Development of a Joint Prediction Model Based on Both the Radiomics and Clinical Factors for Predicting the Tumor Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer.

PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for locally advanced rectal cancer (LARC). However, the accuracy of traditional clinical indicators in predicting tumor response is poor. Recently, radiomics based on magnetic resonance imaging (MRI) has been regarded as a promising noninvasive assessment method. The present study was conducted to develop a model to predict the pathological response by analyzing the quantitative features of MRI and clinical risk factors, which might predict the therapeutic effects in patients with LARC as accurately as possible before treatment. PATIENTS AND METHODS: A total of 82 patients with LARC were enrolled as the training cohort and internal validation cohort. The pre-CRT MRI after pretreatment was acquired to extract texture features, which was finally selected through the minimum redundancy maximum relevance (mRMR) algorithm. A support vector machine (SVM) was used as a classifier to classify different tumor responses. A joint radiomics model combined with clinical risk factors was then developed and evaluated by receiver operating characteristic (ROC) curves. External validation was performed with 107 patients from another center to evaluate the applicability of the model. RESULTS: Twenty top image texture features were extracted from 6192 extracted-radiomic features. The radiomics model based on high-spatial-resolution T2-weighted imaging (HR-T2WI) and contrast-enhanced T1-weighted imaging (T1+C) demonstrated an area under the curve (AUC) of 0.8910 (0.8114-0.9706) and 0.8938 (0.8084-0.9792), respectively. The AUC value rose to 0.9371 (0.8751-0.9997) and 0.9113 (0.8449-0.9776), respectively, when the circumferential resection margin (CRM) and carbohydrate antigen 19-9 (CA19-9) levels were incorporated. Clinical usefulness was confirmed in an external validation cohort as well (AUC, 0.6413 and 0.6818). CONCLUSION: Our study indicated that the joint radiomics prediction model combined with clinical risk factors showed good predictive ability regarding the treatment response of tumors as accurately as possible before treatment.

Combination of TMB and CNA Stratifies Prognostic and Predictive Responses to Immunotherapy Across Metastatic Cancer.

PURPOSE: Although tumor mutation burden (TMB) has been well known to predict the response to immune checkpoint inhibitors (ICI), lack of randomized clinical trial data has restricted its clinical application. This study aimed to explore the significance and feasibility of biomarker combination based on TMB and copy-number alteration (CNA) for the prognosis of each tumor and prediction for ICI therapy in metastatic pan-cancer milieu. EXPERIMENTAL DESIGN: Non-ICI-treated MSK pan-cancer cohort was used for prognosis analysis. Three independent immunotherapy cohorts, including non-small cell lung cancer (n = 240), skin cutaneous melanoma (n = 174), and mixed cancer (Dana-Farber, n = 98) patients from previous studies, were analyzed for efficacy of ICI therapy. RESULTS: TMB and CNA showed optimized combination for the prognosis of most metastatic cancer types, and patients with TMBlowCNAlow showed better survival. In the predictive analysis, both TMB and CNA were independent predictive factors for ICI therapy. Remarkably, when TMB and CNA were jointly analyzed, those with TMBhighCNAlow showed favorable responses to ICI therapy. Meanwhile, TMBhighCNAlow as a new biomarker showed better prediction for ICI efficacy compared with either TMB-high or CNA-low alone. Furthermore, analysis of the non-ICI-treated MSK pan-cancer cohort supported that the joint stratification of TMB and CNA can be used to categorize tumors into distinct sensitivity to ICI therapy across pan-tumors. CONCLUSIONS: The combination of TMB and CNA can jointly stratify multiple metastatic tumors into groups with different prognosis and heterogeneous clinical responses to ICI treatment. Patients with TMBhighCNAlow cancer can be an optimal subgroup for ICI therapy.

Use of Hematocrit for Short-Term Prognosis of Patients with Traumatic Brain Injury After Decompressive Craniectomy.

OBJECTIVE: To discuss the effects of the hematocrit (Hct) in patients with traumatic brain injury after decompressive craniectomy (DC). METHODS: Demographic data, inspection and treatment procedures, and 30-day prognosis were obtained for 158 patients with head injury who underwent unilateral DC in our hospital between January 2013 and June 2018. Uni- and multivariate logistic regression was applied to analyze independent risk factors for 30-day outcome. The quantitative analysis of postoperative Hct, ΔHct (postoperative Hct minus initial Hct), and their combination for the prognosis of patients with TBI was displayed graphically using receiver operating characteristic (ROC) curves. Multiple linear regression was used to explore factors influencing postoperative Hct and ΔHct. RESULTS: Short-term mortality was 29.7%. Uni- and multivariate logistic regression analysis showed that age (odds ratio [OR], 1.064; P = 0.024), Glasgow Coma Scale score (OR, 0.711; P = 0.027), Injury Severity Score (ISS) (OR, 1.156; P = 0.047), midline shift in millimeters (OR, 1.809; P <0.001), postoperative Hct (OR, 0.743; P = 0.001), and ΔHct (OR, 1.242; P =0.048) were independent risk factors for short-term death. In ROC curves, a combination of postoperative Hct and ΔHct showed the highest sensitivity (77.5%) and highest specificity (89.4%). When using this combination to predict prognosis, we could achieve an accuracy of 94.5%. ISS (ß = -0.172, P = 0.022), initial Hct (ß = 0.243, P = 0.001), principal hematoma location (ß = -2.628, P < 0.001), hours of operation (ß = -0.884, P = 0.048), and colloid quantity (ß = -0.002, P = 0.001) were independent contributing factors for ΔHct, which was similar to postoperative Hct. CONCLUSIONS: A combination of postoperative Hct and ΔHct could better predict short-term survival of patients with TBI. Developing an appropriate treatment strategy to increase postoperative Hct and reduce the ΔHct may be good for the short-term prognosis of patients with TBI after DC.

Polycyclic heteroaromatic ring construction driven by silver/cobalt co-catalyzed desulfonylative and defluorinative fragment-recombination of enol nonaflates with amidines.

We present a Ag(i)/Co(ii) co-catalyzed tandem fragmentation and recombination reaction commencing from detachable nonaflates and amidines. This catalytic method offers a unique and expeditious access to various fluoroalkylated dihydrobenzo[h]quinazolines and benzo[h]quinazolines in the absence of external fluorine sources through a rationally designed radical desulfonylation, migration, defluorination, and polar condensation relay.

Copper-catalyzed three-component cyclization of amidines, styrenes, and fluoroalkyl halides for the synthesis of modular fluoroalkylated pyrimidines.

An efficient copper-catalyzed three-component cyclization for the construction of highly functionalized pyrimidine derivatives from readily available amidines, styrenes and fluoroalkyl halides is developed. This protocol distinguishes itself by the formation of three new C-C/C-N bonds and a new six-membered ring through a radical addition/oxidation/cyclization sequence in a one-pot manner.

Role of an MDM4 polymorphism in the early age of onset of nasopharyngeal carcinoma.

Mouse double minute 4 (MDM4) is a critical negative regulator of the tumor suppressor p53. The results of studies have revealed that an MDM4 polymorphism (rs1563828) may contribute to the earlier onset of several malignant diseases. However, the correlation between this polymorphism and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. We performed a case-control study with 210 NPC patients and 200 healthy controls. Significant associations were found when comparing the age of onset of NPC according to the rs1563828 genotype (P=0.01). The average age of onset of NPC in patients with the TT, CC and CT genotypes was 39.3, 48.2 and 45.5 years, respectively. Homozygous variant (TT) carriers developed NPC at an earlier age than homozygous (CC) carriers, such that the age of onset was accelerated by 8.9 years (P=0.002). Our data suggest that rs1563828 is a modifier of the age of onset of NPC in the population studied. The age of onset for NPC with TT homozygotes was earlier than CC carriers.

[Effect of gemcitabine in enhancing the radiosensitivity of HepG2 hepatoma cells and the possible mechanism].

OBJECTIVE: To evaluate the effect of gemcitabine in enhancing the radiosensitivity of hepatoma cell line HepG2 and explore its mechanisms. METHODS: Clonogenic survival assay is employed to calculate the ratios of L-Q model radiation biology parameters and radiosensitization after different doses of irradiation. Flow cytometry was used to detect the changes in HepG2 cell cycle and apoptosis rate after gemcitabine treatment and radiation exposure. RESULTS: The survival fraction at 2 Gy of HepG2 cells treated with gemcitabine was significantly lower, and the value of alpha was significantly higher than those of untreated cells. GEM treatment increased the percentage of radiation-induced G0/G1 phase cells and cell apoptosis. CONCLUSION: Gemcitabine can significantly enhance the radiosensitivity of HepG2 cells by enhancing radiation-induced cell cycle arrest in G0/G1 phase and cell apoptosis.

Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma cells.

PURPOSE: To test the radiosensitising effects of a tumour-suppressor gene, phosphatase and tensin homologue deleted from chromosome 10 (PTEN), in hepatocellular carcinoma cells (HCC). MATERIALS AND METHODS: Radiation-induced wild-type PTEN or mutant PTEN was transfected into the SMMC-7721 human hepatocellular carcinoma cells. The expressions of PTEN and serine/threonine protein kinase (Akt) were detected by Western blot analysis. 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) absorbance and clonogenic survival assays were used to determine cell viability, proliferation and radiosensitivity. By performing cell-cycle analysis, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP biotin nick end labelling (TUNEL) assays and gamma-histone H2A (γ-H2AX) formation assays, we were able to explore the mechanism of PTEN enhancement of radiosensitivity. RESULTS: Restoration of wild-type PTEN induced growth suppression and sensitised the cells to ionising radiation specifically by its lipid phosphatase activity through the PTEN-phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathway. Restoring PTEN function correlated with G2/M arrest, apoptosis and the retardation of repair of radiation-induced double strand breaks (DSB). CONCLUSIONS: Our study suggests that strategies designed to restore the expression of PTEN may represent promising new therapies for sensitising HCC cells to ionising radiation.