What Is Tumor Fraction and Why Is It Important in Cancer?
Learn how quantifying the proportion of cancer in a sample provides a key biomarker to help guide personalized treatment and monitor patient progress.
The landscape of cancer diagnostics is evolving, with a shift towards more precise and personalized approaches. One measurement that has gained prominence is tumor fraction. This metric offers a quantitative look into the genetic makeup of a tumor and is a component in personalized medicine. Its application is expanding, providing insights that help guide patient care from diagnosis through treatment.
Defining Tumor Fraction
Tumor fraction is a measurement representing the proportion of cancerous material within a given biological sample. In a solid tissue biopsy, it is often called tumor purity, indicating the percentage of cells in the removed tissue that are cancerous versus healthy cells. A high tumor purity means the sample is dense with cancer cells, while a low purity indicates a greater mix of non-cancerous cells.
The concept extends to liquid biopsies, which analyze fluids like blood for circulating tumor DNA (ctDNA) fraction. ctDNA is genetic material shed from tumor cells into the bloodstream. The ctDNA fraction is the percentage of the total cell-free DNA (cfDNA) in a blood sample that originates from the tumor. For example, a 1% ctDNA fraction means one of every 100 cfDNA fragments analyzed is from a cancer cell.
Methods for Measuring Tumor Fraction
The methods for determining tumor fraction differ based on the sample type. For solid tissue biopsies, a pathologist can visually estimate tumor cellularity by examining a stained tissue slice under a microscope. Computational methods can also analyze genomic data from the tissue to infer tumor purity by identifying genetic alterations specific to the cancer.
For liquid biopsies, measuring the ctDNA fraction requires highly sensitive laboratory techniques. Next-generation sequencing (NGS) is a method used to analyze millions of DNA fragments in a blood sample simultaneously. By sequencing the cfDNA, scientists can identify mutations known to be in the patient’s tumor and calculate the proportion of cfDNA with these signatures. Droplet digital PCR (ddPCR) is another sensitive technique suitable for measuring low levels of ctDNA.
Clinical Relevance of Tumor Fraction
Measuring tumor fraction has several clinical applications as a biomarker in oncology. The level of ctDNA fraction can provide prognostic information, as higher levels are often associated with a larger tumor burden or more aggressive disease. This information helps clinicians better understand a patient’s cancer and anticipate its course.
This measurement is also valuable in guiding treatment decisions. For instance, detecting specific genetic mutations in ctDNA can determine if a patient is eligible for a particular targeted therapy. Monitoring changes in ctDNA fraction over time can show how well a treatment is working. A decrease in the fraction can indicate a positive response, while a rise may signal that the cancer is growing or has become resistant, allowing for timely adjustments to the treatment plan. This monitoring can also help detect minimal residual disease after treatment.
Interpreting Tumor Fraction Results
Interpreting a tumor fraction result requires careful consideration of several factors. A high tumor fraction, particularly in a liquid biopsy, often correlates with a higher overall tumor burden in the body. Conversely, a low or undetectable tumor fraction can have multiple interpretations. It could mean the tumor is small, is not shedding much DNA into the bloodstream, or that the current treatment is effectively controlling the disease.
A low result could also be due to technical limitations of the test or sample quality. The tumor fraction itself can be informative; a very low ctDNA fraction might suggest that a liquid biopsy result is less reliable. A ctDNA fraction of less than 1% is often considered low, and in such cases, a negative result from a liquid biopsy might warrant confirmation with a tissue biopsy to avoid missing potential treatment targets.
The specific type and stage of cancer can heavily influence tumor fraction values, as some cancers shed more DNA than others. The location of the tumor can also play a role. Not all analytical methods yield identical results, and the sensitivity of the test used is an important consideration. Clinicians interpret tumor fraction as one piece of a larger puzzle, integrating it with imaging scans, other lab results, and the patient’s overall health to make informed decisions.