Abstract P060

Total metabolic tumor volume impairs the successful detection of circulating tumor DNA (ctDNA) in early-stage Hodgin lymphoma patients – the preliminary report from the RAFTING trial.

Background: Liquid biopsy detects cell-free tumor-specific DNA (ctDNA) circulating in plasma. In Hodgkin Lymphoma (HL), despite the scarcity of neoplastic cells, ctDNA is detected in the plasma of 90% of patients. However, there is no data correlating the disease burden and ctDNA assay.

Methods: RAFTING trial (EudraCT 2020-002382-33, Research financed by the Medical Research Agency, Poland, Project n° 2019/ABM/01/00060) is an example of a personalized medicine treatment in which (1) the total metabolic tumor volume at baseline (bTMTV) determines the treatment intensity and (2) ctDNA is used for monitoring HL recurrence. In RAFTING non-bulky early-stage (I-IIA) HL patients, enrolled from 37 European centers the bTMTV is centrally calculated by an Expert Panel of Nuclear Medicine physicians; low-risk patients (TMTV< 84 ml and negative interim PET2 (PET-2) are treated with ABVD alone (2 or 4 cycles) and addressed to fa watchful follow-up. ctDNA is assessed every 3 months after ABVD end for 1 year and centralized in Bellinzona (CH) for the assay. TMTV is calculated by blinded independent central review with a relative SUV threshold of 41% by three reviewers. The LyV4.0 ctDNA CAPP‐seq assay (sensitivity: 0.1%) was used to qualify and quantify ctDNA. A binary logistic regression was fitted with binary cfDNA (present/absent; as the dependent variable) and the bTMTV (independent variable). In figure 1 the vertical line indicates the bTMTV value at which the predicted probability of the binary cfDNA being detectable is 0.80. The 95% confidence interval was calculated using the bootstrap percentile method based on 1000 replicates. The relationship between cfDNA and baseline TMTV was assessed using Spearman’s rank correlation coefficient.

Results: ctDNA was available for assay in 128/174p, and 7 samples resulted of low quality. So far 88/121 collected samples (73%) analyzed; (Figure: Panel a). ctDNA was not detected in 21 (24%),while normal cell-free DNA (Figure 1 Panel A). The median measured TMTV value was 34 ml (3 – 86 ml). Upon binary logistic regression, a TMTV value <30 ml reduced the ctDNA detection rate in plasma by 80% the detection of ctDNA below 80% (Panel b and C). The Spearman's correlation between cfDNA and bTMTV was ρ=0.325 (p-value 0.0072).

Conclusion: In this preliminary cohort of p. enrolled in RAFTING trial ctDNA could not be monitored in one quarter (25%) of p. A TMTV value < 30 ml impairs the successful detection of ctDNA in untreated early HL