THE IMPACT OF STEREOTACTIC BODY RADIOTHERAPY ON THE DYNAMICS OF CIRCULATING TUMOUR DNA IN PATIENTS WITH OLIGO-PROGRESSIVE DISEASE

Purpose:

Stereotactic Body Radiotherapy (SBRT) is increasingly used as an ablative treatment in patients with limited progressive metastatic disease (oligo-progression (OP)). Results from recent trials are controversial, suggesting a need for better patient selection. Novel biomarkers such as circulating DNA (ctDNA) offers a unique opportunity to utilize early on-treatment changes in ctDNA for real-time assessment of therapeutic response and outcome, with a potential to ultimately aid clinical decision in this setting. Herein we aim to assess early ctDNA changes in patients with OP treated with SBRT as part of a prospective clinical trial.

Materials and Methods:

RADIANT is a Phase II prospective single institutional study of patients with OP (≤5 progressing metastatic lesions), treated with SBRT. We prospectively collected frozen plasma samples (3-4mL) and whole blood (Peripheral blood mononuclear cells or germline DNA-MTM/mL) at five timepoints (TP)-baseline (TP1), post fraction 1 of SBRT (TP2), post final fraction (TP3), 6-weeks (TP4) and 3-months post SBRT (TP5). Descriptive statistics were computed using SAS.

Results:

Of 70 patients enrolled, nineteen with 73 plasma samples were included in this analysis, of which 5 (26%), 9 (47%), 4 (21%) and 1 (5%) had a gastrointestinal (GI), hormone receptor positive breast, genito-urinary (GU) and skin cancer diagnosis respectively. Median progression free survival in this cohort was 4.8 months (IQR 3.2-7.7), and median time to change in next line systemic therapy was 5.6 (IQR 4.6-10.3) months. Among all plasma samples (n=73), ctDNA levels were detectable in 49 (67%) samples. Seventeen (89.5%) patients had detectable ctDNA in at least one TP. Median ctDNA level for patients with detectable ctDNA at each TP (1-5) was: 2.4 (n=13) [TP1], 5.1 (n=9) [TP2], 0.6 (n=14) [TP3], 0.6 (n=8) [TP4], and 0.1 (n=5) [TP 5] MTM/mL. At baseline, 13 patients had detectable ctDNA levels; of those, 2 (breast/GU) cleared by TP4, 1 (breast) cleared by TP5. Six patients had undetectable levels at baseline; 2/6 (Breast) were never detectable, 1/6 (GU) experienced a small rise at TP2 (0.06MTM/ Ml), and 3/6 patients at TP3 [0.38 (Breast), 0.45 (Prostate), 0.94 (Breast) MTM/mL], all returned to undetectable levels by week 6 post SBRT. Gastro-intestinal cancers (N=5) had detectable ctDNA at each TP. Compared with other cancer types, GI cancers had significantly higher ctDNA levels at TP1 (14.9 versus 0.17, p=0.04) and TP3 (16.2 versus 0.33 p=0.04).

Conclusions:

Among patients with OP, ctDNA levels at each TP varied according to primary diagnosis, with lower median levels post SBRT completion. Patients with GI cancer had greater levels compared to other cancers. ctDNA holds promise as a non-invasive tool to potentially guide treatment for patients with OP cancer. Its predictive and prognostic role in the OP setting warrants further investigations.