Dataset Information

Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma.

ABSTRACT: Molecular profiling of glioblastoma has revealed complex cytogenetic, epigenetic, and molecular abnormalities that are necessary for diagnosis, prognosis, and treatment. Our neuro-oncology group has developed a data-driven, institutional consensus guideline for efficient and optimal workup of glioblastomas based on our routine performance of molecular testing. We describe our institution's testing algorithm, assay development, and genetic findings in glioblastoma, to illustrate current practices and challenges in neuropathology related to molecular and genetic testing. We have found that coordination of test requisition, tissue handling, and incorporation of results into the final pathologic diagnosis by the neuropathologist improve patient care. Here, we present analysis of O⁶-methylguanine-DNA-methyltransferase promoter methylation and next-generation sequencing results of 189 patients, obtained utilizing our internal processes led by the neuropathology team. Our institutional pathway for neuropathologist-driven molecular testing has streamlined the management of glioblastoma samples for efficient return of results for incorporation of genomic data into the pathological diagnosis and optimal patient care.

SUBMITTER: Nasrallah MP

PROVIDER: S-EPMC6537274 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma.

Nasrallah MacLean P MP Binder Zev A ZA Oldridge Derek A DA Zhao Jianhua J Lieberman David B DB Roth Jacquelyn J JJ Watt Christopher D CD Sukhadia Shrey S Klinman Eva E Daber Robert D RD Desai Arati A Brem Steven S O'Rourke Donald M DM Morrissette Jennifer J D JJD

Academic pathology 20190101

Molecular profiling of glioblastoma has revealed complex cytogenetic, epigenetic, and molecular abnormalities that are necessary for diagnosis, prognosis, and treatment. Our neuro-oncology group has developed a data-driven, institutional consensus guideline for efficient and optimal workup of glioblastomas based on our routine performance of molecular testing. We describe our institution's testing algorithm, assay development, and genetic findings in glioblastoma, to illustrate current practices ...[more]

PMID: 31206012

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Project description:Practice guidelines aim to improve the standard of care for people living with HIV/AIDS. Successfully implementing guidelines requires tailoring them to populations served and to social and organizational influences on care.To examine dimensions of context, which nurses and midwives described as having a significant impact on their care of patients living with HIV/AIDS in Kenya, Uganda, South Africa, and Jamaica and to determine whether HIV/AIDS guidelines include adaptations congruent with these dimensions of context.Two sets of data were used. The first came from a qualitative study. In-depth interviews were conducted with purposively selected nurses, midwives, and nurse managers from 21 districts in four study countries. A coding framework was iteratively developed and themes inductively identified. Context dimensions were derived from these themes. A second data set of published guidelines for HIV/AIDS care was then assembled. Guidelines were identified through Google and PubMed searches. Using a deductive integrative analysis approach, text related to context dimensions was extracted from guidelines and categorized into problem and strategy statements.Ninety-six individuals participated in qualitative interviews. Four discrete dimensions of context were identified: health workforce adequacy, workplace exposure risk, workplace consequences for nurses living with HIV/AIDS, and the intersection of work and family life. Guidelines most often acknowledged health human resource constraints and presented mitigation strategies to offset them, and least often discussed workplace consequences and the intersections of family and work life.Guidelines should more consistently acknowledge diverse implementation contexts, propose how recommendations can be adapted to these realities, and suggest what role frontline healthcare providers have in realizing the structural changes necessary for healthier work environments and better patient care. Guideline recommendations should include more explicit advice on adapting their recommendations to different care conditions.

Project description:BackgroundTumor molecular profile analysis by Next Generation Sequencing technology is currently widely applied in clinical practice and has enabled the detection of predictive biomarkers of response to targeted treatment. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy, with Programmed Death-ligand 1 (PD-L1), Microsatellite instability (MSI), and Tumor Mutational Burden (TMB) analysis being the biomarkers employed most commonly.MethodsIn the present study, tumor molecular profile analysis was performed using a 161 gene NGS panel, containing the majority of clinically significant genes for cancer treatment selection. A variety of tumor types have been analyzed, including aggressive and hard to treat cancers such as pancreatic cancer. Besides, the clinical utility of immunotherapy biomarkers (TMB, MSI, PD-L1), was also studied.ResultsMolecular profile analysis was conducted in 610 cancer patients, while in 393 of them a at least one biomarker for immunotherapy response was requested. An actionable alteration was detected in 77.87% of the patients. 54.75% of them received information related to on-label or off-label treatment (Tiers 1A.1, 1A.2, 2B, and 2C.1) and 21.31% received a variant that could be used for clinical trial inclusion. The addition to immunotherapy biomarker to targeted biomarkers' analysis in 191 cases increased the number of patients with an on-label treatment recommendation by 22.92%, while an option for on-label or off-label treatment was provided in 71.35% of the cases.ConclusionsTumor molecular profile analysis using NGS is a first-tier method for a variety of tumor types and provides important information for decision making in the treatment of cancer patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offer actionable information in the majority of patients. Furthermore, our data suggest that one in two patients may be eligible for on-label ICI treatment based on biomarker analysis. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of treatment strategy.

Dataset Information

Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma.

Publications

Molecular Neuropathology in Practice: Clinical Profiling and Integrative Analysis of Molecular Alterations in Glioblastoma.

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