by Dr. C.H. Weaver M.D. 6/2019

Blood analyses of whole-genome cell-free DNA (cfDNA) can determine Molecular Progression of metastatic solid cancers a few weeks into treatment.

Most cancer patients are unnecessarily treated with chemotherapy or continue to receive chemotherapy after it has stopped working. The ineffective use of chemotherapy exposes cancer patients to unnecessary side effects, inconvenience, cost, and delays access to the next potentially beneficial treatment.

What if a simple blood test were available that could quickly determine when chemotherapy was ineffective? Research presented at the 2019 American Society of Clinical Oncology on liquid biopsy analyses of serial changes in whole-genome cell free DNA suggests that such a blood test may soon become available.(1,2)

Current clinical practice is to begin chemotherapy treatment and then use medical imaging with CT, MRI, and PET scans to monitor any response to treatment. In this way doctors monitor or measure the “response” of a cancer to treatment. Response assessment has been performed in this manner for decades, but it usually takes several months and multiple imaging procedures to determine the effectiveness of therapy.

All medical imaging in this setting is designed to support comparisons over time, thus radiologists inspect new images to observe any changes compared with prior images from the same case. These visually observable changes in the shape, contour and density of the cancer are lagging indicators of what has already happened inside the patient biologically. The delay this creates in determining the effectiveness of any given therapy can expose patients to several courses of unnecessary chemotherapy, and all the side effects, in addition to a delay in getting access to potentially effective therapy.

Blood contains an abundance of information about a patient's cancer and immune response, from cells including cell free DNA and small vesicles from the tumor and its environment. Advances in biology and technology enable a simple blood draw - a liquid biopsy - to provide clinically actionable information about cancer diagnosis and treatment. For example, doctors can already predict which patients with breast cancer don't benefit from receiving chemotherapy and other genomic biomarker tests can match the treatment to the cancer by identifying specific genomic abnormalities that can be targeted with a precision cancer medicine. (3,4)

In the current study shared at ASCO, clinical information and blood samples were collected from 69 advanced cancer patients prior to beginning treatment on average 21 and 42 days after starting treatment. Changes in the fraction of tumor-derived cell free DNA were evaluated over the initial course of treatment and used to predict whether the cancer progressed or not.(2)

The researchers reported that cancer progression could be accurately predicted in 63 days on average using cfDNA obtained by liquid biopsy.

The study demonstrates an ability to accurately detect early cancer progression using whole genome cell free DNA -- molecular progression -- long before conventional imaging techniques could make a definitive call. This blood-based approach was consistent across multiple types of cancer and treatments, including immunotherapy. This novel liquid biopsy could aid in clinical decision making for early treatment changes and is undergoing additional validation. It should be available for use in routine clinical practice sometime in late 2020.


  1. Whole-genome cell-free DNA (cfDNA) changes as a dynamic blood-based biomarker for early response assessment of advanced tumors. | 2019 ASCO Annual Meeting Abstracts
  2. A prospective study tracking longitudinal changes in genome-wide cell-free DNA (cfDNA) methylation to identify early nonresponders to cancer treatment. | 2019 ASCO Annual Meeting Abstracts
  3. Lo SS, Mumby PB, Norton J et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. Journal of Clinical Oncology [early online publication]. January 11, 2009.