Dynamic ctDNA evaluation of a patient with BRAFV600E metastatic melanoma demonstrates the utility of ctDNA for disease monitoring and tumor clonality analysis

Purpose Circulating tumor DNA (ctDNA) allows noninvasive disease monitoring across a range of malignancies. In metastatic melanoma, the extent to which ctDNA reflects changes in metabolic disease burden assessed by 18F-labeled fluorodeoxyglucose positron emission tomography (FDG-PET) is unknown. We assessed the role of ctDNA analysis in combination with FDG-PET to monitor tumor burden and genomic heterogeneity throughout treatment. Patients and Methods We performed a comprehensive analysis of serial ctDNA and FDG-PET in 52 patients who received systemic therapy for metastatic melanoma. Next-generation sequencing and digital polymerase chain reaction were used to analyze plasma samples from the cohort. Results ctDNA levels were monitored across patients with mutant BRAF, NRAS, and BRAF/NRAS wild type disease. Mutant BRAF and NRAS ctDNA levels correlated closely with changes in metabolic disease burden throughout treatment. TERT promoter mutant ctDNA levels also paralleled changes in tumor burden, which provide an alternative marker for disease monitoring. Of note, subcutaneous and cerebral disease sites were not well represented in plasma. Early changes in ctDNA and metabolic disease burden were important indicators of treatment response. Patients with an early decrease in ctDNA post-treatment had improved progression-free survival compared with patients in whom ctDNA levels remained unchanged or increased over time (hazard ratio, 2.6; P = .05). ctDNA analysis contributed key molecular information through the identification of putative resistance mechanisms to targeted therapy. A detailed comparison of the genomic architecture of plasma and multiregional tumor biopsy specimens at autopsy revealed the ability of ctDNA to comprehensively capture genomic heterogeneity across multiple disease sites. Conclusion The findings highlight the powerful role of ctDNA in metastatic melanoma as a complementary modality to functional imaging that allows real-time monitoring of both tumor burden and genomic changes throughout therapy.

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Abstract #917: Ipilimumab Induced Hypophysitis in a Patient with Metastatic Melanoma

Endocrine Practice ◽

10.1016/s1530-891x(20)45207-3 ◽

2016 ◽

Vol 22 ◽

pp. 202

Author(s):

Samaneh Dowlatshahi ◽

Ronald A. Codario

Keyword(s):

Metastatic Melanoma

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Systemic therapy of metastatic melanoma

Therapeutische Umschau ◽

10.1024/0040-5930.56.6.330 ◽

1999 ◽

Vol 56 (6) ◽

pp. 330-333

Author(s):

Dummer ◽

Nestle ◽

Hofbauer ◽

Burg

Keyword(s):

Metastatic Melanoma ◽

Systemic Therapy ◽

Interleukin 2 ◽

Kurative Therapie

Das metastasierende Melanom (MM) gehört zu den schwierig behandelbaren Malignomen, wobei Allgemeinzustand und Motivation des Patienten neben Zahl und Lokalisation der Metastasen das therapeutische Vorgehen bestimmen. Solitäre Metastasen in Lunge, ZNS, Weichteilen und Lymphknoten sollten primär chirurgisch entfernt werden. Multiple Metastasen, insbesondere abdominal, werden nur in Ausnahmefällen chirurgisch angegangen. Hier ist vielmehr ein systemische Chemoimmuntherapie angebracht. Aussichtsreiche Behandlungskonzepte beinhalten Interleukin-2, Interferon, und verschiedenen Zytostatika wie DTIC, Temozolamid, Vindesine oder Cisplatin. Bei ZNS- und Skelettfiliae ist die Radiotherapie einzusetzen. Durch diese Chemoimmuntherapien hat sich die Prognose des metastasierenden Melanoms bezüglich des Überlebens verbessert. Langfristig wird aber nur eine Kombination von zeitraubenden Multicenterstudien und experimentellen Ansätzen in der Lage sein, uns langsam an eine kurative Therapie heranzuführen.

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