Radiotherapy Combined With Targeted Therapy And Prognositic Biomarkers For Esophageal Squamous Cell Carcinoma Intraoperative Radiotherapy For Abdominal Carcinoma

Purpose Concurrent chemoradiotherapy is the standard care in the treatment of patients with locally advanced esophageal squamous cell carcinoma, but at the expense of increased toxicities. There are quite a number of patients who can not tolerate chemoradiotherapy due to their old age or malnutrition. Erlotinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, was effective in treating esophageal carcinoma with mild toxicities. This pilot study is to investigate the safety and efficacy of concurrent erlotinib and radiotherapy for esophageal carcinoma patients who can not tolerate chemoradiotherapy, which may provide an alternative treatment model.Methods Pathologically diagnosed esophageal squamous cell carcinoma patients who need but could not tolerate current chemoradiotherapy were enrolled. All patients were treated with concurrent erlotinib and intensity-modulated radiation therapy. Erlotinib was given orally150mg per day for60days. Radiotherapy of60Gy was given by30times2Gy. Immunohistochemical staining was performed to assess epidermal growth factor receptor expression. Toxicities were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events3.0. The overall survival, progression free survival and local-regional relapse free survival were calculated using the Kaplan-Meier method.Results Between December2007and March2011, eighteen patients were enrolled. The median age was71.5years. The primary disease was stage Ⅱ, Ⅲ and Ⅳ in3,8and4patients, respectively. There were3patients with recurrent disease after radical surgery. The median follow up time was17.2months. Grade3esophagitis and skin rash were observed in5(27.8%) and2patients (11.1%), respectively. Radiation pneumonitis of grade2and5was observed in one patient each. No grade3/4impaired liver function or hematological toxicity was observed. At one month post-radiotherapy, there were2(11.1%) complete response,11(61.1%) partial response and5(27.8%) stable disease. The median time of overall survival and progression free survival were21.1and12 months, respectively. Two-year overall survival, progression free survival and local-regional relapse free survival were44.4%,38.9%and66.7%, respectively. Five of6patients examined for epidermal growth factor receptor expression had3+. The relationship between epidermal growth factor receptor expression and treatment results could not be concluded.Conclusions For esophageal squamous cell carcinoma patients who need but can not tolerate chemoradiotherapy, concurrent erlotinib and radiotherapy is tolerable and effective. Valuable markers to predict the effect of erlotinib should be exploited in the future study. Purpose Radiotherapy or che mo radiotherapy is the main treatment for locally advanced esophageal squamous cell cancer, but at expense of severe toxicities. Some patients are also resistant to chemoradiotherapy treatment. Early prediction of chemoradiotherapy efficacy can identify resistant patients to receive other optimal therapy, thus avoid the damage from toxicities of chemoradiotherapy treatment. MicroRNAs (miRNAs) are closely related with tumor genesis, diagnosis and prognosis. Serum miRNAs, steadily expressed and easily to test, are expected to be ideal markers in predicting chemoradio-therapeutic efficacy. Our study is to explore serum miRNAs that can be a predicting marker for locally advanced esophageal squamous cell carcinoma.Methods Patients with primary pathologically diagnosed esophageal squamous cell carcinoma, with disease of stage T3-4/N1, MO-M1a were enrolled. Before starting the treatment, patients received a baseline blood draw for miRNA expression profiling. Radiotherapy combined with chemotherapy or targeted therapy or not were delivered. Tumor assessment and follow up were performed every3months. According to overall survival time and local regional relapse free survival time, patients were divided into good and poor outcome groups. We selected15patients in each group (Group A with good prognosis, Group B with poor prognosis) and their characteristics were without significant differences from chi-square test. The differentially expressed serum miRNAs between the two groups are detected by ABI TaqMan miRNA chip method. MiRNAs with RQ value≤0.5or>2and P value≤0.05were defined to be associated with therapeutic efficacy.Results From August2007to December2010,187patients were enrolled. Among these patients,30patients were selected for miRNA profiling. The gender (P=0.543), age (P=0.477).location (P=0.519),treatment (P=0.706) and stage (P=0.879) were comparable between the15patients from Group A and the15patients from Group B. The median survival time of the two group were not reached and6.2months, respectively (P<0.001). High level of miR-Q1, miR-R1and miR-S1were observed in Group A compared with Group B. The RQ values were3.6269,4.3804and3.6661, respectively and P values were0.0499,0.0191, and0.0129, respectively.Moreover, miR-A2, miR-B2, miR-H1and miR-H2were deemed as prognostic markers by log-rank test.Conclusion These data suggest that circulating miR-A2, miR-B2, miR-H1, miR-H2, miR-Q1, miR-R1and miR-S1expressios are potentially associated with radiotherapeutic and chemotherapeutic results for locally advanced esophageal squamous cell carcinoma. The large sample test as well as researched related targets are necessary in order to confirm it. Purpose To investigate the safety and acute toxicities of intraoperative electron radiotherapy.Methods From May2008to August2009,14patients with breast cancer,19patients with pancreatic cancer,3patients with cervical cancer,4patients with ovarian cancer,1patients with endometrial carcinoma,6patients with sarcoma,1patients with rectal cancer and4patients with other carcinomas, were treated with intraoperative electron radiotherapy in Cancer Hospital Chinese Academy of Medical Science. Fifteen of them were recurrent cases. The intraoperative radiotherapy was performed using Mobetron mobile electron accelerator, with a median dose of12Gy. A complete resection was performed in29patients. Other4patients received palliative resection and19patients underwent exploratory operation. All the complications within6months after operations were graded according to NCI-CTCAE3.0.Results Median duration of surgery was190minutes. Intraoperative complications were observed in5patients,3with hemorrhage,1with hypotension,1with hypoxemia, all of which were treated conservatively. Median hospitalization was12days and the in-hospital mortality was3.9%. Twenty-four patients suffered adverse events, including3postoperative infections. Two deaths were recorded during the hospitalizations. Median healing time was13days. With a median follow-up of183days, there were a total of19.6%grade3to5adverse events. The most common complication was hematological toxicities, followed by bellyache. Grade1toxicities which is definitely associated with intraoperative radiotherapy was27.5%, while grade2was3.9%.None of grade3-5complications were proved to be exactly caused by intraoperative radiotherapy.Conclusions Intraoperative electron radiotherapy was accompanied by longer healing time, still is well tolerated. Moreover, intraoperative radiotherapy has not caused more morbidity and toxicity than surgery alone and can be widely used. Purpose To estimate the safety and function of the electron intraoperative radiotherapy in unresectable pancreatic carcinoma (T4) defined during the operation.Methods The enrollment criteria included histological or cytological diagnosed pancreatic carcinoma, unresectable pancreatic carcinoma during operation,with T4stage, any N stage and any M stage. Sixteen to20Gy were delivered as well as the bypass surgery when necessary. From December,2009to July,2011,16patients were enrolled. Seven were male, and9were female. The median age was67.5years old. The maximum diameters of the tumors ranged from3to7cm. The median intraoperative radiation dose was18Gy.The time of the operation, hospitalization and local control and survival were recorded. Adverse events were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events3.0.Results The median duration of the operation and the hospitalization after surgery were180minutes and10.5days respecitively. There is no more than grade3toxicity. One year local control and survival were80%and12.5%respectively. The median survival time was9.5months.Conclusion A single dose of16to20Gy intraoperative radiotherapy was well tolerated and achieved favorable local control. The survival was equally to the external beam radiotherapy alone. Postoperative chemotherapy was recommended for suitable patients due to the high metastasis rate.