【作者】 马金波；

【导师】 于金明；

【作者基本信息】 山东大学 ， 临床医学， 2012， 博士

【摘要】 背景和目的文献显示肿瘤FDG代谢反应能够预测食管癌放疗的组织病理反应,但是各种临床试验应用的肿瘤FDG代谢反应参数是不同的,包括放疗后SUVmax (post-SUVmax)、放疗前后SUVmax降低的百分比(%DetaSUVmax),以及放疗前后由SUVmax确定的肿瘤病灶长度降低的百分比(△L)等,如何评价和分析这些参数存在着争论。该实验的目的是在相同的食管癌群体中,观察以上各种代谢反应参数在预测组织病理学反应的差异,并且观察根据代谢反应和组织病理学反应分层后生存曲线的区别。材料和方法共有60例适合入组的食管鳞癌患者接受了新辅助放化疗和食管切除术。治疗前和放疗后1周患者接受了两次18FDG-PET检查。计算代谢反应参数post-SUVmax、%DctaSUVmax和△L。按照以上参数post-SUVmax (3.0)、%DetaSUVmax(75%)和△L(33%)阂值对患者分层为完全代谢反应(CMR)和非完全代谢反应(non-CMR)。观察术后食管肿瘤标本病理反应,确定完全病理反应(CR)或者非完全病理反应(non-CR)。然后分析各项代谢反应参数预测病理反应的敏感性、特异性、阳性预测值和阴性预测值；观察按照代谢反应参数分层后的生存曲线和按照组织病理反应分层后的生存曲线的差异。结果在PET各项代谢参数中,%DetaSUVmax75%和△L33%均能够预测食管癌放疗后组织病理反应,其敏感性和特异性为91.6%、86.7%和81.4%、89.5%,且与患者局部控制时间、总生存时间相关(相关系数R：0.747/0.704和0.705/0.684,P<0.05)。多因素COX风险比例模型也支持该参数是预后因素(HR0.897和0.813,P<0.05)；并且这两个参数代谢反应生存曲线和组织病理反应的差异小。结论在食管癌放疗后各项代谢反应参数中,以%DetaSUVmax75%和△L33%预测组织病理反应为佳,且在生存曲线上比较符合。目的该项实验目的是研究接受后程加速超分割放疗的食管癌患者的生存时间和局部控制时间,是否与肿瘤FDG吸收值下降的百分比有线性相关性；并且确定从后程加速超分割放疗中获得增益者。方法共有50例合适入组的食管鳞癌患者接受了三次PET检查和后程加速超分割放疗方案,总放疗剂量为68.4Gy/41次6.5周。肿瘤FDG吸收值下降的百分比(%DeltaSUVmax)计算出后,按照常规照射方案中计算出%DeltaSUVmax对患者进行分层：高度敏感性组(HR)、中度敏感性组(MR)和低度敏感性组(LR)。然后统计患者的生存时间和%DeltaSUVmax之间的线性相关系数。患者分层后比较局部控制率和总生存率。结果只有在MR(中度敏感性)组,常规(照射)方案的%DeltaSUVmax和后程超分割方案的%DeltaSUVmax没有线性相关性(相关系数R<0.4,P值>0.05)。其他的放疗后%DeltaSUVmax与总生存时间和局部控制时间都有线性相关性(相关系数R>0.5,P值<0.05),包括HR组和LR组的常规方案和后程加速超分割方案%DeltaSUVmax之间。在HR、MR和LR组3年局部控制率分别是100%、81.5%和0%(P<0.001)；对HR、MR和LR组来说,3年总生存率分别为92.4%、58.8%和0%(P<0.001)。结论食管癌放疗后的肿瘤FDG吸收值下降百分比(%DeltaSUVmax)与患者的生存时间是相关的。只有常规照射方案后%DeltaSUVmax在30%-60%范围的患者,才能从后程加速超分割放疗中获益。目的同期放化疗累及野照射在治疗颈段和上胸段食管癌的可行性研究。材料和方法总共102例颈段和上胸段食管癌接受了同期放化疗,同期放化疗前1周所有的患者接受颈部超声和颈胸部CT检查。所有的病人被随机分到累及野照射组(IFI)和淋巴结选择性照射组(ENI)。放疗采用三维适形调强放疗,放疗剂量为59.4Gy/33/5.5周。患者接受放疗期间,同时给予2周期以顺铂为基础全身化疗。结果颈段和上胸段食管癌累及野照射和选择性淋巴结照射组总的毒性反应没有统计学意义(P=0.203)。但是血液学毒性包括感染(27.4%v64.7%)和呕吐反应(25.4%v54.9%)之间有统计学意义(P=0.008和0.028)。局部区域总失败率在累及野组和预防组分别为17.6%和13.7%,但没有统计学差异(P=0.837)。累及野组区域淋巴结失败率是9.8%,而淋巴结选择性照射组是7.8%(P=0.837)。累及野组野外淋巴结失败率为2%。淋巴结选择性照射组1-、2-和3-生存率分别是100%、84.0%和41.3%,而累及野组分别是100%、74.7%和32.0%(P=0.336)。在累及野组和淋巴结选择性照射组1-、2-和3年局部控制率分别是90.0%,、80.1%、80.1%和92.8%、92.8%、85.7%(P=0.583)。结论累及野照射不是颈段和上胸段食管癌区域淋巴结失败的重要预后因素。因此累及野照射是颈段和上胸段食管癌放疗可接受的放疗方式,且毒性反应较低。更多还原

【Abstract】 Background And Purpose Published literatures indicated that metabolic response of tumor18F-FDG is able to predict histopathologic response after chemoradiation in esophageal cancer. But all kinds of metabolic parameters and thresholds vary from different clinical trials, including post-radiation SUVmax (post-SUVmax), a decrease percentage of SUVmax on pre-and post-radiation (%DetaSUVmax), and a change percentage of tumor length according to SUVmax (△L), et al. Disputes exist in how to evaluate and analysize the indexes and values. The aim of this trial is to observe the differences about the parameters predicting histopathologic response and survival curve of these after stratification patients according to histopathologic and metabolic response.Material and Methods A total of60patients with squamous esophageal cancer were enrolled in this trial. All patients received chemoradiation followed by esophagectomy and18FDG-PET examination twice on pre-and post-radiation. Then metabolic indexes post-SUVmax,%DetaSUVmax and△L are calculated and all patients are classified to metabolic complete response (CMR) or metabolic nonresponse (non-CMR) according to post-SUVmax3.0,%DetaSUVmax75%and△L33%. Histopathologic response in esophageal sections was observed to determine and classify to pathologic complete response (CR) or pathologic non-response (non-CR). Survival curves were compared to the difference after classification according to histopathologic and metabolic response.Results For all kinds of PET-based indexes, only%DetaSUVmax75%and△L33%predicted histopathologic response and correlated to local control time and overall survival time (Correlation coefficient R:0.747/0.704and0.705/0.684, P<0.05). And the accuracy is higher with the the sensitivity91.6%and81.4%and the specificity86.7%and89.5%. Analysis of Cox Proportional Hazards Model for overall survival and local control indicated that two parameters had a significant survival advantage (hazard ratio [HR]=0.897and0.813, P<0.01). Survival curve after stratification according to a threshold of75%of%DetaSUVmax was minor difference to that of histopathologic response.Conclusion%DetaSUVmax75%and△L33%in all metabolic indexes were optical to predict the histopathologic response, with a minor difference in survival curve after stratification. Objective The aim of this trial was to study whether a decrease percentage of tumor FDG uptake correlate with overall survival and local control times for patients with esophageal cancer, and who would benefit from a late-course accelerated hyperfractionated (LCHF) radiation scheme.Material and Methods A total of50eligible patients with squamous esophageal cancer received PET examination three times and were treated with the LCHF radiation scheme with a dose of68.4Gy/41fractions in6.5weeks. A decrease percentage of FDG uptake (%DeltaSUVmax) was calculated and patients were stratified into high radiosensitive (HR), moderate radiosensitive (MR) and low radiosensitive (LR) subgroups according to%DeltaSUVmax in the CF scheme. Then a linear correlation was calculated between patients’survival time and%DeltaSUVmax. Local control and overall survival were compared after stratification.Results Only in the MR subgroup there was no linear correlation for%DetaSUVmax between the CF and LCHF scheme (Correlation coefficients R<0.4, P values>0.05). And other%DeltaSUVmax after radiation correlated to overall survival or local control times (Correlation coefficients R>0.5, and P value<0.05), including between the CF and LCHF scheme in the HR and LR subgroups.3-year local control rates in the HR, MR and LR subgroups were100%,81.5%and0%respectively (P<0.001). And3-year overall survival rates were92.4%,58.8%and0%for HR, MR and LR subgroups respectively (P<0.001).Conclusion%DetaSUVmax on postradiation positively correlated to patients’survival time for esophageal cancer. Patients who benefited from LCHF schedules were patients with a30%-60%decrease of tumor FDG uptake after the completion of CF radiation. Objective To investigate the feasibility of involved-field irradiation (IFI) for the treatment of cervical and upper-thoracic esophageal cancer with concurrent chemoradiation.Material and Methods A total of102eligible patients with cervical and upper-thoracic esophageal cancer were treated with concurrent chemoradiation and randomized into either an IFI or elective nodal irradiation (ENI) group. Before chemoradiation, PET/CT scan was used to all patients. All patients received a dose of59.4Gy/33fractions in5.5weeks. A total of2cycles of cisplatin-based chemotherapy were delivered for patients.Results Total acute toxicities didn’t reach a statistical significance for the IFI versus the ENI group(P=0.203), but hematologic toxicity included infect ion (27.4%v64.7%) and nausea (25.4%v54.9%)were a statistical significance group(P=0.008and0.028). There was no statistical difference for late radiation reaction. The cumulative incidence of local/regional failure (13.7%v17.6%) was lower in the ENI versus the IFI group in three years, with no statistical significance(P=0.837). Regional lymph failure was9.8%for the IFI group versus7.8%for the ENI group(P=0.837). And out-field lymph failure only2%for the IFI group. The1-,2-, and3-year survival rates were100%,84.0%, and41.3%for the ENI group, and100%,74.7%, and32.0%for the IFI group, respectively (P=0.336). The1-,2-, and3-year local control rates were90.0%,80.1%, and80.1%in the IFI group, and92.8%,92.8%, and85.7%in the ENI group(P=0.583), respectively.Conclusion IFI as treatment for cervical and upper-thoracic esophageal cancer did not cause significant failure in lymph node regions. IFI remains an acceptable and toxicity-minimizing method of treatment.更多还原