Perioperative neurocognitive disorders(PND)is one of the common complications in the perioperative period,especially in elderly patients,and the incidence of PND is high and it is closely related to the prognosis of surgery.The currently accepted pathogenesis of PND includes central nervous sys-tem inflammation,synaptic dysfunction,apoptosis,oxidative stress,and neurofibrillary tangles,etc.Mi-croRNAs(miRNAs),as key gene expression regulators of neurological development and function,are not only directly involved in these processes,but also indirectly affect PND development through the modulation of the microbiota-gut-brain axis,perioperative mood regulation,and postoperative pain.In this paper,we review the role of miRNA in regulating perioperative neurocognitive disorders,with the aim of providing new ideas for the diagnosis and prevention of PND,as well as for the development of targeted therapies for this disease.

Objective On the premise of meeting the image quality requirements of simulated location for pediatric radiotherapy,the simulated localizable CT parameters are optimized through phantom scanning to reduce the radiation dose.Methods CatPhan700 phantom was used to simulate the child's body,Philip 24-row large-aperture spiral simulated localizable CT was performed,and the CT images were obtained by scanning the phantom at different mAs and tube voltages.The mAs range was set at 60-400 mAs,the scanning was performed every 20 mAs interval,and the kV was set at 80,100,and 120 kV.Image evaluation was carried out using parameters such as image noise(N10 and mean SD),uniformity,low contrast resolution,high contrast resolution,and the stabilities of HU values of Air,Acrylic,50%bone,LDPE,20%bone,Teflon,Polystyrene,DelrinTM,Lung,PMP and Water.The CTDIVol and DLP automatically calculated by the simulated localizable CT system were read to evaluate the radiation dose.Results At 100 kV,as mAs increased,both CTDI and DLP showed upward trends,and the fitting results were linear correlated,with slopes of 0.034 5 and 0.932 4.Image noise was decreased nonlinearly with the increasing mAs.When mAs increased from 60 to 140 mAs,N10 decreased from 0.25%to 0.14%,and SD reduced from 3.74 HU to 2.54 HU.When mAs reached 180 mAs or higher,N10 fluctuated between 0.1%and 0.12%,the mean SD fluctuated between 2.0 and 2.5 HU,and the downward trends obviously slowed down.When mAs increased from 60 to 200 mAs,the low contrast resolution of the image dropped from 0.53 to 0.29.The image uniformity,high contrast resolution and HU values of different substances were less affected by mAs.The image quality of 100 kV and 200 mAs scanning was close to that of 120 kV scanning,but the image quality of 80 kV scanning failed to meet the clinical requirements.Conclusion In order to reduce the radiation dose as much as possible,the mAs should be set at 200 mAs when the tube voltage is set at 100 kV for a simulated cylinder with a diameter of 20 cm.In the actual simulation scanning for pediatric radiotherapy,the scanning parameters should be fine-tuned according to the phantom results and the actual physical characteristics of children to satisfy the optimization principle for radiation protection.

Oral cancer is one of the most prevalent malignant tumors of the head and neck region.In China,the incidence of oral cancer ranks second among all cancers of the head and neck and second only to that of nasopharyngeal carcinoma.More than 50%of patients with oral cancer are either at a locally advanced stage at initial diagnosis or have already developed distant metastasis.Depending on the cancer stage in a patient,multidisciplinary treatment,including surgery,radiotherapy,chemotherapy,immunotherapy,and targeted therapy,is cur-rently the standard treatment for oral cancer.Despite the variety of treatment modalities,the 2-/5-year overall survival rate of patients with oral cancer is rather low and cannot meet clinical needs.Therefore,there is an urgent need to develop more effective and comprehensive treatment modalities to improve the prognosis of oral cancer.In this study,we reviewed a new multidisciplinary comprehensive treatment mode for oral cancer in recent years and the progress in radiotherapy for oral cancer under this new mode.

Intensity-modulated radiotherapy (IMRT) is a radical treatment for oropharyngeal carcinoma. The 5-year overall survival (OS) is approximately 60%, and 80% for human papillomavirus (HPV)-related oropharyngeal carcinoma patients. Late toxicities after IMRT, including xerostomia, dysphagia, hypothyroidism, trismus, osteoradionecrosis and caries, and lower cranial neuropathy, seriously affect the quality of life of long-term survivors. The research on treatment de-intensification for HPV-related oropharyngeal cancer has been widely carried out at home and abroad, but there is little research focusing on late toxicity. In this article, related research progress in the incidence, treatment, prediction of late toxicity after IMRT was reviewed, aiming to provide reference for research on radiation-induced injury in de-intensification therapy research, thereby further optimizing comprehensive treatment strategies.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective:To investigate the relationship between the inflammatory cytokines level in the plasma of nasopharyngeal carcinoma patients before radiotherapy and acute radiotherapy adverse reactions, and to establish a preliminary model for predicting the risk of severe acute adverse reactions during radiotherapy.Methods:A cross-sectional study was conducted. A total of 85 nasopharyngeal carcinoma patients who received radical radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from May 2016 to March 2019 were retrospectively collected. The highest grade adverse reactions of radiation oral mucositis, radiation dermatitis and xerostomia during radiotherapy were evaluated according to the American Cancer Radiotherapy Collaboration (RTOG) acute radiation injury evaluation criteria, and the above adverse reactions ≥ grade 3 were treated as the severity. Olink proteomics technology was used to detect the level of 92 inflammatory cytokines (the standardized protein expression values) in the plasma of patients before radiotherapy for the first time. Single factor analysis of variance and independent sample t-test were used to analyze the relationship between inflammatory cytokines and clinical factors, as well as acute adverse reactions during radiotherapy. Based on inflammatory cytokines and/or the clinical factors, binary logistic regression was used to construct a predictive model for the risk of severe acute radiotherapy adverse reactions. Whether the most severe adverse reactions assessed by the American RTOG acute radiation injury evaluation criteria during radiotherapy were severe or not were taken as the gold standard. Receiver operating characteristic (ROC) curve was used to analyze the effectiveness of the established models for judging the severe acute adverse reactions. Results:Among the 85 patients, 68 were males and 17 were females, with the median age [ M ( Q1, Q3)] of 49 years (43 years, 60 years). All patients received radical radiotherapy, of which 64 cases were treated with combination chemotherapy or targeted therapy. A total of 19 cases (22.1%) experienced severe acute radiotherapy adverse reactions. There were statistically significant differences in the levels of interleukin (IL)-22 receptor A1 (IL-22RA1), IL-18 receptor 1(IL-18R1), eotaxin-1 (CCL11), tumor necrosis factor ligand superfamily member 14 (TNFSF14), FMS-like tyrosine kinase 3 ligand (Flt3L), and monocyte chemotactic protein 2 (MCP-2) in the plasma of patients with grade 1, 2, 3 acute radiation oral mucositis before radiotherapy; there were statistically significant differences in the levels of CD244 (all P < 0.05); there were statistically significant differences in the levels of CD244, CC chemokines ligand 20 (CCL20), leukemia inhibitory factor ligand (LIF-R) and IL-4 in the plasma of patients with grade 1, 2, 3 acute radiation dermatitis before radiotherapy (all P < 0.05); there were statistically significant differences in the levels of IL-12B, CXC chemokines ligand 11 (CCL11), LIF-R and IL-33 in the plasma between patients with grade 1 and grade 2 xerostomia before radiotherapy (all P<0.05). The result of single factor analysis of variance showed that the clinical factors were not associated with severe acute radiation adverse reactions (all P > 0.05). Binary logistic regression model M1 was established by selecting 6 clinical factors including age, T staging, N staging, clinical staging, whether to receive chemotherapy or not and whether to suffer from diabetes or not in the literatures. Based on cytokine function and previous literatures, the binary logistic regression model M2 was established by selecting IL-22RA1, IL-18R1, MCP-2, CCL11, CD244, CCL20 and IL-33 from the differential cytokines. A binary logistic regression model M3 was established by combining the above clinical factors with cytokines. The ROC curve analysis showed that the area under the curve of the M1, M2, M3 predictive models for judging the severe acute radiation adverse reactions was 0.781, 0.841, 0.868, respectively. Conclusions:There were differences in the expression levels of various inflammatory cytokines in plasma before radiotherapy among patients with different grades of acute radiotherapy adverse reactions. Building the models based on plasma inflammatory cytokine levels combined with clinical factors before the first radiotherapy could effectively predict the risk of severe acute radiotherapy adverse reactions in patients with nasopharyngeal carcinoma.

Objective:To investigate and understand current status of radiotherapy resources in the Association of Southeast Asian Nations (ASEAN) and analyze the radiotherapy needs of ASEAN countries, aiming to provide suggestions for China's radiotherapy technology international assistance work.Methods:We created a database of 10 ASEAN countries using open-source data, including data on population size, per capita gross national income, new cancer cases, and radiotherapy equipment (megavolt units). We also estimated the number of cases requiring radiotherapy and the demand for radiotherapy equipment. Descriptive statistics were used to present aggregate data and national data.Results:In 2020, the number of new cancer cases in ASEAN countries was 1.0992 million, and the estimated total number of cancer patients requiring radiotherapy was 700 300. The number of radiotherapy equipment required was 1 406. At present, the actual number of radiotherapy equipment in ASEAN countries is 564, and there is a certain gap between the existing radiotherapy resources in some ASEAN countries and the actual needs of cancer patients in their own countries. In 2040, the estimated number of new cancer cases in ASEAN countries will be 1.803 million, and the estimated total number of cancer patients who need radiotherapy in ASEAN countries will be 1.141 2 million. The number of required radiotherapy equipment will be 2 287. By 2040, the growth rate of radiation therapy equipment demand in ASEAN countries will be 305%, and all ASEAN countries need to allocate more radiotherapy resources to cope with the increase in the number of cancer patients and radiotherapy demand.Conclusions:ASEAN countries have a huge demand for radiotherapy in the next two decades, while there are significant differences among different countries. China's precision radiotherapy science and technology have huge potential for ASEAN countries. Radiotherapy science and technology international assistance work based on the needs of ASEAN countries will help China's radiotherapy continue to exert influence and promote the health and well-being of people in ASEAN countries.

Objective:To evaluate the efficacy and safety of nimotuzumab in the treatment of advanced head and neck tumors by using meta-analysis.Methods:Randomized controlled trials (RCT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) treated with nimotuzumab were searched from databases (Cochrane Library, PubMed, Embase, Wanfang Data and CNKI) for meta-analysis. The efficacy evaluation indexes included overall survival, progression-free survival, disease-free survival, objective response rate, and complete response rate. Adverse reactions were analyzed for safety evaluation. The heterogeneity results were evaluated by Chi-square test, the degree of heterogeneity was evaluated by I2, and the literature was statistically analyzed by random effects model. Results:A total of 11 RCT were included, consisting of 1 202 patients (602 in the intervention group and 600 in the control group). Compared with the control group, the overall survival was significantly prolonged, death risk was decreased by 22% ( HR=0.78, 95% CI=0.63-0.95, P=0.014), the progression-free survival was prolonged and the risk of disease progression was declined by 35% ( HR=0.65, 95% CI=0.53-0.81, P<0.01), and the disease-free survival was prolonged and the risk of recurrence was decreased by 29% ( HR=0.71, 95% CI=0.55-0.91, P<0.01), the objective response rate ( RR=1.37, 95% CI=1.20-1.55, P<0.01) and complete response rate ( RR=1.30, 95% CI=1.15-1.46, P<0.01) were significantly improved in the intervention group. In addition, adding nimotuzumab did not increase the incidence of adverse reaction ( RR=0.98, 95% CI=0.93-1.03, P=0.41). Conclusion:Nimotuzumab can significantly prolong long-term survival and improve short-term efficacy with high safety in LA-HNSCC patients.

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.
Male ; Humans ; Cohort Studies ; Chemoradiotherapy ; Carcinoma ; Hypopharyngeal Neoplasms/therapy* ; Induction Chemotherapy

Objective:To analysis the clinical features and prognosis in oropharyngeal carcinoma with secondary primary tumor. Methods:A retrospective analysis was performed on 468 pathologically confirmed oropharyngeal cancer as the primary tumor patients with p16 status, excluded distant metastasis, and admitted to the Chinese Academy of Medical Sciences from January 2010 to December 2020. The clinical features and prognosis of the secondary primary tumor were analyzed. Results:Among 468 patients with oropharyngeal cancer treated at initial diagnosed, 222 cases were P16-negative. With a median follow-up time of 64.3 months, 66 cases developed second primary cancer, with an incidence of 29.3%, among which 63.6%（42/66） were synchronous and 36.4%（24/66） were heterochronous, esophagus was the most commonly involved site. The 5-year OS of p16-negative oropharyngeal carcinoma with synchronous second primary cancer, without second primary cancer and with heterogeneous second primary cancer were 26.3% and 57.3% and 73.2%（P=0.001）; The second primary cancer accounted for 11.2%（12/107） of the deaths in the whole group, among them, the heterochronous second primary accounted for 75.0%（9/12）. There were 246 patients with p16 positive, with a median follow-up time of 52.4 months, 20 patients developed second primary cancer（8.1%）. Among them, 65.0%（13/20） were synchronous and 35.0%（7/20） were heterochronous. Esophagus was the most commonly involved site. The 4-year OS of p16-positive with synchronous, heterochronous and non-second primary cancer group were 51.9%, 80.7% and 83.3%. Secondary primary cancer accounted for 3.8%（2/52） of all deaths in p16 positvie group. Conclusion:The incidence of second primary cancer of p16 positive and negative oropharyngeal carcinoma were different. The esophagus was the most commonly involved site regardless of p16 status. Regardless of p16 status, the survival of patients with synchronous second primary cancer was worse than those without second primary cancer. For p16-negative oropharyngeal carcinoma, the prognosis was better in patients with heterogeneous second primary cancer, the second primary cancer is one of the main causes of death.
Humans ; Carcinoma/diagnosis* ; Oropharyngeal Neoplasms/diagnosis* ; Retrospective Studies ; Neoplasms, Second Primary/diagnosis*