Neha Jain, Senior Director Precision Medicine at OneOncology, shared a post on LinkedIn:
“Just today, I was asked to review ct-DNA ans tissue NGS reports for a newly diagnosed IV lung adenocarcinoma patient.
The ct- DNA test declared with >99% confidence that the patient was biomarker negative. Thankfully a tissue based NGS test had also been ordered for this patient, and guess what we found on that test?
A ROS1 fusion!
Thanks to the concurrent testing approach taken by the oncologists at One Oncology this patient has targeted therapy options available in the first-line setting. The oncologist didn’t stop at the “negative” ct- DNA.
“Negative” should prompt the question- negative by what method?
In lung cancer, a negative result is often treated as a definitive answer. But too often, it’s just a reflection of how we tested—not what’s actually there.
Negative PCR ≠ no EGFR alteration.
PCR only interrogates predefined, recurrent variants. If the tumor harbors a rare, atypical, or complex EGFR alteration, PCR will confidently report “negative”-even when an actionable driver is present.
Negative ctDNA ≠ no driver mutation
Plasma testing is powerful, but biology matters:
– Low tumor shedding
– Intrathoracic-only disease
– Small tumor burden
All can lead to false-negative ctDNA results. A negative plasma test should never be the end of the molecular workup.
The clinical risk.
When negative results from limited assays are overinterpreted, patients may:
- Miss targeted therapy opportunities
- Be funneled prematurely into chemotherapy or immunotherapy
- Experience delays while reflex testing is ordered—if tissue is even left
NGS reframes “negative” correctly.
Comprehensive tissue-based NGS doesn’t just look for what’s common-it looks for what’s possible. And when ctDNA is negative, tissue NGS remains essential.
The key message:
A result is only as definitive as the assay behind it.
“Negative” should prompt the question: negative by what method?
Precision oncology depends not just on testing—but on interpreting negative results with humility and context.
Would be interested to hear how others approach negative PCR or ctDNA results in their lung cancer workflows.”
More posts featuring Neha Jain on OncoDaily.