Original Article
Next generation sequencing of cell free circulating tumor DNA in blood samples of recurrent and metastatic head and neck cancer patients
Abstract
Background: Effective targeted therapy is lacking in head and neck cancer (HNC). The use of next generation sequencing (NGS) has been suggested as a way to potentially expand therapeutic options and improve outcomes. This study was performed in order to further characterize blood sample cell-free circulating tumor DNA (ctDNA) in advanced HNC patients, to determine its ability to identify actionable mutations, and to elucidate its potential role in patient management.
Methods: Retrospective analysis of 60 patients with recurrent and metastatic (R/M) HNCs who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene ctDNA NGS platform. ctDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures.
Results: The most common tumor type was oropharyngeal squamous cell carcinoma (n=21). Other cancer types included salivary gland (n=8) and thyroid (n=4). The most common mutations identified by blood analysis were TP53 (68% of patients), PIK3CA (34% of patients), NOTCH1 (20% of patients), and ARID1A (15% of patients). These findings were consistent with results from tumor sequencing data (n=30) where TP53 (48%) and PIK3CA (24%) were also the most common. Seventy-three percent (n=22) of patients had alterations identified in blood that were not present in tumor specimens. In patients with squamous cell carcinoma, 66% had an off-label option identified and 90% had a trial option identified, while 50% of patients with salivary primaries had off-label option identified and 75% had trial options identified. All patients (n=3, 100%) with thyroid primaries had off-label and clinical trial options identified. Of patients with actionable mutations, 13% (n=8) received matched targeted therapy (MTT). Three patients had stable disease (37.5%), 3 had progressive disease (37.5%), and 2 (25%) were not evaluated at the time of follow up. Of those who did not receive targeted therapy (n=21), 11 patients had stable disease (52.4%), 9 had progressive disease (42.9%), and 1 had a complete response (4.8%).
Conclusions: Alterations identified by ctDNA may help inform management decisions in advanced HNC. The majority of patients had unique mutations identified on ctDNA. The role of NGS of ctDNA should be explored in future studies.
Methods: Retrospective analysis of 60 patients with recurrent and metastatic (R/M) HNCs who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene ctDNA NGS platform. ctDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures.
Results: The most common tumor type was oropharyngeal squamous cell carcinoma (n=21). Other cancer types included salivary gland (n=8) and thyroid (n=4). The most common mutations identified by blood analysis were TP53 (68% of patients), PIK3CA (34% of patients), NOTCH1 (20% of patients), and ARID1A (15% of patients). These findings were consistent with results from tumor sequencing data (n=30) where TP53 (48%) and PIK3CA (24%) were also the most common. Seventy-three percent (n=22) of patients had alterations identified in blood that were not present in tumor specimens. In patients with squamous cell carcinoma, 66% had an off-label option identified and 90% had a trial option identified, while 50% of patients with salivary primaries had off-label option identified and 75% had trial options identified. All patients (n=3, 100%) with thyroid primaries had off-label and clinical trial options identified. Of patients with actionable mutations, 13% (n=8) received matched targeted therapy (MTT). Three patients had stable disease (37.5%), 3 had progressive disease (37.5%), and 2 (25%) were not evaluated at the time of follow up. Of those who did not receive targeted therapy (n=21), 11 patients had stable disease (52.4%), 9 had progressive disease (42.9%), and 1 had a complete response (4.8%).
Conclusions: Alterations identified by ctDNA may help inform management decisions in advanced HNC. The majority of patients had unique mutations identified on ctDNA. The role of NGS of ctDNA should be explored in future studies.
