Results showed that the risk ratio (HR) for SSM at 4, 12 and 24 week time points with longitudinal cDNA positivity was 46.8 (95% CI, 11.1-197 , 0; P <.001 the sensitivity recurrence rate was at months mss rates were ci to and for patients with cdna-negative positive disease respectively.>
Additionally, preoperative cDNA was detected in 95% of patients with stage II disease (n = 267/280) and 96% with stage III CRC (n = 288/301). Although stage T was significant for preoperative cDNA positivity, stage N was related to postoperative cDNA positivity at 4 weeks. No association with RAS / BRAF Neither V600E mutational status nor microsatellite instability (MSI) were observed.
“Further investigation [on] whether the cDNA status could become [a] a new substitution endpoint beyond DFS is warranted, âsaid study lead author Hiromichi Shirasu, MD, of the Shizuoka Cancer Center in Shizuoka, Japan, and the co-investigators in a presentation. virtual presentation during the meeting.
CDNA can be used to predict the risk of recurrence by detecting minimal residual disease (MRD) in patients with CRC. In the CIRCULATE-Japan program, researchers recruited patients with resectable stage II to IV CRC to assess the utility of cDNA analysis. The study is made up of several parts: the GALAXY observational trials, the VEGA phase 3 trials and the ALTAIR phase 3 trials.
In GALAXY, researchers used the Signatera bespoke multiplex polymerase chain reaction next-generation sequencing assay, which was based on sequencing the entire exome of tumor tissue and corresponding normal samples. Plasma samples were taken before surgery and again at 4, 12, 24, 36, 48, 72, and 96 weeks after surgery. The investigators also evaluated the link between the perioperative status of ctDNA and the pathological stage (pStage), RAS / BRAF V600E and MSI status, and short term results.
A total of 1236 patients were recruited between June 5, 2020 and February 28, 2021. Four hundred and twenty-eight patients were excluded from recruitment due to an unavailable pStage from electronic data entry (n = 400) , incomplete resection (n = 15), confirmed pStage 0 (n = 1), matched results not available from pre- and postoperative cDNA at 4 weeks (n = 6) and withdrawal of informed consent (n = 6 ). The final analysis included 808 patients with stage I to III colon cancer (n = 654) or stage IV CRC (n = 154).
The median follow-up was 5.5 months and the data cut-off date was March 25, 2021; the rate of test not performed with Signatera was 2.1%.
The success rates for ctDNA results before surgery, at 4 weeks, 12 weeks and 24 weeks after resection were 99.0% (n = 799/807), 99.5% (n = 797/801) , 99.6% (n = 531/533) and 100% (n = 263/263), respectively.
In the overall population (n = 808), 51% of patients were male and most (87%) had an ECOG performance index of 0. Patients had stage I (8%), II (35%) , III (38%). , or IV disease (19%). Half of the patients were doubly wild type for RAS / BRAF, 43% of patients had RAS-mutant disease, and 7% had BRAF Mutant disease V600E. Most of the patients (91%) had stable microsatellite disease (MSS).
In the pStage I to III subset, the distribution of tumor invasion was T1 (3%), T2 (12%), T3 (59%) and T4 (26%). Regarding lymph node metastases, 54% of patients had N0 disease, 34% N1 disease and 12% N2 disease.
Overall, the preoperative detection rate of cDNA was 92% (n = 734/799); these rates were 77% (n = 50/65), 95% (n = 267/280), 96% (n = 288/301) and 84% (n = 129/153) for stage I patients, II, III and IV, respectively. In the 4-week postoperative setting, these rates were 5% (n = 3/66), 5% (n = 15/278), 25% (n = 74/301) and 32% (n = 48 / 152), respectively; the overall cDNA detection rate was 18%.
Further results showed that postoperative cDNA positivity at 4 weeks was strongly associated with lower SSM in the overall population (RR: 19.5; 95% CI: 7.9-47.8 ; P P <.001 the sensitivity recurrence rates were and respectively. in general population of mss at months ci for patients with cdna-negative those positive disease. people stage i to iii disease these>
These data suggest that 4 weeks after surgery is an appropriate time for an adjuvant ctDNA-based trial, Shirasu noted in the presentation.
Multivariate analyzes for ActDNA positivity were performed both preoperatively and postoperatively. In the pStage I to III subset, the covariates that were compared included T3 to T4 vs T1 to T2 (odds ratio [OR], 5.9; 95% CI: 3.0-11.9; P <.001 n1 to n2 vs n0 ci>P = .31), RAS wild type vs RAS mutant (OR, 1.8; 95% CI, 0.9-3.7; P = .12), BRAF wild type vs BRAF mutant (OR, 2.9; 95% CI: 0.7-11.6; P = 0.14) and high MSS vs MSI status (OR, 0.8; 95% CI, 0.2-2.9; P = .68). No significant difference with cDNA positivity was observed with respect to gender or performance status.
In the 4-week postoperative multivariate analysis for ActDNA positivity, N1 to N2 disease vs N0 disease was the most significant factor (OR, 6.1; 95% CI: 3.5-10, 8; P <.001 additionally the correlations were t3 to t4 vs t1 t2 ci>P = .29), RAS wild type vs RAS mutant (OR, 0.7; 95% CI, 0.5-1.2; P = 0.22), BRAF wild type vs BRAF mutant (OR, 1.1; 95% CI, 0.3-3.8; P = 0.86) and high MSS vs MSI status (OR, 2.0; 95% CI, 0.6 to 6.4; P = .24).
Beyond the known prognostic factors, multivariate analyzes showed that ActDNA was the only significant factor of recurrence in patients with stage I to III disease (RR: 17.1; 95% CI: 4 , 6-63.1; P <.001 at the time of presentation no recurrence was reported in patients with t1 to t2 disease or those high msi status.>
SSM was measured by the preoperative status of the cDNA in both subsets. In the general population, the rates of MSS at 6 months were 98.4% (95% CI, 89.4% -99.8%) and 95.5% (95% CI, 93.1% 97.0%) for ctDNA-negative and positive patients, respectively (RR: 1.3; 95% CI: 0.3-5.3; P = 0.76). It wasn’t a significant difference, Shirasu concluded.
- Shirasu H, Taniguchi H, Watanabe J, et al. Surveillance of residual molecular disease by circulating tumor DNA in resectable colorectal cancer: molecular subgroup analyzes of a prospective observational study GALAXY in CIRCULATE-Japan. Anne Oncol. 2021; 32 (53): S222-S223. doi: 10.1016 / j.annonc.2021.05.015