The ability to detect microscopic amounts of measurable residual disease (MRD) by measuring circulating tumor DNA (ctDNA) in the blood is changing the management of cancer and can be used in a variety of ways to improve lymphoma management. ctDNA can be used to predict outcomes, assess response to treatment, and may even be useful in guiding escalation and de-escalation of treatment.
About ctDNA
Cancer is caused by genetic mutations, and these mutations can be detected by measuring circulating tumor DNA, or ctDNA, in the blood. Detection of ctDNA allows for personalized cancer surveillance based on an individual’s unique set of cancer mutations.
Circulating tumor DNA is 150–200-base-pair fragments of DNA, which originate from cancer cells and are present in the bloodstream or other body fluids. ctDNA is different than cell-free DNA (cfDNA) which is ALL the DNA in the bloodstream including germline DNA and tumor DNA. ctDNA is the portion of cfDNA that is derived specifically from the cancer.
Applications in Lymphoma
Prognosis
Higher baseline levels of ctDNA correlate with adverse outcomes in patients with both aggressive non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma, and failure of ctDNA to become undetectable during and after therapy for aggressive NHL, mantle cell lymphoma, and Hodgkin lymphoma predicts a higher likelihood of recurrence.
Response Assessment
Recurrence surveillance in lymphoma currently relies on computerized tomography (CT) and positron emission tomography (PET). These imaging tools are limited in their ability to detect MRD – ctDNA can be detected in the blood long before it appears on a CT or PET scan and has the potential to change how lymphomas are managed.
When used at the end of treatment in aggressive lymphoma measurement of ctDNA appears superior to PET/CT scans for assessing response to therapy in aggressive lymphomas, at predicting which patients will relapse. Can PET/CT scans be reduced or replaced thereby reducing cost and exposure to potentially harmful radiation
Patients should discuss the potential role of ctDNA in the management of lymphoma with their treating physician and how MRD results during treatment may be used to tailor therapy. Important clinical trials are ongoing to determine its exact role
Can patients who achieve undetectable MRD during therapy have their therapy shortened or reduced? Should patients who do not achieve undetectable MRD during or after therapy have their therapy intensified.
Connect With Others for Support and Information
CancerConnect was the first social network created for people with lymphoma. Founded by oncologists to support myeloma patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating lymphoma from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References
- https://www.nature.com/articles/s41375-022-01618-w
- Roschewski, Mark J. Circulating Tumor DNA in Lymphoma: When Will This Be Ready for Prime Time? Presented at: 11th Annual Meeting of the Society Hematologic Oncology (SOHO 2023), September 6, 2023. Houston, TX.
- Kurtz DM, Sherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol. 2018;36(28):2845-2853. doi: 10.1200/JCO.2018.78.5246.
- Kostakoglu L, Martelli M, Sehn LH, et al. End-of-treatment PET/CT predicts PFS and OS in DLBCL after first-line treatment: results from GOYA. Blood Adv. 2021;5(5):1283-1290. doi:10.1182/bloodadvances.2020002690.
- Roschewski M, Kurtz DM, Westin J, et al. MRD-negativity after frontline DLBCL therapy: pooled analysis of 6 clinical trials. Hematol Oncol. 2023;41(S2):177-179. doi:10.1002/hon.3163_112.
- Zinzani PL, Fanti S, Battista G, et al. Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients. British Journal of Cancer. 2004; 91: 850-854.
