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.
We present the case of a 50-year-old male patient reporting intermittent upper abdominal pain throughout 2012 and 2013. In February 2014, the patient experienced breathing difficulties and exacerbation of pain. Fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed high FDG uptake in a large, heterogeneous intrathoracic mass in the middle mediastinum abutting the right atrium and the right hemidiaphragm, without evidence of distant metastases. The patient underwent subtotal primary tumor resection in April 2014. The histopathology demonstrated a poorly differentiated thymic carcinoma though without primary malignant manifestation in the gland itself. The patient received three adjuvant chemotherapy sessions (Carboplatine/Vepesid) followed by fractionated radiotherapy (2 Gy/day, 30 sessions = 2 Gy × 30 = 60 Gy) to the right thoracic region (July to September 2014). The patient developed paroxysmal atrial fibrillation after thoracic surgery as well as a series of respiratory infections during and after his radiochemotherapy, though without serious sequelae. His general condition remained otherwise stable. By February 2015, the patient developed progressive expressive dysphasia. A brain magnetic resonance imaging (MRI) in May 2015 showed a 3.5 cm ring-enhancing lesion in the left temporal lobe with extensive edema (metastasis # 1 = M1). Speech impairment resolved shortly after gross total resection (GTR). The histopathology proved the lesion to be a thymic carcinoma metastasis with MIB 1 proliferation index of up to 50%. Postsurgical hypofractionated LINAC-radiotherapy (6 Gy/day, 5 sessions = 30 Gy) was delivered to the surgical cavity in June 2015. CT of the neck, thorax, and abdomen in September 2015 showed no signs of distant metastases. However, a follow-up brain MRI in October 2015 demonstrated three new intracranial lesions – the first a 1.9 cm lesion in the right cerebellar hemisphere (metastasis # 2 = M2), the second, a larger extra-axial left temporal mass measuring 3.9 cm with adjacent edema and mass effect threatening the hippocampus, uncus, and language areas (metastasis # 3 = M3), and the third, a 3.0 cm dural-based left parietal lesion exerting mass effect on the sensory cortex (metastasis # 4 = M4). There was no evidence of recurrence in the surgical cavity (M1). Although M2 was relatively small, M3 and M4 were quite large (≥3 cm) and both threatened eloquent areas of the brain. By this time, the patient once again developed expressive dysphasia and mental fatigue [Karnofsky Performance Score (KPS) 90–100], though without evidence of extracranial tumour proliferation (RPA 1) on prior screening CT scan September 2015; the patient remained free from systemic treatment at this stage and was referred to our unit for further management (October 2015).\nThe radiosurgical plan was designed based on a series of factors – past/present radiological evolution, tumor localization, identification of organs at risk (OAR), tumor volume, histopathological traits of prior resected metastasis (M1), general and neurological health status (KPS/RPA), absence of extracranial tumor activity at the time of radiosurgery, positive outcome after microsurgery, and good response to prior anti-tumoral treatments (including chemotherapy and extra/intracranial radiation). Our strategy aimed to rapidly relieve/salvage the language areas, the hippocampus, and the post-central gyrus from the larger left-sided lesions (M3 and M4) within a time frame of 7 days (treatment time between RS1 and RS3) to 4 weeks (MRI at 1 month). Because of the patient's previous positive response to extra and intracranial radiotherapy, we considered the tumor to be radiosensitive and proceeded to plot a peripheral prescription dose biologically isoeffective to the cranial hypofractionated treatment delivered to the surgical cavity earlier (6 Gy × 5). To achieve maximal probability of local tumor control while minimizing the risk of focal radiation-induced adverse reaction, treatment settings included an adaptive and MRI-guided hypofractionated radiosurgical approach; the procedure would allow tumor bed dose distribution readjustments in relation to local tumor volume variations during the course of treatment. The treatment was structured on three radiosurgeries (RS) delivered every third day i.e., day 1 (RS 1), day 4 (RS 2), and day 7 (RS 3). Cranial fixation was achieved by applying a Leksell Coordinate Frame G (Elekta AB, Stockholm) prior to each RS. A stereotactic MRI was performed before each RS session (s-MRI 1, 2, 3) for proper gross tumor volume (GTV) delineation; we set no margins to the GTV (GTV = CTV = PTV). As described in Tables and , the s-MRI at the onset of treatment (day 1) showed further growth of the tumors with substantial perifocal edema, particularly adjacent to M3 (see for tumor volumes at Day 1). M2 was volumetrically optimal for conventional single dose treatment (volume = 2.7 cc). Its marginal dose (GTV = CTV) was set at 19 Gy at the 50% isodose line []. Because of their volumetric traits, aggressive growth pattern, and critical localization, we chose RRR as the best approach to treat M3 and M4. Using standard biological effective dose calculations, we set the initial GTV-prescription dose (fraction 1) for M3 and M4 to 8 Gy at the 35% isodose line []. Dural tail and peripheral zones of hemorrhage were to be included in the field of treatment. Due to underlying extensive perifocal edema, the patient was to be kept on cortisone during the course of the treatment and approximately 4 weeks thereafter.