Precision medicine is the customization of therapy for specific groups of patients using genetic or molecular profiling. Noninvasive imaging is one strategy for molecular profiling and is the focus ...of this review. The combination of imaging and therapy for precision medicine gave rise to the field of theranostics. In breast cancer, the detection and quantification of therapeutic targets can help assess their heterogeneity, especially in metastatic disease, and may help guide clinical decisions for targeted treatments. Positron emission tomography (PET) or single-photon emission tomography (SPECT) imaging has the potential to play an important role in the molecular profiling of therapeutic targets in vivo for the selection of patients who are likely to respond to corresponding targeted therapy. In this review, we discuss the state-of-the-art nuclear imaging agents in clinical research for breast cancer. We reviewed 17 clinical studies on PET or SPECT agents that target 10 different receptors in breast cancer. We also discuss the limitations of the study designs and of the imaging agents in these studies. Finally, we offer our perspective on which imaging agents have the highest potential to be used in clinical practice in the future.
We evaluate the topographic distribution of diffuse midline gliomas and hemispheric high-grade gliomas in children with respect to their normal gene expression patterns and pathologic driver mutation ...patterns. We identified 19 pediatric patients with diffuse midline or high-grade glioma with preoperative MRI from tumor board review. 7 of these had 500 gene panel mutation testing, 11 patients had 50 gene panel mutation testing and one 343 gene panel testing from a separate institution were included as validation set. Tumor imaging features and gene expression patterns were analyzed using Allen Brain Atlas. Twelve patients had diffuse midline gliomas and seven had hemispheric high-grade gliomas. Three diffuse midline gliomas had the K27M mutation in the tail of histone H3 protein. All patients undergoing 500 gene panel testing had additional mutations, the most common being in ACVR1, PPM1D, and p53. Hemispheric high-grade gliomas had either TP53 or IDH1 mutation and diffuse midline gliomas had H3 K27M-mutation. Gene expression analysis in normal brains demonstrated that genes mutated in diffuse midline gliomas had higher expression along midline structures as compared to the cerebral hemispheres. Our study suggests that topographic location of pediatric diffuse midline gliomas and hemispheric high-grade gliomas correlates with driver mutations of tumor to the endogenous gene expression in that location. This correlation suggests that cellular state that is required for increased gene expression predisposes that location to mutations and defines the driver mutations within tumors that arise from that region.
Introduction
The study aimed to describe the brain metastases (BM) incidence, at diagnosis and follow-up, in patients initially presenting with stage III or IV melanoma and characterize their ...metastatic brain lesions. We also sought to describe the association of common genetic mutations and immunotherapy with BM development in advanced melanoma.
Methods
Using our institution’s tumor registry, we identified patients with initial diagnoses of stage III and stage IV melanoma. In this cohort, we obtained BM incidence at diagnosis and follow-up, characterized the metastatic brain lesions and primary tumor’s genetic profile.
Results
During the follow-up period, 22.9% of patients with an initial diagnosis of stage III developed BM. In this cohort, the median time for BM occurrence was 20 months; 95% CI (14–29). Likewise, 37.7% of patients with Stage IV melanoma presented with BM at the time of diagnosis, and 22.7% of remaining patients developed BM at follow-up over a median duration of 6 months 95% CI (4–11). Therefore, suggesting an overall incidence of 51.9% in stage IV melanoma. Next, we observed that the incidence of BM development during the follow-up period significantly decreased from 2012 to 2017 (p < 0.001). Lastly, we found a significantly higher frequency of mutational BRAF in the primary tumor of patients with BM (68.7% vs. 31.2%; p = 0.02).
Conclusions
While the overall incidence of BM remains high, the decreasing incidence of BM over the follow-up period is promising. Similar BM incidence in patients with an initial diagnosis of stage III or stage IV warrants appropriate imaging surveillance regimen for stage III patients.
Central nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective ...systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome.PURPOSECentral nervous system (CNS) metastases from lung cancers and melanoma, significantly contribute to morbidity and mortality. Despite advances in local therapies, there is a need for effective systemic treatments. Pembrolizumab, a PD-1 inhibitor, has shown promise for some patients with untreated brain metastases from melanoma and non-small cell lung cancer (NSCLC). This study aims to analyze the response of brain metastasis to pembrolizumab and associate characteristics like size and location with treatment outcome.This retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions).METHODSThis retrospective study used imaging data from a phase II trial of pembrolizumab in melanoma or NSCLC patients with untreated brain metastases. MRI evaluations were conducted at 2 month intervals, with each brain metastasis treated as a distinct tumor for response assessment, based on modified RECIST criteria (maximum 5 lesions, 5 mm target lesions).Of 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks.RESULTSOf 130 individual target metastases (> 5 mm), in 65 patients with NSCLC (90 metastases) and Melanoma (40 metastases), 32 (24.6%) demonstrated complete resolution, 24 (18.5%) had partial resolution, 32 (24.6%) were SD and 42 (32.3%) demonstrated PD. Those smaller than 10 mm were more likely to show complete resolution (p = 0.0218), while those ≥ 10 mm were more likely to have PR. There was no significant association between size, number or location (supratentorial vs. infratentorial) and lesion progression. The median time to metastatic lesion progression in the brain was 5.7-7 weeks.Pembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.CONCLUSIONPembrolizumab is effective in brain metastases from NSCLC and melanoma, showing response (CR + PR) in 43% and progression (PD) in 32% of metastases. With the median time to CNS progression of 5.7-7 weeks, careful radiographic monitoring is essential to guide timely local treatment decisions.
There is a rapidly increasing number of artificial intelligence (AI) products cleared by the Food and Drug Administration (FDA) for quantification, identification, and even diagnosis in clinical ...radiology. This review article aims to summarize the landscape of current commercial software products in neuroimaging and musculoskeletal radiology. We will discuss key applications, provide an overview of current FDA cleared products, and summarize relevant peer reviewed publications of these products when available.
Response on imaging is widely used to evaluate treatment efficacy in clinical trials of pediatric gliomas. While conventional criteria rely on 2D measurements, volumetric analysis may provide a more ...comprehensive response assessment. There is sparse research on the role of volumetrics in pediatric gliomas. Our purpose was to compare 2D and volumetric analysis with the assessment of neuroradiologists using the Brain Tumor Reporting and Data System (BT-RADS) in
V600E-mutant pediatric gliomas.
Manual volumetric segmentations of whole and solid tumors were compared with 2D measurements in 31 participants (292 follow-up studies) in the Pacific Pediatric Neuro-Oncology Consortium 002 trial (NCT01748149). Two neuroradiologists evaluated responses using BT-RADS. Receiver operating characteristic analysis compared classification performance of 2D and volumetrics for partial response. Agreement between volumetric and 2D mathematically modeled longitudinal trajectories for 25 participants was determined using the model-estimated time to best response.
Of 31 participants, 20 had partial responses according to BT-RADS criteria. Receiver operating characteristic curves for the classification of partial responders at the time of first detection (median = 2 months) yielded an area under the curve of 0.84 (95% CI, 0.69-0.99) for 2D area, 0.91 (95% CI, 0.80-1.00) for whole-volume, and 0.92 (95% CI, 0.82-1.00) for solid volume change. There was no significant difference in the area under the curve between 2D and solid (
= .34) or whole volume (
= .39). There was no significant correlation in model-estimated time to best response (ρ = 0.39,
>.05) between 2D and whole-volume trajectories. Eight of the 25 participants had a difference of ≥90 days in transition from partial response to stable disease between their 2D and whole-volume modeled trajectories.
Although there was no overall difference between volumetrics and 2D in classifying partial response assessment using BT-RADS, further prospective studies will be critical to elucidate how the observed differences in tumor 2D and volumetric trajectories affect clinical decision-making and outcomes in some individuals.
Case 245: Erdheim-Chester Disease Mamlouk, Mark D; Aboian, Mariam S; Glastonbury, Christine M
Radiology,
09/2017, Letnik:
284, Številka:
3
Journal Article
Recenzirano
Odprti dostop
History A 53-year-old man experienced headache and double vision that progressed over 1 year. After a traumatic fall, he was hospitalized, and proptosis was identified at physical examination. ...Laboratory tests were remarkable for leukocytosis. Hematocrit level, thyroid stimulating hormone level, autoimmune antibody level, erythrocyte sedimentation rate, and C-reactive protein level were normal. Computed tomography (CT) of the head revealed bilateral intraconal masses, for which magnetic resonance (MR) imaging of the orbits was subsequently performed ( Fig 1 ). CT imaging of the chest and abdomen ( Fig 2 ) revealed periaortic and retroperitoneal stranding. Perinephric biopsy was performed, and a diagnosis of immunoglobulin G4 (IgG4)-related disease was made based on identification of a few plasma cells per high-power field that were positive for IgG4. Orbital biopsy was then performed, but the results were inconclusive for IgG4-related disease. The patient was discharged and given steroid therapy for presumed IgG4-related disease. Figure: see textFigure: see textFigure: see textFigure: see textFigure: see textFigure: see text Several months later, the patient returned to our institution with progressive symptoms despite ongoing steroid treatment. His case was reviewed by several specialists to develop alternative treatments for IgG4-related disease. After review of the available images, a neuroradiology fellow (M.D.M.) performed history taking and a physical examination and subsequently recommended radiography of the lower extremities ( Fig 3 ). Figure: see textFigure: see text.
Purpose
Pilomyxoid astrocytomas (PMA) are pediatric brain tumors predominantly located in the suprasellar region, third ventricle and posterior fossa, which are considered to be more clinically ...aggressive than pilocytic astrocytomas (PA). Another entity, intermediate pilomyxoid tumors (IPT), exists within the spectrum of pilocytic/pilomyxoid astrocytomas. The 2021 WHO CNS classification refrained from assigning grade 1 or 2 status to PMA, thereby reflecting the need to further elucidate their clinical and imaging characteristics.
Methods
We included a total of 15 patients with PMA, IPT and suprasellar PA. We retrospectively evaluated immunohistochemistry, imaging findings and diffusion characteristics within these tumors as well as whole exome sequencing for three of the cases.
Results
87% of the tumors were supratentorial with 11 cases suprasellar in location, 1 case located in the frontal white matter and 1 in the hippocampus. 6 cases demonstrated intraventricular extension. ADC values were higher in PMA and IPT than PA. 3 cases demonstrated
KIAA1549-BRAF
-fusion, 2 had
BRAF
V
600
E
-mutation and 6 were
BRAF
-wildtype. All cases had recurrence/progression on follow-up.
Conclusion
PMA and IPT do not demonstrate aggressive imaging characteristics in respect to their diffusion imaging with ADC values being higher than PA. Lack of
BRAF
-alteration in PMA corresponded to atypical location of tumors with atypical driver mutations and mechanisms.
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