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 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.