Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma

Background The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). Methods Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. Results A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). Conclusion Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome

Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary regulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, isorhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irradiation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair process, which is presumably associated with the suppressive effect against GI syndrome.

Peculiarities of Using Lymphocyte Test to Predict the Severity of Acute Radiation Injury

One of the methods of biological dosimetry is the use of information on the concentration of lymphocytes in the peripheral blood of victims in the first days after irradiation. The aim of the study was to validate the lymphocyte test method for predicting the severity of acute radiation injury, taking into account the dose rate factor. Materials and research methods. The method of investigation was a correlational analysis of clinical, dosimetric and laboratory data of the victims of the accident at the Chernobyl nuclear power plant in 1986 (n=65) and in radiation accidents with gamma-neutron irradiation (n=19). The data were taken from the database of acute radiation injuries in humans of A.I. Burnazyan Federal Medical Biophysical Center of the Federal Medical and Biological Agency of Russia. Results of the study and their analysis. The results of correlation analysis indicated that average lymphocyte concentration in the range of 0.4-0.8×109/l on day 3-6 post-irradiation with dose rates greater than 2 Gy/h resulted in an average dose estimate which was 40.0% higher than that for dose rates of less than 2 Gy/h. Absolute error of dose estimation is (±1.0-1.5) Gy. For lymphocyte concentrations higher than 0.8×109/l the prognosis is uncertain: the range of dose assessment variability is 1-4 Gy. At a lymphocyte concentration of less than 0.4×109/l the average dose estimate is more than 4.0 Gy, corresponding to a severe or extremely severe degree of acute radiation disease. The predicted degree of severity of radiation injuries in the presence of the neutron component of radiation is lower in comparison with the predictions based on the data on the victims of the Chernobyl accident. It is concluded that the identified dependencies can be used for medical triage of the victims at advanced stages of medical evacuation. For the purpose of correct routing of medical evacuation to specialized centers, it is advisable to allocate 4 treatment-evacuation groups.

Application of Regenerative Cell Technologies in the Treatment of Severe Local Radiation Injuries in Victims of Emergency Situations: from the Experience of the Specialists of the Federal Medical Biophysical Center Named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia

It has been noted that one of the most common types of radiation injuries when a person is exposed to ionizing radiation is radiation burns — severe local radiation injuries. The aim of the study is to apply stromal and vascular fraction of adipose tissue to increase the efficiency of complex therapy for local radiation lesions. Materials and methods of the study. In 2017-2019, 7 patients (all male; mean age — (54.83±9.41) years) with local radiation lesions of the skin — ulcerative-necrotic lesions of the skin and underlying tissues — were treated at the Federal Medical Biophysical Center named after A.I. Burnazyan of FMBA of Russia. For more than 6 months the patients received conventional conservative therapy of local radiation lesions and a single injection of cell suspension of autologous cells of stromal-vascular fraction of adipose tissue — the average number of cells was (60.33×106±64.04). Results of the study and their analysis. All patients had no serious adverse events and reactions associated with the introduction of autologous regenerative cells of adipose tissue. During the whole period of observation after stromal-vascular fraction of adipose tissue was injected, late radiation ulcers remained without signs of inflammation and infiltration. The patients were discharged from the hospital in satisfactory condition. According to the authors, the use of stromal-vascular fraction of adipose tissue in local radiation lesions provides favorable conditions: to increase the effectiveness of complex therapy; to reduce healing time of the wound surface; to regulate and activate immune and reparative processes in the dermis; to restore the damaged vascular network, lost skin without severe scarring changes; to heal and achieve a satisfactory result, decent quality of life of patients.

Effects of captopril against radiation injuries in the Göttingen minipig model of hematopoietic-acute radiation syndrome

Our laboratory has demonstrated that captopril, an angiotensin converting enzyme inhibitor, mitigates hematopoietic injury following total body irradiation in mice. Improved survival in mice is correlated with improved recovery of mature blood cells and bone marrow, reduction of radiation-induced inflammation, and suppression of radiation coagulopathy. Here we investigated the effects of captopril treatment against radiation injuries in the Göttingen mini pig model of Hematopoietic-Acute Radiation Syndrome (H-ARS). Minipigs were given captopril orally (0.96 mg/kg) twice daily for 12 days following total body irradiation (60Co 1.79 Gy, 0.42–0.48 Gy/min). Blood was drawn over a time course following irradiation, and tissue samples were collected at euthanasia (32–35 days post-irradiation). We observed improved survival with captopril treatment, with survival rates of 62.5% in vehicle treated and 87.5% in captopril treated group. Additionally, captopril significantly improved recovery of peripheral blood mononuclear cells, and a trend toward improvement in recovery of red blood cells and platelets. Captopril significantly reduced radiation-induced expression of cytokines erythropoietin and granulocyte-macrophage colony-stimulating factor and suppressed radiation-induced acute-phase inflammatory response cytokine serum amyloid protein A. Using quantitative-RT-PCR to monitor bone marrow recovery, we observed significant suppression of radiation-induced expression of redox stress genes and improved hematopoietic cytokine expression. Our findings suggest that captopril activities in the Göttingen minipig model of hematopoietic-acute radiation syndrome reflect findings in the murine model.

Comparison of Radiotherapy Combined with Nimotuzumab vs. Chemoradiotherapy for Locally Recurrent Nasopharyngeal Carcinoma

BackgroundThe present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC).MethodsPatients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated by the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint.ResultsA total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P=0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P=0.011). ConclusionRadiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Evaluation of the effectiveness of the method of microinjection autotransplantation of tissues based on immunological parameters

Relevance of the topic. Chronic radiation damage to the rectum occurs in 5-10% of patients. The development and application of a method for treating patients with post-radiation rectal injuries using autologous regenerative cells of adipose tissue in a clinic will make it possible to achieve high results in treatment. Purpose – to conduct a comparative analysis of the effectiveness of the method of microinjection autotransplantation of tissues based on immunological parameters. Patients and methods. The study involved 66 patients – women aged 28 to 83 years inclusive with complications of radiation therapy (rectovaginal fistulas, radiation proctitis, radiation ulcers). We carried out a comparative analysis of the condition of patients with post-radiation injuries before and after treatment, and also evaluated the role of microinjection autotransplantation of tissues in the treatment of post-radiation injuries of the rectum. The results and effectiveness of treatment were judged by changes in the main immunological parameters. Results. Our results indicate the high efficiency of the method of microinjection autotransplantation of adipose tissue in the treatment of post-radiation damage to the rectum. Impaired repair of damaged tissue in patients with post-radiation damage to the rectum is accompanied by changes in the T-cell level of immunity and an imbalance of pro- and anti-inflammatory cytokines, which leads to a decrease in reparation capabilities, prolonged non-healing of the defect, and progression of the disease. The revealed changes in cellular immunity and cytokine profile are mutually aggravating. At the same time, the use of SVF makes it possible to normalize these indicators, and, accordingly, allows achieving sustainable results in treatment, reducing the risk of complications, and preventing the likelihood of relapses. All this will allow in a short time to objectively assess the somatic status of the patient, the degree of operational risk, choose the most adequate treatment tactics, predict the outcome of treatment in each specific case, and will also give high clinical results (elimination of inflammation, epithelialization of the defect), and will improve the quality of life of patients. Conclusion. The use of SVF will not only eliminate the pathology, but also prevent further relapses by stimulating the regenerative capabilities of the affected tissues, as well as by achieving an immunostimulating, anti-inflammatory effect.