The Study On Target Volume Definition And Clinical Application Of Three-dimensional Conformal Radiotherapy In Esophageal Carcinoma

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.