As an oncologist, I have seen the importance of using circulating tumor DNA (ctDNA) analysis in cancer diagnosis and treatment. ctDNA is a simple blood test that can provide valuable information about a patient’s cancer, making it a valuable tool in the fight against this disease.
Signatera is a technology developed by Natera that uses tumor-informed circulating tumor DNA (ctDNA) analysis for cancer monitoring. The technology uses ultra-sensitive digital PCR to detect minute amounts of ctDNA in a patient’s bloodstream, which can be an indicator of the presence and progression of cancer. The goal of Signatera is to provide a highly accurate and non-invasive method for monitoring cancer treatment response and detecting cancer recurrence earlier than traditional methods. It has been used in several clinical trials and has shown promising results.
Here are the top 5 reasons why ctDNA is a game-changer in cancer treatment and how it can help us better understand and give us an advantage in the fight against this disease:
Early Detection of Cancer Recurrence:
Imagine that cancer is like a burglar breaking into a house. With ctDNA, we can detect the burglar (microscopic cancer) before they cause any significant damage to the house (macroscopic metastatic disease to the body). This early detection potentially allows us to act quickly and prevent further spread of the disease. As an example, I saw a patient today with Stage II colon cancer. Based on clinical factors alone, her recurrence cancer risk is about 15-20% within 5 years. Per guidelines we would prefer to observe alone and avoid the use of chemotherapy. However, this patient had positive ctDNA which increases her risk for recurrent disease to greater than 85-90%. No oncologist feels comfortable observing patients with this considerable risk especially if they have the tools that can help improve the outcomes of not seeing cancer come back. Recent studies suggest that using chemotherapy sooner can lead to converting this detectable quantifiable ctDNA to undetectability which has been highly associated with an improved recurrence free survival. Further studies are ongoing to confirm this effect, the data is already compelling enough to have an informed discussion with the patient outside of clinical trials about the risk, benefits, pros, cons, and uncertainties for mitigating cancer recurrence if there is a positive ctDNA. If the ctDNA was negative, cure rates were above 95% and we are all happy spare the drugs.
Monitoring Treatment Response
With ctDNA, we can monitor how well the treatment is working and quickly adjust if we need to. This helps us ensure that we are on the right track in beating cancer. Another patient I saw in the past week had Stage III colon cancer who received adjuvant chemotherapy or chemotherapy to mitigate the risk for recurrence. The ctDNA was positive prior to starting therapy and remained detectable and rising after 2-3 months of adjuvant chemotherapy. This ctDNA is fragments of cancer specific DNA shedding from occult disease not yet detected on CT or PET scan. The recurrence risk based on this positive and persistent ctDNA is above 85-90%. It is not IF this patient will develop recurrent cancer but WHEN this patient will have it. Studies show the median time to detectable tumors on a CT scan is 8-9 months later and in some cases 16 months later. Fortunately, for this patient, there were biomarkers that the tumors were sensitive to immunotherapy and after a risk, benefit, pros, cons discussion, the patient was agreeable to switch to immunotherapy. More studies are needed to learn how best to use this test with early intervention especially for patients who have had prior therapy and continue to have a positive ctDNA.
Differentiating immunotherapy pseudo-progression vs true progression
We all love to see tumors shrink and/or see stable disease after taking on therapy but we do not like to see progressive disease on repeat imaging. With chemotherapy, progressive disease would mean failure of the treatment and the immediate need to switch therapy. With immunotherapy, progressive disease could be a good thing with an inflammatory effect causing progressive changes and physicians/patients can continue therapy that is potentially working for them. However, in MOST cases, the progressive disease we see on scans is due to just progressive cancer. And unfortunately, patients and physicians continue treatment that is potentially futile. ctDNA can help determine pseudoprogressive changes with declining ctDNA versus rising numbers with true progressive disease despite objective radiographic or clinical assessment.
Intratumoral therapy response
I see a lot of melanoma patients with palpable visible tumors where I can inject modified viral therapy, cytokines, or other biologics with the intent to stimulate the immune system to attack the tumor that I am actually injecting. The problem I have is that I can continue to inject the tumors if they remain stable or shrink and we do not see any new tumors popping up elsewhere. But I really do not know with any significant certainty if I am still injecting a tumor full of viable cancer cells or if the tumor is now becoming dead or fibrotic over time. ctDNA in my experience has been useful to differentiate the good responders from the non-responders.
Non-Invasive
ctDNA analysis is like a simple blood test, just like checking your blood sugar level. It’s easy, painless, and provides important information about your health without the need for any painful procedures. We can use the ctDNA periodically without the need for repeat painful biopsies. Potentially we could see new mutations that may help explain resistance to ongoing treatment and perhaps open doors to adding treatment to overcoming the resistant mutation.
Personalized Medicine:
Imagine that every person’s cancer is like a unique puzzle. With ctDNA, we can better understand the pieces of each puzzle and create a tailored treatment plan that fits each person’s specific needs. Historically, we always prefer to look under the hood of the car with direct genomic testing on the cancer tissue. With ctDNA, we can potentially detect all potential actionable mutations without the need for additional tissue biopsy.
ctDNA is a valuable tool in the fight against cancer. By using ctDNA, we can detect cancer recurrence earlier, monitor treatment response, provide personalized medicine, and improve patient outcomes. If you or a loved one has been diagnosed with cancer, be sure to ask your doctor about ctDNA analysis and how it can help you in your fight against this disease.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
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