Missed opportunities: Germline testing following tumor sequencing.

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Tumor next-generation sequencing (NGS) can reveal potential germline DNA mutations linked to cancer susceptibility.
• Identifying these mutations is crucial for understanding hereditary cancer syndromes and guiding treatment decisions.

Purpose of the Study:

• To determine the frequency of actionable germline mutations identified via tumor NGS in patients meeting ESMO 2019 guidelines for germline genetic testing (GT).
• To investigate the reasons why eligible patients do not undergo germline GT.
• To assess the proportion of patients with actionable mutations who were not referred for GT.

Main Methods:

• Retrospective study of patients undergoing tumor NGS between September 2019 and February 2022.
• Identification of patients meeting ESMO guidelines for potentially actionable germline mutations.
• Analysis of reasons for not undergoing germline GT among eligible patients.

Main Results:

• Of 3470 patients, 326 (9.4%) had potential actionable germline mutations on tumor NGS.
• 189 (58.0%) eligible patients did not receive germline GT, most commonly due to lack of referral (67.2%).
• Among those not referred, 50.4% had mutations in BRCA1/2 and/or Lynch syndrome genes; 62.8% of those who did undergo GT were positive.

Conclusions:

• A significant proportion (60%) of patients eligible for germline GT based on ESMO criteria did not receive it, primarily due to insufficient referrals.
• Over half of patients not referred for GT harbored mutations in well-known cancer susceptibility genes (e.g., BRCA1/2).
• Improved education on germline eligibility and implementation of reflex clinical protocols are necessary to ensure timely genetic testing.