Corresponding ctDNA and tumor burden dynamics in metastatic melanoma patients on systemic treatment
•Longitudinal analysis of corresponding measurements of plasma ctDNA and tumor burden of melanoma subjects during therapy.•Evidence to explain the poor correlation between tumor burden measurements and plasma ctDNA concentration is due to differences in disease status.•Work has implications relative...
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| Published in | Translational oncology Vol. 42; p. 101883 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.04.2024
Neoplasia Press Elsevier |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1936-5233 1936-5233 |
| DOI | 10.1016/j.tranon.2024.101883 |
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| Abstract | •Longitudinal analysis of corresponding measurements of plasma ctDNA and tumor burden of melanoma subjects during therapy.•Evidence to explain the poor correlation between tumor burden measurements and plasma ctDNA concentration is due to differences in disease status.•Work has implications relative to the interpretation of ctDNA test results and reconciliation with radiographic standard of care.
Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R2= 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R2= 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. |
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| AbstractList | Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R2= 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R2= 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. •Longitudinal analysis of corresponding measurements of plasma ctDNA and tumor burden of melanoma subjects during therapy.•Evidence to explain the poor correlation between tumor burden measurements and plasma ctDNA concentration is due to differences in disease status.•Work has implications relative to the interpretation of ctDNA test results and reconciliation with radiographic standard of care. Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R2= 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R2= 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R = 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R = 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R2= 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R2= 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden.Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R2= 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) (p = 0.012); this difference was independent of total tumor burden (p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R2= 0.88, p<0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. • Longitudinal analysis of corresponding measurements of plasma ctDNA and tumor burden of melanoma subjects during therapy. • Evidence to explain the poor correlation between tumor burden measurements and plasma ctDNA concentration is due to differences in disease status. • Work has implications relative to the interpretation of ctDNA test results and reconciliation with radiographic standard of care. Radiographic imaging is the current standard for monitoring progression of tumor-burden and therapeutic resistance in patients with metastatic melanoma. Plasma circulating tumor DNA (ctDNA) has shown promise as a survelience tool, but longitudinal data on the dynamics between plasma ctDNA concentrations and radiographic imaging is lacking. We evaluated the relationship between longitudinal radiographic measures of tumor burden and ctDNA concentrations in plasma on 30 patients with metastatic melanoma on systemic treatment. In 9 patients with no radiographic evidence of disease over a total of 15 time points, ctDNA concentrations were undetectable. In 21 patients with radiographic tumor burden, ctDNA was detected in 81 % of 58 time points. Plasma ctDNA concentrations demonstrated a modest positive correlation with total tumor burden (TTB) measurements (R 2 = 0.49, p < 0.001), with the greatest degree of correlation observed under conditions of progressive disease (PD) (R 2 = 0.91, p = 0.032). Plasma ctDNA concentrations were significantly greater at times of RECIST v1.1 progression (PD; 22.1 % ± 5.7 %) when compared to samples collected during stable disease (SD; 4.99 % ± 3.0 %) ( p = 0.012); this difference was independent of total tumor burden ( p = 0.997). Changes in plasma ctDNA showed a strong correlation with changes in TTB (R 2 = 0.88, p <0.001). These data suggest that measurements of plasma ctDNA during therapy are a better surrogate for responding versus non-responding disease compared to absolute tumor burden. |
| ArticleNumber | 101883 |
| Author | Van Meter, Tracy Valdes, Roland Kong, Maiying Hall, Melissa Barousse Linder, Mark W. Egger, Michael E. Alexander, Evan Maung, Aye Aye |
| Author_xml | – sequence: 1 givenname: Michael E. orcidid: 0000-0002-8263-751X surname: Egger fullname: Egger, Michael E. organization: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA – sequence: 2 givenname: Evan orcidid: 0000-0002-9713-0260 surname: Alexander fullname: Alexander, Evan organization: Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY, USA – sequence: 3 givenname: Tracy orcidid: 0000-0002-2333-3364 surname: Van Meter fullname: Van Meter, Tracy organization: Department of Radiology, University of Louisville School of Medicine, Louisville, KY, USA – sequence: 4 givenname: Maiying surname: Kong fullname: Kong, Maiying organization: Biostatistics and Bioinformatics Facility, James Graham Brown Cancer Center, Louisville, KY, USA – sequence: 5 givenname: Aye Aye orcidid: 0009-0006-0668-1304 surname: Maung fullname: Maung, Aye Aye organization: Biostatistics and Bioinformatics Facility, James Graham Brown Cancer Center, Louisville, KY, USA – sequence: 6 givenname: Roland surname: Valdes fullname: Valdes, Roland organization: Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY, USA – sequence: 7 givenname: Melissa Barousse surname: Hall fullname: Hall, Melissa Barousse organization: UofL Health Brown Cancer Center, Louisville, KY, USA – sequence: 8 givenname: Mark W. surname: Linder fullname: Linder, Mark W. email: mark.linder@louisville.edu organization: Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38306914$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1186_s13046_025_03328_4 crossref_primary_10_1016_j_jmoldx_2024_07_001 crossref_primary_10_1016_j_esmogo_2025_100148 |
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| Keywords | Tumor burden Treatment monitoring Plasma ctDNA Tumor proliferation Melanoma |
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| Title | Corresponding ctDNA and tumor burden dynamics in metastatic melanoma patients on systemic treatment |
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