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PO-0978: Potential predictive biomarkers to chemoradiotherapy response in rectal cancer: a lipidomic study
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with pCR. This effect was most pronounced for the PC lipid species (Fig. 1). Furthermore, preliminary results identified changes in plasma lipid species during CRT. A steeper increase in lipogenicity (PC, PE, Cer) was observed during CRT (time point 1 to 3) for patients achieving pCR in comparison to patients without pCR. Statistical analyses on the complete patient group are ongoing in order to validate our findings and to develop a discriminative marker panel with the most promising lipid markers.
Conclusion Plasma lipidomics is a novel field for biomarker development. Preliminary analyses show the potential of lipid profiling to discriminate rectal cancer patients with heterogeneous responses, treated with standard CRT. Further work will lead to the development of a predictive lipid plasma marker panel. Such a predictive panel might be used to stratify patients for an individualized treatment, thereby improving the quality of li fe for these patients. PO-0978 Potential predictive biomarkers to chemoradiotherapy response in rectal cancer: a lipidomic study. F. Perrotti1, P. Del Boccio2, D. Pieragostino2, L. Caravatta1, M. Di Tommaso1, C. Rosa1, M. Di Perna1, P. Sacchetta2, D. Genovesi1 1 "SS Annunziata" Hospital, Radiotherapy, Chieti, Italy 2 "G. D'Annunzio" University, Medical Oral and Biotechnological Sciences, Chieti, Italy Purpose or Objective To highlight the lipid signature able to predict the tumor response to chemoradiotherapy (CRT), in patients with advanced rectal cancer (LARC), by using a Lipidomics approach. Material and Methods Between March 2013 and September 2014, 18 patients with LARC were treated with preoperative CRT at the Radiation Oncology Unit of SS Annunziata Hospital in Chieti – Italy. Sera were prospectively collected during routine chemistry tests before treatment (T0) and at day 14° (T14) and 28° (T28) of CRT. An open Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) analysis was performed to characterize lipid expression at T0. Differential lipids were validated by an independent targeted approach and studied during treatment. Results Sixty-five lipids significantly differentiated responder (RP) vs no-responder (NRP) patients; five lipids were validated as predictive of response to CRT: Sphingomyelin (SM, d18:2/18:1), Lysophosphatidylcholine (LPC, 16:0/0:0), Lysophosphatidylcholine (LPC, 15:1(9z)/0:0), Lysophosphatidylethanolamine (LPE, 22:5/0:0) and Phosphatidylcholine (PC, 40:2). Receiver Operator Characteristic curve (ROC curve), generated combining the pattern of the 5 validated lipids, showed an AUC of 0.95. Conclusion The prediction of response to neoadjuvant CRT in LARC allows to personalize treatments and to improve response rate and survival outcomes. In this study we focused on serum lipids to define a differential profile able to predict response. Our results showed a pattern of 5 lipids that differentiated RP and NRP before treatment. The ongoing confirmation of these results could provide a new insight
on lipid metabolism in modulation of CRT response in LARC, in effort to personalize treatments. Poster: Radiobiology track: Radiobiology of cancer (others) PO-0979 Differential response of glioma cell lines to microbeam versus conventional radiotherapy L. Smyth1,2, P. Rogers1, J. Crosbie3, J. Donoghue1,4 1 The University of Melbourne, Department of Obstetrics & Gynaecology, Parkville, Australia 2 Epworth HealthCare, Radiation Oncology, East Melbourne, Australia 3 RMIT University, School of Science, Melbourne, Australia 4 Hudson Institute of Medical Research, Centre for Cancer Research, Clayton, Australia Purpose or Objective Synchrotron microbeam radiotherapy (MRT) has been proposed as an alternative treatment for Diffuse Intrinsic Pontine Glioma (DIPG). The aim of this study was to compare the cellular response of two human DIPG cell lines to MRT and conventional broad-beam radiotherapy (CRT). We hypothesised that MRT would elicit a different cellular response to CRT, and that different DIPG cell lines would have different intrinsic radio-sensitivities. Material and Methods Two human DIPG cell lines, SF7761 and JHH-1, were exposed to MRT (112 to 560 Gy) or CRT (2 to 8 Gy) in vitro to produce clonogenic cell-survival curves which were fit to the linear-quadratic model. Equivalent CRT doses were interpolated for each MRT dose. Apoptosis induction and cell-cycle response assays were performed five days after irradiation via flow cytometry to assess differences in cellular response between the cell lines and radiotherapy modalities at equivalent doses. Results Equivalent CRT and MRT doses for each cell line are summarised in Table 1. The SF7761 cell line, which originated from a six year old female patient with no prior history of radiation treatment, was significantly more radiosensitive to both CRT and MRT compared to the JHH-1 cell line, which originated from a six year old male who had previously undergone combined chemotherapy and radiotherapy (Figure 1). JHH-1 formed polyploid cells and exhibited delayed G2/M arrest following both CRT and MRT. Furthermore, apoptosis and cell cycle assays demonstrated that at equivalent doses, MRT induced more unrepaired DNA damage that was detrimental to the cell-cycle and cell viability for both cell lines five days following irradiation.
with pCR. This effect was most pronounced for the PC lipid species (Fig. 1). Furthermore, preliminary results identified changes in plasma lipid species during CRT. A steeper increase in lipogenicity (PC, PE, Cer) was observed during CRT (time point 1 to 3) for patients achieving pCR in comparison to patients without pCR. Statistical analyses on the complete patient group are ongoing in order to validate our findings and to develop a discriminative marker panel with the most promising lipid markers.
Conclusion Plasma lipidomics is a novel field for biomarker development. Preliminary analyses show the potential of lipid profiling to discriminate rectal cancer patients with heterogeneous responses, treated with standard CRT. Further work will lead to the development of a predictive lipid plasma marker panel. Such a predictive panel might be used to stratify patients for an individualized treatment, thereby improving the quality of li fe for these patients. PO-0978 Potential predictive biomarkers to chemoradiotherapy response in rectal cancer: a lipidomic study. F. Perrotti1, P. Del Boccio2, D. Pieragostino2, L. Caravatta1, M. Di Tommaso1, C. Rosa1, M. Di Perna1, P. Sacchetta2, D. Genovesi1 1 "SS Annunziata" Hospital, Radiotherapy, Chieti, Italy 2 "G. D'Annunzio" University, Medical Oral and Biotechnological Sciences, Chieti, Italy Purpose or Objective To highlight the lipid signature able to predict the tumor response to chemoradiotherapy (CRT), in patients with advanced rectal cancer (LARC), by using a Lipidomics approach. Material and Methods Between March 2013 and September 2014, 18 patients with LARC were treated with preoperative CRT at the Radiation Oncology Unit of SS Annunziata Hospital in Chieti – Italy. Sera were prospectively collected during routine chemistry tests before treatment (T0) and at day 14° (T14) and 28° (T28) of CRT. An open Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) analysis was performed to characterize lipid expression at T0. Differential lipids were validated by an independent targeted approach and studied during treatment. Results Sixty-five lipids significantly differentiated responder (RP) vs no-responder (NRP) patients; five lipids were validated as predictive of response to CRT: Sphingomyelin (SM, d18:2/18:1), Lysophosphatidylcholine (LPC, 16:0/0:0), Lysophosphatidylcholine (LPC, 15:1(9z)/0:0), Lysophosphatidylethanolamine (LPE, 22:5/0:0) and Phosphatidylcholine (PC, 40:2). Receiver Operator Characteristic curve (ROC curve), generated combining the pattern of the 5 validated lipids, showed an AUC of 0.95. Conclusion The prediction of response to neoadjuvant CRT in LARC allows to personalize treatments and to improve response rate and survival outcomes. In this study we focused on serum lipids to define a differential profile able to predict response. Our results showed a pattern of 5 lipids that differentiated RP and NRP before treatment. The ongoing confirmation of these results could provide a new insight
on lipid metabolism in modulation of CRT response in LARC, in effort to personalize treatments. Poster: Radiobiology track: Radiobiology of cancer (others) PO-0979 Differential response of glioma cell lines to microbeam versus conventional radiotherapy L. Smyth1,2, P. Rogers1, J. Crosbie3, J. Donoghue1,4 1 The University of Melbourne, Department of Obstetrics & Gynaecology, Parkville, Australia 2 Epworth HealthCare, Radiation Oncology, East Melbourne, Australia 3 RMIT University, School of Science, Melbourne, Australia 4 Hudson Institute of Medical Research, Centre for Cancer Research, Clayton, Australia Purpose or Objective Synchrotron microbeam radiotherapy (MRT) has been proposed as an alternative treatment for Diffuse Intrinsic Pontine Glioma (DIPG). The aim of this study was to compare the cellular response of two human DIPG cell lines to MRT and conventional broad-beam radiotherapy (CRT). We hypothesised that MRT would elicit a different cellular response to CRT, and that different DIPG cell lines would have different intrinsic radio-sensitivities. Material and Methods Two human DIPG cell lines, SF7761 and JHH-1, were exposed to MRT (112 to 560 Gy) or CRT (2 to 8 Gy) in vitro to produce clonogenic cell-survival curves which were fit to the linear-quadratic model. Equivalent CRT doses were interpolated for each MRT dose. Apoptosis induction and cell-cycle response assays were performed five days after irradiation via flow cytometry to assess differences in cellular response between the cell lines and radiotherapy modalities at equivalent doses. Results Equivalent CRT and MRT doses for each cell line are summarised in Table 1. The SF7761 cell line, which originated from a six year old female patient with no prior history of radiation treatment, was significantly more radiosensitive to both CRT and MRT compared to the JHH-1 cell line, which originated from a six year old male who had previously undergone combined chemotherapy and radiotherapy (Figure 1). JHH-1 formed polyploid cells and exhibited delayed G2/M arrest following both CRT and MRT. Furthermore, apoptosis and cell cycle assays demonstrated that at equivalent doses, MRT induced more unrepaired DNA damage that was detrimental to the cell-cycle and cell viability for both cell lines five days following irradiation.