A previously healthy 56-year-old man developed gradual left- side hemiparesis, more accentuated in the lower limb (July 2016). A brain computerized tomography (CT)-scan and complementary magnetic resonance imaging (MRI) showed a solitary metastatic lesion (Met 1) in the right central sulcus (11.95 cc) with extensive perilesional edema [ and ]. The investigative tumor screening, including a CT- scan of the thorax and abdomen, revealed a suspect primary tumor in the left kidney as well as multiple, disseminated metastatic lesions in the lungs, liver, peri-aortic abdominal nodes, and left adrenal gland. A thrombotic mass positioned within the boundaries of the left renal vein was also reported. The subsequent biopsy revealed a clear cell renal cancer, Fuhrman Grade 2, as the primary. Due to the underlying extension of metastatic activity, nephrectomy was not indicated. Because of his relatively young age and previous healthy condition, the patient was accepted for upfront RRR- treatment of Met 1, structured on three separate fractions (GKRS 1–3) over a 7-day period [ and ]. This strategy aimed to sustain the patient’s performance status by avoiding further neurological deterioration while providing a window to start first-line targeted therapy (sunitinib). The rationale behind RRR can be found elsewhere in the literature.[-,]\nFollow-up MRI at 1, 3, and 6 months confirmed subsequent tumor volume reduction of Met 1 with ensuing significant improvement of the patient’s motor function []. Notably, a discrete, nonsymptomatic adverse radiation effect (ARE) around Met 1 was reported at 3 months, however, this subsequently resolved at 6 and 10 months. Despite the positive evolution of Met 1, the corresponding follow-up MRI at 10 months demonstrated a new, large metastatic lesion (17.3 cc) with extensive perilesional edema within the confinements of the left frontotemporal region, threatening the area of Broca and the insular region (Met 2). A parasagittal micrometastasis in the posterior boundaries of the left temporal lobe was also reported (Met 3). Despite further thoracic disease progression on anti-PD1 treatment (nivolumab), the patient’s clinical condition remained stable (Karnofsky Performance Scale [KPS] 90, recursive partitioning analysis [RPA] Class II); it was, therefore, decided to treat Met 2 with RRR and Met 3 with SF-GKRS [ and ] before switching systemic treatment to axitinib.\nMet 2 decreased in volume by 15% between GKRS 1 and GKRS 3. Follow-up MRI at 14 months after RRR-treatment of Met 1 (=2 months after RRR-treatment of Met 2) showed further tumor volume reduction of Met 2 while Met 1 and Met 3 remained unchanged [-]. However, edema increment around Met 2 was also reported, suggesting an additional focal (yet asymptomatic) ARE. Due to further radiological evidence of extracranial disease progression (CT-scan thorax and abdomen, October 2017), low- tolerance to axitinib and the patient’s own choice, further systemic therapy was altogether disrupted 14 months post- RRR of Met 1. Last follow-up MRI (20 months after RRR of Met 1) showed almost complete ablation of all GKRS-treated lesions and a reduction in perifocal edema surrounding Met 2, without major corticosteroid intervention [- and -]. Despite remaining free from motor-sensory deficits, epileptic seizures (Engel score of 1) or cognitive impairment, the patient promptly deteriorated at this stage due to extracranial disease progression (KPS 50, RPA 3). The patient succumbed to his disease 21 months post-RRR-treatment of Met 1.
A 75-year-old man was diagnosed in June 2016 with right-sided pleural desmoplastic mesothelioma. He had a previous history of smoking and exposure to asbestos as well as substantial underlying cardiovascular comorbidity. Curative treatment was deemed not feasible. While awaiting palliative antitumoral treatment, the patient experienced impaired balance, severe rotational vertigo, nausea, and vomiting. Brain CT and MRI in July 2016 revealed a solitary 20-mm metastasis with slight surrounding edema in the left middle cerebellar peduncle and extending along the tentorium (M1). V4 was minimally compressed without hydrocephalus. Corticosteroid therapy was initiated but microsurgery was deemed not feasible due to previous cardiovascular morbidity. Systemic palliative chemotherapy was initiated and he was referred for GKRS as no other treatment options remained available for M1. The patient underwent 3R-intervention for his solitary lesion in August 2016. KPS was estimated as 70–80 and RPA as 2 at GKRS 1 during steroid treatment de-escalation. KPS subsequently improved to 80 at GKRS 2 and 90–100 at GKRS 3 despite decreased steroid dose. M1 underwent a volume reduction of 22% between GKRS 1 and GKRS 3 (10.2 cm3 to 7.9 cm3) while V4 volume increased from 0.79 cm3 to 0.93 cm3 (21%). One-month follow-up with clinical assessment and MRI revealed mild fatigue presumed due to ongoing systemic antitumoral treatment (KPS 90) though without major neurological impairment, and substantial tumor volume reduction of almost 50% (10.2 cm3 at GKRS 1 to 5.6 cm3 at 4 weeks after GKRS 3). V4 volume had also increased significantly (from 0.79 cm3 at GKRS 1 to 1.31 cm3 at 4 weeks) []. A follow-up MRI at 3 months showed a small suspected recurrence with mild surrounding edema at the inferior aspect of the previous radiation field which was successfully treated in December 2016 along with ten new metastases; all eleven lesions were treated with SF-GKRS. No clinical signs of neurological deficits or radiological evidence of ARE were reported. The patient died 6 months after completion of 3R due to an aggressive, drug-resistant pneumonia.