Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

BiomechanicaI finite eIement anaIysis on the bone interface of posterior mandibuIar area under different setting forces after incIined impIantation with angIed abutment / 中国组织工程研究

BACKGROUND: Single tooth loss at posterior mandibular area is difficult to complete regularly axial implantation under limited conditions. Concerning this problem, some scholars employ the skill of tilted implantation with abutment angulations to restore it. However, the security study of this design has been limited until now. OBJECTIVE: To provide theoretical evidence for tilted implantation in the posterior mandibular area, and to make a biomechanical analysis on bone-implant interface after titled implantation under the same dynamic force stress. METHODS: First, restoration models of implant crown at different tilting angles in posterior mandibular area were built and optimized using the software CBCT and DICOM. Then dynamic force stress was applied in chewing cycles of the crown model. Finally, the stress-strain analysis of bone-implant interface was made by utilizing the three-dimensional finite element software Ansys. RESULTS AND CONCLUSION: (1) When the dental implant in the axis implantation was tilted to the lingual side at 5° or 10°, the maximum stress and strain values at the bone interface were 53.8 MPa and 2 671, respectively, under three loading conditions: the force during the chewing cycle was given vertical to the implant, toward the lingual side from the buccal side at 45° with the long axis of the tooth, and toward the buccal side from the lingual side at 45° with the long axis of the tooth. (2) When the implant inclined to the lingual side at a 15° angle, the rear edge of the implant was close to the interface between the cortical and cancellous bone, and the stress and strain values were bigger than those at any other implantation angle. (3) When the implant inclined to the lingual side at a 20° angle, the rear edge of the implant was beyond the interface between the cortical and cancellous bone, and contacted with the cortical bone that provided a support for the rear part of the implant. The stress and strain values on the bone interface were both reduced. The stress was concentrated in the cortex around the neck of the implant, and reduced a lot in the cancellous bone. The maximum strain value appeared at the contact site between the bone interface and the implant neck or rear part. It is concluded that in posterior mandibular area, the dental implant can be implanted at a < 10° linguoclination angle.

Preparation and bioIogicaI properties of TiN/Ag composite coating on pure titanium surface / 中国组织工程研究

BACKGROUND: It is of vital importance to fabricate an interface on the titanium implant surface which can promote early cell adhesion, proliferation, and differentiation, and exert better antibacterial effects with no cytotoxicity. OBJECTIVE: To prepare a TiN/Ag composite coating on the surface of pure titanium implant, and to explore its antibacterial properties and effects on MC3T3-E1 biobehaviors. METHODS: Acid etching blasting and multi-arc ion plating were adopted to prepare TiN/Ag composite coating on the smooth surface of pure titanium. Then, MC3T3-E1 cells that grew well were inoculated onto pure titanium plate, sandblasted and acid-etched titanium plate, and TiN/Ag-coated titanium plate. Twenty-four hours later, cell adhesion and viability were observed under confocal laser scanning microscope, and cell morphology was observed under scanning electron microscope. Cell counting kit-8 was used to detect cell proliferation and cytotoxicity at 24,48,72 hours after inoculation.In addition,Staphylococus aureus solution was dropped onto the smooth titanium plated, acid-etched and sandblasted titanium and TiN/Ag-coated titanium plate, and the growth of bacteria was observed by the laser confocal scanning microscope at 16 hours. RESULTS AND CONCLUSION: Under the confocal laser scanning microscope, spindle cells with bipolar or three poles were observed on the smooth titanium surface, and there was less F-actin and filopodia expression; cells on the TiN/Ag-coated titanium surface and sandblasted and acid-etched titanium surface were scattered with a large amount of interconnected filopodia that were fully stretched and adhered to the titanium surface, highly expressed F-actin was detected, and actin fibers were thickened. Under the scanning electron microscope, the cells on the smooth titanium surface were not fully adhered and stretched, and those on the TiN/Ag-coated titanium surface or the sandblasted and acid-etched titanium surface exhibited better adhesion and extension. Findings from the cell counting kit-8 showed that after 72 hours of inoculation,the cells on the smooth titanium surface grew well,with cytotoxicity level 1.In addition,Staphylococus aureus grew well on the smooth titanium surface under the confocal laser scanning microscope,while a large amount of Staphylococus aureus died on the TiN/Ag-coated titanium surface or on the sandblasted and acid-etched titanium surface. These findings indicated that TiN/Ag coating has good biocompatibility and antibacterial properties.