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Integrating RNA sequencing into neuro-oncology practice.

ABSTRACT: Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity. Currently, RNA-seq is beginning to be incorporated into regular neuro-oncology practice in the form of precision neuro-oncology programs, which use information from tumor sequencing to guide implementation of personalized targeted therapies. These programs show great promise in improving patient outcomes for tumors where single agent trials have been ineffective. As RNA-seq is a relatively new technique, many further applications yielding new advances in CNS tumor research and management are expected in the coming years.

SUBMITTER: Rogawski DS

PROVIDER: S-EPMC5659901 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Integrating RNA sequencing into neuro-oncology practice.

Rogawski David S DS Vitanza Nicholas A NA Gauthier Angela C AC Ramaswamy Vijay V Koschmann Carl C

Translational research : the journal of laboratory and clinical medicine 20170708

Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumen ...[more]

PMID: 28746860

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Project description:The incorporation of genomic testing to identify targetable somatic alterations and predisposing germline mutations into the clinical setting is becoming increasingly more common. Despite its potential usefulness, to the authors' knowledge physician confidence with regard to understanding and applying genomic testing remains unclear, particularly within the realm of pediatric oncology.Before initiating an institutional feasibility study regarding the integration of clinical genomic testing, the authors surveyed pediatric oncologists regarding their confidence around understanding of genomic testing, perceived usefulness of test results, preferences around the disclosure of germline test results, and possible risks and benefits of testing.Among survey respondents (52 of 88 contacted; response rate of 59%), only a minority were confident in interpreting, using, and discussing somatic (35%) or germline (27%) genomic test results. Providers who were confident in interpreting somatic results were significantly more likely to anticipate using the results to plan the treatment of patients with relapsed or refractory cancers (P?=?.009). Similarly, providers who reported confidence in interpreting germline results were significantly more likely to discuss and use these results as part of clinical care (P<.0001). The majority of physicians (93%), regardless of their level of confidence, wanted to speak to a genetic counselor before disclosing germline test results.Among physicians at a comprehensive pediatric cancer center, confidence in the interpretation, use, and discussion of oncology-based genomic test results appears to be low, both in terms of somatic and germline testing. To optimize the integration of genomic sequencing into cancer care, methods must be developed to improve basic competencies around cancer-based genomic testing. Given the complexities surrounding variant interpretation and genotype-phenotype relationships, interdisciplinary collaborations are warranted. Cancer 2017;123:2352-2359. © 2017 American Cancer Society.

Project description:ObjectivesMRI remains the preferred imaging investigation for glioblastoma. Appropriate and timely neuroimaging in the follow-up period is considered to be important in making management decisions. There is a paucity of evidence-based information in current UK, European and international guidelines regarding the optimal timing and type of neuroimaging following initial neurosurgical treatment. This study assessed the current imaging practices amongst UK neuro-oncology centres, thus providing baseline data and informing future practice.MethodsThe lead neuro-oncologist, neuroradiologist and neurosurgeon from every UK neuro-oncology centre were invited to complete an online survey. Participants were asked about current and ideal imaging practices following initial treatment.ResultsNinety-two participants from all 31 neuro-oncology centres completed the survey (100% response rate). Most centres routinely performed an early post-operative MRI (87%, 27/31), whereas only a third performed a pre-radiotherapy MRI (32%, 10/31). The number and timing of scans routinely performed during adjuvant TMZ treatment varied widely between centres. At the end of the adjuvant period, most centres performed an MRI (71%, 22/31), followed by monitoring scans at 3 monthly intervals (81%, 25/31). Additional short-interval imaging was carried out in cases of possible pseudoprogression in most centres (71%, 22/31). Routine use of advanced imaging was infrequent; however, the addition of advanced sequences was the most popular suggestion for ideal imaging practice, followed by changes in the timing of EPMRI.ConclusionVariations in neuroimaging practices exist after initial glioblastoma treatment within the UK. Multicentre, longitudinal, prospective trials are needed to define the optimal imaging schedule for assessment.Key points• Variations in imaging practices exist in the frequency, timing and type of interval neuroimaging after initial treatment of glioblastoma within the UK. • Large, multicentre, longitudinal, prospective trials are needed to define the optimal imaging schedule for assessment.

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Integrating RNA sequencing into neuro-oncology practice.

Publications

Integrating RNA sequencing into neuro-oncology practice.

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