Detection of metastases using circulating tumour DNA in uveal melanoma

Aaron B. Beasley; Daniël P. de Bruyn; Leslie Calapre; Zeyad Al-Ogaili; Timothy W. Isaacs; Jacqueline Bentel; Anna L. Reid; Roy S. Dwarkasing; Michelle R. Pereira; Muhammad A. Khattak; Tarek M. Meniawy; Michael Millward; Erwin Brosens; Annelies de Klein; Fred K. Chen; Emine Kiliҫ; Elin S. Gray

doi:10.1007/s00432-023-05271-3

Detection of metastases using circulating tumour DNA in uveal melanoma

Aaron B. Beasley^*, Daniël P. de Bruyn, Leslie Calapre, Zeyad Al-Ogaili, Timothy W. Isaacs, Jacqueline Bentel, Anna L. Reid, Roy S. Dwarkasing, Michelle R. Pereira, Muhammad A. Khattak, Tarek M. Meniawy, Michael Millward, Erwin Brosens, Annelies de Klein, Fred K. Chen, Emine Kiliҫ, Elin S. Gray^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background:

Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response.

Methods:

We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients.

Results:

Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy.

Conclusions:

Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

Original language	English
Pages (from-to)	14953-14963
Number of pages	11
Journal	Journal of Cancer Research and Clinical Oncology
Volume	149
Issue number	16
Early online date	22 Aug 2023
DOIs	https://doi.org/10.1007/s00432-023-05271-3
Publication status	Published - Nov 2023

Bibliographical note

Funding Information:
Open Access funding enabled and organized by CAUL and its Member Institutions. This study was funded by a Raine Medical Research Foundation Priming Grant and an Ophthalmic Research Institute of Australia Grant to ESG and an Australian Melanoma Research Foundation Postgraduate research grant awarded to ABB.

Publisher Copyright:
© 2023, The Author(s).

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Detection of metastases using circulating tumour DNA in uveal melanomaFinal published version, 1.79 MBLicence: CC BY

Cite this

Beasley, A. B., de Bruyn, D. P., Calapre, L., Al-Ogaili, Z., Isaacs, T. W., Bentel, J., Reid, A. L., Dwarkasing, R. S., Pereira, M. R., Khattak, M. A., Meniawy, T. M., Millward, M., Brosens, E., de Klein, A., Chen, F. K., Kiliҫ, E., & Gray, E. S. (2023). Detection of metastases using circulating tumour DNA in uveal melanoma. Journal of Cancer Research and Clinical Oncology, 149(16), 14953-14963. https://doi.org/10.1007/s00432-023-05271-3

@article{5ec8b4724ea84b578cab23a153da3c97,

title = "Detection of metastases using circulating tumour DNA in uveal melanoma",

abstract = "Background: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. Methods: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. Results: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. Conclusions: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.",

author = "Beasley, {Aaron B.} and {de Bruyn}, {Dani{\"e}l P.} and Leslie Calapre and Zeyad Al-Ogaili and Isaacs, {Timothy W.} and Jacqueline Bentel and Reid, {Anna L.} and Dwarkasing, {Roy S.} and Pereira, {Michelle R.} and Khattak, {Muhammad A.} and Meniawy, {Tarek M.} and Michael Millward and Erwin Brosens and {de Klein}, Annelies and Chen, {Fred K.} and Emine Kiliҫ and Gray, {Elin S.}",

note = "Funding Information: Open Access funding enabled and organized by CAUL and its Member Institutions. This study was funded by a Raine Medical Research Foundation Priming Grant and an Ophthalmic Research Institute of Australia Grant to ESG and an Australian Melanoma Research Foundation Postgraduate research grant awarded to ABB. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

doi = "10.1007/s00432-023-05271-3",

language = "English",

volume = "149",

pages = "14953--14963",

journal = "Journal of Cancer Research and Clinical Oncology",

issn = "0171-5216",

publisher = "Springer Science+Business Media",

number = "16",

}

Beasley, AB, de Bruyn, DP, Calapre, L, Al-Ogaili, Z, Isaacs, TW, Bentel, J, Reid, AL, Dwarkasing, RS, Pereira, MR, Khattak, MA, Meniawy, TM, Millward, M, Brosens, E , de Klein, A, Chen, FK, Kiliҫ, E & Gray, ES 2023, 'Detection of metastases using circulating tumour DNA in uveal melanoma', Journal of Cancer Research and Clinical Oncology, vol. 149, no. 16, pp. 14953-14963. https://doi.org/10.1007/s00432-023-05271-3

TY - JOUR

T1 - Detection of metastases using circulating tumour DNA in uveal melanoma

AU - Beasley, Aaron B.

AU - de Bruyn, Daniël P.

AU - Calapre, Leslie

AU - Al-Ogaili, Zeyad

AU - Isaacs, Timothy W.

AU - Bentel, Jacqueline

AU - Reid, Anna L.

AU - Dwarkasing, Roy S.

AU - Pereira, Michelle R.

AU - Khattak, Muhammad A.

AU - Meniawy, Tarek M.

AU - Millward, Michael

AU - Brosens, Erwin

AU - de Klein, Annelies

AU - Chen, Fred K.

AU - Kiliҫ, Emine

AU - Gray, Elin S.

N1 - Funding Information: Open Access funding enabled and organized by CAUL and its Member Institutions. This study was funded by a Raine Medical Research Foundation Priming Grant and an Ophthalmic Research Institute of Australia Grant to ESG and an Australian Melanoma Research Foundation Postgraduate research grant awarded to ABB. Publisher Copyright: © 2023, The Author(s).

PY - 2023/11

Y1 - 2023/11

N2 - Background: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. Methods: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. Results: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. Conclusions: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

AB - Background: Approximately 50% of uveal melanoma (UM) patients will develop metastatic disease depending on the genetic features of the primary tumour. Patients need 3–12 monthly scans, depending on their prognosis, which is costly and often non-specific. Circulating tumour DNA (ctDNA) quantification could serve as a test to detect and monitor patients for early signs of metastasis and therapeutic response. Methods: We assessed ctDNA as a biomarker in three distinct UM cohorts using droplet-digital PCR: (A) a retrospective analysis of primary UM patients to predict metastases; (B) a prospective analysis of UM patients after resolution of their primary tumour for early detection of metastases; and (C) monitoring treatment response in metastatic UM patients. Results: Cohort A: ctDNA levels were not associated with the development of metastases. Cohort B: ctDNA was detected in 17/25 (68%) with radiological diagnosis of metastases. ctDNA was the strongest predictor of overall survival in a multivariate analysis (HR = 15.8, 95% CI 1.7–151.2, p = 0.017). Cohort C: ctDNA monitoring of patients undergoing immunotherapy revealed a reduction in the levels of ctDNA in patients with combination immunotherapy. Conclusions: Our proof-of-concept study shows the biomarker feasibility potential of ctDNA monitoring in for the clinical management of uveal melanoma patients.

UR - http://www.scopus.com/inward/record.url?scp=85168579894&partnerID=8YFLogxK

U2 - 10.1007/s00432-023-05271-3

DO - 10.1007/s00432-023-05271-3

M3 - Article

C2 - 37608028

AN - SCOPUS:85168579894

SN - 0171-5216

VL - 149

SP - 14953

EP - 14963

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

IS - 16

ER -

Detection of metastases using circulating tumour DNA in uveal melanoma

Abstract

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