Circulating tumor DNA in Hodgkin lymphoma

Abstract

Somatic mutations of genes involved in NF-κB, PI3K/AKT, NOTCH, and JAK/STAT signaling pathways play an important role in the pathogenesis of Hodgkin lymphoma (HL). HL tumor cells form only about 5% of the tumor mass; however, it was shown that HL tumor-derived DNA could be detected in the bloodstream. This circulating tumor DNA (ctDNA) reflects the genetic profile of HL tumor cells and can be used for qualitative and quantitative analysis of tumor-specific somatic DNA mutations within the concept of liquid biopsy. Overall, the most frequently mutated gene in HL is STAT6; however, the exact spectrum of mutations differs between individual HL histological subtypes. Importantly, reduction of ctDNA plasma levels after initial treatment is highly correlated with prognosis. Therefore, ctDNA shows great promise as a novel tool for non-invasive tumor genome analysis for biomarker driven therapy as well as for superior minimal residual disease monitoring and treatment resistance detection. Here, we summarize the recent advancements of ctDNA analysis in HL with focus on ctDNA detection methodologies, genetic profiling of HL and its clonal evolution, and the emerging prognostic value of ctDNA.

Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma

“…Here, the question arises, how to improve the negative predictive value of PET-2 in order to allow for the omission of RT in selected patients. Novel tools such as circulating tumor DNA and metabolic tumor volume are currently under evaluation and might improve risk prediction in the future [ 16 , 17 ].…”

Recent Advancements in the Application of Circulating Tumor DNA as Biomarkers for Early Detection of Cancers

“…46,47 However, some individuals have a poor prognosis, particularly those who relapse after receiving first-line of therapy. 48 Several lymphoma types have been associated with mutations in the genes exportin-1 (XPO1), EZH2, MYD88, BRAF, and RHOA. 49 Hodgkin and Reed-Sternberg (HRS) cells, make up a small portion of the cellular infiltrate in Hodgkin lymphoma (HL) tumors.…”

Liquid biopsy: A promising tool for driving strategies and predicting failures in patients with classic Hodgkin lymphoma

“…28 In the same way, in the report by Camus et al a consistent de- According to many trials (GHSG HD18 trial, LYSA AHL2011, RATHL trial) interim PET/CT results guide the subsequent treatment, either in terms of intensification to improve the response (GHSG HD18 trial), or in terms of de-escalation when a response is already successful (LYSA AHL2011, RATHL trial). 29 The real prognostic significance of interim PET/CT in HL is yet to be completely validated; thus, patients would probably benefit from the inclusion of additional strategies to complement the therapeutic strategy of PET indication. Decazes et al 27 prospectively analysed the correlation between cfDNA and PET/TC parameters in 50 patients with cHL.…”

“…According to many trials (GHSG HD18 trial, LYSA AHL2011, RATHL trial) interim PET/CT results guide the subsequent treatment, either in terms of intensification to improve the response (GHSG HD18 trial), or in terms of de‐escalation when a response is already successful (LYSA AHL2011, RATHL trial) 29 …”