A 67-year-old previously healthy male presented in September 2011 with a 3-week history of fatigue, dizziness, balance impairment, left-sided motor/sensory deficits, and transient mainly right-sided headache. Brain CT and MRI demonstrated a 25-mm large metastasis in the superior left cerebellar hemisphere (M1) with slight compression of the brainstem in addition to three smaller metastases in the right frontal lobe and one in the left occipital lobe. Further investigations revealed a small pulmonary lesion which was deemed unlikely to be the primary tumor. A stereotactic biopsy was, therefore, performed on one of the frontal lesions to establish a definitive diagnosis; the microscopic evaluation demonstrated a metastasis from malignant melanoma with underlying BRAF-mutation.\nThree weeks after the biopsy, the patient underwent GKRS for all metastases. At the time of treatment, his neurological condition had deteriorated with increasing paresis of the left leg requiring assisted mobilization by wheelchair (KPS 60–70; RPA 2–3). The stereotactic MRI at GKRS 1 revealed a short-interval significant size increase of M1 to 37 mm (approximately 15 cm3) with central necrosis and slight surrounding edema despite ongoing corticosteroid therapy. V4 proved now deformed and partially compressed though without radiological evidence of hydrocephalus. The lesion was assessed as inaccessible for microsurgical decompression. Due to the size of the lesion and high risk for ARE in the brainstem, M1 was adaptively treated by means of 3R []; the remaining four lesions were treated with SF-GKRS. During the three-part treatment time M1 experienced a tumor reduction of almost 10% (from 15.1 at GKRS 1 to 13.8 cm3 at GKRS 3); V4 volume increased slightly (from 0.83 cm3 at GKRS 1 to 0.93 cm3 at GKRS 3). The dose fractionation schedule is described in . The first follow-up MRI was planned 4 weeks after the third GKRS; because of increased headache/dizziness and to assess the need for post-GKRS systemic treatment the examination was performed 10 days earlier than planned (MRI at 3 weeks).\nAlthough volume assessments by LGP were technically not possible on this particular MRI due to image artefacts, M1 had higher signal on T2 with a more necrotic appearance whereas V4 remained almost unchanged. However, with supportive/ongoing corticosteroid therapy, the patient recovered some balance and strength in his left leg shortly after his examination; systemic antitumoral treatment (BRAF inhibitor dabrafenib) was started at this stage. A new follow-up MRI at 8 weeks revealed decreased volume of M1 (41% compared to MRI at GKRS 1) and diminished compression of V4 (volume of V4 increased from 0.83 cm3 at GKRS 1 to 1.43 cm3 at 8 weeks) []. Local edema had diminished. The remaining treated lesions were under control. However, a CT scan at 10 weeks was performed due to general deterioration over the previous few weeks; the examination demonstrated new areas of hemorrhage and surrounding edema adjacent to two frontal metastases which were treated with SF-GKRS, and slightly increased edema surrounding M1 although with stable V4 conditions. He died 2 weeks later (10 weeks after GKRS) in palliative care. No autopsy was performed. According to the available medical data, the patient might have died of extracranial tumor activity and possible intracranial complications.
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.