Abstract 110P
Background
In HPV-positive gynaecological cancers, predicting relapse and overall survival remains a challenge. Tumor burden can be defined as the total amount of cancer in the body, that can be measured biologically by circulating tumor DNA (HPV ctDNA) and radiologically by total tumor volume for instance. We hypothesized that detecting HPV ctDNA and integrating radiological tumor volume measurement could improve the prediction of outcomes.
Methods
This retrospective monocentric study included 30 metastatic patients with HPV positive gynaecological cancers. Patients were enrolled in the MOSCATO trial at Gustave Roussy. We aimed to develop a multiplex digital PCR-based assays allowing screening for 12 HPV genotypes classified as carcinogenic (high-risk) by the IARC (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59). Our HPV 13-plex assay detected HPV ctDNA by droplet digital PCR (naica® system workflow by Stilla TechnologiesTM), using targeted fluorescent probes. We calculated on CT-scans the total tumor volume by measuring and adding all lesion volumes, using manually outlined annotations of each lesion in its largest surface axial slice by two expert radiologists. Progression free survival (PFS) was defined as the date of treatment initiation until date of relapse or death. Correlation analyses were performed using Pearson's coefficient with a one-tailed test of significance.
Results
We enrolled 30 metastatic patients with HPV gynecological cancer, diagnosed from 2001 to 2017. We report the biological and radiological tumor burden for the first 8 of these 30 patients. The median age was 44 years. 4 patients were positive for HPV 16 (50%), 2 for HPV 18 (25%) and 2 for HPV 45 (25%). We detected HPV ctDNA baseline, in 7 of 8 patients. Our results showed that patients with detectable ctDNA at baseline has significantly worse outcome in terms of PFS (R=-0.44, p=0.14) although non-significant. We did not find a significantly association between total tumor volume, ctDNA and PFS.
Conclusions
The biological tumor burden measured by HPV ctDNA appears to be a prognostic biomarker in metastatic HPV positive cervical cancers. We have developed a non-invasive test to evaluate tumor HPV genotyping potentially on all HPV related cancers. Further validation is warranted on larger number of patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
J. Michels.
Funding
Gustave Roussy.
Disclosure
All authors have declared no conflicts of interest.
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