Zirkulierende Tumor DNA erlaubt Therapiemonitoring in BRAF und NRAS mutiertem malignem Melanom

Abstract: Aim:
We evaluated the use of circulating tumor (ct)DNA as a predictive biomarker in patients with melanoma.
Methods: We analyzed 12 stage III and 50 stage IV melanoma patients with a BRAF exon 15 or NRAS exon 3 mutation in tissue for the corresponding mutation in ctDNA. Blood samples were taken at baseline, at d +8, d +28 and in 3 month intervals for up to two years. Plasma was analyzed for mutant and wild type ctDNA by droplet digital (dd)PCR.

Results:
Pre-treatment samples were positive for mutant ctDNA, LDH and S100 in 36 (80%), 27 (60%) and 30 (66.7%) in 45 patients with stage IV and in 7 (63.6%), 3 (27.3%) and 4 (36.36%) in 11 patients with stage III melanoma after resection of primary. The amount of mutant ctDNA copies correlated with LDH (r=0.50), S100 (r=0.64), tumor volume (r=0.58) and tumor metabolic activity (r=0.83). CtDNA, LDH and S100 detected subsequent progression with a sensitivity of 72.7%, 51.5% and 50%. In stage III, 8 patients ctDNA positive after resection relapsed whereas two ctDNA negative patients remained relapse-free. In stage IV, ctDNA profiles associated with subsequent progression included ctDNA positivity at first follow-up (hazard ratio [HR] 3.36), 10 or more copies/ml at first follow-up (HR 4.05), increase of ctDNA over time (HR 1.82) and increase to 10 copies/ml plasma (HR 3.7).

Conclusion:
Increase of ctDNA was an adverse prognostic marker for clinical tumor progression. These data support the use of ctDNA as an early predictive marker for treatment response.

Highlights:
•CtDNA had superior sensitivity to LDH and S100 to detect active disease and subsequent progression in stage IV melanoma
•Dynamic changes in ctDNA occurred early after initiation or change of treatment and preceded clinical response or progression
•At the first follow up after initiation of treatment in stage IV melanoma, ctDNA positivity and 10 or more ctDNA copies/ml were associated with inferior progression-free survival
•Stage III melanoma patients positive for ctDNA after resection of primary experienced relapse after a median of 70 days

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2021

Klassifikation und Themen

• Schlagwort: Melanom ; Onkologie

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Braune, Jan
• Beteiligte Personen und Organisationen: Bubnoff, Nikolas von ; Albert-Ludwigs-Universität Freiburg. Medizinische Fakultät

Weitere Informationen

• DOI: 10.1200/PO.19.00174
• URN: urn:nbn:de:bsz:25-freidok-1941842
• Rechteinformation: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:48 MEZ