Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

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BackgroundTyrosine Kinases Inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs, bevacizumab) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancer including non-small-cell lung cancer (NSCLC). Cell-free DNA (cfDNA) has been adapted as a convenient liquid biopsy that reflects characteristics of the status of both the primary and metastatic tumors, assisting in personalized medicine. This study aims to evaluate the utility of cfDNA as a prognostic biomarker and efficacy predictor of chemotherapy with or without these precision therapies in NSCLC patients.MethodsPeripheral cfDNA levels were quantified in 154 patients with NSCLC before (baseline) and after (post-chemotherapy) the first target cycle of chemotherapy. These patients were divided into four subgroups receiving chemotherapy only, chemotherapy plus TKIs, chemotherapy plus VEGFIs, and chemotherapy plus immune checkpoint inhibitors (ICIs), respectively. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS), objective response ratio (ORR), and therapy regimens were analyzed.ResultsBaseline cfDNA, but not post-chemotherapy, positively correlates with tumor burden. cfDNA Ratio (post-chemotherapy/baseline) well distinguished responsive individuals (CR/PR) from non-responsive patients (PD/SD). Additionally, cfDNA Ratio was found to be negatively correlated with PFS in lung adenocarcinoma (LUAD), but not in lung squamous-cell carcinoma (LUSC). LUAD patients with low cfDNA Ratio benefit significantly including prolonged PFS and improved ORR, compared with those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs.ConclusionThe kinetics of plasma cfDNA during the chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

In-situ stress is an important indicator for the preferential selection of coalbed methane (CBM) exploration dessert zones, and is a key factor affecting the production capacity of coalbed methane wells. Coal reservoir permeability is one of the key parameters to evaluate the recoverability and modifiability of coalbed methane and reflects the seepage capacity of coal reservoirs. In this study, in situ stress data were collected from multiple injection/fall-off tests of multiple parameter wells in western Guizhou province, China The relationships among parameters such as pore pressure (Pp), closure pressure (Pc), breakdown pressure (Pb), in situ stress, coal permeability, and depth were explore. Using Anderson’s classification method, the distribution of three different in situ stress states was counted. A new simplified model diagram of triaxial principal stress and depth in the study area is proposed by linearly fitting the triaxial principal stress and burial depth. The envelope equation and median equation of the lateral pressure coefficient k-value stress ratio with depth of burial obtained by Brown and Hoek method were calculated using hyperbolic regression algorithm. The k-values were found to be discrete at shallower depths and converge at deeper depths, gradually converging to .65. The control of in situ stress on the permeability of coal reservoirs was explored, and a strong positive correlation was found between the permeability and the Z-shaped variation of the lateral pressure coefficient k-values at shallow depths of 1,000 m. Also, the distribution pattern of vertical permeability basically corresponds to the stress transition zone from the strike-slip fault mode to the normal fault mode. The coal seam permeability has a strong sensitivity to effective in situ stress (EIS). In this study, the least squares method with multiple fitting of power exponents is applied to analyze the control mechanism of EIS on permeability in depth and reveal a new relationship between permeability and EIS that is different from that considered by previous authors. Summarizing the above research results, the vertical CBM in western Guizhou is divided into three development potential zones, and 400–1,000 m burial depth is the most favorable vertical development zone.

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