Clinical Use of Precision Oncology Decision Support.

Area of Science:

• Oncology
• Genomics
• Clinical Decision Support

Background:

• Precision oncology relies on understanding genomic alterations for targeted therapies.
• Lack of decision support hinders the interpretation of tumor genomic alterations and identification of clinical options.
• The Precision Oncology Decision Support (PODS) team was established to address this knowledge gap.

Purpose of the Study:

• To provide alteration-level annotations for functional and therapeutic significance.
• To assess the impact of these annotations on clinical decision-making and trial enrollment.

Main Methods:

• Genomic alterations were annotated for actionability based on functional and therapeutic significance.
• Medical records were reviewed for trial enrollment among patients annotated in 2015.
• A web-based survey captured reasons for not pursuing genotype-matched therapies.

Main Results:

• PODS processed 1,669 requests, annotating 4,084 alterations across 49 tumor types for 1,197 patients.
• 66% of patients had at least one actionable or potentially actionable alteration.
• Trial enrollment was significantly higher for patients with actionable/potentially actionable alterations (27.6%) compared to unknown (11.8%) or non-actionable (3%) alterations (p=0.00004).

Conclusions:

• Over half of annotated alterations were of unknown or non-actionable significance.
• Physician likelihood of enrolling patients in genotype-matched trials increased with annotation support for actionability.
• Further research is required to demonstrate the impact of decision support on trial enrollment and oncologic outcomes.