scholarly journals High-resolution MRI demonstrates that more than 90% of small intracranial melanoma metastases develop in close relationship to the leptomeninges

2019 ◽  
Author(s):  
Arian Lasocki ◽  
Chloe Khoo ◽  
Peter K H Lau ◽  
David L Kok ◽  
Grant A Mcarthur
Keyword(s):  
Local Therapy ◽  
Leptomeningeal Disease ◽  
Pia Mater ◽  
Preferential Site ◽  
High Resolution Mri ◽  
Melanoma Metastases ◽  
Close Relationship ◽  
Size And Morphology ◽  
Brain Parenchymal ◽  
Novel Therapeutic Strategies

Abstract Background Despite classic teaching that intracranial metastases typically arise at the gray–white matter junction, small intracranial melanoma metastases (IMM) are frequently observed at the interface between the cortex and leptomeninges (ie, “corticomeningeal interface”), suggesting possible leptomeningeal origin. Methods MRI brain examinations of melanoma patients treated at a specialist oncology center from July 2015 to June 2017 were retrospectively reviewed. The MRI examination on which IMM were first visible was identified, utilizing 1 mm volumetric postcontrast imaging prior to local therapy. Individual metastases (up to 10 per patient) were assessed for the presence of leptomeningeal contact, as well as their number, size, and morphology. Lesions ≥10 mm in long axis were excluded, in order to examine early metastatic disease. Results Seventy-five patients had evidence of IMM. Fifteen patients had only lesion(s) measuring ≥10 mm at diagnosis, leaving 60 patients. One hundred ninety-two individual metastases were examined (median 2 per patient; interquartile range, 1–4), 174 (91%) demonstrating leptomeningeal contact. A nodular morphology was observed in 154 of 192 (82%), 32 (17%) were ovoid but elongated along the cortex, and 6 (3%) were linear. Only 3 patients (5%) also exhibited a “classic” linear leptomeningeal disease appearance. Conclusions Most IMM measuring between 2 and 9 mm in diameter are corticomeningeal nodules. These data raise the hypothesis that deeper parenchymal extension of IMM occurs secondarily. If the leptomeninges provide a preferential site for establishment of IMM, further investigation of the underlying biology of this phenomenon may provide opportunities for novel therapeutic strategies for patients with IMM. Key Points 1. Most small IMM develop at the corticomeningeal interface, rather than the gray‒white junction. 2. This suggests that the pia mater provides a preferential site for establishment of IMM. 3. Deeper brain parenchymal extension may occur secondarily.

Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9508-9508
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Phase 2 Study ◽  
Melanoma Brain Metastases ◽  
Secondary Endpoints ◽  
Local Brain ◽  
Clinical Trial Information

9508 Background: Preliminary data from the ABC (76 pts) and CheckMate 204 (94 pts) trials showed that nivo and nivo+ipi have activity in active melanoma brain metastases, with durable responses in a subset of pts. Here, we report updated 5-yr data from all pts enrolled on the ABC trial (NCT02374242). Methods: This open-label ph2 trial enrolled 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014-Apr 2017. Pts with asymptomatic brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3Wx4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets i) that failed local therapy, ii) with neuro symptoms and/or iii) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥wk12. Key secondary endpoints were IC PFS, overall PFS, OS, & safety. Results: A total of 76 pts (med f/u 54 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. Efficacy and toxicity are shown in the table. There were no treatment-related deaths. 1/17 deaths in cohort A & 4/16 in cohort B were due to IC progression only. Conclusions: Nivo monotherapy and ipi+nivo are active in melanoma brain mets, with durable responses in the majority of patients who received ipi+nivo upfront. A study of upfront ipi+nivo+/-SRS is underway (NCT03340129). Clinical trial information: NCT02374242. [Table: see text]

A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9508-9508 ◽  
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Alexander M. Menzies ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Previously Treated

9508 Background: Nivolumab (nivo) and the combination of nivo + ipilimumab (ipi) improve response rates (RR) and progression-free survival (PFS) compared with ipi alone in clinical trials of metastatic melanoma pts, but pts with untreated brain mets were excluded. Brain mets are a major cause of morbidity and mortality in melanoma and their management is critical. We sought to determine the antitumour activity and safety of nivo and nivo+ipi in pts with active melanoma brain mets (NCT02374242). Methods: This open-label, ph II trial enrolled 3 cohorts of pts naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014 - Feb 2017. Pts with asymptomatic melanoma brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3W x4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets 1) that failed local therapy (new +/- progressed in previously treated met), 2) were neurologically symptomatic and/or 3) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥ wk12. Secondary endpoints were best extracranial response (ECR), best overall response (OR), IC PFS, EC PFS, overall PFS, OS, and safety. Results: A total of 66 pts (med f/u 14 mo) were included in this analysis of total 76 planned; median age 60y, 77% male. For cohorts A, B and C: elevated LDH 48%, 58% and 19%; V600BRAF 44%, 56% and 81%; prior BRAFi 24%, 24%, 75%. Table shows RR, PFS and OS. ICR in cohort A treatment naïve vs prior BRAFi was 53% vs 16%. Treatment-related gd 3/4 toxicity in cohorts A, B and C were 68%, 40% and 56%, respectively. There were no treatment-related deaths. Conclusions:Nivo monotherapy and ipi+nivo and are active in melanoma brain mets. Ipi+nivo had reduced activity in pts who progressed on BRAFi. Pts with symptomatic brain mets, leptomeningeal mets or previous local therapy responded poorly to nivo alone. Clinical trial information: NCT02374242. [Table: see text]

P14.70 BMScope: A systematic mapping review of brain/leptomeningeal metastasis clinical studies from 2010 to 2020

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii51-ii51
Author(s):  
V W T Cheng ◽  
R Heywood ◽  
R Zakaria ◽  
R Burger ◽  
A Fitzpatrick ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Brain Metastasis ◽  
Clinical Studies ◽  
Web Application ◽  
Observational Studies ◽  
Local Therapy ◽  
Leptomeningeal Metastasis ◽  
Bibliographic Databases ◽  
Leptomeningeal Disease ◽  
Geographical Regions

Abstract BACKGROUND Brain metastasis (BM) and leptomeningeal disease (LMD) are typified by a poor prognosis and are an area of unmet clinical need. Historically, patients with central nervous system (CNS) disease have been excluded from systemic therapy clinical trials, particularly with active/leptomeningeal disease. However, increasing prevalence of CNS metastasis is leading to greater interest in BM/LMD. We performed a descriptive analysis of clinical studies investigating BM/LMD management, published between Jan 2010 to Mar 2020. METHODS A comprehensive, customised search strategy was devised for 12 online bibliographic databases, using the following concepts: “clinical study”, “brain metastasis”, “leptomeningeal disease”, “intervention”, “patient-related outcome”. Double screening for inclusion/exclusion was performed on the Rayyan QCRI web application. Published abstracts were also screened for inclusion from ASCO, ESMO, SNO and EANO between 2015–2020. Following full text screening, conflicts were resolved by consensus and data were extracted using an online standardised tool. Data analysis and data visualisation were performed on the R statistical package. RESULTS Overall, 33118 published studies were double screened; 2632 full publications and 628 abstracts were included. Of these, 14.7% reported on unique interventional clinical trials (phase 2 = 267; phase 3 = 80). More than three times the number of clinical trials investigating systemic agents as the sole therapy for BM/LMD were published in Q1 2020 compared to the whole of 2010 (16 vs 5). 42.5% of clinical trials employed a form of local therapy (brain targeted radiotherapy or neurosurgery). Studies reported on patients with BM (n = 2738), LMD (n = 110) or both (n = 119). The majority of studies were performed in North America, Europe or East Asia (88.5% vs 11.5% rest of the world). The top 3 nations involved in published studies were the USA (n = 1155), China (n = 351) and Germany (n = 334). Network analysis demonstrated increasing links between countries. In line with expected BM prevalence, the main tumour sites studied were lung (23.4%), gastrointestinal (17.5%), breast (15%) and melanoma (12.5%). A rising trend of published BM/LMD studies over time was noted, with 83 observational studies/10 clinical trials in 2010 vs. 454 observational studies/80 clinical trials in 2019. CONCLUSION These findings demonstrate that over the last decade there has been a growth in BM/LMD research; likely reflecting an increasing disease prevalence, availability of novel and potentially CNS active agents, as well as more advanced local therapy modalities. BM/LMD clinical research is dominated by a few geographical regions and nations; however, there is an apparent shift to more international collaboration. This comprehensive mapping exercise will enable targeted systematic reviews of the existing evidence base on BM/LMD management.

scholarly journals Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

2021 ◽  
Vol 9 (12) ◽  
pp. e003730
Author(s):  
Giuseppe Minniti ◽  
Gaetano Lanzetta ◽  
Luca Capone ◽  
Martina Giraffa ◽  
Ivana Russo ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Combined Treatment ◽  
Leptomeningeal Disease ◽  
Group 14 ◽  
Resection Cavity ◽  
Secondary Endpoints ◽  
Radiation Induced ◽  
Brain Parenchymal

PurposeImmunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS.Patients and methodsOne hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity.ResultsSixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02).ConclusionsPostoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.

Functional information from magnetic resonance imaging

1995 ◽  
Vol 53 ◽  
pp. 84-85
Author(s):  
Alan P. Koretsky ◽  
Afonso Costa e Silva ◽  
Yi-Jen Lin
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
High Resolution ◽  
Cancer Biology ◽  
Imaging Modality ◽  
Magnetic Resonance Images ◽  
Great Success ◽  
Functional Information ◽  
Resonance Imaging ◽  
High Resolution Mri

Magnetic resonance imaging (MRI) has become established as an important imaging modality for the clinical management of disease. This is primarily due to the great tissue contrast inherent in magnetic resonance images of normal and diseased organs. Due to the wide availability of high field magnets and the ability to generate large and rapidly switched magnetic field gradients there is growing interest in applying high resolution MRI to obtain microscopic information. This symposium on MRI microscopy highlights new developments that are leading to increased resolution. The application of high resolution MRI to significant problems in developmental biology and cancer biology will illustrate the potential of these techniques.In combination with a growing interest in obtaining high resolution MRI there is also a growing interest in obtaining functional information from MRI. The great success of MRI in clinical applications is due to the inherent contrast obtained from different tissues leading to anatomical information.

Minding the Close Relationship

1999 ◽  
Author(s):  
John H. Harvey ◽  
Julia Omarzu
Keyword(s):  
Close Relationship

The Solution Strategy as an Indicator of the Developmental Stage of Preschool Children’s Mental-Rotation Ability

2010 ◽  
Vol 31 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Claudia Quaiser-Pohl ◽  
Anna M. Rohe ◽  
Tobias Amberger
Keyword(s):  
Preschool Children ◽  
Mental Rotation ◽  
Latent Class ◽  
Preschool Age ◽  
Stage Model ◽  
Solution Strategy ◽  
Thinking Aloud ◽  
Transition Analysis ◽  
Solution Strategies ◽  
Close Relationship

The solution strategies of preschool children solving mental-rotation tasks were analyzed in two studies. In the first study n = 111 preschool children had to demonstrate their solution strategy in the Picture Rotation Test (PRT) items by thinking aloud; seven different strategies were identified. In the second study these strategies were confirmed by latent class analysis (LCA) with the PRT data of n = 565 preschool children. In addition, a close relationship was found between the solution strategy and children’s age. Results point to a stage model for the development of mental-rotation ability as measured by the PRT, going from inappropriate strategies like guessing or comparing details, to semiappropriate approaches like choosing the stimulus with the smallest angle discrepancy, to a holistic or analytic strategy. A latent transition analysis (LTA) revealed that the ability to mentally rotate objects can be influenced by training in the preschool age.

Speeded Paper-Pencil Sustained Attention and Mental Speed Tests

2008 ◽  
Vol 29 (4) ◽  
pp. 205-216 ◽  
Author(s):  
Stefan Krumm ◽  
Lothar Schmidt-Atzert ◽  
Kurt Michalczyk ◽  
Vanessa Danthiir
Keyword(s):  
Sustained Attention ◽  
Time Pressure ◽  
Factor Model ◽  
Higher Order ◽  
Future Research ◽  
Perceptual Speed ◽  
Speed Factor ◽  
Close Relationship ◽  
Task Processing ◽  
Order Factor

Mental speed (MS) and sustained attention (SA) are theoretically distinct constructs. However, tests of MS are very similar to SA tests that use time pressure as an impeding condition. The performance in such tasks largely relies on the participants’ speed of task processing (i.e., how quickly and correctly one can perform the simple cognitive tasks). The present study examined whether SA and MS are empirically the same or different constructs. To this end, 24 paper-pencil and computerized tests were administered to 199 students. SA turned out to be highly related to MS task classes: substitution and perceptual speed. Furthermore, SA showed a very close relationship with the paper-pencil MS factor. The correlation between SA and computerized speed was considerably lower but still high. In a higher-order general speed factor model, SA had the highest loading on the higher-order factor; the higher-order factor explained 88% of SA variance. It is argued that SA (as operationalized with tests using time pressure as an impeding condition) and MS cannot be differentiated, at the level of broad constructs. Implications for neuropsychological assessment and future research are discussed.

How Can We Explain a Close Relationship?

PsycCRITIQUES ◽  
2012 ◽  
Vol 57 (41) ◽  
Author(s):  
Victor Cicirelli
Keyword(s):  
Close Relationship
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