European Conference on Interventional Oncology

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

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ProgrammectDNA: a new instrument for surveillance after ablative treatment

ctDNA: a new instrument for surveillance after ablative treatment

 

Three things you will learn from my lecture:

  • ctDNA measurement is a powerful pan-cancer tool
  • ctDNA detection post ablative therapy can be a powerful method to detect MRD and early failure
  • We are in the early days of ctDNA in the oligometastatic setting and its great potential must lead to the design of relevant clinical prospective studies

Prof. Karen-Lise Garm Spindler
Speaker bio
 

Click here to watch this lecture via the ECIO 2023 congress platform.

Finding tumour-specific DNA

Investigations of the clinical utility of circulating DNA in cancer treatment has gained strong interest during the past decade. The small free DNA fractions which are measurable in a simple blood sample are a mixture of DNA from both healthy and cancer cells. Therefore, it is possible to detect and measure DNA with tumour-specific characteristics in many different tumour types. The biology of ctDNA is far from fully understood, but development of laboratory methods for ctDNA measurement has been fast and impressive and now allows for large-scale clinical trials and explorative studies in many different tumour types.

ctDNA: our best chance to indicate recurrence risk early?

The presence of ctDNA in a blood sample indicates the presence of cancer cells in the body, since the half-life degradation of the cfDNA is only a few hours. Studies have shown that detection of ctDNA in blood samples from patients after a curatively intended treatment modality such as surgery implies an extremely high risk of recurrence of the disease. [1] This information is now being explored in multiple clinical trials in primary colorectal cancer investigating the use of ctDNA as a marker of minimal residual disease (MRD), as a tool for guiding adjuvant systemic therapy and follow-up programmes. [2] The potential for this is very promising, and the first results from clinical trials were presented last year. [3] In the follow-up programme after cancer treatment, the sensitivity of ctDNA detection may exceed the clinical and imaging-based assessments, and studies have described a clinical lead time between the ctDNA based detection and the clinical determination of recurrences from months to years. Clearly, this calls for prospective testing in multiple tumour types to investigate if ctDNA testing can provide clinically relevant early detection of treatment failure and recurrences. This is particularly relevant in the high-risk situations such as after local ablation of metastatic lesions.

Now, where should this method best be used?

The detection rate of ctDNA in low-risk disease can be limited, whereas patients with spread of the disease to other organs, especially the liver, show higher concentrations in their blood. [4] In the clinical situation with oligometastatic disease which could allow for local ablative therapies, there is an unmet need for reliable tools to select patients for active strategies, and to support decisions of post-treatment adjuvant therapy and follow-up schedules. The potential of ctDNA as pre-and post-treatment prognostic factor is presented in a recent review in colorectal cancer. [5] As adjunct to advanced imaging procedures, the ctDNA guided strategies can become highly valuable. Therefore, prospective observational studies that investigate the biological clearance of ctDNA after the different ablative options are urgently needed, since still only a limited number of studies have been published on ctDNA detection in the oligometastatic setting. The full potential is clearly far from described. The shedding and mutational recovery from the different organs needs to be elucidated, as does the potential role of combining ctDNA with advanced imaging and AI tools.

Very few prospective studies have been initiated to investigate ctDNA guided treatment and follow-up in a randomized stringent way, and more such initiatives should be undertaken to confirm the great potential ctDNA testing can have in this clinical setting.

I look forward to presenting an overview of the current knowledge on ctDNA biology, methodology, and the huge clinical potential for its use. In addition, I will discuss some of the few clinical trials designed to prospectively investigate its clinical utility in oligometastatic disease.

 

Karen-Lise Garm Spindler

Aarhus University Hospital, Aarhus/DK

Prof. Garm Spindler is a clinical oncologist trained in Denmark and the UK. She has been working at Aarhus University Hospital since 2014, primarily focusing on lower GI cancer. Her clinical responsibilities include systemic treatment of lower GI cancer as well as radiotherapy. She has formed and leads the Danish Anal Cancer Group, DACG, and has led the formation of the International Multidisciplinary Consortium (and Conferences) for Anal Cancer – IMACC. Prof. Garm Spindler is the chairperson of a translational science group under the International Rare Cancers Initiative (IRCI), and is a member of the EORTC gastrointestinal working group. She currently chairs the Danish Cancer Society’s Scientific Committee.
Dr. Garm Spindler is a professor in Precision and Translational Medicine in Gastrointestinal Cancer at Aarhus University and supervises translational laboratory and clinical research with several PhD. students and junior physicians in her group.
Prof. Garm Spindler has a special interest is the clinical utility of liquid biopsies in cancer, which she has explored since her PhD studies finalized in 2007 on the EGFR system in colorectal cancer. Her pivotal results were detailed in the higher doctoral degree on circulating DNA in metastatic colorectal cancer awarded by Aarhus University in 2019. She is a founding member of the Danish Research Center for ctDNA studies, and a member of the European Liquid Biopsy Society. Her work has resulted in the launch of several clinical intervention trials using ctDNA for treatment guidance in different clinical situations, including the first worldwide clinical trial investigating the use of ctDNA for treatment decisions and follow-up in oligometastatic colorectal cancer treated with local procedures.

 

References

  1. Faulkner LG, Howells LM, Pepper C, et al. The utility of ctDNA in detecting minimal residual disease following curative surgery in colorectal cancer: a systematic review and meta-analysis. Br J Cancer 2022; Nov 8.PMID: 36347967
  2. Masfarré L, Vidal J, Fernández-Rodríguez C, Montagut C. ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC). Cancers (Basel). 2021 Jun 8;13(12):2869. PMID: 34201274
  3. Tie J, Cohen JD, Lahouel K, Lo SN, Wang Y, Kosmider S, Wong R, Shapiro J, Lee M, Harris S, Khattak A, Burge M, Harris M, Lynam J, Nott L, Day F, Hayes T, McLachlan SA, Lee B, Ptak J, Silliman N, Dobbyn L, Popoli M, Hruban R, Lennon AM, Papadopoulos N, Kinzler KW, Vogelstein B, Tomasetti C, Gibbs P; DYNAMIC Investigators. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med. 2022 Jun 16;386(24):2261-2272. PMID: 35657320
  4. Hamfjord J, Guren TK, Glimelius B et al. Clinicopathological factors associated with tumour-specific mutation detection in plasma of patients with RAS-mutated or BRAF-mutated metastatic colorectal cancer. Int J Cancer 2021; 149: 1385-1397
  5. Louise B. Callesen, Tana Takacova, Julian Hamfjord, Florian Würschmidt, Karl J. Oldhafer, Roland Brüning, Dirk Arnold, Karen-Lise G. Spindler. Circulating DNA in patients undergoing locoregional treatment of colorectal cancer metastases: A systematic review and meta-analysis. Ther Adv Med Oncol. 2022 Nov 2;14: PMID: 36339929
  6. Callesen LB, Hansen TF, Andersen RF, Pallisgaard N, Kramer S, Schlander S, Rafaelsen SR, Boysen AK, Jensen LH, Jakobsen A, Spindler KG. OPTIMISE: Optimisation of treatment selection and follow-up in oligometastatic colorectal cancer – a ctDNA-guided phase II randomised approach. Study protocol. Acta Oncol. 2022 Sep 12:1-5. PMID: 36094310