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.
A 72-year-old male presented to his family doctor with a 3 week history of headache and dizziness. His medical history was unremarkable except for left-sided nephrectomy for clear cell renal cell cancer stage T2 N0 M0 8 years earlier. Diagnostic imaging with brain computed tomography (CT) scan followed by magnetic resonance imaging (MRI) revealed a 3 cm large contrast-enhancing infratentorial tumor (Figure ). No additional brain lesions were detected. CT of chest and abdomen revealed 2 small lung nodules (one left-sided, one right-sided) and enlarged mediastinal lymph nodes (Figure ). Neurosurgical resection of the intracranial tumor confirmed metastasis from clear cell carcinoma. Neither postoperative radiotherapy nor systemic treatment was recommended at this time. Surveillance CT scans showed very slow enlargement of the lung and lymph node metastases during the next year. Seventeen months after resection of the cerebellar metastasis, local recurrence was detected. The patient was treated with gamma knife SRS (peripheral dose 21 Gy). Six months later, a single new brain metastasis was found (8 mm large, left occipital lobe), which also was treated with SRS. Seven months after the second SRS procedure, a third one was added after diagnosis of two new infratentorial brain lesions (cerebellum and brain stem, respectively). Treatment planning MRI also revealed a contrast-enhancing extramedullary mass at the level of the 5th cervical vertebra. Additional scans of the spine showed at least two more small metastases in the lower thoracic and upper lumbar region (Figure ). No cerebrospinal fluid (CSF) examination was performed as imaging and history were consistent with a diagnosis of NM. The involved regions were treated with fractionated external beam radiotherapy (10 fractions of 3.5 Gy). At that time, the patient had a Karnofsky performance status (KPS) of 70. He had no new focal neurologic deficits, but continued to experience dizziness and gait disturbance since his first SRS procedure. Because of intense pain in different skeletal regions, a radioisotope bone scan was performed, which showed bone metastases in the corresponding areas. These metastases were confirmed by radiographs and/or CT. Analgetic treatment with opiods was started and external beam radiotherapy fields were added to parts of the pelvis, femur and shoulder. For the first time during follow-up, elevated lactate dehydrogenase levels (266 U/L) and lymphopenia (0.3 × 109/L) were seen. The known lung and lymph node lesions continued to progress slowly (Figure ). Three weeks after radiotherapy, the first systemic treatment was initiated, consisting of sunitinib 50 mg per day. After two weeks on sunitinib, the patient presented to the emergency room with chills and reduced general condition. Fever (38.7°C), elevated C-reactive protein (CRP) level (235 mg/L), leukopenia (3.2 × 109/L) and thrombopenia (73 × 109/L) were found. Blood- and urine cultures were negative. Chest X-ray showed a small infiltrate. Sunitinib treatment was stopped and antibiotic therapy initiated. The patient recovered, but was still unable to reduce analgesics and had a KPS of 50. The treating oncologists decided to stop active cancer treatment. Three weeks later, he began to lose strength in the lower extremities. Steroid treatment was unsuccessful. Imaging was not repeated as management would not have been altered. Another three weeks later, the patient again presented to the emergency room with chest pain, dyspnea and tachycardia. Chest X-ray revealed pneumonia, CRP was elevated to 228 mg/L, leukocyte counts normal (6.6 × 109/L). In spite of antibiotic treatment, the patient succumbed to his disease a few hours after admission. Survival was 11 years from nephrectomy, 35 months from initial diagnosis of brain and lung metastases, and 4 months from NM and bone metastases.