Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer

Abstract

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

Prognostic and predictive value of circulating DNA for hepatic arterial infusion of chemotherapy for patients with colorectal cancer liver metastases

“…This is in concordance with a recent comparative study of CEA and cfDNA for patients with mCRC, demonstrating a possible diagnostic superiority of cfDNA compared to CEA (24). The majority of studies on cfDNA and CRC has emphasis on either widespread metastatic disease, in a palliative setting (11) or patients with locally advanced rectal cancer scheduled for chemo-radiation (25,26). Few studies have explored the utility of cfDNA in the clinical setting of CRCLM, where some patients might still be within the range of curability.…”

Correlation between early dynamics in circulating tumour DNA and outcome from FOLFIRI treatment in metastatic colorectal cancer

“…This is in line with previous observations 13,17 . Equally high total cfDNA at diagnosis correlated to shorter PFS, as previously reported 18,19 . We did not find any correlation between the number or type of metastasis and the ctDNA levels (data not shown).…”

Total cell-free DNA, carcinoembryonic antigen, and C-reactive protein for assessment of prognosis in patients with metastatic colorectal cancer

“…Reactions consisted of 5 mL sample, 1 mL of each primer-probe mix, and 10 mL 2 3 ddPCR Supermix for probes (Bio-Rad). 9 Primers and probes are previously published 11 and shown in Supplementary Table 1. The cycling steps for the ddPCR were as follows: 95°C for 10 min, 40 cycles of 94°C for 30 s, and 60°C for 1 min, and finally 98°C for 10 min.…”