Heterogeneity in brain metastases – advanced MRI at the brain-tumour interface predicts aggressive growth patterns.

Background Brain metastases are increasingly common tumours treated as a homogenous group with SRS, surgery and whole brain radiotherapy. However, there are significant rates of local recurrence. We prospectively investigated intra- and inter-tumour heterogeneity in a series of brain metastases undergoing advanced MRI followed by image guided neurosurgical sampling from the leading edge in the course of resection. Method Pre-surgery 3T-MRI was obtained using 32 direction DTI and T1 with gadolinium. Image guided sampling was performed at the leading edge of the tumour as it was removed with reference samples from the core. Histogram analysis of regions of interest were matched to tissue locations. Growth pattern was assessed by a pathologist using a previously described classification and CD34, Ki67, necrosis and cellularity were scored semi-automatically using NIH ImageJ software. Survival and brain recurrence were recorded. Results Twenty-six cases were included. The mean diffusivity (MD) values recorded at the edge of metastases were significantly different in distribution, median and mean from those at the core (Wilcoxon matched pairs, p=.001). There was significantly higher necrosis (p=.026) and a trend to higher CD34 density at the leading edge versus the core. MD and the change in MD across the leading edge correlated with cellularity (r=-.41, p=.047) but did not predict clinical outcomes nor pathological growth pattern. Metastases which appeared more diffusely invasive pathologically had a significantly lower peritumoral fractional anisotropy (FA) (p=.039) suggesting more tract white matter disruption. These tumours also had more dense CD34 staining (r=-.55, p=.041) at their leading edge and a trend to lower survival and more rapid intracranial recurrence. Conclusion There is significant intra-tumoral heterogeneity among brain metastases and assessment of the brain-tumour interface radiologically and biologically may yield more useful information about behaviour and prognosis than assessing the whole metastasis

Surgical management of posterior fossa metastases

The diagnosis of brain metastases is associated with a poor prognosis reflecting uncontrolled primary disease that has spread to the relative sanctuary of the central nervous system. 20 % of brain metastases occur in the posterior fossa and are associated with significant morbidity. The risk of acute hydrocephalus and potential for sudden death means these metastases are often dealt with as emergency cases. This approach means a full pre-operative assessment and staging of underlying disease may be neglected and a proportion of patients undergo comparatively high risk surgery with little or no survival benefit. This study aimed to assess outcomes in patients to identify factors that may assist in case selection. We report a retrospective case series of 92 consecutive patients operated for posterior fossa metastases between 2007 and 2012. Routine demographic data was collected plus data on performance status, primary cancer site, details of surgery, adjuvant treatment and survival. The only independent positive prognostic factors identified on multivariate analysis were good performance status (if Karnofsky performance score >70, hazard ratio (HR) for death 0.36, 95 % confidence interval (CI) 0.18–0.69), adjuvant whole brain radiotherapy (HR 0.37, 95 % CI 0.21–0.65) and adjuvant chemotherapy where there was extracranial disease and non-synchronous presentation (HR 0.51, 95 % CI 0.31–0.82). Patients presenting with posterior fossa metastases may not be investigated as thoroughly as those with supratentorial tumours. Staging and assessment is essential however, and in the meantime emergencies related to tumour mass effect should be managed with steroids and cerebrospinal fluid diversion as required

Extent of resection predicts risk of progression in adult pilocytic astrocytoma.

OBJECT:Pilocytic astrocytomas are rare tumours in adults. Presentation, management and prognostic factors are poorly characterised. METHODS:Retrospective single centre study from 2000 to 2016. RESULTS:50 cases were identified (median age 29 years; range 16-76). Symptoms at presentation were neurological deficit (n = 21), headache (n = 18) and seizures (n = 6). Five were incidental findings. Five patients had hydrocephalus at presentation and required emergent management, two by endoscopic third ventriculostomy and three by external ventricular drain. Symptoms were present for a median of 16 weeks (range 1 week to 34 years). Surgery consisted of gross total resection (n = 23), subtotal resection (n = 21) or biopsy (n = 6). Progression occurred in 20 patients at a median time of 7 years following surgery and was asymptomatic in just over half of these cases. A greater degree of resection (complete vs. subtotal) was associated with longer time to progression (Kaplan-Meier analysis, log rank test = 3.58, p = 0.059). At their first progression 12 patients underwent re-resective surgery and the remainder received radiotherapy. The median 5-year survival was 80%. CONCLUSIONS:In adult patients with a pilocytic astrocytoma, a macroscopic resection should be the aim at the first resective operation. Emergency management of hydrocephalus may be required in the first instance

Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes.

DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases

Use of diffusion-weighted MRI to modify radiosurgery planning in brain metastases may reduce local recurrence

Stereotactic radiosurgery (SRS) is an effective and well tolerated treatment for selected brain metastases; however, local recurrence still occurs. We investigated the use of diffusion weighted MRI (DWI) as an adjunct for SRS treatment planning in brain metastases. Seventeen consecutive patients undergoing complete surgical resection of a solitary brain metastasis underwent image analysis retrospectively. SRS treatment plans were generated based on standard 3D post-contrast T1-weighted sequences at 1.5T and then separately using apparent diffusion coefficient (ADC) maps in a blinded fashion. Control scans immediately post operation confirmed complete tumour resection. Treatment plans were compared to one another and with volume of local recurrence at progression quantitatively and qualitatively by calculating the conformity index (CI), the overlapping volume as a proportion of the total combined volume, where 1 = identical plans and 0 = no conformation whatsoever. Gross tumour volumes (GTVs) using ADC and post-contrast T1-weighted sequences were quantitatively the same (related samples Wilcoxon signed rank test = −0.45, p = 0.653) but showed differing conformations (CI 0.53, p < 0.001). The diffusion treatment volume (DTV) obtained by combining the two target volumes was significantly greater than the treatment volume based on post contrast T1-weighted MRI alone, both quantitatively (median 13.65 vs. 9.52 cm(3), related samples Wilcoxon signed rank test p < 0.001) and qualitatively (CI 0.74, p = 0.001). This DTV covered a greater volume of subsequent tumour recurrence than the standard plan (median 3.53 cm(3) vs. 3.84 cm(3), p = 0.002). ADC maps may be a useful tool in addition to the standard post-contrast T1-weighted sequence used for SRS planning

Subcutaneous emphysema in a case of infective sinusitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Subcutaneous emphysema with pneumomediastinum is a rare phenomenon with a high morbidity and may occur spontaneously.</p> <p>Case presentation</p> <p>A 30-year-old Caucasian man presented with sudden onset of a painful, swollen neck and was found, via clinical and radiological examination to have subcutaneous emphysema. A swallow study showed no oesophageal perforation. Computed tomography of his neck and thorax demonstrated pneumomediastinum but no other pathology. Management was conservative with intravenous antibiotics, fluids and no oral intake. He had a history of a productive cough and a flexible nasoendoscopy found purulent sinusitis which was treated with topical nasal washes. The patient was discharged after 72 hours and will be followed up by the otolaryngology-head and neck service.</p> <p>Conclusions</p> <p>Infective sinusitis is a rare cause of subcutaneous emphysema and pneumomediastinum. It may be managed conservatively provided there is early recognition and exclusion of more serious pathology, such as a ruptured trachea or oesophagus.</p

Genomic alterations and the incidence of brain metastases in advanced and metastatic non-small cell lung cancer: a systematic review and meta-analysis.

BackgroundBrain metastases (BM) in patients with advanced and metastatic non-small cell lung cancer (NSCLC) are linked with poor prognosis. Identifying genomic alterations associated with BM development could influence screening and determine targeted treatment. We aimed to establish prevalence and incidence in these groups, stratified by genomic alterations.Patients and methodsA PRISMA-compliant systematic review and meta-analysis was conducted (PROSPERO ID CRD42022315915). Articles published in MEDLINE, EMBASE, and Cochrane Library between January 2000-May 2022 were included. Prevalence at diagnosis, and incidence of new BM per year were obtained, including patients with EGFR, ALK, KRAS, and other alterations. Pooled incidence rates were calculated using random effects models.ResultsSixty-four unique articles were included (24,784 NSCLC patients with prevalence data from forty-five studies and 9,058 NSCLC patients with incidence data from forty studies). Pooled BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0), and highest in patients that are ALK-positive (34.9%) or with RET-translocations (32.2%). With a median follow-up of 24 months, per-year incidence of new BM was 0.13 in the wild-type group (14 studies, 95% CI 0.11-0.16). Incidence was 0.16 in the EGFR group (16 studies, 95% CI 0.11-0.21), 0.17 in the ALK group (5 studies, 95% CI 0.10-0.27), 0.10 in the KRAS group (4 studies, 95% CI 0.06-0.17), 0.13 in the ROS1 group (3 studies, 95% CI 0.06-0.28), and 0.12 in the RET group (2 studies, 95% CI 0.08-0.17).ConclusionsComprehensive meta-analysis indicates a higher prevalence and incidence of BM in patients with certain targetable genomic alterations. This supports brain imaging at staging and follow-up, and the need for targeted therapies with brain penetrance

Management evaluation of metastasis in the brain (MEMBRAIN)—a United Kingdom and Ireland prospective, multicenter observational study

Background:In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. Methods:A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. Results:A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. Conclusions:This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making