ESTRO 36 Abstract Book

S358 ESTRO 36 _______________________________________________________________________________________________

influence of liver irradiation on the pharmacokinetics (PK) of sorafenib using rats as an experimental model. Material and Methods Free-moving rat model was used in the current study. Image-guided RT with 2 Gy was delivered to the whole liver of Sprague-Dawley rats. The rats were feeding with sorafenib at 40 mg/kg after RT 1 hour (concurrent model) or post RT 24 hours (sequential model) for the plasma system. The experimental animals were randomized to the sham RT (0 Gy with sorafnib), concurrent group and sequential group, respectively. The PK of sorafenib in the plasma system was calculated. Each group’s data was collected from six to eight rats Results Compared to the sham-irradiated controls, the area under the concentration versus time curve (AUC) of sorafenib (40 mg/kg) was increased by 132% in concurrent group (719 versus 1669 min*ug/mL, p = 0.046). In contrast, the AUC of sorafenib was decreased by 59% in sequential group (719 versus 297 min*ug/mL, p = 0.036). Compared with the concurrent and sequential group, there was a statistically significant difference between both groups (1669 vs 297 min*ug/mL, p = 0.012). There were no differences at Tmax and Cmax between groups. Conclusion A whole liver RT modulates the systemic PK of sorafenib of the rats. Interestingly, the AUC of sorafenib is increased at concurrent with RT and decreased in sequential model. The RT-PK phenomena are not only noted in chemotherapy agents but also in target therapy drug. The RT-PK phenomena are worth further investigation. PO-0685 The value of postoperative adjuvant therapy for pT2-3 esophageal cancer treated by radical resection S. Zhu 1 , L. Shuguang 2 , L. Youmei 2 , S. Wenbin 3 , L. Juan 2 , L. Zhukun 2 , S. Jingwei 2 , L. Teng 2 1 Fourth Hospital of Hebei Medical University, Department Radiation Oncology, Sijiazhuang- Hebei, China 2 Fourth Hospital of Hebei Medical University, Department of Radiation Oncology, Shijiazhuang, China 3 Fourth Hospital of Hebei Medical University, Department of RadiationOncology, Shijiazhuang, China Purpose or Objective The aim of this study was to analyze failure modalities and evaluate efficacy of postoperative treatment of pT 2-3 N 0 M 0 esophageal squamous cell carcinoma. The endpoint was to find an efficient way of postoperative adjuvant therapy for this type esophageal cancer. Material and Methods The clinical data of 702 patients with pT 2-3 N 0 M 0 esophageal squamous cell carcinoma who received radical resection in our hospital from 2007 to 2010 were retrospectively analyzed. Male 482, female 220, median age 60 years. All did not receive any preoperative treatment, were performed with curative esophagectomy included removal of primary tumor and draining lymph nodes, and 343 cases surgical alone. Postoperative adjuvant chemotherapy 279 cases, four courses with an interval of 4 weeks with 80 mg/m2 of cisplatin on day 1and 600 mg/m2/day of 5- fluorouracil given by continuous intravenous infusion on day1-4. Postoperative prophylactic radiotherapy alone 40 cases with 50.4-59.4Gy of external beam radiation at 1.8- 2.0Gy per fraction, and postoperative chemoradiotherapy 40 cases. Analysis of prognostic survival was determined by Kaplan-Meier method and checked by the log-rank test. Cox proportional hazard model was used for multivariate analysis. Results The overall failure rate of all patients was 48.4%, and surgical alone 54.8%, postoperative chemotherapy alone 42.7%, radiotherapy alone 42.5% and chemoradiotherapy 40.0% (χ 2 =11.021,P=0.012). The local regional failure rate

of all patients was 37.5%, and surgical alone 41.7%, postoperative chemotherapy alone 35.5%, radiotherapy alone 27.5% and chemoradiotherapy 25.0% (χ 2 =7.430,P=0.059). In 343 cases surgical alone, the overall failure rate 58.5% and the local regional failure rate 46.2% of stage T 3 was significantly higher than T 2 stage 42.4% (χ 2 =11.235,P=0.001) and 33.1% (χ 2 =5.524,P=0.019). The local regional failure rate 68.0% of thoracic-upper carcinoma was higher than that of thoracic-middle or- lower 35.7%(χ 2 =17.101,P=0.001). Compared with surgery alone, postoperative chemotherapy, radiotherapy and chemoradiotherapy all improved the 5-year local control rate. Postoperative chemotherapy and chemoradiotherapy significantly increased 5-year PFS (P=0.001, 0.024),and 5-year OS rates (P=0.001, 0.025). Multivariate analysis revealed that the location, stage of pathology, postoperative adjuvant therapy were independently prognostic factors. Conclusion The failure rate was high with pT 2-3 N 0 M 0 thoracic esophageal squamous carcinoma after radical esophagectomy alone. Postoperative adjuvant therapy could obviously improve local control, postoperative chemotherapy and chemoradiotherapy could improve PFS and OS. PO-0686 Perfusion imaging of colorectal liver metastases treated with bevacizumab and SBRT H. Chung 1 , J. Detsky 1 , P. Munoz-Schuffenegger 1 , L. Milot 1 , W. Chu 1 , C. MacDonald 1 , Y. Ko 1 1 Odette Cancer Centre - Sunnybrook Health Science, Radiation Oncology, North York- Toronto, Canada Purpose or Objective SBRT is an accepted alternative to surgical resection of liver metastases from colorectal cancer (CRC). The addition of bevacizumab holds promise as a radiosensitizer and is an active agent in metastatic CRC. There is increasing interest in the use of imaging biomarkers as a method to evaluate and predict response to treatment. Dynamic contrast-enhanced CT (DCE-CT) measures perfusion parameters and has been used to evaluate primary CRC tumors and liver metastases. Contrast- enhanced ultrasound (CEUS) is another method using a microbubble contrast agent to characterize vascular properties of liver lesions. The purpose of this prospective study was to evaluate the temporal evolution of perfusion parameters in CRC liver metastases treated with SBRT and bevacizumab. Material and Methods Patients with 1 – 3 liver metastases from CRC were prospectively enrolled in this trial. Bevacizumab was administered for 2 doses 2 weeks apart, with the second dose within 48 hours of starting SBRT. SBRT was delivered in 5 fractions. Functional imaging including DCE-CT and CEUS were performed at three time points: at baseline, just prior to SBRT, and within 7 days post-SBRT. DCE-CT output parameters were permeability surface area (PSA), blood volume (BV), and blood flow (BF). CEUS images were used to calculate a quantitative perfusion index (PI). Patients were then followed with physical and imaging assessments every three months. Results The trial enrolled 11 patients, with 1 dropout. Six patients had a complete set of DCE-CT images (one patient had 2 of 3 scans). Of the 7 evaluable patients, 3, 3 and 1 had evidence of local, distant and simultaneous failure, respectively. Mean PSA and BV decreased in 5 of 6 patients from baseline to post-bevacizumab (-17% ± 37%, p=0.22 and -25% ± 33%, p=0.1 respectively), while BF was not affected. BF and PSA was reduced in all 7 patients pre to post-SBRT (-47% ± 22%, p=0.07 and -40% ± 21%, p=0.18, respectively) while BV remained stable (0.4% ± 22%, p=0.8). CEUS was attempted in 10 patients but adequate image acquisition was only technically feasible in 4. CEUS PI significantly decreased from baseline to post-