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Updated: Jan 17, 2026
Cell-Free DNA Integrity Analysis in Urine Samples
Published on: January 5, 2017
Cell-free DNA as a complementary marker of therapeutic futility in adenoid cystic carcinoma
Joanna Blocka1, Klothilda Lim2, Hannah Stuart2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany; Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Background:
Adenoid cystic carcinoma (ACC) is a malignancy for which currently no therapies are approved by the FDA. Thus, there is an urgent need to identify novel treatments. Although imaging is the standard to evaluate responses to experimental drugs, accurate radiologic assessments can be challenging. CT and MRI may lead to an underestimation of the tumor burden, whereas PET is limited by the slow growth rate of ACC. Here, we demonstrate that liquid biopsy to detect ACC-derived cell-free DNA can serve as a complementary marker for assessing tumor burden and therapeutic futility.
Patients And Methods:
We investigated 47 blood samples from 15 patients with advanced ACC who received all-trans retinoic acid in a phase II clinical trial and determined the kinetics of circulating tumor DNA (ctDNA) over time. We established two independent methods for ctDNA detection: an unbiased approach based on low-pass whole genome sequencing (lpWGS) (<1x) and a targeted sequencing approach focused on known somatic mutations.
Results:
lpWGS performed better in detecting the ctDNA than targeted sequencing (in 47 vs. 20 % of patients who provided plasma samples, respectively), and has the advantage of not requiring a prior knowledge of the mutational landscape of the tumor. Overall, the presence of ctDNA and higher tumor fraction pointed toward a correlation with shorter progression-free survival and time spent on therapy as well as higher probability of progressive versus stable disease, although statistical significance was not achieved, possibly due to the limited size of the patient cohort.
Conclusion:
Our findings suggest that ctDNA may serve as an additional tool for therapeutic guidance in ACC patients.
Insights
Liquid biopsy detecting cell-free DNA (cfDNA) shows promise for monitoring adenoid cystic carcinoma (ACC) treatment. This approach may help assess tumor burden and guide therapy when imaging is insufficient.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genomics
Background:
- Adenoid cystic carcinoma (ACC) lacks FDA-approved therapies, necessitating novel treatment strategies.
- Current imaging methods (CT, MRI, PET) have limitations in accurately assessing ACC tumor burden and treatment response.
- Liquid biopsy offers a potential complementary approach to evaluate treatment efficacy in ACC.
Purpose of the Study:
- To evaluate the utility of circulating tumor DNA (ctDNA) as a biomarker for assessing tumor burden in patients with advanced ACC.
- To compare the effectiveness of low-pass whole genome sequencing (lpWGS) and targeted sequencing for ctDNA detection in ACC.
- To explore the correlation between ctDNA levels and clinical outcomes in ACC patients undergoing treatment.
Main Methods:
- Analysis of 47 blood samples from 15 patients with advanced ACC treated with all-trans retinoic acid.
- Development and application of two ctDNA detection methods: unbiased lpWGS and targeted sequencing.
- Assessment of ctDNA kinetics and tumor fraction over time.
Main Results:
- lpWGS demonstrated superior ctDNA detection rates (47%) compared to targeted sequencing (20%) and does not require prior knowledge of tumor mutations.
- Higher ctDNA presence and tumor fraction correlated with shorter progression-free survival and increased likelihood of progressive disease.
- Statistical significance was limited by the small patient cohort size.
Conclusions:
- ctDNA detection via liquid biopsy is a promising tool for monitoring ACC.
- ctDNA analysis can serve as a complementary marker to imaging for assessing tumor burden and therapeutic futility.
- These findings suggest ctDNA can aid in therapeutic guidance for ACC patients.
