Three dimensional conformal radiation therapy is promising advance in radiation therapy that affords the potential of decreased toxicity in the management of esophageal cancer.This article reviewed the current approaches to achieving the desired dose to the esophagus and regional lymph nodes,with an emphasis on the does constraints to adjacent normal structures,particularly the heart and lungs.The delineation of target is also explored.

Background and purpose: Alternative splicing is an important regulation mechanism of gene expression. Aberrant alternative splicing is associated with dysregulation of the cell cycle, activation of oncogenes and inactivation of the tumor suppressor genes. Thus, it is closely correlated with the pathogenesis and progression of various tumors. DNA methylation is an important part of epigenetic phenomena. Aberrant methylation of the gene promoter can result in gene silencing. Hypermethylation of tumor suppressor genes and DNA repair genes correlates with the onset of many different cancers. Additionally, DNA methylation acts as a pivotal factor for alternative splicing. Aberrant methylation disrupts the stabilization of the alternative splicing. This study investigated the promoter methylation and expression of RNA binding protein, fox-1 homolog 1 (RBFOX1) gene in esophageal squamous cell carcinoma (ESCC), and to elucidate its role in ESCC. Methods: MassARRAY approach and RT-PCR were used respectively to examine the methylation level of RBFOX1 gene and its expression at mRNA level in tumors and corresponding adjacent normal tissues. The correlation between methylation level and clinicopathological features was analyzed. Results:RBFOX1 methylation level and mRNA expression in tumor tissues were signiifcantly lower than those in corresponding adjacent normal tissues (41.8% vs 68.3%, P<0.01). No significant correlation was observed between methylation level and clinicopathological features. The cut-off (33.6%) was calculated as the mean of the normal samples to which we applied 2.5 SD. According to the cut-off value, the object of the study was divided into two groups. The methylation level lower than the cut-off was deifned as group 1;methylation level higher than the cut-off was deifned as group 2. The 5-year overall survival rates of the two groups were 57.0%and 35.7%, respectively (P=0.06);5-year progression-free survival rates were 48.7%and 28.9%, respectively (P=0.03). However, the multivariate analysis results indicated that TNM stage was the independent factor of prognosis.Conclusion: The methylation level and mRNA expression of RBFOX1 in tumor specimens are signiifcantly lower than those in corresponding adjacent normal tissues. The methylation level of the RBFOX1 promoter is not an independent factor of prognosis.

The diagnosis of local recurrence after radiochemotherapy for esophageal cancer requires the combination of multiple imaging methods (esophageal X-ray,computed tomography,endoscopic ultrasonography,and positron emission tomography-computed tomography),dynamic changes in esophagoscopy,and biopsy.The main treatment of recurrence includes salvage surgery,radiochemotherapy,endoscopic mucosal resection,and chemotherapy.The overall survival rate after the above treatment is improved compared with palliative care but still unsatisfactory.Early diagnosis of recurrence is fundamental for improved treatment outcomes.

Background and purpose:It may improve local control to increase radiation dose for esophageal cancer.The purpose of the study is to obtain the maximum tolerance dose(MTD)and assess toxicity of 3-D conformal radiation therapy(3-DCRT)for esophageal cancer.Methods:The scheduled dose escalation ranged from 70 Gy to 76 Gy.All patients received conventional fractionation irradiation to a dose of 46 Gy/23 Fx/4.5 weeks,followed by accelerated hyperfractionation irradiation using reduced fields,1.5 Gy twice a day,to a dose of 24 Gy/16 Fx.The criteria for stopping dose escalation was grade ≥3 radiation-induced toxicity in ≥15% patients.Results:From July,2000 to July,2001,18 patients were enrolled.Five patients completed a total dose of 70 Gy and an additional 5 patients received 73 Gy.Eight patients completed a total dose of 76 Gy.No patient occurred grade ≥3 radiation-induced toxicity at the level of 70 Gy.Four patients(80%)experienced grade ≥3 radiation-induced late toxicity(2 patients died of late radiation-induced pneumonitis)at the level of 73 Gy.Five patients(62.5%)experienced grade ≥3 radiation-induced acute toxicity and 6 patients(75%)had grade≥3 late toxicity(1 patients died of late radiation-induced esophagitis,and 2 patients died of late radiation-induced pneumonitis)at the level of 76 Gy.Conclusions:Based on the clinical trial,there were more severe radiation-induced toxicities when the patients with esophageal cancer received more than 70 Gy.

Objective To define the prognostic factors and local failure in late course accelerated hyperfractionation radiotherapy(LCAHR) for esophageal carcinoma.Methods A retrospective study was conducted in 201 esophageal squamous cell carcinoma patients treated by LCAHR during the period between August 1994 to January 2000.The radiotherapeutic portals were set and based on CT scan and esophagograms. All patients received a mean dose of 41.4 Gy /23 F/4～5 WK. With conventional fractionation regimen during the first two thirds of the course,and followed by LCAHR with reduced fields, at dose of 27 Gy/18 d,1.5 Gy per fraction,twice daily. The total dose varied up to 67～70 Gy/40～43 F/40～49 d. Results The 1 ,3 and 5 year actuarial survivals were 72.5% ,35.6% and 31.1%. The 1 ,3 and 5 year local control rates were 82.2%, 71.3% and 71.3%,respectively. Of the 95 patients who died, 34(35.8%) did so from local failure , 32(33.7%) from distant metastasis(33.7 %), 13(3.7%) from lymphatic metastasis, 4(4.2%) frome both local and distant metastasis and 12(12.7%) from complications.Conclusions It is showed that significant improvement in local control and survival are observed after LCAHR for esophageal carcinoma in comparison to conventional fractionated regimen. The prevention and management of distant metastasis and lymphatic spread have become the major problems in the future.

With the development of molecular biology,the study of biological markers will probably help to predict the prognosis and to improve the method of treatment and the survival. Advances in biological markers of esophageal cancer prognosis were reviewed. [

Purpose:To compare the survival and toxicities of concureent chemoradiotherapy followed by adjuvant chemotherapy in patients with N1 esophageal carcinoma. Analysis was made for reasons of failure in the patients with N1 esophageal carcinoma. Methods:From August 1998 to August 2000,65 eligible patients with N1 esophageal carcinoma were randomized into the following arms: 33 patients were randomized to concurrent chemoradiotherapy arm, 32 patients to radiotherapy followed by chemotherapy. The schedules of radiotherapy were the same, which were conventional fractionation, total dose 60～70 Gy. The regimen of chemotherapy all consisted of DDP and 5 FU,4 cycles. It started on the first day of radiotherapy, and 15 days after radiotherapy chemoradiotherapy was given. Results:The survival rates at 1,2 and 3 years were 60.2%,43.5% and 25.9% in the concurrent chemoradiotherapy arm, 66.3%, 22.5% and 11.3% in the radiotherapy followed by chemoradiotherapy arm, respectively ( P =0.109). 18.2% in the radiotherapy followed by chemoradiotherapy arm had grad Ⅲ esophagitis, while the concurrent group had 43.7% P

Objective To study the clinical results and prognostic factors of late course accelerated hyperfractionation radiotherapy (LCAHR) in the treatment of esophageal carcinoma in the elderly. Methods 105 over 60 year-old patients with esophageal carcinoma who received radical LCAHR, were retrospectively analysed. Radical tumoricidal dose of 67.9～72.0?Gy was delivered in 39～43 fractions over 42～53 days. Results The 5-year local control rate was 63.7%. The 5-year disease-free survival and overall survival rate were 22.6% and 34.4%. Acute esophagitis and bronchitis were the most common but acceptable radioreactions Grade 1～2. No significant differences were found either in the clinical response or complication, between the 60～69 year and 70～80 year groups. By multivariate analysis, T stage and KPS score were two independent prognostic factors. Of 67 death cases, 31 died of local relapse, 23 of distant metastases, 8 of both and 5 of other causes. Conclusions LCAHR toxicity ,being tolerable for the older esophageal carcinoma patients,may improve their survival and quality of life.

Background and purpose: With the increase of aging population, elderly patients (age ≥70 years) with esophageal squamous cell carcinoma occurred more and more. However, few studies have focused on elderly esophageal squamous cell carcinoma patients. This study aimed to assess the outcomes and prognostic factors for elderly patients with esophageal squamous cell carcinoma treated after deifnitive chemoradiotherapy. Methods:We retrospectively analyzed 53 patients (age≥70 years) with esophageal squamous cell carcinoma and treated with deifnitive radiotherapy with or without chemotherapy from Fudan University Shanghai Cancer Center from Mar. 2009 to Dec. 2011. Results:Median age was 74 years. Twenty-nine patients underwent radiotherapy, 24 patients underwent radiochemotherapy. 1-, 2-, 3-, and 5- year survival was 62%, 44%, 33% and 19% respectively. Grade 2 and above acute radiation-induced esophageal toxicity and radiation pneumonitis occur rate was 6% and 9% respectively. No treatment-related deaths occurred and no patients experienced any grade 4 and above toxicities. Multivariate analysis identiifed treatment modality, tumor site and smoking history as independent prognostic factors for overall survival. Conclusion:Radiotherapy may be an acceptable treatment option for elderly patients with esophageal squamous cell carcinoma. In appropriately selected patients, concurrent chemotherapy could bring a better overall survival.

Objective To study the effect of different dose fractionation on overall survival in patients with limited-stage small cell lung cancer (LS-SCLC). Methods LS-SCLC patients treated with radical combined chemotherapy and radiotherapy (RT) between January 2001 and Dec 2007 were analyzed retrospectively. According to the dose fractionation schemes, patients were divided into three groups:conventional fractionated RT (1. 8 -2.0 Gy,once daily), hyperfractionated RT (1.4 Gy, twice daily) and hypofractionated RT (2. 5 Gy,once daily). Overall survival, disease free survival and pattern of failures of the three groups were compared. A total of 177 patients were enrolled, including 63 patients in conventional fractionated RT group, 79 in hyperfractionated RT group and 35 in hypofractionated RT group. Results The overall follow-up rate was 96. 6%. The patient numbers with follow-up of more than 2 and 5 years were 153 and 92, respectively. The median survival time of the entire group was 22. 4 months, and the 2-and 5-year survival rates were 43.4% and 23. 5%, respectively. The 2-year survival rates for three groups were 31%, 46% and 59% (x2 =7.94,P=0.019), respectively. The 2-year disease free survival for three groups were 20%, 31% and 40% ( x2 = 4. 86, P = 0. 088 ), respectively. In the pairwise comparisons,patients in hypofractionated RT group have better survival than those in conventional fractionated RT group ( x2 = 7. 81, P = 0. 005 ), the effect of hyperfractionated RT group lies between the hypo-and the conventional fractionated RT groups, but no significant differences were detected ( x2 = 2. 31, P = 0. 128; x2 = 2. 95, P =0. 086). The mildest side effect was found in the hypofractionated RT group. No statistically significant differences were found in the patterns of first failure. Conclusion The hypofractionated RT scheme showed potential survival benefits for patients with LS-SCLC and should be considered in the setting of randomized clinical trials.