Teledentistry as a Supportive Tool for Dentists in Diagnosing MRONJ in Northern Cyprus

Objective. This web-based survey, as a tool of teledentistry, is aimed at assessing the level of knowledge, attitudes, and awareness regarding MRONJ among dental professionals in Northern Cyprus. Methods. An online self-administered questionnaire about MRONJ was sent to all dentists in Northern Cyprus through Google Forms. The first part of the questionnaire consists of demographic and professional information, and the second part included questions about knowledge and awareness questions about MRONJ. The SPSS software was used for statistical data analysis. A Chi-square test was performed to compare between the groups. The significance level was set at p < 0.05 . Results. A total of 112 dentists participated in this survey. The participants showed an insufficient level of knowledge regarding MRONJ, as only 56.6% of the participants stated that they had general knowledge about MRONJ. Regarding the practical questions of the survey, the participants showed poor knowledge about implant and tooth extraction procedures while a patient is using antiresorptive or antiangiogenic drugs, particularly the usage of oral antiresorptive or antiangiogenic drugs for less than 3 years. Participants showed adequate knowledge in terms of usage area of medications and administration of them. Conclusion. Teledentistry can be used as a supportive tool for dentists in diagnosing MRONJ. Similar to previous studies, the knowledge and awareness of MRONJ of dentists in Northern Cyprus were found to be inadequate. There is a significant need to provide more professional information as part of undergraduate programs so that the next generation of dentists can practice more confidently.

Antiangiogenic Compound Axitinib Demonstrates Low Toxicity and Antitumoral Effects against Medulloblastoma

Background: Despite the improvement of medulloblastoma (MB) treatments, survivors face severe long-term adverse effects and associated morbidity following multimodal treatments. Moreover, relapses are fatal within a few months. Therefore, chemotherapies inducing fewer adverse effects and/or improving survival at relapse are key for MB patients. Our purpose was to evaluate the last-generation antiangiogenic drugs for their relevance in the therapeutic arsenal of MB. Methods: We screened three EMA- and FDA-approved antiangiogenic compounds (axitinib, cabozantinib and sunitinib) for their ability to reduce cell viability of five MB cell lines and their low toxicity towards two normal cell lines in vitro. Based on this screening, single-agent and combination therapies were designed for in vivo validation. Results: Axitinib, cabozantinib and sunitinib decreased viability of all the tested tumor cells. Although sunitinib was the most efficient in tumor cells, it also impacted normal cells. Therefore, axitinib showed the highest selectivity index for MB cells as compared to normal cells. The compound did not lead to acute toxicity in juvenile rats and crossed the blood–brain barrier. Moreover, axitinib efficiently reduced the growth rate of experimental brain tumors. Analysis of public databases showed that high expression of axitinib targets correlates with poor prognosis. Conclusion: Our results suggest that axitinib is a compelling candidate for MB treatment.

A Retrospective Analysis of the Effect of Anlotinib in Patients With Lung Cancer With or Without Previous Antiangiogenic Therapy

ObjectiveThe purpose of this study was to initially investigate the effect of previous antiangiogenic therapy (bevacizumab and endostatin) on the efficacy of anlotinib in patients with advanced or metastatic lung cancer (LC).MethodsWe retrospectively collected the clinical data of patients with LC treated with anlotinib and divided them into group A (treated with anlotinib after the failure of previous antiangiogenic drugs and group B (no prior use of antiangiogenic drugs). We used propensity score matching (PSM) for confounding factors between the groups. Progression-free survival (PFS) and overall survival (OS) were also recorded.ResultsA total of 160 patients were included in the analysis. The median OS in groups A and group B was 11.8 months and 16.1 months (P=0.120), whereas the median PFS was 3.1 months and 4.7 months (P=0.009), respectively. Moreover, the objective response rate (ORR) of the two groups was 9.6% and 10.4% (P=0.874), and the disease control rate (DCR) was 71.1% and 80.5% (P=0.165).After PSM (n=46), baseline characteristics were comparable between groups A and B. Furthermore, the median OS of the two groups was 14.6 months and 16.2 months (P=0.320), whereas the median PFS was 3.5 months and 4.5 months (P=0.040), respectively. Moreover, the ORR of the two groups were 13.0% and 10.9% (P=0.748), and the DCR were 78.3% and 82.6% (P=0.599), respectively.ConclusionsPrevious antiangiogenic treatments may affect the PFS of patients who receive anlotinib later, but it might not affect the patient’s ORR and OS.

A New Antitumor Direction: Tumor-Specific Endothelial Cells

Targeting tumor blood vessels is an important strategy for tumor therapies. At present, antiangiogenic drugs are known to have significant clinical effects, but severe drug resistance and side effects also occur. Therefore, new specific targets for tumor and new treatment methods must be developed. Tumor-specific endothelial cells (TECs) are the main targets of antiangiogenic therapy. This review summarizes the differences between TECs and normal endothelial cells, assesses the heterogeneity of TECs, compares tumorigenesis and development between TECs and normal endothelial cells, and explains the interaction between TECs and the tumor microenvironment. A full and in-depth understanding of TECs may provide new insights for specific antitumor angiogenesis therapies.

A Glimpse in the Future of Malignant Mesothelioma Treatment

Malignant mesothelioma (MMe) is a rare neoplasm with few therapeutic options available. The landscape of effective therapy for this disease remained unchanged in the last two decades. Recently, however, the introduction of Immune Checkpoint Inhibitors (ICIs) led to small, but nevertheless, promising improvements. However, many efforts are still needed to radically improve the prognosis of MMe. In this review, we analyze all those therapeutic strategies for MMe that are still in a preclinical or early clinical phase of development. In particular, we focus on novel antiangiogenic drugs and their possible combination with immunotherapy. Furthermore, we describe also more complex strategies such as microRNA-loaded vectors, oncolytic viruses, and engineered lymphocytes.

Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), one of the most fatal malignancies in the world, is usually diagnosed in advanced stages due to late symptom manifestation with very limited therapeutic options, which leads to ineffective intervention and dismal prognosis. For a decade, tyrosine kinase inhibitors (TKIs) have offered an overall survival (OS) benefit when used in a first-line (sorafenib and lenvatinib) and second-line setting (regorafenib and cabozantinib) in advanced HCC, while long-term response remains unsatisfactory due to the onset of primary or acquired resistance. Recently, immunotherapy has emerged as a promising therapy in the treatment of several solid tumors, such as melanoma and non-small cell lung cancer. Moreover, as the occurrence of HCC is associated with immune tolerance and immunosurveillance escape, there is a potent rationale for employing immunotherapy in HCC. However, immunotherapy monotherapy, mainly including immune checkpoint inhibitors (ICIs) that target checkpoints programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and the cytotoxic T lymphocyte antigen-4 (CTLA-4), has a relatively low response rate. Thus, the multi-ICIs or the combination of immunotherapy with other therapies, like antiangiogenic drugs and locoregional therapies, has become a novel strategy to treat HCC. Combining different ICIs may have a synergistical effect attributed to the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of antiangiogenic drugs in ICIs can enhance antitumor immune responses via synergistically regulating the vasculature and the immune microenvironment of tumor. In addition, locoregional treatments can improve antitumor immunity by releasing the neoplasm antigens from killed tumor cells; in turn, this antitumor immune response can be intensified by immunotherapy. Therefore, the combination of locoregional treatments and immunotherapy may achieve greater efficacy through further synergistic effects for advanced HCC. This review aims to summarize the currently reported results and ongoing trials of the ICIs-based combination therapies for HCC to explore the rational combination strategies and further improve the survival of patients with HCC.

A Pilot Study to Evaluate Early Predictive Value of Thorax Perfusion-CT in Advanced NSCLC

Background: The role of perfusion computed tomography (pCT) in detecting changes in tumor vascularization as part of a response to antiangiogenic therapy in non-small cell lung cancer (NSCLC) remains unclear. Methods: In this prospective pilot study (IMPACT trial, NCT02316327), we aimed to determine the ability of pCT to detect early changes in blood flow (BF), blood volume (BV), and permeability (PMB), and to explore whether these changes could predict the response at day +42 in patients with advanced, treatment-naive, non-squamous NSCLC treated with cisplatin and gemcitabine plus bevacizumab. Results: All of the perfusion parameters showed a consistent decrease during the course of treatment. The BV difference between baseline and early assessment was significant (p = 0.013), whereas all perfusion parameters showed significant differences between baseline and day +42 (p = 0.003, p = 0.049, and p = 0.002, respectively). Among the 16 patients evaluable for efficacy, a significant decline in BV at day +7 from baseline was observed in tumors with no response (p = 0.0418). Conclusions: Our results confirm that pCT can capture early changes in tumor vasculature. A substantial early decline of BV from baseline might identify tumors less likely responsive to antiangiogenic-drugs.

EP.FRI.154 Could Antiangiogenic Drugs be the Solution to Tendon Injury? A Literature Review on the use of Antiangiogenic Drugs for Tendon Regeneration

Background Tendinopathy accounts for more than half of reported musculoskeletal injuries worldwide. The subsequent healing process results in a disorganised tendon structure secondary to neovascularisation, forming a bulky tendon with overall reduced strength. Current treatment options remain controversial as re-rupture rates following surgical intervention are high. It has been proposed that the use of anti-vascular endothelial growth factors could improve tendon healing. Methods This literature review employed a systematic approach. The search strategy incorporated an adjusted PICO format and PRISMA flow diagram. Search findings were critically appraised using the CASP tool checklist. Identified studies investigated the effect of injectable anti-angiogenic drugs on tendon healing. Results Three final studies were identified. Tempfer et al. showed a reduction in cross sectional tendon area in the intervention group (5.6mm²+1.8), comparatively to the control group (9.1mm² +2.0), and increased tendon strength in the intervention group (47.7N+6.41) comparatively to the control group(32.41N+9.23). Dallaudiere (2014) et al. showed reduced cross-sectional area in the intervention group (0.95mm²+0.01) compared with the control group (0.75mm²+0.01). Dallaudiere (2013) et al. also showed reduced cross sectional areas in the intervention group (1.10mm²+0.01) compared with the control group (1.11mm²+0.03). Conclusion All studies supported the use of anti-angiogenic drugs to support tendon healing. The use of injectable anti-angiogenic drugs may potentially serve in conjunction with surgical intervention or as an alternative minimally invasive intervention to improve tendon rehabilitation. This review recommends that further randomised control studies will be needed to strengthen the current evidence.

To the Question of Terminology, Expert Criteria for Evaluating the Effectiveness of Antiangiogenic Therapy and the Prevalence of Refractory Forms of Neovascular Age-Related Macular Degeneration. Review

The authors presented a review of studies aimed at assessing the effectiveness of antiangiogenic therapy in patients with neovascular form of age-related macular degeneration. The purpose of this review was to clarify the prevalence of true refractory forms of WMD on literary data. The vast majority of experts consider the marker of “refractory” the exit of the dye from the vessels on fluorescent angiography (FAG), fibrovascular detachment of pigment epithelium with intraretinal and/or subretinal fluid on optical coherent tomography, an increase in hemorrhage on the eye compared to the initial level of post-loading phase therapy. The analysis showed a wide corridor of indicators, due to different approaches and timing of the assessment of the respondent’s status, as well as expert criteria for the effectiveness of antiangiogenic therapy. In addition, the authors drew attention to the different understanding of the terms tahiphylaxis and tolerance, presented by the researchers. Many papers are replacing these perceptions. The our work presents the fundamental differences of these biological phenomena in the clinic and morphometric data, as well as the timing of development. Meanwhile, overcoming resistance involves an accurate diagnosis of the pharmacological cause and a subsequent differentiated approach to solving the problem. An overview of the work on overcoming refractory to antiangiogenic drugs in various ways is presented.