Therapeutic Response Evaluation in Advanced Melanoma Patients Incorporating Plasma cfDNA, LDH, VEGF, PD-L1, and IFN-γ Measurements

Anticancer Res. 2022 Feb;42(2):801-810. doi: 10.21873/anticanres.15538.

Abstract

Background/aim: Current treatment strategies for advanced melanoma require serial assessment of disease status in affected patients. In this study, we sought to examine the relationship between radiographic tumour burden and blood borne biomarkers including plasma cfDNA, serum LDH, plasma VEGF, PD-L1 and IFN-γ in advanced melanoma patients receiving immunotherapy. We hypothesized that a combination of these explanatory variables in a suitable regression analysis model may predict changes in tumour burden during patient treatment.

Materials and methods: We extracted and quantified circulating cfDNA, LDH, VEGF, PD-L1, and IFN-γ from thirty patients with stage IV melanoma at baseline and at six months. All participating patients were evaluated with paired blood sample collection and CT scan assessments during treatment.

Results: Changes in radiographic tumour burden correlated with changes in levels of cfDNA (p≤0.001), LDH (p≤0.001), VEGF (p≤0.001), and PD-L1 (p<0.05) during treatment. Multiple regression analysis consisting of the follow-up to baseline assessment ratios of cfDNA, LDH, VEGF and PD-L1 explained changes in tumour burden (F (4, 23)=32.05, p<0.001); with an R2 of 0.8479 (Y=β0+β1*B+β2*C+β3*D+β4*E).

Conclusion: A quantitative measure of cfDNA, LDH, VEGF and PD-L1 may complement current methods of assessing tumour burden in advanced melanoma patients.

Keywords: LDH; PD-L1; VEGF; cfDNA; tumour-burden.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / blood
  • Biomarkers, Tumor / blood
  • Cell-Free Nucleic Acids / blood
  • Female
  • Humans
  • Immunotherapy
  • Interferon-gamma / blood
  • L-Lactate Dehydrogenase / blood
  • Male
  • Melanoma / blood*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Middle Aged
  • Regression Analysis
  • Tumor Burden
  • Vascular Endothelial Growth Factor A / blood

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Cell-Free Nucleic Acids
  • IFNG protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Interferon-gamma
  • L-Lactate Dehydrogenase