Integrating Somatic and Germline Next-Generation Sequencing Into Routine Clinical Oncology Practice

Abstract

Next-generation sequencing (NGS) is rapidly expanding into routine oncology practice. Genetic variations in both the cancer and inherited genomes are informative for hereditary cancer risk, prognosis, and treatment strategies. Herein, we focus on the clinical perspective of integrating NGS results into patient care to assist with therapeutic decision making. Five key considerations are addressed for operationalization of NGS testing and application of results to patient care as follows: (1) NGS test ordering and workflow design; (2) result reporting, curation, and storage; (3) clinical consultation services that provide test interpretations and identify opportunities for molecularly guided therapy; (4) presentation of genetic information within the electronic health record; and (5) education of providers and patients. Several of these key considerations center on informatics tools that support NGS test ordering and referencing back to the results for therapeutic purposes. Clinical decision support tools embedded within the electronic health record can assist with NGS test utilization and identifying opportunities for targeted therapy including clinical trial eligibility. Challenges for project and change management in operationalizing NGS-supported, evidence-based patient care in the context of current information technology systems with appropriate clinical data standards are discussed, and solutions for overcoming barriers are provided.

Electronic Health Record Data in Cancer Learning Health Systems: Challenges and Opportunities

“…Disease classification standards used in EHRs, like the Systematic Nomenclature of Medicine-Clinical Terms (SNOMED-CT) used in EHR problem lists 59 and structured pathology reporting, 60 frequently classify cancer types by histology and location but not molecular testing although clinical genetic testing has become routine. 61 Furthermore, data quality has plagued EHRs. Administrative coding systems like International Classification of Diseases version 10 have too many codes for providers and coders to document accurately without substantial computer support, [62][63][64] and these codes document billing, not patient care.…”

Complete response to alectinib in ALK-fusion metastatic salivary ductal carcinoma

“…Next-generation sequencing (NGS) has allowed for a more comprehensive identification of novel therapeutic targets which can lead to improved outcomes for patients with such oncogenedriven cancers 5 . This coupled with the continued rapid development of targeted therapeutics can help to get the right drugs to the right patient even for rare cancers [6][7][8] .…”

Tumor and Constitutional Sequencing for Neurofibromatosis Type 1

“…7,[14][15][16] Applied to a cohort of tumors, such sequencing can yield variants, genes, and potentially mutation mechanisms underlying tumor pathophysiology, particularly in tumors with limited burden of pathogenic variants. The data may also help with inferring pathogenicity attributed to variants in tumor and germline [17][18][19][20] The study presents paired sequencing from samples from individuals with NF1, analyzes types of tumors undergoing surgery, and explores the spectrum of second hits in NF1, including copy-neutral LOH. MPNST is analyzed for mutational patterns in NF1 and non-NF1.…”

“… 7 , 14 - 16 Applied to a cohort of tumors, such sequencing can yield variants, genes, and potentially mutation mechanisms underlying tumor pathophysiology, particularly in tumors with limited burden of pathogenic variants. The data may also help with inferring pathogenicity attributed to variants in tumor and germline 17 - 20 …”