The efficacy and safety of anti-angiogenic combination therapy in patients with driver gene-negative non-small cell lung cancer (NSCLC) with brain metastases (BM) are uncertain. Eighty-eight records of driver gene-negative patients with NSCLC treated with craniocerebral radiotherapy (RT) and programmed death factor-1 (PD-1) inhibitors between May 2021 and May 2023 were collected. Based on whether anti-angiogenic therapy (AT) is combined or not, patients are categorized into the AT group and the non anti-angiogenic therapy (NAT) group. The NAT group patients received craniocerebral RT and PD-1 inhibitor and those in the AT group received craniocerebral RT and PD-1 inhibitor with ≥ 4 cycles of AT. Comparing the clinical efficacy and safety in these two patient cohorts was the main goal of the study. By May 1, 2024, the iORR was 94.0

BACKGROUND:Ubiquitin-conjugating enzyme 2T (UBE2T) has been reported to be associated with uncontrolled cell growth and tumorigenesis in multiple cancer types. However, the understanding of its regulatory role in the carcinogenesis of Head And Neck Squamous Cell Carcinoma (HNSC) is limited. METHODS:UBE2T expression in HNSC patient samples and the correlation between its expression and patients' survival rates were evaluated using The Cancer Genome Atlas (TCGA) database. Cell survival and proliferation were investigated in UM-SCC1 and UM-SCC15 cells infected with control and shUBE2T lentivirus. The xenograft mouse model was established using UM-SCC15 cells to examine HNSC tumorigenesis with or without UBE2T. Western blot, qRT-PCR, and ferroptosis assays were carried out to disclose the interaction between UBE2T and NF-κB signaling and ferroptosis. RESULTS:The increased expression of UBE2T was noted in tumor tissues of patients with HNSC, correlating with a significantly reduced overall survival time in this patient cohort. Knockdown of UBE2T inhibited HNSC tumorigenesis and tumor growth. Mechanistically, inhibition of UBE2T suppressed NF-κB signaling and induced ferroptosis in HNSC. CONCLUSION:Our study underscores the multifaceted role of UBE2T in HNSC, illuminating its potential as a biomarker and therapeutic target.

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

Tumor cell lysate (TCL)-based vaccines contain a large number of tumor-specific and related antigens, albeit at low levels, that require active transfer and presentation by antigen-presenting cells (APCs) in vivo, which stimulate a weak immune response. The artificial APC (aAPC) system presented herein is a cell-based therapeutic system that can significantly enhance the immune response compared to TCL-based vaccines. This study combines these two treatment strategies to assess their in vitro and in vivo effects. We successfully prepared TCL-poly(lactic-co-glycolic acid)-PEI (TPP) and demonstrated that it was phagocytosed by the APCs and enhanced the maturation of DCs in vitro. The use of TPP in combination with the aAPCs resulted in better antitumor effects compared to the individual therapies. The combination therapy induced a higher proportion of CD4+ T, CD8+ T, and TRP2180–188-specific CD8+ T cells in comparison with the individual therapies. Additionally, the combination therapy enhanced the in vitro proliferation activity; greater inhibited regulatory T cells; and promoted inflammatory cytokine secretion, while reduced the production of inhibitory cytokines. In conclusion, the combination therapy consisting of the TPP tumor nanovaccine and the aAPC system enabled a broader immune response and achieve better antitumor effects compared to treatment with the individual therapies.

Standard treatments for patients with metastatic non-small cell lung cancer (NSCLC) include palliative chemotherapy and radiotherapy, but with limited survival rates. With the development of improved immunotherapy and targeted therapy, NSCLC prognoses have significantly improved. In recent years, the concept of oligometastatic disease has been developed, with randomized trial data showing survival benefits from local ablation therapy (LAT) in patients with oligometastatic NSCLC (OM-NSCLC). LAT includes surgery, stereotactic ablation body radiation therapy, or thermal ablation, and is becoming an important treatment component for OM-NSCLC. However, controversy remains on specific management strategies for the condition. In this review, we gathered current randomized trial data to analyze prognostic factors affecting patient survival, and explored ideal treatment conditions for patients with OM-NSCLC with respect to long-term survival.

Background : With continued improvement in radiotherapy technology, hypofractionated radiotherapy has helped achieve good results in the local control and toxicity of pulmonary oligometastases. This study aimed to investigate the efficacy of radiotherapy and the prognostic factors that affect survival in patients with pulmonary oligometastases who undergo helical tomotherapy (TOMO) hypofractionated radiotherapy. Methods : Ninety pulmonary oligometastases in 40 patients (26 males, 14 females; median age 57 years) were retrospectively investigated and treated with hypofractionated radiotherapy in the Department of Oncology and Radiotherapy of the First Affiliated Hospital of Bengbu Medical College during 2018-2020. Their Karnofsky performance status (KPS) was ≥70 points. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), and we determine the related influencing factors. Results : The median gross tumor volume (GTV) and planning target volume (PTV) were 9.7 cm³ (range 1.1–287.0 cm³) and 56.9 cm³ (range 16.3–494.2 cm³), respectively, the median biological effective dose, α/β=10 (BED10), was 76.8 Gy (range 56-96 Gy), and four-dimensional computed tomography positioning was applied to 52.5% of the patients. All patients completed the treatment plan during a median follow-up of 16.1 months (range 4.9–33.3 months). The 1- and 2-year OS rates were 90.3% and 55.2%, respectively. The 1- and 2-year LC rates were 80.8% and 64.7%, respectively. The 1- and 2-year PFS rates were 47.3% and 28.4%, respectively. Univariate analysis revealed that colorectal primary (p=0.004), age >57 years (p=0.037), and number of organ metastases ≥2 (p=0.046) were associated with OS, whereas disease-free interval (DFI) ≤17.4 months (p=0.032), number of lung metastases≥2 (p=0.049), and PTV >56.9 cm³ (p=0.041) were associated with LC; and number of metastatic organs ≥2 (p=0.015) was independently associated with PFS. In multivariate analysis, colorectal cancer (p=0.010) and age >57 years (p=0.009) were significantly associated with OS. No > grade 3 toxic reaction. Conclusions : The median OS, LC, and PFS rates of TOMO hypofractionated radiotherapy for pulmonary oligometastases were 24.9, 25.9, and 11.8 months, respectively, showing that good survival rates and low toxicity could still be achieved using the medium dose.

目的:分析在临床见习本科生肿瘤放射治疗学教学中应用PBL结合CBL教学法的效果.方法:选取2015级临床医学本科生46名,随机分为传统教学组23名和PBL+CBL教学组23人,比较教学满意度及出科考试成绩.结果:传统教学组在提高自学能力、提高临床实践能力和培养临思维能力方面的满意度,显著低于PBL+CBL教学组的满意度,两组相比,差异具有统计学意义(P<0.05).在出科考试中,传统教学组学生成绩为(75.15±4.32),P B L+C B L教学组成绩为(83.35±3.68),两组出科考试成绩相比,差异具有统计学意义(P<0.05).结论:在临床医学本科生肿瘤放射治疗学临床见习带教中应用PBL+CBL相结合的教学模式,极大地调动了学生的学习主动性,激发学习热情,提高了学生分析问题、解决问题的能力,起到较好的教学效果.

Objective:To compare the survival rate and adverse reactions of patients with advanced hypopharyngeal squamous cell carcinoma undergoing surgery combined with chemoradiotherapy, and to analyze the prognostic factors of patients.Methods:The clinicopathologic data of 78 patients with advanced hypopharyngeal squamous cell carcinoma admitted to the Department of Radiation Oncology of the First Affiliated Hospital of Bengbu Medical University from August 2013 to December 2018 were retrospectively analyzed. The patients were divided into surgery combined with chemoradiotherapy group ( n=27) and chemoradiotherapy group ( n=51) according to different treatment methods. The median follow-up time was 46 months (20-84 months). The main observation indicators were overall survival (OS), progression-free survival (PFS) and local control rate (LCR). Cox regression model was used to analyze the prognostic factors. Results:Until July 31, 2020, 51 of the 78 patients with advanced hypopharyngeal squamous cell carcinoma died, including 6 cases of local recurrence, 11 cases of distant metastasis, and 34 cases of other causes (15 cases of hemorrhage, 15 cases of cachexia, and 4 cases of other diseases). In the surgery combined with chemoradiotherapy group, 12 patients died, accounting for 44.44%. In the chemoradiotherapy group, 39 patients died, accounting for 76.47%. The 1-, 3- and 5-year OS rates of 78 patients were 57.7%, 36.3% and 27.2% respectively, the 1-, 2- and 3-year PFS rates were 49.5%, 38.7% and 32.6% respectively, and the 1-, 2- and 3-year LCR were 53.4%, 40.0% and 34.2% respectively. The 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group were 74.1%, 50.1% and 44.6%, and those in the chemoradiotherapy group were 49.0%, 29.3% and 12.8%, with a statistically significant difference ( χ2=5.142, P=0.023). The 1-, 2- and 3-year PFS rates in the surgery combined with chemoradiotherapy group were 62.1%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 43.1%, 30.6% and 26.7%, with no statistically significant difference ( χ2=3.222, P=0.073). The 1-, 2- and 3-year LCR of the surgery combined with chemoradiotherapy group were 69.8%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 45.1%, 32.9% and 29.6%, with no statistically significant difference ( χ2=3.576, P=0.059). The results of univariate analysis showed that tumor T stage ( χ2=7.140, P=0.008), N stage ( χ2=4.493, P=0.034) and treatment method ( χ2=5.142, P=0.023) were all independent influencing factors of the OS of patient with advanced hypopharyngeal squamous cell carcinoma; T stage ( χ2=5.807, P=0.016) and N stage ( χ2=6.587, P=0.010) were both independent influencing factors of PFS. The results of multivariate analysis showed that tumor T stage ( HR=2.121, 95% CI: 1.142-3.938, P=0.017), N stage ( HR=2.088, 95% CI: 1.144-3.811, P=0.016) and treatment method ( HR=0.430, 95% CI: 0.226-0.815, P=0.010) were all independent prognostic factors of the OS of patients with advanced hypopharyngeal squamous cell carcinoma; T stage ( HR=1.884, 95% CI: 1.011-3.510, P=0.046) and N stage ( HR=1.904, 95% CI: 1.058-3.429, P=0.032) were both independent prognostic factors of PFS. During the treatment period, there were statistically significant differences in the incidences of radioactive pharyngitis [7.41% (2/27) vs. 39.22% (20/51), χ2=8.821, P=0.003] and radioactive dermatitis [3.70% (1/27) vs. 29.41% (15/51), χ2=7.156, P=0.007] between the surgery combined with chemoradiotherapy group and the chemoradiotherapy group. However, there were no statistically significant differences in the incidences of radioactive oral mucositis [11.11% (3/27) vs. 17.65% (9/51), χ2=0.186, P=0.666], bone marrow suppression [37.04% (10/27) vs. 50.98% (26/51), χ2=1.381, P=0.240], pharynx infection [11.11% (3/27) vs. 5.88% (3/51), χ2=0.143, P=0.706] and tracheal fistula [7.41% (2/27) vs. 0 (0/51), P=0.117] between the two groups. Conclusion:The 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group are higher than those in the chemoradiotherapy group, and the incidences of adverse reactions are low. T stage, N stage and treatment method are independent prognostic factors for OS of advanced hypopharyngeal squamous cell carcinoma patients, while T stage and N stage are independent prognostic factors for PFS.

目的:观察外周血中性粒细胞与淋巴细胞比值(NLR)在食管鳞癌(ESCC)患者放疗/同步放化疗期间的变化及与总生存率(OS)的关系,评估NLR变化对ESCC患者生存的预测价值.方法:回顾性分析某院接受根治性放疗/放化疗的148例符合条件的ESCC患者的临床资料.收集放疗前、放疗中及放疗后患者的外周血指标,并计算NLR,通过绘制ROC曲线确定NLR预测ESCC患者生存的最佳截断值.根据截断值将其分为高NLR组和低NLR组,分析放疗前后NLR的变化与ESCC患者的临床特征及预后关系,评估影响患者预后的因素.结果:全组患者3年OS为37.8％,放疗前低NLR组与高NLR组患者3年OS分别为63.3％、30.5％;放疗后低NLR组与高NLR组患者3年OS分别为47.9％、28.6％.放疗前及放疗后高NLR组的患者预后均较差.单因素分析显示:T分期、N分期、放疗前NLR、放疗后NLR、放疗前及放疗后NLR差值变化趋势为OS的影响因素.多因素分析表明T分期、N分期、放疗前及放疗后NLR是影响ESCC患者OS的独立因素(P值均<0.05).结论:放疗前NLR、放疗后NLR及放疗前后NLR变化趋势升高对接受放疗/放化疗的ESCC患者可能是影响生存的预后不良因素,但仍需进一步研究.

目的 探讨鼻咽癌多药耐药基因的表达及药物逆转机制.方法 取人鼻咽低分化鳞癌细胞系HNE1,用新辅助化疗药奈达铂(NDP)作为体外诱导剂,建立耐NDP的人鼻咽癌细胞系HNE1/NDP.qRT-PCR和免疫印迹检测HNE1和HNE1/NDP中多药耐药基因1(MDR1)、多药耐药相关蛋白1(MRP1)和P-糖蛋白(P-gp)的mRNA和蛋白表达差异;不同浓度的贝伐单抗(5、10、20、40、80μg/ml)处理HNE1和HNE1/NDP,48 h后CCK8法检测贝伐单抗对HNE1和HNE1/NDP细胞的增殖作用.不同浓度贝伐单抗联合1 ug/ml奈达铂处理HNE1/NDP后,CCK8检测贝伐单抗对HNE1/NDP的耐药逆转作用.流式细胞仪检测贝伐单抗处理HNE1/NDP细胞后细胞凋亡率.结果 qRT-PCR和免疫印迹结果显示HNE1/NDP中MDR1、MRP1和P-gp的mRNA和蛋白表达显著上调;贝伐单抗呈浓度依赖性地抑制HNE1和HNE1/NDP细胞的增殖,同时逆转HNE1/NDP的耐药性;qRT-PCR结果显示贝伐单抗处理HNE1/NDP细胞后,抑制MDR1、MRP1和P-gp的mRNA表达.PI染色结果显示贝伐单抗促进HNE1/NDP细胞的凋亡.结论 贝伐单抗通过下调多药耐药相关基因的表达,同时促进HNE1/NDP细胞凋亡,从而实现耐药逆转作用.

目的:比较鼻咽癌螺旋断层放疗(TOMO)与固定野静态调强放疗(IMRT)的剂量学指标.方法:选择蚌埠医学院第一附属医院2018年1月至2019年12月期间收治的80例鼻咽癌患者,按照随机数字法分为两组,各40例.观察组给予TOMO处理,对照组给予IMRT处理.比较两组靶区剂量、危及器官剂量.结果:观察组患者肿瘤靶区、颈部转移淋巴结、亚临床病灶及预防照射区D95剂量低于对照组,差异具有统计学意义(P＜0.05).观察组危及脑干、脊髓、视交叉剂量显著低于对照组,差异具有统计学意义(P＜0.05).结论:观察组与对照组均能用于临床,但观察组在放疗中的剂量分布优势更明显,危及器官剂量更低,能更好地保护正常组织.

BACKGROUNDNasopharyngeal carcinoma (NPC) is a kind of head-neck malignant neoplasm originated from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. KiSS-1 is an inhibitor of tumor metastasis in a range of cancers.METHODSWe establish a cell substrain of SUNE-1-5-8F (NPC cell line from humans) that trsnfected with lentiviral vectors carried with KiSS-1 gene and were selected by puromycin. A transplantation tumor animal model in BALB/c-nu mice was successfully established with a substrain that stably overexpressed KiSS-1.RESULTSOur result showed that the size of transplantation tumor in the nude mice with KiSS-1 overexpression in transplantation tumor was not difference from the size of transplantation tumor in the controlled transplantation tumor mice. We detected metastatic tumor in lung but not in liver. Moreover, we also found that in the nude mice with KiSS-1 overexpression in transplantation tumor showed extremely fewer metastatic tumor in lung compared with the controlled transplantation tumor mice model. In conclusion, KiSS-1 may be beneficial for the inhibition of metastasis of human NPC.CONCLUSIONThis study may throw light on the treatment of NPC and may help improve the prognosis of patients with NPC.

Objective To investigate the efficacy of radiotherapy,as well as the prognostic factors of survival in patients with extracranial oligometastases. Methods A total of 164 patients who underwent intensity-modulated radiotherapy ( IMRT ) of the extracranial oligometastases, from January 2013 to December 2016, were enrolled in the study. The short-term efficacy, local control rate, overall survival, progression free survival and adverse effects of treatment were observed. Results Short-term efficacy was assessed within the first 1-3 months after the end of radiotherapy. The objective response rate (CR+PR) was 78. 7% and the short-term efficacy is mainly related to the T stage of primary tumor ( P＝0. 004).Until the last follow-up,all patients with 1-,2-and 3-year LC were 89. 8%,82. 5% and 74. 9% respectively.Univariate analysis showed that the influencing factors of LC include tumor size and gross tumor volume dose ( all P＜0. 05),multivariate analysis found no significant influence factors. The 1-,2- and 3-year OS were 83. 4%, 69. 6% and 54. 6% respectively. Univariate and multivariate analysis showed that the primary tumor sources, metastasis organs,whether synchronous or adjuvant chemotherapy and short-term efficacy were independent prognostic factors in patients of OS ( P＜0. 05 ).Main toxicity-associated events were grade 1-2 acute reactions,with only 6 patients experiencing grade 3 toxicity;no grade≥4 toxic reactions or treatment-related deaths occurred. Conclusions Radiation therapy for the treatment of extracranial oligometastases can achieve good curative effect,is well-tolerated and has low toxicity.

BACKGROUND Endothelial progenitor cells (EPCs) are regarded as promising targeted vectors for delivering therapeutic genes or agents in cancer therapy. The purpose of this study was to investigate the role of intravenously administered KAI1/CD82 genetically transduced EPCs in the tumorigenesis and metastasis of nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS EPCs were isolated from human umbilical cord blood, expanded in culture, and stably transduced with lentiviral vectors expressing KAI1/CD82. The KAI1/CD82 EPCs were injected intravenously into nude mice bearing human NPC xenografts. Tumor growth and the incidence of liver and lung metastases were observed. Expression of KAI1/CD82 was determined by immunofluorescent staining. RESULTS The NPC model was successfully established. Tumor growth was not suppressed when mice were injected with KAI1/CD82 EPCs (KAI1/CD82 EPCs group) compared with when non-transduced EPCs was present (EPCs group) or the control (1.485±0.234, 1.388±0.204, and 1.487±0.223g, respectively; P>0.05). However, the incidence of lung metastasis was significantly reduced in the KAI1/CD82+ EPCs group compared with the EPCs group and the control group (10%, 55% and 45%, respectively; P=0.005), and there was a significant decrease in the number of metastatic foci on the lung surface (17.50±3.54, 34.27±5.35, and 38.44±9.63 respectively; P=0.007). Moreover, KAI1/CD82 was expressed in lung metastatic foci of the KAI1/CD82 EPCs group, but not in the EPCs group and control group. CONCLUSIONS EPCs can be used as a delivery vehicle for suppressor genes KAI1/CD82 to NPC, and the migration of KAI1/CD82 genetically engineered EPCs can inhibit NPC lung metastasis in a mouse model.

目的 研究Kiss1对鼻咽癌转移能力的影响及其可能机制.方法 首先通过裸鼠鼻咽癌肺转移模型观察移植瘤与转移瘤中Kiss1的表达差异,继而通过transwell实验在细胞水平检测Kiss1细胞过表达后的侵袭转移能力的变化,通过qRT-PCR和western-blot检测MMPs家族的相关分子表达变化.结果 裸鼠实验发现Kiss1在肺转移瘤中的表达较移植瘤低,细胞实验发现过表达Kiss1后鼻咽癌细胞的转移能力降低,qRT-PCR和western-blot检测发现过表达Kiss1后MMP9表达降低.结论 通过动物实验论证Kiss1基因可抑制鼻咽癌细胞的侵袭转移.推测MMP9是Kiss1的下游靶基因,在Kiss1基因抑制肿瘤转移过程中发挥着重要作用.