【作者】 宋轶鹏；

【导师】 胡立宽；

【作者基本信息】 山东大学 ， 肿瘤学， 2011， 博士

【摘要】 第一部分食管癌三维适形放射治疗靶区勾画的相关研究第一部分A病理特征在食管鳞癌放射治疗临床靶区外放边界确定中的价值目的研究食管鳞癌镜下浸润转移的特点及临床病理特征对其影响,为食管鳞癌放射治疗临床靶体积(CTV)边界的确定提供参考依据。方法根据每个标本的收缩比计算食管组织在体时每厘米(cm)长度对应的固定后长度并取材,观察64例食管鳞癌标本大体肿瘤外纵向每cm范围浸润转移情况。并用统计学方法分析临床病理特征与肿瘤浸润转移间的关系。结果1.大体肿瘤外纵向每cm长度浸润转移阳性率随着距肿瘤边缘距离的增加而降低,近端和远端3cm组出现浸润转移的概率分别为4.8%和6.9%,4cm组分别为3.6%和3.6%；2.近端浸润转移率(53.1%)高于远端(32.8%),差异具有统计学意义(P<0.05),主要体现在lcm组和2cm组。3.单变量分析显示：肿瘤长度>5cm、分化程度低、有淋巴结转移及T3期病例浸润转移发生率高(P<0.05)；多因素分析显示：分化程度及肿瘤长度是影响食管鳞癌浸润转移的主要因素(P<0.05)。结论食管鳞癌精确放疗若要包括95%的浸润转移病灶CTV应在GTV基础上纵向上放3cm、下放4cm,若要包括90%的浸润转移病灶则需在GTV基础上上、下均外放3cm。食管鳞癌组织有易于上行浸润转移的倾向性。此外,靶区勾画时要综合考虑病理特征对靶区范围的影响。第一部分B18FDG PET-CT判断食管癌转移淋巴结价值荟萃分析目的评价18FDG PET-CT判断食管癌患者区域转移淋巴结的价值。方法计算机检索从1990年1月到2010年3月的18FDG PET-CT相关原始文献。金标准为病理分析。两人独立搜索文献和提取数据。利用meta-disc软件汇总计算出18FDG PET-CT的敏感性、特异性、诊断优势比,并绘制SROC曲线探讨其总的诊断效能。结果8篇文献纳入此meta分析。基于单个淋巴结组分析,汇总的18FDG PET-CT的敏感性、特异性和Q值及95%可信区间分别为0.752(0.707-0.793)、0.969(0.960-0.976)和0.9161(0.8747-0.9575)。基于单个淋巴结分析,汇总的18FDG PET-CT的敏感性、特异性和Q值及95%可信区间分别为0.826(0.747-0.889)、0.958(0.941-0.971)和0.9205(0.8856-0.9554)。结论：18FDG PET-CT判断食管癌区域转移淋巴结具有较高的特异性和准确性。第二部分食管癌三维适形放射治疗临床应用的相关研究第二部分A三维适形大分割照射治疗临床T3-4N0-1M0期食管癌的Ⅰ-Ⅱ期研究目的相对于常规分割剂量放疗,大剂量分割放疗能够提高肿瘤杀伤效应。然而,目前局部区域进展期食管癌大分割放疗临床试验较少。本研究的目的是评价大分割三维适形放疗治疗临床分期为T3-4N0-1M0食管癌的有效性和治疗毒性。方法从2003年9月到2005年12月共有45名患者进入该研究,方案为通过三维适形放疗技术的组间分次剂量递增研究。在3-4周时间内给予总放疗剂量为50-54Gy(组间分次剂量从3Gy递增到6Gy,每周3次),同时患者接受4周期全身化疗。结果生存者的中位随访时间为38个月。1.分次剂量3-5Gy组,患者的耐受率为78.8%。21.2%患者出现3级以上急性毒性反应。2.分次剂量6Gy组,患者的耐受性较差(55.6%)。3.患者1年、2年、3年总的局部控制率分别为62%、49%、31%。1年、2年、3年的总生存率分别为34%、21%、9%。中位总生存时间为17个月。4.随访过程中13(31.0%)名患者出现食管晚期并发症,主要包括食管穿孔、出血、狭窄或者初始狭窄加重。结论大分割照射治疗临床T3-4N0-1M0食管癌是可行的。分次剂量≤5Gy对食管癌大分割照射相对合适,患者耐受性较好,但仍需进一步研究。第二部分B泰欣生联合同期放化疗治疗局部进展期食管癌近期疗效目的观察泰欣生联合同期放化疗治疗局部进展期食管癌的近期疗效和毒副反应。方法2009年1月～2010年12月共21例局部进展期食管癌患者接受同期放化疗联合泰欣生治疗,并与同时期接受同期放化疗的21例患者非随机对照分析。放疗方案为调强适形放疗,同期加量,PTV处方剂量50.4Gy/28f, PGTV处方剂量60Gy/28f。治疗组在放疗的第1～5天、第22～26天接受氟尿嘧啶化疗,500mg/m2/d,在放疗的第1～3、第22～24天接受顺铂化疗,20mg/m2/d,在放疗的第1天接受泰欣生200mg,以后每周1次至放疗结束,剂量不变,配对组放化疗方案与治疗组相同,未联合应用泰欣生。记录治疗急性毒副反应,评价近期疗效。结果治疗组患者完全缓解率、总有效率分别为47.6%、85.7%；对照组患者完全缓解率、总有效率分别为38.1%、71.4%,两组间疗效无统计学差异。急性毒副反应主要为食管炎、骨髓抑制,发生率和严重程度两组间无显著差异。泰欣生相关急性副反应轻,发生率低,未增加放化疗的急性毒副反应。结论同期放化疗联合泰欣生治疗局部进展期食管癌近期疗效较好,泰欣生未增加放化疗的急性毒副反应。长期的疗效、毒副反应有待长期随访结果。更多还原

【Abstract】 Part IThe study on target volume definition in three-dimensional conformal radiotherapy of esophageal carcinomaPart I AThe value of pathological features in defining the longitudinal margin of the clinical target volume in radiotherapy of esophageal squamous-cell carcinoma.Objective To study the characteristics of microscopic spread of esophageal squamous-cell carcinoma (ESCC) and the influence of clinicopathological features on it to help define the clinical target volume (CTV) margin in radiotherapy.Methods 64 surgical specimens of ESCC were observed for microscopic spread per centimeter extent both proximally and distally along from the margin of the gross tumor. The shrinkage ratio of each specimen after fixation which was exactly equal to the length of 1cm in vivo was calculated and used for tissue incision. Statistical method was used to analyze the relationship between clinicopathological features and microscopic spread.Results 1. The further the distance there was beyond the tumor, the lower the incidence there was of microscopic spread. Positive ratios of microscopic spread in group 3cm both proximal and distal were 4.8% and 6.9%, respectively, and in group 4cm were both 3.6%.2. Ratio of microscopic spread proximally(53.1%) was statistically higher than that of distally(32.8%)(P<0.05), which mainly showed in group lcm and group 2 cm.3. Univariate analysis showed that tumors longer than 5cm in length* with poorer differentiation, lymph nodes metastasis and more aggressive phase had higher positive ratios(P<0.05). Multiplicity methods showed that differentiation and tumor length were main factors contributing to microscopic spread. Conclusions To cover 95% of the microscopic spread, a margin of 3.0cm proximal and 4.0cm distal beyond gross tumor volume is needed and as to 90%, a margin of 3.0cm both proximal and distal is needed in radiotherapy of ESCC. It seems that microscopic spread is much more likely to happen upward than downward in ESCC. Moreover, the influence of pathological features should be taken into account when target volume is being delineated. Key words Esophageal neoplasms; Radiotherapy; Clinical target volume; Pathological featuresPartⅠBValue of FDG PET-CT for metastatic regional lymph nodes in patients with esophageal cancer. A meta-analysisObjective To evaluate the value of 18FDG PET-CT for detection of metastatic regional lymph nodes in patients with esophageal cancer.Methods A computer search about 18FDG PET-CT original articles was conducted from January 1990 to March 2011. The reference standard was histopathologic analysis. Two reviewers independently searched articles and extracted data. Sensitivity, specificity, and diagnostic odds ratio were pooled using a software called "Meta-Disc". Summary receiver operating characteristic (SROC) curves were also used to summarize overall test performance.Results Eight articles were included in this meta-analysis. The pooled sensitivity, specificity and Q index with 95% confidence interval for FDG PET-CT on a group-based analysis of lymph nodes were 0.752(0.707-0.793),0.969 (0.960-0.976), 0.9161(0.8747-0.9575), respectively. Corresponding values for 18FDG PET-CT on a single-based analysis of lymph nodes were 0.826(0.747-0.889),0.958(0.941-0.971) and 0.9205 (0.8856-0.9554).Conclusions 18FDG PET-CT has higher specificity and accuracy for detection of metastatic regional lymph nodes in patients with esophageal cancer.PartⅡThe study of the clinical application of three-dimensional conformal radiotherapy in esophageal carcinomaPartⅡAPhaseⅠ/Ⅱstudy of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinomaObjective Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.Methods From September 2003 to December 2005,45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3DCRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54Gy (fractionated dose of from 3.0 to 6.0Gy,3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy.Results The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5Gy. There are 21.2% patients occurring Grade≥3 acute toxicities. But patients couldn’t tolerate daily dose of 6Gy (55.6%). The 1-year,2-year and 3-year local control rates were 62%, 49% and 39%, respectively. And the 1-year,2-year and 3-year overall survival rates were 34%,21% and 9%, respectively. The median overall survival time was 17 months. At the time of following up,13patients(31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggrevation.Conclusion Hypofractionated irradiation is thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of≤5Gy is comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also. Key words Esophageal neoplasms; Radiotherapy; Hypofractionated irradiation; RradiotoxicityPartⅡBConcurrent chemoradiation combined with nimotuzumab treatment of locally advanced esophageal carcinomaObjective To observe the recent efficacy and toxicities of concurrent chemoradiation combined with nimotuzumab treatment of locally advanced esophageal carcinoma.Methods From January 2009 to December 2010,42 patients with locally advanced esophageal carcinoma were nonrandomized to the trial group and the control group and received concurrent chemoradiation combined with nimotuzumab and concurrent chemoradiation, with every group 21 patients. Radiation scheme was concurrent dose-escalating intensity-modulated radiation therapy with the prescribed doses of PTV 50.4Gy/28 fractions, and PGTV 60Gy/28 fractions. Chemotherapy scheme consisted of 500mg/m2 of 5-fluorouracil dl-5,22-26 plus 20mg/m2 of cisplatin dl-3,22-24. Then nimotuzumab was performed 200mg weekly from first day of radiation to the completion of radiation in the trial group. Recent efficacy and toxicities were observed and evaluated.Results Complete response and the effective rates were 47.6%,85.7% and 38.1%, 71.4% in the trial and control groups, without statistically significant difference. Acute toxicities were mainly radiation-related esophagitis and bone marrow depression with nimotuzumab minor treatment-related toxicities. Conclusions There is good efficacy of concurrent chemoradiation combined with nimotuzumab treatment of locally advanced esophageal carcinoma without the increase of acute treatment-related toxicities for nimotuzumab. But long-term survival and late reacts would be further observed.更多还原