Nineteen-Month Immunity to Adverse Radiation Effects Following 5-Fraction Re-radiosurgery With 43.6 Gy for Local Progression After Prior 3-Fraction Radiosurgery for Brain Metastasis From Pan-Negative Lung Adenocarcinoma.

Clinical management of patients with local control failure following stereotactic radiosurgery (SRS) for brain metastasis (BM) can be frequently challenging. Re-irradiation with multi-fraction (fr) SRS by using a biological effective dose of ≥80 Gy, based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED), can be an efficacious option for such a scenario with the BED of <80 Gy. However, its long-term safety beyond one year remains unclear. In this report, we describe the case of a patient with a single metachronous BM from lung adenocarcinoma (LAC), without major genetic alterations, in which re-SRS with 43.6 Gy/5 fr (BED 81.6 Gy) for local progression, following prior 3-fr SRS of the BM, resulted in sustained regression without any local adverse radiation effects (AREs) for 19 months. The BM with a gross tumor volume (GTV) of 1.12 cm in the left parietal lobe was initially treated with SRS of 27 Gy/3 fr (50% isodose). Despite steroid administration for nivolumab-induced bullous pemphigoid associated with transient elevation of tumor markers, the BM showed local progression with T1/T2 matching at 38.3 and eight months after SRS and discontinuation of nivolumab, respectively. In the 5-fr re-SRS, 99% of the GTV (1.18 cm) was covered with 43.6 Gy (63% isodose). However, along with the thoracic disease progression, multiple new BMs developed 15.5 months after the re-SRS, for which volumetric-modulated arc-based whole brain radiotherapy (WBRT) was administered, with simultaneously integrated boosts to 17 lesions and moderate dose attenuation in the pre-irradiated region. However, concurrent administration of gemcitabine and WBRT might have led to persistent severe anorexia for 2.5 months. The patient died 10.8 years after the initial chemotherapy. The relatively small GTV with the superficial location may have rendered the re-irradiated region immune to AREs after the high BED re-SRS. Long-term survival can be achieved by chemoimmunotherapy in patients with pan-negative LAC, with limited systemic metastases who are unfit for targeted agents. Therefore, SRS for limited BMs in such scenarios should aim for complete local tumor eradication beyond a partial response in either a first-line or re-irradiation setting.