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 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.