A recent publication by Dr Eroglu et al. in Cancer can be found here! Hope this articles helps!
As an oncologist, my days are filled with fascinating and challenging cases, but one recent patient in particular caught my attention. He was a young man who had just undergone surgery to remove high-risk Stage IIC malignant melanoma. While he was doing well clinically, the possibility of recurrence was a concern, with a 20-30% chance over the next 5-10 years. That means for every 100 patients with the same stage melanoma, 20-30 individuals will develop recurrent local-regional or metastatic disease. I may not have a crystal ball at my disposal, I do have access to an ever-expanding array of medical tools and technologies that can help me and the patient make informed decision. One such intriguing tool is circulating tumor DNA (ctDNA).
Can circulating tumor DNA predict those who are most likely to recur with detectable cancer specific DNA in the patient’s blood and perhaps consideration for escalation of care to the use of clinical trials, adjuvant immunotherapy and/or targeted RAF/MEK inhibitors? Or perhaps we can leave those patients with no detectable ctDNA alone, de-escalate their treatment course to observation alone or a limited course of treatment?
Adjuvant therapy is a potential option for reducing the risk of recurrence, but as with any treatment, there is a delicate balance to be struck. Treat too aggressively, and we risk causing unnecessary harm to the patient. Treat too conservatively, and we risk missing the chance to catch a recurrence early. My patient initially opted to observe alone given the real concern for potential adverse effects with immune related side effects and endocrinopathies. I had planned to see him again in 4-6 months with a repeat CT scan however I had real concerns about his melanoma. Perhaps if we could test him to see if there was detectable shedding melanoma DNA in the blood, would that change our management? After a careful discussion the benefits, uncertainties of ctDNA testing, we opted to test and within 6 weeks we had detectable, quantifiable melanoma specific ctDNA in his blood. What does this mean for the patient? We didn’t have much information to share in this situation until most recently.
A small retrospective study by Dr. Eroglu and colleagues demonstrated the feasibility of a personalized ctDNA assay for detecting molecular residual disease (MRD) after surgical resection and monitoring response to immune checkpoint inhibitor (ICI) treatment in stage III-IV melanoma patients. What sets this assay apart is that it tracks up to 16 somatic, clonal single nucleotide variants (SNVs), making it more sensitive to tumor dynamics in clinical practice. Already prime-time in the world of resectable colon cancer!
Using this assay, the researchers were able to detect distant melanoma relapse with a sensitivity of 83% and specificity of 96% in the adjuvant stage III setting. Moreover, the outcomes were improved in MRD positive patients treated with adjuvant immunotherapy suggesting that monitoring ctDNA dynamics is valuable. Vice versa, increasing ctDNA levels after six weeks of adjuvant anti-PD-1 treatment were predictive of significantly shorter distant metastasis-free survival (DMFS). The lead-time to detectable progressive disease on radiographic imaging was about 3-4 months.
This is exciting news, as it suggests that ctDNA testing could help us identify high-risk patients ahead of radiologic and/or clinical progression who may benefit from modifying their therapeutic regimen. By tailoring our approach based on personalized ctDNA data, we potentially may be able to spare those patients who are most likely cured by surgery alone from unnecessary treatment while giving those who are truly high risk the best chance at a favorable outcome.
Of course, it’s important to approach ctDNA testing with caution and carefully weigh the pros, cons, risks, benefits, and uncertainties with each patient. This is early but exciting data and certainly, more prospective studies are needed to validate this approach! I am very hopeful that we can shift the paradigm for the treatment of high-risk melanoma from clinical-pathological factors to the real-time detection and informed choice of ctDNA testing in the adjuvant setting.
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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