Background
Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.
Methods
From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.
Results
Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.
Conclusions
Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.
[1] In situ P-V-T measurements of stishovite have been performed throughout its stability field from 17 to 54 GPa and from 300 to 1700 K, by using a sintered-diamond multianvil apparatus and synchrotron radiations. The P-V-T equation of state of stishovite was precisely determined on the basis of the Mie-Grüneisen-Debye model using both Morse-Rydberg (Vinet) and third-order Burch-Murnaghan equations for reference isotherms. The new equation of state of stishovite gives the thermoelastic properties such as density, adiabatic bulk modulus, thermal expansivity, and isobaric heat capacity without extrapolation to mid-lower mantle conditions, and these properties at zero pressures are consistent with those of previous measurements. The present equation of state yields a lower density and larger adiabatic modulus at lower mantle conditions compared to those obtained by extrapolate on using a previous equation of state determined at upper mantle conditions. Our new equation of state and thermoelastic properties for stishovite at lower mantle conditions is important for quantitatively modeling the fate of subducted silica-rich rocks such as MORB and pelagic sediments, and for interpreting seismological observations.
Abstract:In previous studies, heterocyclic amines (HCAs) have been identified as carcinogenic and a risk factor for human cancer. Therefore, the present study was designed to identify bioactive natural products capable of controlling the formation of HCAs during cooking. For this purpose we have evaluated the effect of Rosa rugosa tea extract (RTE) on the formation of HCAs in ground beef patties fried at 160˝C or 220˝C. RTE is rich in phenolic compounds and capable of inhibiting the formation of free radicals. The pyrido [3,4-b] 4, were not detected in any sample. Total HCAs were positively correlated with cooking loss. In the RTE-treated groups, 75% of the total HCAs were decreased at 160˝C and 46% at 220˝C, suggesting that RTE is effective at both temperatures and can be used during cooking at high temperatures to lessen the amount of HCAs formed.
Ultrafine Pt nanocrystals with an average particle size of 2.2 ± 1 nm coupled over the petaloid Fe 2 P surface are proposed as a novel, efficient, and robust catalyst for alcohol fuel electro-oxidation. The strong coupling effect of metal−support imparts a strong electronic interaction between the Fe 2 P and Pt interface that can weaken the adsorption of poisoning CO species according to the d-band theory. Defects and increased surface area of the petaloid Fe 2 P are beneficial to the Pt nanoparticle anchoring and dispersion as well as the charge transfer and reactant transportation during the electrochemical reaction. These features make the Pt−Fe 2 P catalyst system exhibit excellent catalytic activity, antipoisoning ability, and catalytic stability for alcohol fuel of methanol and ethanol electro-oxidation compared with a controlled Pt/C catalyst. The high catalytic efficiency is proposed to come from the strong coupling effect of Pt and petaloid Fe 2 P interface that can maintain the mechanical and chemical stability of the catalyst system. This kind of phosphide-supported ultrafine Pt nanocrystals will be a promising catalyst in fuel cells.
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