TEST:

DELFI-Tumor Fraction assay

Patients with lower DELFI-TF scores during treatment have longer overall survival (62.8 vs 29.1 months, HR = 3.12, 95% CI 1.62-6.00, p < 0.001) and the approach predicts clinical outcomes more accurately than imaging. These results demonstrate the potential of using cfDNA fragmentomes to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

To evaluate the prognostic performance of the DELFI-TF change between baseline and the first follow up (6 weeks) in relation to RECIST for monitoring treatment response, longitudinal blood samples (n=84) from patients with mNSCLC (n=42) were collected from the phase II PEMBRO-RT clinical trial (NCT02492568)...Conclusions DELFI-TF is a tumor and mutation independent approach that correlates well with maxMAF and is prognostic at the early timepoints. Here, we externally validated the DELFI-TF approach in two separate ICI cohorts for monitoring treatment responses and revealed prognostic insights that could guide future clinical trials.

We evaluated 689 plasma samples from 153 patients with metastatic colorectal cancer who were treated with fluoropyrimidine-based chemotherapy and bevacizumab in the phase III CAIRO5 study. The DELFI-TF scores were strongly correlated with RAS/BRAF cfDNA mutant allele fractions measured by droplet digital polymerase chain reaction (r=0.90, p<0.0001, Pearson correlation) and predicted the presence of circulating tumor DNA (ctDNA) even in cases where mutations were undetectable... These results demonstrate the potential of using cfDNA fragmentomes to estimate tumor burden in cfDNA for treatment response monitoring and clinical outcome prediction.

However, tests currently available require deep-targeted sequencing to detect cancer-specific mutations at low mutant allele frequency (MAF) levels in the circulation. Recently, we developed a tumor-agnostic approach called DELFI Tumor Fraction (DELFI-TF), a Bayesian probabilistic model designed to predict plasma tumor fractions based on genome-wide fragmentation-related features.

Cohort 1 enrolled patients with relapsed SCLC across Arms A (bintrafusp alfa 2400 mg q3 wks), B (bintrafusp alfa 2400 mg on D1 plus topotecan 1 mg/m2/day on D1-5 q3 wks), and C (bintrafusp alfa 1200 mg on D1 q2 wks plus temozolomide 200 mg/m2/day on D1-5 q4 wks). Concomitant TGF-beta and PD-L1 blockade is associated with a high frequency of HPD in SCLC patients. cfDNA could be critical for monitoring HPD. Tumor and blood immune signatures may inform the likelihood of HPD, with immune excluded tumors more likely to develop HPD.NCT Number: NCT03554473Bintrafusp alfa was provided by EMD Serono (CrossRef Funder ID: 10.13039/100004755)

DELFI-TF is a tumor and mutation independent approach that is cost-efficient with high performance comparable to current ctDNA assays for estimating tumor burden and monitoring response in cancer patients.

Since the inclusion of the first patient in March 2023, 117 patients have been included in the DOLPHIN study (November 2023). Seven hospitals throughout the Netherlands are currently open for patient inclusion and more sites have been approached to participate. The DOLPHIN study will assess the added clinical value of longitudinal ctDNA-testing in treatment response monitoring of mCRC patients and whether imaging can be complemented and/or partly replaced by ctDNA-testing. The results of this study may lead to novel strategies for monitoring treatment response and to ctDNA-guided treatment decision making in mCRC patients.