Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients
© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society..
BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment.
METHODS: A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease.
RESULTS: In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression.
CONCLUSION: Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.
| Errataetall: |
CommentIn: Cancer. 2023 Jun 1;129(11):1646-1648. - PMID 36869645 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
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| Enthalten in: |
Cancer - 129(2023), 11 vom: 01. Juni, Seite 1723-1734 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Eroglu, Zeynep [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.05.2023 Date Revised 24.05.2023 published: Print-Electronic CommentIn: Cancer. 2023 Jun 1;129(11):1646-1648. - PMID 36869645 Citation Status MEDLINE |
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| doi: |
10.1002/cncr.34716 |
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| Förderinstitution / Projekttitel: |
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| 500 | |a CommentIn: Cancer. 2023 Jun 1;129(11):1646-1648. - PMID 36869645 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. | ||
| 520 | |a BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment | ||
| 520 | |a METHODS: A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease | ||
| 520 | |a RESULTS: In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression | ||
| 520 | |a CONCLUSION: Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a DNA, Neoplasm |2 NLM | |
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| 700 | 1 | |a Kalashnikova, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Sudhaman, Sumedha |e verfasserin |4 aut | |
| 700 | 1 | |a Ozturk Topcu, Turkan |e verfasserin |4 aut | |
| 700 | 1 | |a Nichols, Matt |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Justin |e verfasserin |4 aut | |
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