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// Peipei Wu 1, 2, * , Jing Liu 1, * , Xiaorong Sun 3 , Xiaolin Li 1 , Ligang Xing 1 and Jinming Yu 1 1 Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China 2 Department of Oncology, Jining No.1 People’s Hospital, Jining 272011, Shandong, China 3 Department of Radiology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medicine Science, Jinan 250117, Shandong, China * These authors have contributed equally to this work Correspondence to: Ligang Xing, email: xinglg@medmail.com.cn Keywords: esophageal cancer, sodium glycididazole, radiosensitizer, tumor bed effect, hypoxia Received: December 15, 2016 Accepted: June 05, 2017 Published: July 10, 2017 ABSTRACT Re-irradiation is challenging for esophageal cancer patients with local-regional recurrence after initial radiotherapy. The purpose of this study is to establish a recurrent esophageal tumor model and investigate radiosensitizing effects of sodium glycididazole (CMNa). Tumor models were established by pre-irradiation (0 Gy, 10 Gy or 20 Gy) to the right hind leg of the nude mice 24 hours before tumor transplantation (ECA109 human esophageal carcinoma cells). Tumor growth curves were analyzed. Hypoxic microenvironment was exhibited in tumor frozen slides stained for pimonidazole, Hoechst 33342, hematoxylin-eosin and CD34. Mice bearing primary (0 Gy pre-irradiation) and recurrent (10 Gy pre-irradiation) tumors were randomized into control (no treatment), radiation (30 Gy in 3 weekly fractionations), or radiation combined with CMNa (1 mmol/kg i.p. injected 60 min before radiation) respectively. The data showed tumors from 10 Gy and 20 Gy pre-irradiated sites grew significantly slower than those in the 0 Gy pre-irradiated group. The recurrent xenograft tumors showed increased necrotic fractions, decreased micro-vascular density, increased pimonidazole-positive fraction, and decreased Hoechst-positive fraction. In the primary xenograft tumors, CMNa adding to radiation did not lead to significant tumor growth delay than radiation alone. However, for the recurrent tumor model, the growth rate was remarkably reduced as CMNa combined with radiation as comparison with radiation alone. In conclusion, the recurrent esophageal xenograft model with tumor bed effect was successfully established characterized by slow growth, increased hypoxia fraction and decreased blood flow. Significant radiosensitization by CMNa was demonstrated in the recurrent model.

// Bingjie Fan 1 , Pingping Fan 1, 2, 3 , Li Kong 1, 2, 3 , Xindong Sun 1, 2, 3 , Shuqiang Zhao 1, 2, 4 , Xiaorong Sun 1, 2, 4 , Zheng Fu 1, 2, 4 , Jinsong Zheng 1, 2, 4 , Li Ma 1, 2, 4 , Shijiang Wang 1, 2, 3 , Man Hu 1, 2, 3 and Jinming Yu 1, 2, 3 1 Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 2 Shandong Academy of Medical Sciences, Jinan, China 3 Departments of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China 4 Departments of Nuclear Medicine, Shandong Cancer Hospital and Institute, Jinan, China Correspondence to: Man Hu, email: hu5770@sina.com Jinming Yu, email: sdyujinming@163.com Keywords: esophageal squamous cell carcinoma, radiotherapy, FDG PET/CT, concurrent chemoradiotherapy, local failure Received: October 15, 2016 Accepted: January 04, 2017 Published: February 22, 2017 ABSTRACT Esophageal squamous cell carcinoma (ESCC) patients are at risk for local failure (LF) following treatment. Predicting tumor regions at high risk for local failure before radiotherapy may increase treatment efficacy by permitting an escalated radiation dose specifically to those regions critical for tumor control. Forty-one patients with non-resectable locally advanced ESCC underwent 18 F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging before concurrent chemoradiotherapy (CCRT). After CCRT, a second (failure) FDG PET/CT was performed in cases of relapse. Failure FDG PET/CT scans were fused to pre-treatment scans to identify tumor regions at high risk for LF. Within a median follow-up time of 26 months, 20 patients (48.8%) had LF. In 19 patients, the failure occurred within a pre-treatment high FDG uptake region; the failure occurred outside these regions in only one patient. Pre-treatment metabolic tumor volume (MTV) was independently associated with LF ( P

// Xinzhe Dong 1, 2 , Xiaorong Sun 3 , Xianguang Zhao 1 , Wanqi Zhu 1 , Lu Sun 4 , Yong Huang 3 , Wenwu Li 3 , Honglin Wan 5 , Ligang Xing 1, 2 , Jinming Yu 1, 2 1 Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, Shandong, China 2 Key Laboratory of Radiation Oncology of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China 3 Department of Radiology, Shandong Cancer Hospital and Institute, Jinan, Shandong, China 4 Jinan University, Jinan, Shandong, China 5 College of Physics and Electronic Science, Shandong Normal University, Jinan, Shandong, China Correspondence to: Ligang Xing, email: sdcancerhospital@163.com Keywords: positron emission tomography, FDG, esophageal carcinoma, intratumoral heterogeneity, prognosis Received: July 18, 2016 Accepted: January 10, 2017 Published: January 19, 2017 ABSTRACT Objective: To evaluate the impact of intratumoral metabolic heterogeneity measured by 18F-FDG PET imaging on postoperative recurrence and survival for patients with esophageal squamous cell carcinoma (ESCC). Results: AUC-CSH, metabolic tumor volume and pN-stage were significant prognostic factors for RFS. Additionally, tumor recurrence of the low AUC-CSH group (≤ 0.478) was 3 times higher than high group ( P = 0.015). The median OS of patients with advanced AJCC stage or low AUC-CSH was also significantly shorter than that of patients with stage I & II or high AUC-CSH ( P = 0.021, 0.009). Multivariate analysis identified the AUC-CSH to be the only significant risk factor for postoperative recurrence and overall survival in whole-group and stage III patients. Materials and Methods: 116 ESCC patients who underwent staging 18F-FDG PET-CT scan and surgical resection were reviewed. The metabolic parameters were assessed as follows: maximum standardized uptake value (SUV max ), metabolic tumor volume, and the area under the curve of the cumulative SUV-volume histogram (AUC-CSH), which is known to reflect the intratumoral metabolic heterogeneity. Regression analyses were used to identify clinicopathological and imaging variables associated with relapse-free survival (RFS) and overall survival (OS). Conclusions: Intratumoral metabolic heterogeneity characterized by AUC-CSH can predict postoperative recurrence and survival in patients with resectable ESCC.

There are few effective treatment options for radiation-induced dermatitis in breast cancer patients. We conducted a single-arm trial to tested the hypothesis that topical epigallocatechin-3-gallate (EGCG) is effective against radiation-induced dermatitis in breast cancer patients undergoing radiotherapy. Forty-nine patients participated in this study. The patients underwent mastectomy followed by adjuvant radiotherapy. Topical EGCG was applied daily, starting when grade I dermatitis appeared and ending two weeks after radiotherapy. The maximum dermatitis observed during the EGCG treatment was as follows: Grade 1 toxicity, 71.4% (35 patients); grade 2 toxicity, 28.6% (14 patients); there were no patients with grade 3 or 4 toxicity. The majority of the radiation-induced dermatitis was observed 1 week after the end of radiotherapy. EGCG reduced the pain in 85.7% of patients, burning-feeling in 89.8%, itching in 87.8%, pulling in 71.4%, and tenderness in 79.6%. These findings suggest topical EGCG may be an effective treatment for radiation-induced dermatitis and has acceptable toxicity.

Bortezomib, a novel proteasome inhibitor, has been approved for treating multiple myeloma and mantle cell lymphoma and studied pre-clinically and clinically for solid tumors. Preferential cytotoxicity of bortezomib was found toward hypoxic tumor cells and endothelial cells in vitro. The purpose of this study is to investigate the role of a pretreatment hypoxic tumor microenvironment on the effects of bortezomib in vitro and ex vivo, and explore the feasibility of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) to noninvasively evaluate the biological effects of bortezomib. It was shown in vitro by Western blot, flow cytometry, and ELISA that bortezomib accumulated HIF-1α in non-functional forms and blocks its hypoxia response in human colorectal cancer cell lines. Ex vivo experiments were performed with fluorescent immunohistochemical staining techniques using multiple endogenous and exogenous markers to identify hypoxia (pimonidazole, HRE-TKeGFP), blood flow/permeability (Hoechst 33342), micro-vessels (CD31 and SMA), apoptosis (cleaved caspase 3) and hypoxia response (CA9). After bortezomib administration, overall apoptosis index was significantly increased and blood perfusion was dramatically decreased in tumor xenografts. More importantly, apoptosis signals were found preferentially located in moderate and severe pretreatment hypoxic regions in both tumor and endothelial cells. Meanwhile, DCE MRI examinations showed that the tumor blood flow and permeability decreased significantly after bortezomib administration. The present study revealed that bortezomib reduces tumor hypoxia response and blood perfusion, thus, presenting antivascular properties. It will be important to determine the hypoxic/perfusion status pre- and during treatment at further translational studies.