Monitoring of circulating tumor DNA (ctDNA) from patients’ blood samples can provide prognostic value for advanced cancer. Sequencing and monitoring the levels of circulating tumor DNA through the cancer patients’ treatment journey can help clinicians decide on the duration and potency of treatment options.
What is Circulating tumor DNA (ctDNA)?
Circulating tumor DNA (ctDNA) are small pieces of DNA that are shed from the cancer cells into the blood. DNA is mostly found inside the nucleus of cells but as the tumor grows, expands and gets replaced by new cells, DNA is shed from tumor cells into the surrounding environment. The quantity of ctDNA can vary among cancer patients and will depend on the type of tumor, its location and stage of the disease.
How is Circulating tumor DNA (cTDNA) screening helpful?
Information about quantity and sequence of ctDNA (Circulating tumor DNA) can help with cancer disease diagnosis and prognosis, selecting personalized treatment options and also continued monitoring of the disease for treatment impact and recurrence.
How is ctDNA Screening and Assessment done?
ctDNA assessment can be done from blood samples and therefore a circulating tumor DNA test can be done as many times during the cancer patient’s course of the disease. Assessment of ctDNA from blood can be done based on different techniques including a liquid biopsy and sequencing approach or through a technique called digital droplet polymerase chain reaction (ddPCR). The liquid biopsy sequencing approach gives a more detailed information on the specifics of the genomic mutations in the cancer genes being tested, it takes longer to get back the results and can be more expensive, hence may not be possible to do as often. The ddPCR technique does not give the granularity of information one can get through the sequencing approach but has a shorter turnaround time, less expensive and more likely to be reimbursed, therefore can be done more frequently during the patient’s journey. The ddPCR approach can give information on the quantity of ctDNA present in the blood but will not be able to give specific details on the genomic nature of the ctDNA unless the sample is sequenced.
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IDEA Study – ctDNA (circulating tumor DNA) Assessment in Colon Cancer
A recent Phase III IDEA-France (International Duration Evaluation of Adjuvant (IDEA)) clinical trial for Stage III colon cancer patients, assessed the impact of shorter (3 months) vs. longer (6 months) duration of oxaliplatin based chemotherapy adjuvant treatment on disease free survival. In this study, the investigators also analyzed ctDNA of the patients prior to starting chemotherapy (Andre T. et al, J Clin. Oncol., 2018). The details and findings of the study and analysis of levels of ctDNA with patient survival are as follows:
- A total of 805 patients had their blood samples analyzed for ctDNA (circulating tumor DNA) prior to starting chemotherapy. Of these 696 (86.5%) patients were ctDNA negative and 109 (13.5%) of the patients were ctDNA positive.
- Those with ctDNA positive tumors were found to have more advanced tumors with poor differentiation.
- The 2-year disease free survival rate for ctDNA positive patients was 64% while for ctDNA negative patients it was 82%.
- The trend of reduced disease free survival was observed for ctDNA positive patients that were in the high risk or low risk stage III colon cancer, as confirmed by multivariate analysis.
- The conclusion of the researchers of the IDEA study on the use of oxaliplatin as adjuvant for 3 months or 6 months was that 6 months produced better outcomes than the 3 month treatment, both in patients with ctDNA negative samples or ctDNA positive samples. However, the 3-year survival difference between the 6 month vs 3 month oxaliplatin adjuvant treatment was only 3.6% with the 6 month 3-year disease free survival being 75.7% and 3 month being 72.1%.
Conclusion from the Study
The data on the analysis of ctDNA from the IDEA study colon cancer patients, and correlation with disease free survival, was presented at the ESMO Congress in September, 2019 (Taieb J et al, Abstract LBA30_PR, ESMO Congress, 2019). This data does indicate that ctDNA assessment with ddPCR can be an independent prognostic marker for advanced cancers. The sequencing and monitoring of ctDNA (Circular Tumor DNA) can be integrated into the cancer patient’s treatment workflow and could help clinicians decide on the duration and potency of adjuvant therapy that the patient will need, based on the levels of ctDNA prior to starting therapy.
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