MRgFUS is a safe, noninvasive method to deliver spatially targeted monoclonal antibody across the BBB in patients with brain tumors.

Background/Objectives: Radiotherapy for tumors of the central nervous system (CNS) could be improved by incorporating advanced imaging techniques into treatment planning and response assessment. The objective of this narrative review is to highlight the recent developments in magnetic resonance imaging (MRI) and positron emission tomography (PET) for applications in CNS radiotherapy. Methods: Recent articles were selected for discussion, covering the following topics: advanced imaging on MRI-linear accelerators for early response assessment in glioma; PET for guiding treatment planning and response assessment in glioma; and contrast-enhanced imaging and metabolic imaging for differentiating tumor progression and radiation necrosis for brain metastasis treatment. Where necessary, searches of scholarly databases (e.g., Google Scholar, PubMed) were used to find papers for each topic. The topics were chosen based on the perception of promise in advancing specific applications of CNS radiotherapy and not covered in detail elsewhere. This review is not intended to be comprehensive. Results: Advanced MRI sequences and PET could have a substantial impact on CNS radiotherapy. For gliomas, the tumor response to therapy could be assessed much earlier than using the conventional technique of measuring changes in tumor size. Using advanced imaging on combined imaging/therapy devices like MR-Linacs would enable response monitoring throughout radiotherapy. For brain metastases, radiation necrosis and tumor progression might be reliably differentiated with imaging techniques sensitive to perfusion or metabolism. However, the lack of level 1 evidence supporting specific uses for each imaging technique is an impediment to widespread use. Conclusions: Advanced MRI and PET have great promise to change the standard of care for CNS radiotherapy, but clinical trials validating specific applications are needed.

Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change.

To determine if synchronous extrapulmonary malignancies in early stage lung cancer impact survival and cost of care in the current era of improved therapies and diagnostics. Patients with stage I and II lung cancer were identified from the Ontario Cancer Registry and prognostic factors were obtained from provincial health administrative databases. Synchronous extrapulmonary malignancies were defined as those detected within 6 months from diagnosis of the lung primary. Survival was calculated using the Kaplan-Meier method and examined based on a 6-month landmark time point. The log-rank test and Cox proportional hazards regression was used to examine the effect of synchronous primaries on survival, univariately and after adjusting for prognostic factors. Cost of care was calculated by summing fees for all provincially funded services over 3 years. In a cohort of 6890 patients, those with synchronous malignancy had a HR of 1.32 (p = 0.026) for death in stage I patients, adjusted for other factors, while no association was found for stage II patients (HR=1.00, p = 0.99). 18F-FDG-PET/CT up to 6 months prior to lung cancer diagnosis had a HR of 0.84 (p = 0.003) for death adjusted for other factors. 3-year costs of care for these patients were $79,540 versus $54,520 in those without a synchronous malignancy (p<0.001). Extrapulmonary malignancies in stage I lung cancer patients may negatively impact survival with no such association for stage II patients. 18F-FDG-PET/CT performed before lung cancer diagnosis is associated with better survival. Cost of care is higher in patients with synchronous malignancies.

Familial early-onset Alzheimer's disease (EOAD) is a rare form of dementia often caused by autosomal dominant mutations in APP , PSEN1, or PSEN2 . We report a novel PSEN2 missense variant (c.359T > G, p.Ile120Ser) that has been detected in four siblings; three of whom are affected by predominantly amnestic EOAD or mild cognitive impairment in their fifties (supported by neuroimaging biomarkers), while the youngest sibling is currently asymptomatic at age 50. Two of the siblings were also heterozygous for a variant in PSEN1 (c.118_120del, p.Asp40del). Between the two genes, the PSEN2 variant was deemed to be likely pathogenic based on segregation with EOAD, imaging biomarker analyses, and bioinformatic analyses. Reporting genetic findings in familial EOAD cases can help in classifying their pathogenic significance and improving genetic conceptualization within Alzheimer's disease.