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.[]
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.