Risk of radiation necrosis after hypofractionated stereotactic radiotherapy (HFSRT) for brain metastases: a single center retrospective study

Introduction While hypofractionated stereotactic radiotherapy (HFSRT) is being increasingly used for treating brain metastases, clinical data concerning the incidence and risk factors of its main side-effect, namely radiation necrosis (RN), remain limited. In this context, we assessed risk factors of RN in a single center series of patients with brain metastases treated with three common HFSRT dose regimens: 27 Gy in 3 fractions (27 Gy/3#), 30 Gy in 5 fractions (30 Gy/5#), and 35 Gy in 5 fractions (35 Gy/5#). Methods In total, 360 HFSRT treatments in 294 consecutive patients were retrospectively analysed. Univariable analysis (UVA) and multivariable analysis (MVA) were performed to evaluate the relationship between clinical and dosimetric factors and RN risk. Results The 12-month RN rate was 8.8%. On MVA, risk was higher in lesions receiving 27 Gy/3# (HR 3.07 95%CI [1.13;8.36], p = 0.03) and 35 Gy/5# (HR 4.22 95%CI [1.46,12.21], p < 0.01) than in lesions receiving 30 Gy/5#. Risk was also higher in patients having received immunotherapy within 3 months of HFSRT (HR 2.69 95%CI [1.10;6.56], p = 0.03) compared with those who did not. We found no association between RN risk and other tested factors, in particular prior irradiation, lesion histology, lesion location, lesion volume, or brain dosimetric factors. Conclusion In the present series, HFSRT was associated with limited RN risk. Incidence of RN was higher with dose regimens delivering a higher biologically effective dose, as well as in patients having received immunotherapy within 3 months of HFSRT.