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The treatment of relapses of already irradiated primary brain tumors and metastases is difficult, given the limited effectiveness of systemic therapy and the risks of  surgery or re-irradiation. Here we present the results of salvage Stereotactic Radiotherapy (SRT)  for the treatment of recurrent primary brain tumors and metastases (mts) after previous radiotherapy (RT).

From January 2018 to January 2021, 100 intracranial lesions in 24 patients (pts) were re-irradiated with robotic SRT. Six pts had recurrent mts of breast cancer, eight of NSCLC, one of prostate cancer, one of melanoma, three glioblastoma, two meningioma, one intracranial hemangiopericytoma, one oligodendroglioma and one  pituitary adenoma. Previous RT on the same volume were performed with: GammaKnife in 8 pts, VMAT SRT in 5 pts, CyberKnife in 4 pts, whole-brain RT in 8 pts, post-operative IMRT in 4 pts, post-operative 3D-CRT in 3 pts. Six pts had multiple previous treatments. Median time from the previous RT was 14.5 (3-96.8) months. GTV was delineated on computed tomography (CT) and contrast-enhanced T1 magnetic resonance (MRI). Median GTV was 0.15 (0.01-36.8) cc. PTV was obtained adding an expansion to GTV of 1 mm (for brain metastases), or 3 mm (for glioblastoma). Median PTV was 0.45 (0.07-62.3) cc. Median prescribed dose was 35 (24-37.5) Gy in 1-5 fractions (median number of fractions was 5), at a median isodose of 78% (69-80%). Prophylactic corticosteroid therapy was prescribed to all pts and mannitol therapy to reduce intracranial pressure to 1 patient simultaneously treated on 21 lesions. The patients were followed up with contrast-enhanced MRI performed every three months.

SRT was delivered on a median number of 2 (1-21) lesions; five pts were treated on > 5 lesions simultaneously (7, 9, 16, 19, and 21 lesions, respectively). Acute toxicity was G2 headache in three pts (GTV>1cc or >3 lesions), controlled by increasing the dose of steroids. Three pts had less than three months of follow-up, and one patient was lost to follow-up. Median follow-up after re-irradiation in 20 evaluable patients was 9 (3.6-36.6) months. Radionecrosis occurred in only one patient (GTV>1cc). He underwent two previous VMAT SRT (prescribed dose 30 Gy in 5 fractions and 21 Gy in 3 fractions) and presented seizures. He was treated with steroids and levetiracetam. Local control was: complete response (CR) in one patient, partial response (PR) in 8 pts, stable disease (SD) in four pts, and progressive disease (PD) in 7 pts. Nine pts were dead at the last follow up (one for systemic progression and 8 with intracranial progressions). Six- and twelve-months OS were 65% and 25% respectively.

SRT for re-irradiation is feasible, with only one case of radionecrosis registered. The treatment is effective with local control registered in 65% of pts. An accurate patient selection is warranted in order to avoid toxicity and a longer follow-up is needed to confirm the low radionecrosis rate.