Is Re-Irradiation of Recurrent Metastatic Brain Tumors an Option? Re-Irradiation for Metastatic Brain Tumors With Whole-Brain Radiotherapy

Background: Relapse after whole-brain radiation therapy (WBRT) for multiple cerebral metastases occurs fairly often and is associated with a poor prognosis. Re-irradiation is an option that many defer because of risks of exceeding brain tolerance and resulting toxicity. Objective: To determine if brain re-irradiation is beneficial. Design: Single-institution retrospective study. Methods: Patients with ≥2 courses of WBRT for relapse or recurrence of metastatic brain tumor between 1994 and 2009 were included. Treatment usually consisted of lateral opposing fields with 6 to 18 MV photon beams 5 days a week. Data reviewed included primary cancer location, patient age and gender, Karnofsky performance status (KPS), radiation doses and fractionation, intervals between irradiation treatments, symptomatic responses, tumor response evaluated by MRI, adverse effects using the Late Radiation Morbidity Scoring Schema, and survival. Results: Of 585 cancer patients treated with WBRT, 31 (26 with lung primary and 5 with breast primary) had at least a second course of WBRT. Mean age at re-irradiation was 56 years; 84% of patients had active extracranial disease at the time of retreatment. Initial WBRT was to 30 Gy in 10 fractions for 87%. Repeat WBRT was to 30 Gy in 10 fractions in 42% of patients. Ninety-seven percent of patients had chemotherapy, including 29% with molecular-target agents. The median interval between initial WBRT and re-irradiation was 10 months. The median survival after initial cancer diagnosis was 26 months, and median survival after reirradiation was 4 months; 65% of patients had symptomatic improvement after re-irradiation, with partial or complete tumor response of 55%. Fifty-two percent of patients had Grade 1 acute radiation reactions, including headache (29%) and nausea (26%); 23% had subacute otitis media. Of the patients studied, 36% had MRI evidence of brain atrophy after initial WBRT, and 74% did so after re-irradiation; 32% had Grade 2 or higher cognitive disturbance or encephalopathy at a median of 3 months after repeat WBRT. Of the 11 patients who died of neurogenic causes, 9 had carcinomatous meningitis. Factors associated with longer survival included lung primary and a KPS score of ≥70 at the time of re-irradiation. Conclusions: Whole-brain re-irradiation showed promising effectiveness with only a slight burden on patients in the acute phase. Reviewer's Comments: Relapse with multiple cerebral metastases after WBRT is difficult to treat. This study shows some additional survival with relatively mild adverse side effects. The authors point out several limitations in their small series -no detailed neuro-cognitive evaluation, no objective evaluation of neurological impairments, and no determination that survival or symptom improvement was related to re-irradiation. Most significantly, which patients were appropriate for re-irradiation was also not defined. A comparison of the survival and symptoms of those who underwent re-irradiation compared to those who did not, despite relapse, would have been helpful. At this point, I would consider re-irradiation with WBRT in carefully selected patients. (Reviewer-N. Scott Litofsky, MD).