scholarly journals P39.04 ALK Positive UK: 42% of UK Patients do not Receive Regular Brain MRI Scans Despite Data Showing up to 70% of Patients Develop Brain Metastases

2021 ◽  
Vol 16 (3) ◽  
pp. S467
Author(s):  
D. Montague
2021 ◽  
Vol 22 (S2) ◽  
Author(s):  
Changhee Han ◽  
Leonardo Rundo ◽  
Kohei Murao ◽  
Tomoyuki Noguchi ◽  
Yuki Shimahara ◽  
...  

Abstract Background Unsupervised learning can discover various unseen abnormalities, relying on large-scale unannotated medical images of healthy subjects. Towards this, unsupervised methods reconstruct a 2D/3D single medical image to detect outliers either in the learned feature space or from high reconstruction loss. However, without considering continuity between multiple adjacent slices, they cannot directly discriminate diseases composed of the accumulation of subtle anatomical anomalies, such as Alzheimer’s disease (AD). Moreover, no study has shown how unsupervised anomaly detection is associated with either disease stages, various (i.e., more than two types of) diseases, or multi-sequence magnetic resonance imaging (MRI) scans. Results We propose unsupervised medical anomaly detection generative adversarial network (MADGAN), a novel two-step method using GAN-based multiple adjacent brain MRI slice reconstruction to detect brain anomalies at different stages on multi-sequence structural MRI: (Reconstruction) Wasserstein loss with Gradient Penalty + 100 $$\ell _1$$ ℓ 1 loss—trained on 3 healthy brain axial MRI slices to reconstruct the next 3 ones—reconstructs unseen healthy/abnormal scans; (Diagnosis) Average $$\ell _2$$ ℓ 2 loss per scan discriminates them, comparing the ground truth/reconstructed slices. For training, we use two different datasets composed of 1133 healthy T1-weighted (T1) and 135 healthy contrast-enhanced T1 (T1c) brain MRI scans for detecting AD and brain metastases/various diseases, respectively. Our self-attention MADGAN can detect AD on T1 scans at a very early stage, mild cognitive impairment (MCI), with area under the curve (AUC) 0.727, and AD at a late stage with AUC 0.894, while detecting brain metastases on T1c scans with AUC 0.921. Conclusions Similar to physicians’ way of performing a diagnosis, using massive healthy training data, our first multiple MRI slice reconstruction approach, MADGAN, can reliably predict the next 3 slices from the previous 3 ones only for unseen healthy images. As the first unsupervised various disease diagnosis, MADGAN can reliably detect the accumulation of subtle anatomical anomalies and hyper-intense enhancing lesions, such as (especially late-stage) AD and brain metastases on multi-sequence MRI scans.


Open Medicine ◽  
2008 ◽  
Vol 3 (4) ◽  
pp. 517-520
Author(s):  
Parmenion Tsitsopoulos ◽  
Ioannis Anagnostopoulos ◽  
Vasileios Tsitouras ◽  
Ioannis Venizelos ◽  
Philippos Tsitsopoulos

AbstractOsteogenesis imperfecta (OI) is a heritable disorder characterized mainly by connective tissue manifestations. In dinstinct cases, several neurological features have also been described. A 46-year-old male with a known family history of OI type I presented with progressive gait disturbances and diminished muscle strength. Brain MRI scans revealed an infiltrative intracranial mass occupying both frontoparietal lobes. The patient underwent surgical intervention. The histological diagnosis was an atypical (Grade II) meningioma. The bony parts demonstrated a mixture of osseous defects due to OI and infiltration by the tumor. At one-year follow up the patient′s muscle power partially returned while repeat MRI scans were negative for tumor recurrence.


2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii5-iii5
Author(s):  
Eugene Teoh ◽  
Alain Chaglassian ◽  
Nancy Tainer

Abstract Background Brain metastases occur in up to 40% of patients with cancer and are associated with poor prognosis and considerable levels of recurrence. Consequently, close follow-up with serial brain MRI is performed post-treatment to monitor for recurrent disease. Although conventional MRI (CE-T1-weighted and FLAIR/T2-weighted) is the recommended follow-up modality, it has poor specificity with limited ability to differentiate between true disease recurrence and treatment-related changes such as radiation necrosis. Therefore, alternative imaging options are sought in order to help physicians confidently diagnose treatment-related changes and thus reliably stratify the risk of continuation of a therapeutic regimen, especially given the morbidity associated with current treatments. Amino acid PET imaging agent, 18F-fluciclovine, has increased uptake in brain tumors relative to normal tissue and may be useful for detecting recurrent brain metastases. Methods NCT04410133 is a prospective, open-label, single-arm, single-dose (185 MBq ±20%) study with a primary objective to confirm the diagnostic performance of 18F-fluciclovine PET (read with conventional MRI for anatomical reference) for detection of recurrent brain metastases where MRI is equivocal. Approximately 150 subjects with solid tumor brain metastases who have undergone radiation therapy will be enrolled in this multicenter trial (~18 US sites) if they have a lesion considered equivocal on MRI that requires further confirmatory diagnostic procedures such as biopsy/neurosurgical intervention or clinical follow-up. Subjects will undergo 18F-fluciclovine PET <28 days after the equivocal MRI and 2–21 days pre-biopsy/neurosurgical intervention. Clinical follow-up will occur for 6m post-18F-fluciclovine PET. Secondary objectives include evaluation of subject- and lesion-level 18F-fluciclovine negative and positive percent agreement (equivalent to specificity and sensitivity respectively) for recurrent brain metastases, inter-reader and intra-reader agreement, and safety evaluations. Enrolment began in October 2020 and the trial is open at the time of submission.


2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv6-iv7
Author(s):  
Samuel T Chao ◽  
Alain Chaglassian ◽  
Nancy Tainer ◽  
Eugene J Teoh

Abstract BACKGROUND Brain metastases occur in up to 40% of patients with cancer and are associated with poor prognosis and considerable levels of recurrence. Consequently, close follow-up with serial brain MRI is performed post-treatment to monitor for recurrent disease. Although conventional MRI (CE-T1-weighted and FLAIR/T2-weighted) is the recommended follow-up modality, it has poor specificity with limited ability to differentiate between true disease recurrence and treatment-related changes such as radiation necrosis. Therefore, alternative imaging options are sought in order to help physicians confidently diagnose treatment-related changes and thus reliably stratify the risk of continuation of a therapeutic regimen, especially given the morbidity associated with current treatments. Amino acid PET imaging agent, 18F-fluciclovine, has increased uptake in brain tumors relative to normal tissue and may be useful for detecting recurrent brain metastases. METHODS NCT04410133 is a prospective, open-label, single-arm, single-dose (185 MBq ±20%) study with a primary objective to confirm the diagnostic performance of 18F-fluciclovine PET (read with conventional MRI for anatomical reference) for detection of recurrent brain metastases where MRI is equivocal. Approximately 150 subjects with solid tumor brain metastases who have undergone radiation therapy will be enrolled in this multicenter trial (~18 US sites) if they have a lesion considered equivocal on MRI that requires further confirmatory diagnostic procedures such as biopsy/neurosurgical intervention or clinical follow-up. Subjects will undergo 18F-fluciclovine PET <42 days after the equivocal MRI and 1–21 days pre-biopsy/neurosurgical intervention. Clinical follow-up will occur for 6m post-18F-fluciclovine PET. Secondary objectives include evaluation of subject- and lesion-level 18F-fluciclovine negative and positive percent agreement (equivalent to specificity and sensitivity, respectively) for recurrent brain metastases, inter-reader and intra-reader agreement, and safety evaluations. Enrolment began in October 2020 and the trial is open at the time of submission.


Stroke ◽  
2001 ◽  
Vol 32 (suppl_1) ◽  
pp. 363-363
Author(s):  
Charles B Bernick ◽  
Lewis H Kuller ◽  
Will T Longstreth ◽  
Corinne Dulberg ◽  
Teri A Manolio ◽  
...  

P136 Objective: Silent infarcts seen on cranial MRI scans are a risk factor for subsequent clinical stroke in the elderly. This study examines the type of clinical strokes seen in those with silent infarcts. Methods: Cranial MRI examination was completed on 3324 Cardiovascular Health Study (CHS) participants aged 65+ who were without a prior history of clinical stroke. Incident strokes were identified over an average follow-up of 4 years and classified as hemorrhagic or ischemic. Ischemic strokes were further subdivided into lacunar, cardioembolic, atherosclerotic or other/unknown. Results: Silent MRI infarcts >3mm were found in approximately 28% (n=923). Of these, 7% (n=67) subsequently had a clinically evident stroke. The characteristics of the silent MRI infarcts in those who sustained an incident stroke were as folows: 56 had only subcortical infarcts, of which 55 were <20mm; 4 had only cortical infarcts; and 7 had both cortical and subcortical infarcts. Of those with only subcortical silent MRI infarcts, 16% (n=9) went on to a hemorrhagic stroke and 84% (n=47) sustained an ischemic stroke. The ischemic strokes were subtyped as 12 cardioembolic, 3 lacunar, 2 atherosclerotic and 30 unknown/other. Considering only those with cortical silent infarcts, either alone or in combination with subcortical infarcts, there was 1 hemorrhagic stroke and 10 ischemic strokes. Half of the ischemic strokes were cardioembolic and half were unknown type. Conclusion: Elderly individuals with silent subcortical infarcts who go onto subsequent stroke may be at risk not only for lacunar infarcts but also cardioembolic or hemorrhagic strokes.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1804
Author(s):  
Georgios Tsakonas ◽  
Caroline Kamali ◽  
Luigi De Petris ◽  
Signe Friesland ◽  
Rolf Lewensohn ◽  
...  

Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors. Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden. Information about demographics and clinicopathological parameters were collected. Predictors of overall survival (OS) were identified by Cox regression analyses. A bootstrap validation with 1000 samples was performed in order to compare the different prognostic scores. Results: The variables found to independently influence OS in the multivariate analysis, i.e., PS, sex and brain metastases at diagnosis, were used as prognostic variables in our new prognostic index (ALK-BPI). Patients were divided into two prognostic groups. The median OS was 65.7 months for the good prognostic group and 22.7 months for the poor prognostic group (p = 0.0068). In the univariate analysis of the different prognostic scores, ALK-BPI performed better than the others (HR = 3.6; 95% CI: 1.3–9.9). The mean C-statistics of the different prognostic scores were compared to each other, and no significant difference was observed. Conclusion: We propose the ALK-BPI score as a new prognostic tool that can easily be applied for ALK-positive lung cancer patients with brain metastases in daily clinical practice, as it has at least the same prognostic value as Lung-molGPA.


2020 ◽  
Vol 6 (1) ◽  
pp. e387 ◽  
Author(s):  
Annalisa Vetro ◽  
Tiziana Pisano ◽  
Silvia Chiaro ◽  
Elena Procopio ◽  
Azzurra Guerra ◽  
...  

ObjectiveTo describe clinical, biochemical, and molecular genetic findings in a large inbred family in which 4 children with a severe early-onset epileptic-dyskinetic encephalopathy, with suppression burst EEG, harbored homozygous mutations of phosphatidylinositol glycan anchor biosynthesis, class P (PIGP), a member of the large glycosylphosphatidylinositol (GPI) anchor biosynthesis gene family.MethodsWe studied clinical features, EEG, brain MRI scans, whole-exome sequencing (WES), and measured the expression of a subset of GPI-anchored proteins (GPI-APs) in circulating granulocytes using flow cytometry.ResultsThe 4 affected children exhibited a severe neurodevelopmental disorder featuring severe hypotonia with early dyskinesia progressing to quadriplegia, associated with infantile spasms, focal, tonic, and tonic-clonic seizures and a burst suppression EEG pattern. Two of the children died prematurely between age 2 and 12 years; the remaining 2 children are aged 2 years 7 months and 7 years 4 months. The homozygous c.384del variant of PIGP, present in the 4 patients, introduces a frame shift 6 codons before the expected stop signal and is predicted to result in the synthesis of a protein longer than the wild type, with impaired functionality. We demonstrated a reduced expression of the GPI-AP CD16 in the granulocytic membrane in affected individuals.ConclusionsPIGP mutations are consistently associated with an epileptic-dyskinetic encephalopathy with the features of early infantile epileptic encephalopathy with profound disability and premature death. CD16 is a valuable marker to support a genetic diagnosis of inherited GPI deficiencies.


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