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. 2022 Nov 10:12:973167.
doi: 10.3389/fonc.2022.973167. eCollection 2022.

Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage II colorectal cancer

Adrien Grancher  1 , Ludivine Beaussire  1   2 , Sylvain Manfredi  3 , Karine Le Malicot  3 , Marie Dutherage  1 , Vincent Verdier  1 , Claire Mulot  4 , Olivier Bouché  5 , Jean-Marc Phelip  6 , Charles-Briac Levaché  7 , Philippe Deguiral  8 , Sophie Coutant  1 , David Sefrioui  1 , Jean-François Emile  9 , Pierre Laurent-Puig  10 , Frédéric Bibeau  11 , Pierre Michel  1 , Nasrin Sarafan-Vasseur  1 , Côme Lepage  3 , Frederic Di Fiore  1   2
Affiliations

Postoperative circulating tumor DNA detection is associated with the risk of recurrence in patients resected for a stage II colorectal cancer

Adrien Grancher et al. Front Oncol. .

Abstract

Circulating tumor DNA (ctDNA) is reported to be promising in localized colorectal cancer (CRC). The present study aimed to retrospectively evaluate the impact of ctDNA in patients with a resected stage II CRC from the PROGIGE 13 trial with available paired tumor and blood samples. A group of recurrent patients were matched one-to-one with nonrecurrent patients according to sex, tumor location, treatment sequence, and blood collection timing. CtDNA was analyzed by digital PCR according to NGS of tumors. Disease-free survival (DFS) and overall survival (OS) were analyzed based on ctDNA, and the risks of recurrence and death were determined. A total of 134 patients were included, with 67 patients in each group. At least one alteration was identified in 115/134 tumors. Postoperative ctDNA was detected in 10/111 (9.0%) informative samples and was detected more frequently in the recurrent group (16.7% versus 1.8%; p = 0.02). The median DFS of ctDNA+ versus ctDNA- patients was 16.8 versus 54 months (p = 0.002), respectively, and the median OS was 51.3 versus 69.5 months (p = 0.03), respectively. CtDNA was associated with recurrence (ORa = 11.13, p = 0.03) and death (HRa = 3.15, p = 0.01). In conclusion, the presence of postoperative ctDNA is associated with both recurrence and survival in stage II CRC.

Keywords: circulating tumor DNA; colorectal cancer; liquid biopsy; next generation sequencing; stage II.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the study population. The overall population consisted of 134 patients with 67 in recurrent and matched nonrecurrent patients. The analysis of ctDNA was based on DNA somatic alterations from tumors detected using two successive NGS panels. At least one alteration was detected in 79/113 patients using the first NGS and in 36/55 remaining patients with the second NGS panel. A total of 115/134 tumors were identified with at least one alteration, corresponding to 58 and 57 patients in the recurrent and nonrecurrent group, respectively. For each patient, ctDNA detection was performed using ddPCR analysis targeting alterations identified with NGS. Timing of blood sample collection was also indicated according to chemotherapy initiation if chemotherapy was used. CRCs, colorectal cancers; CT, chemotherapy; ctDNA, circulating tumor DNA.
Figure 2
Figure 2
Disease-free survival (A) and overall survival (B) according to ctDNA detection. ctDNA, circulating tumor DNA.
See this image and copyright information in PMC

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