scholarly journals Precision medicine biomarkers in brain metastases: applications, discordances, and obstacles

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v35-v42
Author(s):  
Ariane Steindl ◽  
Priscilla K Brastianos ◽  
Matthias Preusser ◽  
Anna S Berghoff
Keyword(s):  
Brain Metastases ◽  
Precision Medicine ◽  
Tumor Tissue ◽  
Metastatic Cancer ◽  
Predictive Biomarkers ◽  
Current Evidence ◽  
Therapeutic Decision ◽  
Molecular Alteration ◽  
Mortality And Morbidity ◽  
Therapeutic Decision Making

Abstract Brain metastases (BM) present a common cause of mortality and morbidity in several metastatic cancer entities. New therapeutic developments during the last decades, including targeted and immune-related therapies, have shown considerable extra- and intracranial response rates in specific subgroups of BM patients. However, differences in the molecular alteration in the BM tumor tissue compared to extracranial tumors leads to heterogeneous therapeutic responses. Therefore, an accurate molecular analyzation of BM tissue, if possible, has become an essential part in therapeutic decision making in BM patients. The concordance of predictive molecular biomarkers between multiple sites including extracranial and intracranial tumor tissue have been analyzed for some but not all biomarkers routinely applied in modern precision medicine approaches. In the present review, we summarize the current evidence of predictive biomarkers for personalized therapy approaches in the treatment of parenchymal BM.

scholarly journals Immunohistochemistry of Pulmonary Biomarkers: A Perspective From Members of the Pulmonary Pathology Society

2017 ◽  
Vol 142 (3) ◽  
pp. 408-419 ◽  
Author(s):  
Erik Thunnissen ◽  
Timothy Craig Allen ◽  
Julien Adam ◽  
Dara L. Aisner ◽  
Mary Beth Beasley ◽  
...  
Keyword(s):  
Predictive Biomarkers ◽  
Small Cell ◽  
Therapeutic Decision ◽  
Small Cell Lung ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Pulmonary Pathology ◽  
Therapeutic Decision Making ◽  
Test Outcomes

The use of immunohistochemistry for the determination of pulmonary carcinoma biomarkers is a well-established and powerful technique. Immunohistochemisty is readily available in pathology laboratories, is relatively easy to perform and assess, can provide clinically meaningful results very quickly, and is relatively inexpensive. Pulmonary predictive biomarkers provide results essential for timely and accurate therapeutic decision making; for patients with metastatic non–small cell lung cancer, predictive immunohistochemistry includes ALK and programmed death ligand-1 (PD-L1) (ROS1, EGFR in Europe) testing. Handling along proper methodologic lines is needed to ensure patients receive the most accurate and representative test outcomes.

Effect of the 92-gene molecular classifier on therapeutic decision-making in cancers of uncertain primary.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15130-e15130
Author(s):  
Brock Schroeder ◽  
Catherine A. Schnabel ◽  
Mark G. Erlander ◽  
Benjamin Kim
Keyword(s):  
Decision Making ◽  
Clinical Diagnosis ◽  
Clinical Utility ◽  
Metastatic Cancer ◽  
Clinical Care ◽  
Molecular Testing ◽  
Tumor Type ◽  
Therapeutic Decision ◽  
Gene Assay ◽  
Therapeutic Decision Making

e15130 Background: Patients with metastatic cancer of uncertain primary site are at risk of suboptimal therapy if tumor type and subtype cannot be determined. Gene expression-based assays for tumor classification are utilized to complement clinicopathologic evaluation in cases with unknown primary sites of tumor origin or differential diagnoses; however, few studies have evaluated their clinical utility and effectiveness in real-world practice. The objective of this study was to evaluate the influence of a 92-gene molecular classification assay on clinical diagnosis and therapeutic decision-making. Methods: Medical oncologists who ordered the 92-gene assay as part of clinical care were invited to participate in a retrospective, questionnaire-based study. To minimize selection and recall biases, recruitment was based on consecutive cases: participating physicians were instructed to review the medical record of the first patient they ordered the 92-gene assay after a specified date and subsequently complete a 61-question survey. Results: Of 1,105 physicians invited, 103 (9.4%) completed the study (82% community practice; median practice time: 10 years). The majority of respondents had not initiated oncologic treatment before ordering the 92-gene assay: 31% had begun treatment, 24% had a specific regimen chosen but were waiting to begin treatment and 45% had not begun treatment or chosen a specific regimen. The 92-gene assay prediction was concordant with the final clinical diagnosis in 84% of cases; in one-third of these, the molecular diagnosis had not been clinically considered prior to molecular testing. Eighty-one percent of study participants reported that the 92-gene assay helped with therapeutic decision-making. Of these, the assay guided initial treatment choice in 52%, changed a considered treatment in 10%, excluded a potential treatment in 6%, and confirmed a previously determined treatment in 29% of cases. Conclusions: The results of this retrospective study demonstrate the clinical utility of molecular cancer classification: the molecular diagnoses provided by the 92-gene assay influenced therapeutic decision-making in the majority of cases.

Avenues to Precision Oncology

2020 ◽  
pp. 36-45
Author(s):  
Alexander Meisel
Keyword(s):  
Precision Medicine ◽  
Trial Design ◽  
Ad Hoc ◽  
Molecular Targets ◽  
Clinical Trial Design ◽  
Predictive Biomarkers ◽  
Precision Oncology ◽  
Companion Diagnostics ◽  
Bona Fide ◽  
The One

Until recently, the clinical management of cancer heavily relied on anatomical and histopathological criteria, with ad hoc guidelines directing the therapeutic choices in specific indications. In the last years, the development and therapeutic implementation of novel anticancer therapies significantly improved the clinical outcome of cancer patients. Nonetheless, such cutting-edge approaches revealed the limitation of the one-size-fits-all paradigm. The newly discovered molecular targets can be exploited either as bona fide targets for subsequent drug development, or as tools to precision medicine, in the form of prognostic and/or predictive biomarkers. This article provides an overview of some of the most recent advances in precision medicine in oncology, with a focus on novel tissue-agnostic anticancer therapies. The definition and implementation of biomarkers and companion diagnostics in clinical trials and clinical practice are also discussed, as well as the changing landscape in clinical trial design.

scholarly journals Differentiating Glioblastomas from Solitary Brain Metastases: An Update on the Current Literature of Advanced Imaging Modalities

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2960
Author(s):  
Austin-John Fordham ◽  
Caitlin-Craft Hacherl ◽  
Neal Patel ◽  
Keri Jones ◽  
Brandon Myers ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Brain Metastases ◽  
Clinical Assessment ◽  
Volume Fraction ◽  
Imaging Modalities ◽  
Current Evidence ◽  
Dynamic Susceptibility ◽  
Advanced Imaging ◽  
Imaging Protocol ◽  
Solitary Brain Metastases

Differentiating between glioblastomas and solitary brain metastases proves to be a challenging diagnosis for neuroradiologists, as both present with imaging patterns consisting of peritumoral hyperintensities with similar intratumoral texture on traditional magnetic resonance imaging sequences. Early diagnosis is paramount, as each pathology has completely different methods of clinical assessment. In the past decade, recent developments in advanced imaging modalities enabled providers to acquire a more accurate diagnosis earlier in the patient’s clinical assessment, thus optimizing clinical outcome. Dynamic susceptibility contrast has been optimized for detecting relative cerebral blood flow and relative cerebral blood volume. Diffusion tensor imaging can be used to detect changes in mean diffusivity. Neurite orientation dispersion and density imaging is an innovative modality detecting changes in intracellular volume fraction, isotropic volume fraction, and extracellular volume fraction. Magnetic resonance spectroscopy is able to assist by providing a metabolic descriptor while detecting variable ratios of choline/N-acetylaspartate, choline/creatine, and N-acetylaspartate/creatine. Finally, radiomics and machine learning algorithms have been devised to assist in improving diagnostic accuracy while often utilizing more than one advanced imaging protocol per patient. In this review, we provide an update on all the current evidence regarding the identification and differentiation of glioblastomas from solitary brain metastases.

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