and PTV2 volumes were not statistically different between those patients who developed CSRN and those who did not (p = .88, p = .40). Median OS of patients with CSRN was 18.4 months versus 16.9 months in those without (p = 0.05). Development of CSRN was not associated with MGMT methylation status (p = 0.66). Four patients underwent re-operation (showing 60-100% necrosis), 13 patients died, and 2/13 underwent autopsy. One patient (survival 10.1 months), showed predominantly RN with scant residual tumor cells, whereas the second (survival 17.5 months) manifested focal RN with extensive, residual, bulky leptomeningeal tumor at surrounding base of brain, brainstem, and spinal cord. CONCLUSIONS: CSRN was extensive in this cohort and not mitigated by BEV. Development of RN not only failed to prolong survival, but in at least one patient allowed development of known late complications of GBM, ie., distant spread beyond original tumor bed.