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 62-year-old female patient was diagnosed in 2005 with ovarian carcinoma. She underwent surgery, several lines of antitumoral treatment, and regional fractionated radiotherapy prior to developing metastases to regional lymph nodes as well as peritoneal carcinomatosis (2008). In January 2016, the patient presented with 2-week history of nausea, vomiting, impaired balance and speech, severe swallowing difficulties, and sensory symptoms. The brain MRI demonstrated a large, solitary, 20-mm metastasis in the upper part of the medulla oblongata (M1) without significant perilesional edema, yet compressing the foramina of Luschka and Magendie with signs of mild hydrocephalus []. Corticosteroid therapy was initiated shortly thereafter. Microsurgical removal/debulking of the metastasis were deemed not feasible and 3R was offered after multidisciplinary in-hospital discussion. At the time of GKRS 1 in February 2016, KPS was estimated to be 60 and RPA 3. The corresponding dose fractionation schedule is described in . No tumor volume reduction or V4 decompression was noted between GKRS 1 and GKRS 3. A follow-up MRI at 4 weeks revealed a 54% decrease in the size of M1 (4.8 cm3 at GKRS 1 to 2.2 cm3 at follow-up). V4 volume increased (1.56 cm3 at GKRS 1 to 2 cm3 at follow-up), and the foramina of Luschka and Magendie were less compressed []. There was no evidence of hydrocephalus. The patient's neurological condition also improved dramatically at this time and KPS was estimated to be 70. The dysphagia, nausea, and vomiting disappeared, and she could articulate much better. Nevertheless, no considerable improvement in balance was reported. The patient continued systemic antitumoral treatment. Consecutive, initially monthly and later bimonthly radiological follow-ups until September 2016 (7 months after 3R) showed further volume decrease of M1. However, the patient developed mild radiation-induced perilesional edema (assessed as ARE) 5 months after treatment which slowly progressed until her last MRI at 7 months (September 2016) though without evidence of hydrocephalus. At this time, the patient was experiencing mild facial numbness almost solely limited to her right cheek and the right side of the jaw. The patient was also experiencing some more fatigue and balance impairment than usual although it was difficult to assess whether it was caused by the lesion itself and/or other factors such as aggressive systemic tumor progression, ongoing systemic treatment, and steroids. Nevertheless, despite the presence of perilesional edema, we assessed her neurological status and quality of life in relation to M1 as stable. She died 7 months after completion of 3R-treatment due to aggressive extracranial tumor disease progression.