Purpose/Objective; A prospective, observational clinical trial was initiated to sequentially monitor a range of circulating biomarkers, including circulating tumour DNA (ctDNA), in patients with non-small cell lung cancer (NSCLC), treated with curative intent radiotherapy or chemoradiotherapy. It was hypothesised that a rapid increase in ctDNA would occur after the first fraction of radiotherapy as a result of radiotherapy-induced tumour destruction. Preliminary ctDNA results are presented here.
Material/Methods; Patients receiving curative intent radiotherapy, +/- concurrent chemotherapy were recruited. Blood was collected at predefined intervals before, during (including 24 hours after the first fraction of radiotherapy or chemoradiation) and after treatment. Tumour specific mutations were identified through routine molecular diagnostic testing, with mutation specific droplet digital PCR assays used to track ctDNA levels throughout treatment.
Results: 75 of a planned 100 patients have so far been recruited to this ongoing NHMRC and CCV funded study. Sequential ctDNA results are currently available for 7 patients, with follow-up of 81 to 552 days (median 266 days). Known tumour-based mutations including in EGFR, KRAS and TP53 that were assayed. Treatments delivered were fractionated radiotherapy (n=6) or stereotactic ablative radiotherapy (SABR) (n=1). Increased ctDNA was observed after the first fraction of radiotherapy in 4 of 5 patients treated with fractionated radiotherapy, including in 2 cases where ctDNA was undetectable prior to treatment. The patient treated with SABR for small volume stage I disease had detectable ctDNA only when distant metastasis was detected 552 days post treatment. One patient who had a partial response to chemoradiotherapy had detectable ctDNA at the end of treatment but cleared ctDNA when immunotherapy with adjuvant durvalumab was initiated.
Conclusion: Serial ctDNA analysis may provide clinical useful information. A “spike” in ctDNA was detected after the first fraction in 4 of 5 patients treated with fractionated radiotherapy. This phenomenon, likely to be related to early cell killing by treatment, could have clinical value as a surrogate for early treatment response and as a means of enriching plasma for ctDNA for mutational profiling.