Postoperative ctDNA in indicating the recurrence risk and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential novel biomarker to predict molecular residual disease (MRD) in lung cancer after definitive treatment. Herein, we investigated the value of ctDNA in prognosing risk of relapse and monitoring the effect of adjuvant therapy in surgical non-small cell lung cancer (NSCLC). METHODS: We enrolled 58 NSCLC patients in a real-world setting, and 58 tumor tissues and 325 plasma samples were analyzed. Tumor tissues and plasma samples were subjected to targeted next-generation sequencing (NGS) of 1021 cancer-related and ultra-deep targeted NGS covering 338 genes, respectively. RESULTS: ctDNA was detected in 31.0% of cases at the first postoperative time, which was associated with advanced tumor stage, T stage and KEAP1 or GRIN2A mutations in tissues. ctDNA positivity at landmark and longitudinal indicated the shorter disease-free survival. For patients with ctDNA positivity at the first postoperative time, regardless of adjuvant therapy, all patients who were persistently ctDNA positive during postoperative surveillance had disease recurrence. Among the patients who were ctDNA negative, only two patients (15.4%, 2/13) receiving adjuvant therapy relapsed, while one patient (50.0%, 1/2) without adjuvant therapy relapsed. For the first postoperative ctDNA negative patients, the recurrence rate of patients with adjuvant therapy was and higher than without adjuvant therapy (22.6% [7/31] vs. 11.1% [1/9]). The patients who became ctDNA positive may also benefit from intervention therapy. CONCLUSION: Postoperative ctDNA is a prognostic marker, and ctDNA-detection may facilitate personalized adjuvant therapy, and applying adjuvant therapy to the patients with detectable ctDNA could bring clinical benefits for them.

[Kinetics and influencing factors of dimethyl phthalate degradation in aqueous solution by ozonation].

The rate constants for the reaction of higher concentrations of DMP with ozone and hydroxyl radical (*OH) were determined by competition kinetics method, in which nitrobenzene (NB) was selected as the reference organic compound. The effects of *OH inhibitor tert-butyl alcohol, pH and a variety of ions on the degradation of DMP were discussed. Experimental results showed that the degradation of DMP by ozonation followed pseudo-first-order kinetics. The rate constants of DMP with ozone and *OH were (0.064 +/- 0.014) L x (mol x s)(-1) and 3.59 x 10(9) L x (mol x s)(-1), respectively. The system pH decreased due to the carboxylic acids intermediates generated by ozonation at initial pH of 6.08 and 9.07, but the system pH was stabilized in strong alkali or acidic solution. A large number of intermediates resulted in the removal rate of COD lagging behind the degradation efficiency of DMP, and part of the intermediates were difficult to be mineralized. The reaction of DMP with *OH was not inhibited by lower concentrations of tert-butyl alcohol. But the reaction was inhibited when the concentration of tert-butyl alcohol was 90.21 times as high as that of DMP, and the degradation efficiency of DMP decreased from 98.7% to 8.8%. The degradation efficiency of DMP was higher with phosphate buffer solution for pH adjustment than NaOH/H2SO4 solution. Low concentrations of cations and anions had no effects on the degradation efficiency of DMP. High concentrations of SO4(2-), NO3(-) and HPO4(2-) had no remarkable effects on ozonation. But high concentrations of Cl(-) and HCO3(-) inhibited the degradation and the inhibitory effect of HCO3(-) was stronger than Cl(-). The degradation efficiency of DMP was only 50.5% and 26.2%, respectively, after 40 min under 7 097 mg x L(-1) of Cl(-) and 6 093 mg x L(-1) of HCO3(-).