For the “research nerds” among us, few things are more fun than picking the most significant abstract from the ASCO annual meeting. My provocative choice from this year’s research is abstract LBA11501: Somatic genomic landscape of over 15,000 patients with advanced-stage cancer from clinical next-generation sequencing analysis of circulating tumor DNA. Follow my logic and see if you agree.
Biopsy specimens are problematic for many reasons:
- Adequate specimens can be difficult to obtain (e.g., lung).
- Specimens may be small and limit diagnostic studies (e.g., as many as one-third of non-small cell lung cancer (NSCLC) patients are not tested for EGFR/ALK mutations due to quantity not sufficient).
- Procedures have risk (liver, lung).
- Tumors are heterogeneous and specimens may not be representative.
- Serial biopsies are impractical for all the above reasons.
- Biopsy procedures are not performed by oncologists themselves (i.e., provenance over specimens in the hands of a hospital pathology lab limits the treating physician’s ability to direct and control testing, timing and lab, etc.).
Observations made a decade ago that even in local and regional tumors, cancer cells and their DNA may be found circulating in the blood raised the possibility that a new source of tumor from an easily obtained source (blood) may provide an alternative to tissue biopsy. If there were enough circulating tumor cells or an ability to identify and amplify circulating cell-free tumor DNA, then a host of possibilities emerges. Research conducted over the past decade has revealed the following:
- Circulating tumor cells and cell-free tumor DNA can be found in high frequency.
- DNA can be amplified, thus allowing meaningful testing on small (10cc) liquid specimens.
- The presence of circulating tumor cells and DNA in a localized cancer correlate with relapse risk and conversely, the absence of circulating tumor cells and DNA after treatment correlate with remission.
- Similar correlates of response are seen with metastatic tumors suggesting that circulating tumor cells and DNA reflect the clones of tumor most likely to threaten life and well-being.
- Proof of all these findings is achievable because serial testing is highly feasible.