Molecular Diagnostics in Pediatric Brain Tumors: Impact on Diagnosis and Clinical Decision-Making — A Selected Case Series

2018 ◽  
Vol 230 (06) ◽  
pp. 305-313 ◽  
Author(s):  
Heidi Bächli ◽  
Jonas Ecker ◽  
Cornelis van Tilburg ◽  
Dominik Sturm ◽  
Florian Selt ◽  
...  
Keyword(s):  
Decision Making ◽  
Molecular Diagnostics ◽  
Clinical Management ◽  
Clinical Decision Making ◽  
Case Series ◽  
Clinical Decision ◽  
Cns Tumors ◽  
Molecular Testing ◽  
Cancer Predisposition Syndrome ◽  
Pediatric Cns Tumors

AbstractCentral nervous system (CNS) tumors account for the highest mortality among pediatric malignancies. Accurate diagnosis is essential for optimal clinical management. The increasing use of molecular diagnostics has opened up novel possibilities for more precise classification of CNS tumors. We here report a single-institutional collection of pediatric CNS tumor cases that underwent a refinement or a change of diagnosis after completion of molecular analysis that affected clinical decision-making including the application of molecularly informed targeted therapies. 13 pediatric CNS tumors were analyzed by conventional histology, immunohistochemistry, and molecular diagnostics including DNA methylation profiling in 12 cases, DNA sequencing in 8 cases and RNA sequencing in 3 cases. 3 tumors had a refinement of diagnosis upon molecular testing, and 6 tumors underwent a change of diagnosis. Targeted therapy was initiated in 5 cases. An underlying cancer predisposition syndrome was detected in 5 cases. Although this case series, retrospective and not population based, has its limitations, insight can be gained regarding precision of diagnosis and clinical management of the patients in selected cases. Accuracy of diagnosis was improved in the cases presented here by the addition of molecular diagnostics, impacting clinical management of affected patients, both in the first-line as well as in the follow-up setting. This additional information may support the clinical decision making in the treatment of challenging pediatric CNS tumors. Prospective testing of the clinical value of molecular diagnostics is currently underway.

scholarly journals INNV-28. MOLECULAR TESTING IN NEURO-ONCOLOGY – ASSESSMENT OF UTILITY AND PRACTICE PATTERNS. A SOCIETY FOR NEURO-ONCOLOGY MEMBERSHIP SURVEY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi136-vi136
Author(s):  
Maciej Mrugala ◽  
Susan Chang
Keyword(s):  
Decision Making ◽  
Clinical Decision Making ◽  
Practice Patterns ◽  
Clinical Decision ◽  
Educational Programs ◽  
Molecular Testing ◽  
Targeted Agents ◽  
Younger Patients ◽  
Tumor Boards ◽  
The Subject

Abstract BACKGROUND Molecular testing (MT) is utilized in neuro-oncology with increasing frequency. Multiple molecular panels are available providing a spectrum of information. We were interested in learning how this information is acquired, what are the practice patterns regarding this type of testing, how are the results utilized in patient care and how prepared neuro-oncologists are to interpret these results. METHODS We conducted a survey using the Society for Neuro-Oncology membership database. We developed a set of 13 questions and administered the survey to 2022 members using the online platform. RESULTS We received 153 responses (7.5% of membership). 89% percent of responders routinely order MT. Of those who do not order MT on all patients, 50% test younger patients and 57% midline tumors. 83% use MT in recurrent glioma. Other common indications for MT included: metastatic tumors, meningioma, medulloblastoma, ATRT. Majority (60%) use in-house panels, followed by Foundation One (35%), TEMPUS (13%), CARIS (10%) and other panels (23%). For 57% of respondents, the data from MT was somewhat useful and for 41% it was very useful. 78% used the results of MT for clinical decision-making. BRAF, EGFR/ALK, H3K27 mutations were most commonly used for treatment decisions. 50% of respondents have molecular tumor boards at their institutions and a majority of practitioners share the results of MT with their patients (95%). Respondents would like to see SNO-endorsed official guidelines on MT, organized lists of targeted agents available for specific mutations, a database of targetable mutations and clinical trials and more educational programs on the subject. CONCLUSIONS Molecular testing is neuro-oncology is commonly done. Many providers rely on the information for clinical decision making where appropriate. In-house and commercial genetic panels are equally used in practice. There continues to be a need for more education on the subject and development of neuro-oncology specific guidelines.

scholarly journals Toward harmonization of clinical molecular diagnostic reports: findings of an international survey

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Deborah A. Payne ◽  
Katarina Baluchova ◽  
Graciela Russomando ◽  
Parviz Ahmad-Nejad ◽  
Cyril Mamotte ◽  
...  
Keyword(s):  
Molecular Diagnostics ◽  
Clinical Decision Making ◽  
Clinical Chemistry ◽  
Clinical Decision ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
End User ◽  
Iso 15189 ◽  
Reporting Practices ◽  
Reporting Phase

Abstract Background: The International Organization for Standardization (ISO) 15189 standard provides recommendations for the postexamination reporting phase to enhance quality in clinical laboratories. The purpose of this study was to encourage a broad discussion on current reporting practices for molecular diagnostic tests by conducting a global survey of such practices. Methods: The International Federation of Clinical Chemistry and Laboratory Medicine’s Committee for Molecular Diagnostics (IFCC C-MD) surveyed laboratories on selected ISO 15189 recommendations and topics. The survey addressed the following aspects: (1) laboratory demographics, (2) report format, (3) result reporting/layout, (4) comments in report and (5) interpretation and clinical decision-making information. Additionally, participants indicated categories needing standardization. Results: Sixteen responses from laboratories located in Asia, Europe, the Middle East, North America and South America were received. Several categories yielded 100% agreement between laboratories, whereas other categories had less than or equal to 50% concordance. Participants scored “nomenclature” and “description of methodologies” as the two most frequently cited aspects needing standardization. Conclusions: The postexamination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. Surveyed laboratories were most likely to follow explicit ISO 15189 recommendations vs. recommendations when the term(s) “where appropriate or where applicable” was used. Interpretation and reporting of critical values varied among participants. Although the outcome of this study may not fully represent the practices of all molecular testing laboratories in countries around the world, the survey identified and specified several recommendations that are requirements for harmonized reporting in molecular diagnostics.

scholarly journals P418 Does capsule endoscopy impact clinical management in established Crohn’s Disease?

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S423-S424
Author(s):  
A Elosua Gonzalez ◽  
M Rullan Iriarte ◽  
S Rubio Iturria ◽  
S Oquiñena Legaz ◽  
C Rodríguez Gutiérrez ◽  
...  
Keyword(s):  
Decision Making ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Capsule Endoscopy ◽  
Clinical Management ◽  
Clinical Decision Making ◽  
Real Life ◽  
Clinical Decision ◽  
Mucosal Inflammation ◽  
Therapeutic Impact

Abstract Background Capsule endoscopy (SBCE) has developed a relevant role in different indications in patients with established Crohn’s Disease (CD). However, evaluation of its impact in clinical management in CD specific modification strategies has been scarce. The purpose of our study was to question therapeutic impact of SBCE in an 11-year real-life cohort of established CD patients. Methods Retrospective single center study including all consecutive patients with CD submitted to SBCE from January 2008 to December 2019. Small bowel patency was evaluated with patency capsule in selected patients. A conclusive procedure was defined as the one that allowed clinical decision-making. Mucosal inflammation was graded as mild (few aphtoid ulcers), moderate (multiple aphtoid ulcers/isolated deep ulcers) or severe (multiple deep ulcers/stenosis). Therapeutic impact was defined as a change in CD related treatment including escalation, de-escalation, dose adjustment or referral to surgery recommended based on SBCE results within the next 3 months after the SBCE. Patients were assigned to four groups regarding CE indication: staging, flare, post-op and remission (fig 1). Results From the 432 CE performed, 378 (87.5%) were conclusive and allowed clinical decision-making. SBCE results guided changes in 51.3% of patients: 199 (46.1%) with escalation and 23 (5.3%) with de-escalation of treatment. Active disease was present in 310 (71.8%) patients; 131 (30.3%) presented mild, 126 (29.2%) moderate and 53 (12.3%) severe activity. Disease activity demonstrated by SBCE correlated with therapeutic changes. With mild activity 24.1% increased therapy, whereas 77.8% and 84.9% increased therapy with moderate or severe disease, respectively (p<0.001). De-escalation was conducted in 12.8% patients with mucosal healing and 6.1% with mild disease but not in moderate or severe activity (p<0.001). Treatment before and after SBCE is shown in the table. Conclusion SBCE is a safe and useful tool when approaching established CD patients guiding therapeutic management in a real-life setting. Its positive impact does not limit to treatment escalation but also helps to de-escalate in patients who can benefit from it.

scholarly journals Best practice guidelines for management of spinal disorders in skeletal dysplasia

2020 ◽  
Author(s):  
Klane White ◽  
Michael B Bober ◽  
Tae-Joon Cho ◽  
Michael J Goldberg ◽  
Julie Hoover-Fong ◽  
...  
Keyword(s):  
Decision Making ◽  
Practice Guidelines ◽  
Skeletal Dysplasia ◽  
Best Practice ◽  
Clinical Decision Making ◽  
Case Series ◽  
Clinical Decision ◽  
Spinal Disorders ◽  
Best Practice Guidelines ◽  
Group A

Abstract Background: Disorders of the spine present a common and difficult management concern in patients with skeletal dysplasia. Due to the rarity of these conditions however, the literature, largely consisting of small, single institution case series, is sparse in regard to well-designed studies to support clinical decision making in these situations. Methods: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, “best practice” guidelines in the care of spinal disorders in patients with skeletal dysplasia. Results: Starting with 33 statements, the group a developed a list of 31 “best practice” guidelines. Conclusions: The guidelines are presented and discussed to provide context for clinicians in their decision making in this often-challenging realm of care.

scholarly journals Molecular Testing Can Impact Clinical Decision Making and Therapeutic Approach in Thyroid Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A893-A894
Author(s):  
Gonzalo J Acosta Garcia ◽  
Stephanie Smooke Praw
Keyword(s):  
Decision Making ◽  
Thyroid Cancer ◽  
Thyroid Nodule ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Surgical Pathology ◽  
Endocrine Surgery ◽  
Molecular Profile ◽  
Molecular Testing ◽  
History Of

Abstract We present the case of a patient with a thyroid nodule of indeterminate cytology on fine-needle aspiration (FNA) biopsy whose molecular profile significantly impacted clinical decision making and treatment. A 77-year-old woman with a history of hyperthyroidism presented to our clinic for a second opinion regarding management of a recently discovered right thyroid nodule. Thyroid ultrasound (US) 6 months prior showed a 2.6 cm, heterogeneous nodule with peripheral vascular flow; not characterized based on ATA or TIRADS criteria. Family history was significant for papillary thyroid cancer in daughter at age 35 years. The patient had no history of head or neck irradiation. She had no compressive symptoms or manifestations of hyper or hypothyroidism. FNA biopsy of the nodule was done twice in 4 months, and cytology was consistent with follicular lesion of undetermined significance (FLUS, Bethesda III) in both occasions. Repeat FNA biopsy at our institution showed follicular neoplasm (FN, Bethesda IV), and molecular testing using ThyroSeq v3 was positive for HRAS and TERT mutations, which conferred a >95% risk of cancer. Patient was referred to Endocrine Surgery and total thyroidectomy was recommended based on nodule’s molecular profile and associated hyperthyroidism. No suspicious lymph nodes were noted on preoperative US. No gross local invasion observed intraoperatively. Surgical pathology showed intrathyroidal FN without invasion. However, given disparity between pathology findings and molecular markers, specimen was sent for outside blinded pathology review which concluded to be a follicular thyroid carcinoma with capsular invasion but no angiolymphatic invasion or extrathyroidal extension. Based on these findings, along with the known HRAS and TERT mutations, it was advised to proceed with radioiodine (RAI) remnant ablation. Patient was prepared with thyrotropin alfa and received 29 millicuries of RAI. Post-treatment scan showed focal neck uptake consistent with ablated thyroid tissue and no distant metastases. Patient had an excellent response to therapy, without evidence of biochemical or structural recurrence 2 years later. Molecular testing of cytologically indeterminate thyroid nodules (Bethesda III, IV) has become an important tool to better refine risk of malignancy. Furthermore, the presence of certain mutations or mutation combinations, such as RAS and TERT co-occurrence, suggests a more aggressive behavior associated with worse outcomes. As a result, a more aggressive approach might be recommended. Our case illustrates how molecular testing can significantly influence therapeutic decisions such as extent of surgery, interpretation of surgical pathology and/or use of RAI. Further research is needed to determine if its routine use may lead to improved cancer-related outcomes or if it is cost-effective in the risk stratification of differentiated thyroid cancer.

scholarly journals Impact on Clinical Decision Making of Next-Generation Sequencing in Pediatric Epilepsy in a Tertiary Epilepsy Referral Center

2019 ◽  
Vol 51 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Hannes Hoelz ◽  
Christian Herdl ◽  
Lucia Gerstl ◽  
Moritz Tacke ◽  
Katharina Vill ◽  
...  
Keyword(s):  
Decision Making ◽  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Clinical Management ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pediatric Epilepsy ◽  
Next Generation ◽  
The Impact ◽  
Generation Sequencing

Background. Next-generation sequencing (NGS) describes new powerful techniques of nucleic acid analysis, which allow not only disease gene identification diagnostics but also applications for transcriptome/methylation analysis and meta-genomics. NGS helps identify many monogenic epilepsy syndromes. Pediatric epilepsy patients can be tested using NGS epilepsy panels to diagnose them, thereby influencing treatment choices. The primary objective of this study was to evaluate the impact of genetic testing on clinical decision making in pediatric epilepsy patients. Methods. We completed a single-center retrospective cohort study of 91 patients (43 male) aged 19 years or less undergoing NGS with epilepsy panels differing in size ranging from 5 to 434 genes from October 2013 to September 2017. Results. During a mean time of 3.6 years between symptom onset and genetic testing, subjects most frequently showed epileptic encephalopathy (40%), focal epilepsy (33%), and generalized epilepsy (18%). In 16 patients (18% of the study population), “pathogenic” or “likely pathogenic” results according to ACMG criteria were found. Ten of the 16 patients (63%) experienced changes in clinical management regarding their medication and avoidance of further diagnostic evaluation, that is, presurgical evaluation. Conclusion. NGS epilepsy panels contribute to the diagnosis of pediatric epilepsy patients and may change their clinical management with regard to both preventing unnecessary and potentially harmful diagnostic procedures and management. Thus, the present data support the early implementation in order to adopt clinical management in selected cases and prevent further invasive investigations. Given the relatively small sample size and heterogeneous panels a larger prospective study with more homogeneous panels would be helpful to further determine the impact of NGS on clinical decision making.

scholarly journals Molecular Testing in Patients With Castration-Resistant Prostate Cancer and Its Impact on Clinical Decision Making

2017 ◽  
pp. 1-11 ◽  
Author(s):  
Derrick L. Tao ◽  
Shawna Bailey ◽  
Tomasz M. Beer ◽  
Erik Foss ◽  
Brooke Beckett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Pten Expression ◽  
Molecular Testing ◽  
Castration Resistant Prostate Cancer ◽  
Molecular Abnormalities ◽  
Castration Resistant ◽  
Guided Therapy

Purpose Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease. Many groups have performed mutational or immunohistochemistry (IHC) testing in metastatic CRPC to identify treatment targets. However, the frequency with which mutational or IHC data have an impact on clinical decision making and the outcomes of molecularly guided therapy in CRPC are largely unknown. We report our institution’s experience with mutational and IHC testing in patients with metastatic CRPC and its impact on clinical decision making and patient outcomes. Methods Between 2012 and 2015, 59 patients with CRPC underwent metastatic tissue biopsies and were genotyped with a 37–cancer gene panel in a Clinical Laboratory Improvement Amendments–certified laboratory. PTEN expression by IHC testing was also measured in 35 of these samples. A retrospective chart review was performed to determine whether the genomic information was acted upon and the outcome of patients whose treatment was guided by molecular testing. Results Forty-six of 59 patients with CRPC (78.0%) had biopsies with adequate tumor for mutational testing. Thirty-one of 46 subjects (67.4%) had mutations identified by sequencing. Of the 35 patients with CRPC whose biopsies were evaluated for PTEN expression by IHC testing, 13 had PTEN loss. Two patients had treatment on the basis of molecular testing, and one of these subjects had greater tumor control with molecularly guided therapy than his immediate prior therapy. Conclusion Targeted sequencing and IHC can identify clinically informative molecular abnormalities in CRPC. Despite this, a small minority of patients in our series underwent therapies guided by mutational or IHC testing. Actionability of abnormalities identified in metastatic CRPC may be improved with access to clinical trials, insurance approval for unapproved uses of existing anticancer drugs, and larger gene sequencing panels that include more frequently mutated genes.

Sign in / Sign up

Export Citation Format

Share Document