A 62-year-old female patient was diagnosed in 2005 with ovarian carcinoma. She underwent surgery, several lines of antitumoral treatment, and regional fractionated radiotherapy prior to developing metastases to regional lymph nodes as well as peritoneal carcinomatosis (2008). In January 2016, the patient presented with 2-week history of nausea, vomiting, impaired balance and speech, severe swallowing difficulties, and sensory symptoms. The brain MRI demonstrated a large, solitary, 20-mm metastasis in the upper part of the medulla oblongata (M1) without significant perilesional edema, yet compressing the foramina of Luschka and Magendie with signs of mild hydrocephalus []. Corticosteroid therapy was initiated shortly thereafter. Microsurgical removal/debulking of the metastasis were deemed not feasible and 3R was offered after multidisciplinary in-hospital discussion. At the time of GKRS 1 in February 2016, KPS was estimated to be 60 and RPA 3. The corresponding dose fractionation schedule is described in . No tumor volume reduction or V4 decompression was noted between GKRS 1 and GKRS 3. A follow-up MRI at 4 weeks revealed a 54% decrease in the size of M1 (4.8 cm3 at GKRS 1 to 2.2 cm3 at follow-up). V4 volume increased (1.56 cm3 at GKRS 1 to 2 cm3 at follow-up), and the foramina of Luschka and Magendie were less compressed []. There was no evidence of hydrocephalus. The patient's neurological condition also improved dramatically at this time and KPS was estimated to be 70. The dysphagia, nausea, and vomiting disappeared, and she could articulate much better. Nevertheless, no considerable improvement in balance was reported. The patient continued systemic antitumoral treatment. Consecutive, initially monthly and later bimonthly radiological follow-ups until September 2016 (7 months after 3R) showed further volume decrease of M1. However, the patient developed mild radiation-induced perilesional edema (assessed as ARE) 5 months after treatment which slowly progressed until her last MRI at 7 months (September 2016) though without evidence of hydrocephalus. At this time, the patient was experiencing mild facial numbness almost solely limited to her right cheek and the right side of the jaw. The patient was also experiencing some more fatigue and balance impairment than usual although it was difficult to assess whether it was caused by the lesion itself and/or other factors such as aggressive systemic tumor progression, ongoing systemic treatment, and steroids. Nevertheless, despite the presence of perilesional edema, we assessed her neurological status and quality of life in relation to M1 as stable. She died 7 months after completion of 3R-treatment due to aggressive extracranial tumor disease progression.
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.