Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression

Marsavela, Gabriela; McEvoy, Ashleigh C.; Pereira, Michelle R.; Reid, Anna L.; Al-Ogaili, Zeyad; Warburton, Lydia; Khattak, Muhammad A.; Abed, Afaf; Meniawy, Tarek; Millward, Michael; Ziman, Melanie; Calapre, Leslie; Gray, Elin S.

doi:10.1038/s41416-021-01507-6

Cited by 25 publications

(25 citation statements)

References 48 publications

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“…Our findings are in line with other published studies regarding the usefulness of ctDNA to monitor treatment success. Differences in the results can be explained by different study designs and patient populations [ 2 , 6 , 7 , 8 , 9 , 20 ]. Most of these were small retrospective studies with a short observation period and inconsistent sampling time points [ 8 , 9 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

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The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma

Boerlin

Bellini

Turko

et al. 2022

Cancers

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Melanoma currently lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Circulating tumor DNA (ctDNA), originating from tumor cells and detectable in plasma, has emerged as a possible biomarker in patients with metastatic melanoma. In this retrospective, single-center study, we collected 129 plasma samples from 79 patients with stage IIIB–IV melanoma as determined by the American Joint Committee on Cancer (AJCC, 8th edition). For the determination of ctDNA levels, we used eight different assays of droplet digital polymerase chain reaction (ddPCR) to detect the most common hotspot mutations in the BRAF and NRAS genes. The aim of the study was to investigate the association of the detectability of ctDNA at a non-prespecified time point in a patient’s treatment with tumor progression, and to correlate ctDNA with commonly used biomarkers (protein S100, LDH, and CRP). Patients with detectable ctDNA progressed more frequently in PET-CT within 12 months than those without detectable ctDNA. Detectability of ctDNA was associated with shorter OS in univariate and multivariate analyses. ctDNA was detectable in a statistically significantly larger proportion of patients with distant metastases (79%) than in patients with no distant metastases or only intracranial metastases (32%). Elevated protein S100 and CRP correlated better with detectable ctDNA than LDH. This study supports the potential of ctDNA as a prognostic biomarker in patients with metastatic melanoma. However, additional prospective longitudinal studies with quantitative assessments of ctDNA are necessary to investigate the limitations and strengths of ctDNA as a biomarker.

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Section: Discussionmentioning

confidence: 99%

“…However, these routine blood markers lack sufficient specificity and sensitivity for the prediction of treatment response and prognosis. For the detection of tumor progression, imaging with PET-CT scans is still the recommended method [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma

Boerlin

Bellini

Turko

et al. 2022

Cancers

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“…Moreover, our results indicated that a liquid biopsy from blood might yield a better representation of the overall spectrum of somatic variants present in the tumor, particularly in the case of metastatic patients. ccfDNA from blood likely contains tumor DNA from multiple tumor localizations, which can better assist in personalized therapy of primary and metastatic brain tumor patients [ 49 , 50 , 51 , 52 ]. A liquid biopsy from blood may be a plausible alternative for elderly brain tumor patients in which a biopsy of CSF is not recommended due to its invasiveness and danger of infection.…”

Section: Discussionmentioning

confidence: 99%

Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients

Szadkowska

Roura

Wojtaś

et al. 2022

Cancers

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Malignant gliomas are the most frequent primary brain tumors in adults. They are genetically heterogenous and invariably recur due to incomplete surgery and therapy resistance. Circulating tumor DNA (ctDNA) is a component of circulating cell-free DNA (ccfDNA) and represents genetic material that originates from the primary tumor or metastasis. Brain tumors are frequently located in the eloquent brain regions, which makes biopsy difficult or impossible due to severe postoperative complications. The analysis of ccfDNA from a patient’s blood presents a plausible and noninvasive alternative. In this study, freshly frozen tumors and corresponding blood samples were collected from 84 brain tumor patients and analyzed by targeted next-generation sequencing (NGS). The cohort included 80 glioma patients, 2 metastatic cancer patients, and 2 primary CNS lymphoma (PCNSL) patients. We compared the pattern of genetic alterations in the tumor DNA (tDNA) with that of ccfDNA. The implemented technical improvements in quality control and library preparation allowed for the detection of ctDNA in 8 out of 84 patients, including 5 out of 80 glioma patients. In 32 out of 84 patients, we found potentially pathogenic genetic alterations in ccfDNA that were not detectable in tDNA. While sequencing ccfDNA from plasma has a low efficacy as a diagnostic tool for glioma patients, we concluded that further improvements in sample processing and library preparation can make liquid biopsy a valuable diagnostic tool for glioma patients.

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“…Numerous studies show that ctDNA levels correlate well with tumor load and therefore ctDNA dynamics can be used as a surrogate of treatment response (86)(87)(88). In addition, the modification of the ctDNA methylation profile has been proposed as an alternative biomarker for treatment response (89).…”

Section: Ctdna To Monitor Treatment Outcomesmentioning

confidence: 99%

Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That may Impact on ctDNA Analysis

et al. 2022

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Cancer cells release nucleic acids, freely or associated with other structures such as vesicles into body fluids, including blood. Among these nucleic acids, circulating tumor DNA (ctDNA) has emerged as a minimally invasive biomarker for tumor molecular profiling. However, certain biological characteristics of ctDNA are still unknown. Here, we provide an overview of the current knowledge about ctDNA biological features, including size and structure as well as the mechanisms of ctDNA shedding and clearance, and the physio-pathological factors that determine ctDNA levels. A better understanding of ctDNA biology is essential for the development of new methods that enable the analysis of ctDNA.

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Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression

Cited by 25 publications

References 48 publications

The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma

The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma

Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients

Circulating Tumor DNA as a Cancer Biomarker: An Overview of Biological Features and Factors That may Impact on ctDNA Analysis

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