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Brain metastases frequently occur in lung cancer and dramatically limit prognosis of affected patients. The influence of tumor-associated macrophages and microglia (TAM/M) and their receptor CX3CR1 on different steps of brain metastasis formation from lung cancer is poorly characterized. We established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intravital 2-photon laser scanning microscopy. This allowed in vivo tracking of fluorescence-expressing tumor cells and TAM/M on a single-cell level over weeks. Intracarotid injection of red tdTomato-fluorescent Lewis lung carcinoma cell was performed in transgenic mice either proficient or deficient for CX3CR1. After intracarotid cell injection, intravascular tumor cells extravasated into the brain parenchyma and formed micro- and mature macrometastases. We observed potential phagocytosis of extravasated tumor cells by TAM/M. However, during later steps of metastasis formation, these anti-tumor effects diminished and were paralleled by TAM/M accumulation and activation. Although CX3CR1 deficiency resulted in a lower number of extravasated tumor cells, progression of these extravasated cells into micro metastases was more efficient. Overall, this resulted in a comparable number of mature macrometastases in CX3CR1-deficient and -proficient mice. Our findings indicate that unspecific inhibition of CX3CR1 might not be a suitable therapeutic option to prevent dissemination of lung cancer cells to the brain. Given the close interaction between TAM/M and tumor cells during metastasis formation, other therapeutic approaches targeting TAM/M function may warrant further evaluation. The herein established orthotopic mouse model may be a useful tool to evaluate such concepts in vivo. [ABSTRACT FROM AUTHOR]

To report cases of extraspinal mimics of cauda equina syndrome (CES) to enable prompt diagnosis and treatment in the future. CES results from compression of spinal nerve roots. Current practice mandates lumbosacral magnetic resonance imaging (MRI) scanning to diagnose CES. However, it may not reveal compression or provide an explanation for the presentation. We present 3 cases of suspected CES who went on to have intracranial pathology. Retrospective review of all patients presenting with CES-type features who were subsequently found to have causative intracranial pathology over a 6-month period. Three cases were found, and these are hereby presented. Case Presentation: Case 1: A 57-year-old lady presented with urinary retention and bilateral leg weakness. She underwent an MRI spine which showed no evidence of CES. She was diagnosed with haemorrhagic intracranial metastases. Case 2: A 52-year-old lady presented with lower back and right buttock pain, with right-sided leg numbness, saddle hypoesthesia, and bowel and bladder incontinence. MRI spine showed no cauda equina compression. MRI neuraxis revealed a subdural haematoma. Case 3: A 69-year-old lady presented with a 6-day history of urinary incontinence, right foot drop, and leg weakness. MRI spine was negative for CES. She was diagnosed with an intraparenchymal haematoma of posterior left frontal lobe. Negative lumbosacral MRI will not exclude extraspinal mimics of CES and, although rare, these cases should be considered. [ABSTRACT FROM AUTHOR]

Small cell neuroendocrine carcinoma of the Bartholin gland is an extremely uncommon gynecologic tumor. Brain metastasis from a malignant gynecologic lesion is rarely encountered and the prognosis for this type of metastasis is quite poor. We report a case of a brain metastasis from a small cell neuroendocrine carcinoma of the Bartholin gland that was treated by surgical resection followed by whole-brain radiation therapy and review the literature. Different treatment options, including resection, stereotactic radiosurgery, and whole-brain radiation therapy, as well as chemotherapy, are available and should each be considered on an individual basis. [ABSTRACT FROM AUTHOR]

Objectives Although nivolumab has shown efficacy against non–small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce. Materials and methods We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance. Results and conclusion Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7–8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3–23%) and 11% (95% CI: 4–26%). Intracerebral control rate was 51% (95% CI: 37–66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8–11.1) and 2.8 (95% CI: 1.8–4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6–not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab’s place in treatment of NSCLC patients with BMs. [ABSTRACT FROM AUTHOR]

Background We tested the prognostic value of cumulative intracranial tumor volume (CITV) in the context of a disease-specific Graded Prognostic Assessment (ds-GPA) model for renal cell carcinoma (RCC) patients with brain metastasis (BM) treated with stereotactic radiosurgery (SRS). Methods Patient and tumor characteristics were collected from RCC cohorts with new BM who underwent SRS. Univariable and multivariable logistic regression model was used to test the prognostic value of CITV, Karnofsky Performance Score (KPS), and the number of BM. Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to assess whether CITV improved the prognostic utility of RCC ds-GPA. Results In univariable logistic regression models, CITV, KPS, and the number of BM were independently associated with RCC patient survival. In a multivariable Cox proportional hazard model, the association between CITV and survival remained robust after controlling for KPS and the number of BM ( P = 0.042). The incorporation of the CITV into the RCC ds-GPA model (consisting of KPS and number of BM) improved prognostic accuracy with NRI >0 of 0.3156 (95% confidence interval [CI], 0.0883–0.5428; P = 0.0065) and IDI of 0.0151 (95% CI, 0.0036–0.0277; P = 0.0183). These findings were validated in an independent cohort of 107 SRS-treated RCC BM patients. Conclusion CITV is an important prognostic variable in SRS-treated RCC patients with BM. The prognostic value of the ds-GPA scale for RCC brain metastasis was enhanced by the incorporation of CITV. [ABSTRACT FROM AUTHOR]

Background The goals of treating a cerebral metastasis (CM) are to achieve local control of the disease and to improve patient quality of life. The aim of this study was to analyze the effect of conventional surgery supported by intraoperative ultrasound (IOUS) to approach a CM. To perform this analysis, we determined the postoperative Karnofsky Performance Status Scale (KPS) scores and tumor resection grades. Methods Patients with a CM diagnosis were included in this study. Surgical treatment was either supported or not by IOUS. Pre- and postoperative KPS scores were determined by the oncology team, and cerebral tumor volume was estimated through pre- and postoperative magnetic resonance imaging. The surgical team determined whether it was possible to perform a total CM resection. Results There were 78 patients treated using surgical management (35 with and 43 without IOUS). In the IOUS group, the postoperative KPS scores were higher (80 vs. 70, respectively; P = 0.045) and the KPS evolution was superior ( P = 0.036), especially in the following subgroups: difficulty of tumor resection ranking score <4 ( P = 0.037), tumor in an eloquent area ( P = 0.043), tumor not associated with vessels or nerves ( P = 0.007), and solitary lesions ( P = 0.038). The residual tumor volume was lower in the IOUS group (9.5% and 1.6 mm 3 vs. 30.8% and 9 mm 3 , respectively; P = 0.05). In patients with a KPS score ≥70, 62% of them had <10% residual tumors (76% in the IOUS group and 45% in the non-IOUS group; P = 0.032; odds ratio, 3.8). Conclusions IOUS may improve postoperative KPS scores and decrease residual tumor volumes in CM surgeries. These findings should be confirmed in future studies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with limited intracranial metastatic disease traditionally have been treated with surgery followed by WBRT. However, there is growing concern for the debilitating cognitive effects after WBRT in long-term survivors. We present a series of patients treated with surgery followed by SRS, while reserving WBRT as a salvage therapy for disease progression. Methods: Medical records from 15 patients with 1 to 2 cerebral metastases who underwent both resection and SRS were reviewed. Outcome measures included overall survival, survival by RPA class, EOR, local tumor control, progression of intracranial disease, need for WBRT salvage therapy, and COD. Results: Fifteen patients with cerebral metastases were treated with the combined surgery-SRS paradigm. Eight of the 15 patients (53.3%) were designated RPA class 1, with 6 of 15 (40.0%) in class 2 and 1 of 15 (6.7%) in class 3. Gross total resection was achieved in 12 cases (80.0%). Overall median survival was 20.0 months, with values of 22.0 and 13.0 months for RPA classes 1 and 2, respectively. Local recurrence occurred in 16.7% of those patients with GTR. Six patients (40.0%) went on to receive WBRT at a median of 8.0 months from initial presentation. Twelve patients (80.0%) had died at the completion of the study, and the COD was CNS progression in 33.3%. Conclusions: Surgical resection combined with SRS is an effective treatment for selected patients with limited cerebral metastatic disease. Survival using this combined treatment was equivalent to or greater than that reported by other studies using surgery + WBRT or SRS + WBRT. [Copyright &y& Elsevier]

Abstract: We present a patient with a solitary cerebral metastasis from a transitional cell carcinoma of the right renal pelvis in the right occipital lobe with intratumoral hemorrhage. Despite aggressive multimodality management the patient died within 3 months of presentation due to widespread systemic disease. [Copyright &y& Elsevier]

Summary: Oral melanoma (OM) is an infrequent neoplasia making up less than 1% of all melanomas, and which exhibits a much more aggressive behaviour than those found on the skin. We present a case of OM located on the hard palate, vestibular alveolar gingiva of the maxilla, and upper lip in a 75-year-old patient who developed a distant metastasis on the left parietal lobe. The advanced stage of the disease contraindicated any surgical intervention and it was decided to carry out palliative radiotherapy, but the patient died before treatment. [Copyright &y& Elsevier]