THE MOLECULAR SECOND OPINION:
NGS, LIQUID BIOPSY & MISSED THERAPY

A molecular second opinion is the expert re-interpretation of your tumour's molecular and genomic data — including next-generation sequencing (NGS) reports, liquid biopsy (cell-free DNA / circulating tumour DNA) results, immunohistochemistry panels, FISH results, and any other biomarker testing — by a specialist molecular oncologist or molecular tumour board. It addresses the gap between having molecular data and acting on it correctly.

“The NGS report is not the end of the process — it is the beginning. Without expert interpretation matched to the current trial landscape, most NGS data goes clinically underused.”

• What the Molecular Second Opinion Covers

  Expert re-reading of all NGS variant calls (including VUS — variants of uncertain significance); cross-referencing against current FDA/EMA/NMPA approvals and open clinical trials; identification of co-mutations that affect response or resistance; and interpretation of liquid biopsy results in the context of prior tissue NGS.

• What Is Frequently Missed at Initial Review

  Uncommon variants in actionable genes (e.g., ERBB2 exon 20 insertions, rare EGFR mutations beyond del19/L858R); co-mutations that indicate resistance to planned targeted therapy; and variants that are only targetable through clinical trials — not visible in a standard prescribing reference but present in active trial protocols.

Published data quantifies how frequently actionable molecular information is missed at the initial treatment planning stage — even after NGS testing is performed.

• 15–30%Patients with NGS-detected actionable mutations not receiving matched therapyMultiple molecular tumour board studies demonstrate that 15–30% of patients who undergo NGS and have actionable alterations detected do not receive matched targeted therapy — primarily due to inadequate report interpretation and lack of trial access knowledge.
• 40%+VUS rate in typical cancer NGS panels40% or more of variants detected by comprehensive NGS panels are classified as 'Variants of Uncertain Significance' (VUS) — which may become clinically actionable as evidence accumulates, requiring expert follow-up interpretation.
• 3–5×More actionable mutations identified when molecular tumour board reviews NGS vs standard oncologist reviewStudies comparing MTB review vs standard oncologist review of the same NGS reports show 3–5× more actionable findings identified — demonstrating the value of specialist molecular interpretation.

These are the most clinically consequential molecular testing gaps — mutations that are present on NGS but frequently not acted upon due to report interpretation limitations.

The CancerFax molecular second opinion is structured to move from raw molecular data to actionable clinical recommendations — including matched therapy identification and trial eligibility.

1. 1

   Submit All Molecular Testing Reports

   Full NGS report with all variant calls (including VUS — not just the oncologist's summary), IHC panel results with antibody names and staining intensities, FISH reports with probe details, MSI/MMR results, TMB score, and any liquid biopsy (ctDNA) reports.

2. 2

   Submit Clinical Context

   Current cancer diagnosis, stage, prior treatment history, and the specific clinical question — 'Am I eligible for any targeted therapy?' or 'Are there trials matching my molecular profile?' Molecular data cannot be interpreted without clinical context.

3. 3

   Expert Molecular Oncologist Review

   A molecular oncologist reviews all variant calls against current drug approvals (FDA, EMA, NMPA), known resistance mechanisms, and co-mutation interactions. VUS are evaluated against emerging evidence databases (ClinVar, OncoKB, COSMIC, current literature).

4. 4

   Molecular Tumour Board Presentation for Complex Cases

   For cases with multiple variants, conflicting or uncertain findings, or rare genomic profiles, CancerFax presents the case to a virtual molecular tumour board — a multi-disciplinary panel of molecular oncologists, pathologists, and clinical trial specialists.

5. 5

   Actionable Report with Trial Matching

   A structured report is delivered covering: confirmed actionable variants, matched approved therapies, matched open clinical trials globally, resistance co-mutations to warn treating team about, and recommended additional testing if molecular panel was incomplete.

Tissue NGS and liquid biopsy (ctDNA) answer different questions — understanding when each is most informative determines which should be used, and when both are needed.

Frequently Asked Questions

Common questions about the molecular second opinion process.

Explore related guides on second opinion processes, pathology review, and specialist centre access.