Abstract book - ESTRO meets Asia

S126 ESTRO meets Asia 2018

Radiobiology: Radiation-induced signalling pathways

tumor response was studied clinically and later, the animals were sacrificed and apoptotic indices were

PO-306 Identification and validation of a Prognostic Signature in Malignant Pleural Mesothelioma J.G. Zhou 1 , M. Hu 1 1 Affiliated Hospital of Zunyi Medical University, Department of Oncology, Zunyi City, China Purpose or Objective Dysregulated genes as critical role in the development and progression of cancer, implying their potentials as novel independent biomarkers for cancer diagnosis and prognosis. Prognostic model-based gene expression profiles were not widely utilized clinically. We investigated the prognostic significance of expression profile-based gene signature for outcome prediction in patients with malignant pleural mesothelioma (MPM). Material and Methods Gene expression profiles of a large cohort of patients with MPM were obtained and analyzed by repurposing the publicly available microarray data. A gene-focus risk score model was developed from the training dataset, and then validated in the TCGA-MESO (mesothelioma) datasets. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic performance for survival prediction. The biological function of prognostic genes was predicted using bioinformatics analysis. Results Three genes were identified to be significantly associated with overall survival (OS) of patients with MPM in the training dataset (GSE2549) and were combined to develop a three-genes prognostic signature to stratify patients into low-risk and high-risk groups. MPM patients of training dataset in the low-risk group exhibited longer OS than those in the high-risk group (HR = 0.25, 95 % CI = 0.11 to 0.56, p <0.001). The similar prognostic values of three- genes signature were observed in the validated TCGA- MESO cohort (HR = 0.53 95 % CI = 0.33 - 0.85, p= 0.008). ROC analysis also demonstrated the better performance for predicting 3-year OS in GEO and TCGA cohorts (KM-AUC for GEO = 0.989, KM-AUC for TCGA = 0.618). The C-statistic for 3-genes model was 0.761. Validation on TCGA-MESO confirmed the model’s ability to discriminate between risk groups in an alternative data set with fair performance (C- statistic 0.68). Functional enrichment analysis suggested that these three mRNAs may be involved in known genetic and epigenetic events linked to MPM. Conclusion This study has identified and validated a novel 3-gene model to reliably discriminate patients at high and lower risk of death from unselected populations of patients with MPM. Further larger, prospective multi-institutional cohort studies are necessary to validate these models. PO-307 the role of EGFR-regulated autophagy signaling pathway in radioresistant nasopharyngeal carcinoma C. Chu 1 1 Fudan University Cancer Hospital, department of radiotherapy, Shanghai, China Purpose or Objective Nasopharyngeal carcinoma is a common malignant tumor in southern China and Southeast Asia. Radiation therapy is the main treatment for patients with nasopharyngeal carcinoma. Radioresistance of nasopharyngeal carcinoma is one of the clinical problems to be solved. This study focuses on the mechanism of radioresistance of nasopharyngeal carcinoma and explores the therapeutic targets and research direction for increasing the radiosensitivity of radioresistant cells.

measured. Conclusion

The synthesized magnetic nanostructures revealed many favorable properties. However, in-vivo studies are being focused to evaluate the functionality of the system, for imaging and treatment in cancer. We have utilized Gd nanoparticle to specifically and uniformly disperse in the cancer cells, hence targeting them and since it is conjugated with iron oxide nanoparticle would also serve to cause cancer cell kill through radiosensitisation, when subjected to alternating electromagnetic field through induction heating along with radiation. Hence, the proposed magnetic nanostructures thus can serve as a versatile nanoplatform for cancer theranostics combining dual-modal imaging and radiation- hyperthermia. PO-305 1 to 6 fractions of carbon ions are more effective than photons in sublines of rat prostate tumors C. Glowa 1 1 University Hospital Heidelberg, Department of Clinical Radiology, Heidelberg, Germany Purpose or Objective Carbon ions ( 12 C-ions) show an increased relative biological effectiveness (RBE) relative to photons. However, the underlying mechanisms in vivo are still unknown. Therefore, it is difficult to identify, which tumor characteristics (e.g. hypoxic status, differentiation) would be suited best for 12 C-ion therapy. To investigate the impact of differentiation on RBE as well as the optimal fractionation schedule, dose-response curves for photons and 12 C-ions were determined for three well characterized sublines of a rat prostate adenocarcinoma after irradiation with 1, 2 and 6 fractions (fx). Material and Methods Tumor fragments of three Dunning prostate tumor R3327sublines (AT1, HI and H) were transplanted s.c. into the distal thigh of male Copenhagen rats. Tumors were treated with single, 2 or 6 fx irradiations with increasing doses of either 12 C-ions or 6 MeV photons. Primary endpoint was local tumor control within 300 days. RBEs were calculated based on TCD 50 -values (dose at 50% tumor control probability) of photons and 12 C-ions, respectively. Results Local tumor control was achieved with both, 12 C-ions and photons, in all sublines and a higher effectiveness was found for 12 C-ions. The RBE for local tumor control after single dose irradiation increased from 1.62±0.11 (H) to 2.08±0.13 (HI) to 2.30±0.08 (AT1). Variation of TCD 50 - values between tumor sublines was significantly smaller for 12 C-ions than for photons and the dose-response curves for 12 C-ions were steeper. With decreasing dose per fraction (increasing number of fractions), the RBE increased, but differently for the tumor sublines. After 6 fx irradiation the fractionation effect for 12 C-ions was much smaller for all tumors then for photons, which was not seen after 2 fx irradiations. Conclusion The RBE of 12 C-ions is highest for the anaplastic AT1-tumor and smallest for the well-differentiated H-tumor, which indicates a clear correlation between decreasing differentiation status and increasing RBE. 12 C-ions may therefore be beneficial especially in undifferentiated tumors, which are highly resistant against photon irradiation. Interrestingly, the RBE of the three sublines after 6 fx irradiations were much closer together than after single dose irradiations. RBE changes were predominantly caused by changes in the photon response. This supports the assumption that the response to 12 C-ions is less dependent on intra- and inter-tumor heterogeneity than for photons.