Liquid Biopsy Impact: Liquid biopsy in melanoma
Summer is a great time to enjoy the nice weather outdoors. It is also an important time of the year to encourage sun safety practices and promote early detection methods, ensuring everyone can have fun in the sun safely. Melanoma, a serious form of skin cancer, often requires close monitoring and in some cases, complex treatment plans. Traditional biopsy methods, while crucial for diagnosis, can be invasive and thus, not always ideal when repetitive testing is required. This is why melanoma is an optimal model for liquid biopsy implementation, which offers a promising, less invasive alternative for melanoma patients.
How liquid biopsy is being applied for melanoma patients?
During the 2023 International Symposium on Minimal Cancer, Dr. Isabel Heidrich from the University Medical Center Hamburg-Eppendorf, Germany, presented results from the monitoring of melanoma patients who were receiving immunotherapy [4].
Her team analysed 267 samples from 42 patients with advanced melanoma receiving immunotherapy. Using Sysmex Inostics‘ Plasma-SeqSensei Solid Cancer IVD kit, they were able to closely track the amount of circulating tumour DNA (ctDNA) and as a result, identify outstanding correlations between its variations.
Melanoma can be quite genetically diverse and using only single tissue samples can result in the loss of crucial information. Liquid biopsies, on the other hand, capture ctDNA shed by the entire tumour, providing a more comprehensive picture. This was especially evident in the study for patients with later-stage cancers.
Dr Heidrich’s data highlights that, in contrast to tissue testing, liquid biopsy identified additional mutations in 7 patients, with 4 mutations being rare BRAF gene mutations.
Similarly to what has been observed in other entities, ctDNA provided prognostic information when detected at base line. In this case, it was related to a shorter progression free survival with a hazard ratio of 0.48.
The interest on this field keeps on growing and other groups have been finding more evidence for the consolidation of this tool in the patient care. During AMP Europe 2024, Dr Ilaria Alborelli presented another longitudinal patient monitoring study [1] and was also able to observe that ctDNA levels can help prediction to treatment response.
Multiparameter approaches have extended beyond ctDNA to incorporate additional analytes, like circulating tumour cells (CTCs). A recent study [6] validated CTCs as a prognostic biomarker, demonstrating a correlation between the detection of at least one cell and early progression. However, despite these insights, CTCs fell short as a predictive marker of treatment response. Challenges in isolation and manipulation further underscore that CTCs are not yet primed for widespread use in patient monitoring.
What can ctDNA reveal on treatment response?
The levels of ctDNA closely mirrored patient response and resistance to the treatment. Drops in the ctDNA concentration indicated complete remission, while increases in ctDNA levels preceded traditional imaging tests in detecting treatment resistance. A significant lead time of 110 days in ctDNA detection compared to radiological imaging, as previously reported by Haselmann et al in 2018 [3], underscored the remarkable potential of ctDNA analysis in providing early warnings of disease progression.
These findings highlight the pivotal role of ctDNA in patient monitoring, offering oncologists a valuable tool for proactive intervention and personalized care.
The power of liquid biopsy: Monitoring melanoma progression
Dr. Isabel Heidrich and Dr. Christoffer Gebhardt presented further insights on their applications of liquid biopsy monitoring at the symposium, solidifying the potential of liquid biopsy as a powerful tool in the fight against melanoma.
With resistance to treatment being the primary cause of death for melanoma patients, accounting for up to 70% of cases at stage IV [7], and taking into consideration ctDNA’s remarkable correlation with therapy predictiveness, its’ only natural to ask when is the right moment to switch treatments?
Unfortunately, the latest ESMO guidelines published in 2022, on the use of ctDNA, do not provide specific recommendations for melanoma care [5]. Since then, a large quantity of research has been conducted on this application.
Despite their known toxicity, immunotherapy using checkpoint inhibitors (Nivo/Ipi) are still recommended as the primary treatment for melanoma, which, if necessary, is followed by targeted therapy. This recommendation is supported and reinforced by the favourable outcomes observed in patients, as demonstrated by the DREAMseq trial [2].
However, ctDNA has been presented as a potentially effective biomarker. It has been especially consistent in patients with mixed radiological response and has been proven to be more significant and sensitive than standard biomarkers, such as LDH. Combined with its ability to identify even the rarest mutations, it's only a matter of time before ctDNA analysis is fully incorporated into the melanoma patient healthcare journey.
For additional resources and in-depth information on liquid biopsy:
References
[1] Calgua, Byron, et al. (2024): Longitudinal Circulating Tumor-DNA Profiling Predicts Therapy Response in Melanoma Patients. The Journal of Molecular Diagnostics 26.6: S35.
[2] Jensen, Roxanne E., et al. (2022): Early quality of life (QOL) and symptom analysis from the DREAMseq phase III randomized control trial of combination immunotherapy versus targeted therapy in patients (pts) with BRAF-mutant metastatic melanoma. (MM)(ECOG-ACRIN EA6134): 9559-9559.
[3] Haselmann, Verena, et al. (2018): Liquid profiling of circulating tumor DNA in plasma of melanoma patients for companion diagnostics and monitoring of BRAF inhibitor therapy. Clinical chemistry 64.5: 830-842.
[4] Heidrich, Isabel, et al. (2023): Monitoring of ctDNA in melanoma patients receiving immunotherapy. Poster presented at the International Symposium on Minimal Residual Cancer, Hamburg.
[5] Pascual, Javier, et al. (2022): ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. Annals of Oncology 33.8: 750-768.
[6] Scaini, Maria Chiara, et al. (2024): A multiparameter liquid biopsy approach allows to track melanoma dynamics and identify early treatment resistance. npj Precision Oncology 8.1: 78.
[7] Ugurel, Selma, et al. (2020): Survival of patients with advanced metastatic melanoma: the impact of MAP kinase pathway inhibition and immune checkpoint inhibition-update 2019. European journal of cancer 130: 126-138.