Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.     

Induction of DNA-double-strand breaks by auger electrons from 99mTc complexes with DNA-binding ligands

The potential of certain Auger electron emitting nuclides for systemic radiotherapeutic applications has recently gained much attention. In particular, the ability of several nuclides, including 111In, 125I, and 123I, to induce DNA double-strand breaks (dsb), a good indicator of cytotoxicity, has been extensively studied. However, this ability has never previously been shown experimentally for 99mTc, which, besides the well-known gamma radiation that is used for diagnostic applications, also emits an average of 1.1 conversion electrons and 4 Auger or Coster-Kronig electrons per decay. Owing to the short range of Auger electrons, the radionuclide needs to be located very close to the DNA for dsb to occur. We synthesized two cationic 99mTcI-tricarbonyl complexes with pendant DNA binders, pyrene and anthraquinone. The X-ray crystal structures of the two complexes could be elucidated. Linear dichroism and UV/Vis spectroscopy revealed that the complex with pyrene intercalates DNA with a stability constant, K, of 1.1 x 10(6) M(-1), while the analogous complex with anthraquinone interacts with DNA in a groove-binding mode and has an affinity value of K=8.9 x 10(4) M(-1). We showed with phiX174 double-stranded DNA that the corresponding 99mTc complexes induce a significant amount of dsb, whereas non-DNA-binding [TcO4]- and nonradioactive Re compounds did not. These results indicate that the Auger electron emitter 99mTc can induce dsb in DNA when decaying in its direct vicinity and this implies potential for systemic radiotherapy with 99mTc complexes.     

一种应用于RTPS的轮廓线修改算法

放射医疗技术中,放射治疗计划系统对CT、MRI等医学影像数据进行处理,以获得体表、器官等医生所关注区域的轮廓,这是进行最终放射剂量计算的重要基础。文章针对自动提取或手动勾画的感兴趣区域的轮廓,提出并实现了一种修改算法。该算法可对自动提取不准确和勾画不正确的区域轮廓线进行修改,以达到用户预期的效果。算法实现方便,运行交互性好,能满足放射治疗计划系统的要求。     

Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes with amino acid ligands

We have synthesized and fully characterized four new complexes comprising the fac-[Re(CO)3]+ moiety and the ligands NH3, L-proline (Pro), or N,N-dimethylglycine (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives trinuclear complexes of general formula [Re(L)(CO)3]3 (where L = amino acid). We have studied the in vitro behavior of these compounds with guanine and DNA in order to understand whether the cytotoxicity exhibited by certain rhenium complexes based on the fac-[Re(CO)3]+ core is due to the formation of nucleobase complexes and inter- or intrastrand links between DNA bases. We have performed model studies with guanine and studied the structural effects induced by different rhenium(I) tricarbonyl complexes on PhiX174 plasmid DNA by electrophoretic methods. Our results show that rhenium complexes with two available coordination sites interact with plasmid DNA to form a stable adduct that is likely to involve two bases.     

用于放疗量传的照射量、空气比释动能和水吸收剂量量值体系比较

用照射量和空气比释动能校准的电离室进行剂量测量时,依据IAEA TRS 277报告,需要经历四级量值转换过程,不确定度也较大,但目前仍是国内使用的量值体系.我国正在建立60Co γ射线以及高能光子下的水吸收剂量基准装置并进行国际比对,之后将拥有水吸收剂量的量值复现的能力.在60Co γ射线参考辐射场和加速器高能X射线辐射场下,使用NE2571和NE2570/1A、PTW TW30013和PTW UNIDOS两套电离室剂量仪,分别按照277和398报告的要求计算并比较2种方法计算出的水吸收剂量值,从而验证了277报告和398报告的一致性.     

放疗病人信息管理系统的设计与实现

癌症是严重威胁人民生活健康的主要疾病。放射治疗的效果评价,放疗病人预后观察,影响放疗的危险因素探讨,都需要建立一个严密而完善的放射治疗病人资料的数据库。放疗病人计算机管理信息系统主要实现医院肿瘤放疗病人的相关信息管理。放疗病人计算机管理系统的实现,为肿瘤患者看病提供方便,也为医生和医学研究人员收集肿瘤患者资料提供了一个好的平台。     

Therapeutic Vaccines for HPV-Associated Oropharyngeal and Cervical Cancer: The Next De-Intensification Strategy?

The rise in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has prompted a quest for further understanding of the role of high-risk HPV in tumor initiation and progression. Patients with HPV-positive OPSCC (HPV+ OPSCC) have better prognoses than their HPV-negative counterparts; however, current therapeutic strategies for HPV+ OPSCC are overly aggressive and leave patients with life-long sequalae and poor quality of life. This highlights a need for customized treatment. Several clinical trials of treatment de-intensification to reduce acute and late toxicity without compromising efficacy have been conducted. This article reviews the differences and similarities in the pathogenesis and progression of HPV-related OPSCC compared to cervical cancer, with emphasis on the role of prophylactic and therapeutic vaccines as a potential de-intensification treatment strategy. Overall, the future development of novel and effective therapeutic agents for HPV-associated head and neck tumors promises to meet the challenges posed by this growing epidemic.     

鼻咽癌放射治疗对听力的影响

本文探讨鼻咽癌患者放疗后对听力的影响,着重测试放疗前、放疗后鼻咽癌患者的听力变化。结果表明：放疗对内耳感音功能无明显影响,而对中耳传音功能有明显的改善作用。使听力得以恢复。     

Androgen Receptor Gene Pathway Upregulation and Radiation Resistance in Oligometastatic Prostate Cancer

Stereotactic ablative body radiotherapy (SABR) is currently used as a salvage intervention for men with oligometastatic prostate cancer (PC), and increasingly so since the results of the Stereotactic Ablative Body Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers (SABR-COMET) trial reported a significant improvement in overall survival with SABR. The addition of androgen deprivation therapy (ADT) to localised prostate radiotherapy improves survival as it sensitises PC to radiotherapy-induced cell death. The importance of the androgen receptor (AR) gene pathway in the development of resistance to radiotherapy is well established. In this review paper, we will examine the data to determine how we can overcome the upregulation of the AR pathway and suggest a strategy for improving outcomes in men with oligometastatic hormone-sensitive PC.     

子宫下段受累可能为Ⅰ期内膜癌辅助放疗的不良预后因素

目的　探讨子宫下段受累对Ⅰ期子宫内膜癌术后放疗患者的预后作用。方法　回顾性分析1999年1月至2012年12月在北京协和医院进行术后放疗的Ⅰ期子宫内膜癌患者265例，中位年龄53岁，病理类型主要为子宫内膜样腺癌(226例，85.3％)。根据病理结果是否有子宫下段受累分为两组：子宫下段受累组和子宫下段未受累组，比较两组患者的预后因素和临床治疗结果，并对其中的高危和高中危患者进行亚组分析。主要研究终点包括总生存率、无进展生存率、局部区域复发率、远处转移率和治疗失败率。使用Kaplan-Meier法统计生存率，不同组间生存率的比较使用Log-rank检验，使用Cox比例风险回归模型进行预后因素分析。结果　所有Ⅰ期内膜癌患者的5年总生存率和无进展生存率分别为92.8%和89.7%，5年局部区域复发率、远处转移率和治疗失败率分别为4.5%、6.4%和7.8%。单因素分析显示，子宫下段受累是影响总生存率和无进展生存率的相关因素（P= 0.015,0.035）。Cox比例风险回归模型显示，子宫下段受累组患者的总生存率和无进展生存率更低（P=0.041, RR=0.346, 95% CI: 0.125~0.959; P=0.041, RR=0.411, 95% CI: 0.175~ 0.963）。亚组单因素分析显示，在高危和高中危患者中，子宫下段受累是影响治疗失败率的相关因素（P=0.034）。结论　子宫下段受累可能是影响Ⅰ期内膜癌辅助放疗患者总生存率和无进展生存率的不良预后因素；在高危和高中危患者中，子宫下段受累主要与治疗失败的发生相关。