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 41-year-old, nonsmoking female was initially diagnosed with metastatic TTF-1 positive lung adenocarcinoma in 2011. She underwent radiotherapy for her primary lesion as well as several lines of systemic treatments with initially positive but later mixed response. In March 2013, the patient reported symmetric sensory symptoms with numbness and tingling around her lips and limbs which eventually caused impaired balance. Brain MRI revealed more than 20 supra and infratentorial metastases including one to the left in the pons (M1) and signs of leptomeningeal carcinomatosis. The lesion in the pons (M1) had central necrosis and measured 25 × 30 × 26 mm at the time of diagnosis. The patient started high-dose systemic corticosteroid therapy and was treated the same month with whole brain radiation therapy (WBRT) with a dose fractionation of 4 Gy delivered over 5 consecutive days (4 Gy × 5). A follow-up MRI in July 2013 revealed volume reduction of all intracranial metastases including the pontine lesion (M1). The ensuing follow-up MRI in October 2013 demonstrated progression of M1 from 19 mm to 27 mm and slight V4 floor compression without hydrocephalus. A previously known small metastasis in the left lateral occipital lobe (M2) showed signs of progression as well. All other metastases were deemed under control at this point. To avoid further neurological impairment and V4 obstruction due to tumor growth and/or posttreatment ARE, M1 was treated by 3R in November 2013 [].\nAt the time of GKRS 1, M1 proved larger (9.2 cm3) with further perilesional edema and more apparent V4 floor compression, though still without signs of hydrocephalus. M2 had also grown slightly (from 10 to 12 mm in diameter) and was treated by SF-GKRS with 21 Gy to the 50% isodose prescription line. Apart from slight fatigue, left-sided facial numbness, and tingling the patient reported no other symptoms at the time of GKRS 1; at this stage, her KPS was estimated to be 90 and the RPA to be 1–2.\nDespite ongoing cortisone treatment, the perilesional edema remained nearly unchanged between GKRS 1 and GKRS 3; cortisone treatment was discontinued shortly after completion of GKRS 3. Nevertheless, V4 proved slightly wider at the time of GKRS 3 (from 0.9 cm3 at GKRS 1 to 1.2 cm3 at GKRS 3) and the tumor had decreased approximately 18% in volume (from GKRS 1 to GKRS 3). At 1-month follow-up, the patient was almost asymptomatic (KPS 90–100); the corresponding MRI revealed a significant reduction of tumor volume of approximately 67% (from 9.2 cm3 at GKRS 1 to 3.1 cm3 at the first follow-up) as well as renormalization of V4 boundaries (0.9 cm3 to 1.7 cm3) [; ].\nM1 developed a local ARE radiologically verified by MRI (follow-ups between March and November 2014) as well as 18F-FDG PET-CT (April and December 2014), which subsequently yielded without cortisone 6 months later (October 2014). Despite the above, the patient remained next to asymptomatic from her treated lesion during the follow-up. Unfortunately, systemic treatment eventually failed; the patient underwent SF-GKRS for several metastases (distant to M1 and M2 boundaries) from April to November 2014; her condition deteriorated steadily in December 2014, and she subsequently died in February 2015 (15 months after 3R) mainly due to intrathoracic tumor progression. Her quality of life was overall good from the time of 3R treatment and 12 months onwards.[]