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.
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.