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.
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.[]