Study Describes Use of Liquid Biopsy in Patients With Solid Tumors

A recent study described the use of a liquid biopsy assay to measure the relative amount of cell-free DNA (cfDNA) in patients with solid tumors and metastatic disease.

The study sought to determine a correlation between response to treatment and tumor load score in patients with stage 2 or stage 3 cancer with solid tumors. Circulating tumor DNA (ctDNA) is linked with more advanced cancer, although it is also affected by tumor type, origin, where the cancer has spread, and treatment. In the adjuvant setting post surgery, residual ctDNA, also known as minimal residual disease, is linked with disease recurrence and worse outcomes.

The investigators hypothesized that early changes seen in the blood might not only predict response status at the time of the first follow-up imaging (FFUI), but also provide clues as to long-term prognosis. Researchers enrolled 96 patients with advanced cancer to perform whole genome (WG) analysis. The patients consented to blood draws before and after systemic therapy during regular clinic treatments.

As per current guidelines, patients were assessed through imaging scans at baseline and again at FFUI; measurable disease changes were interpreted by an independent radiologist.

Patient characteristics were as follows: median age, 70 years; 55% female; and 63% current or former smokers. The most common cancers were lung (44%) or breast (26%), with the remainder including gastrointestinal cancers, genitourinary cancers, melanoma, and sarcoma.

Fifty-three percent of the participants received a first-line therapy and 25% received a second-line therapy. During the study, 46% of all participants received chemotherapy, some with trastuzumab, pertuzumab, panitumumab, ramucirumab, bevacizumab, or olaratumab. In addition, 37% received immunotherapy with or without chemotherapy or a histone deacetylase inhibitor

Plasma cfDNA libraries were created for either WG or WG bisulfite sequencing. Longitudinal changes in the fraction of ctDNA were quantified to retrospectively identify molecular progression (MP) or major molecular response (MMR). Study endpoints were in concordance with FFUI and stratification of progression-free survival (PFS) and overall survival (OS).

Of the 96 patients, 91 were included in the final analysis. Patients with MP (n = 13) had significantly shorter PFS (median 62 vs 310 days) and OS (255 days vs not reached).

Sensitivity for MP to identify clinical progression was 54% and specificity was 100%. MP calls were from samples taken a median of 28 days into treatment and 39 days before FFUI. Patients with MMR (n = 27) had significantly longer PFS and OS compared to those with neither call (n = 51).

"These results demonstrated that ctDNA changes early after treatment initiation inform response to treatment and correlate with long-term clinical outcomes," the authors wrote.

There were some limitations to the study, which was funded by the manufacturer of the assay. It was a prospectively enrolled study from clinical practices. In addition, the authors said, "sensitivity to identify clinical progression early in the treatment course was relatively low. Sensitivity, particularly at the earliest time point, may be improved by including other features such as cancer-associated epigenetic signals." Future improvements could increase the sensitivity of the assay, the authors sad.

Reference

Davis AA, Iams WT, Chan D, et al. Early assessment of molecular progression and response by whole-genome circulating tumor DNA in advanced solid tumors. Mol Cancer Ther. Published online May 5, 2020. doi:10.1158/1535-7163.MCT-19-1060