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Abstracts, 5 th AOS and 9 th Annual Conference of OOTR, 2013 / European Journal of Cancer 49S1 (2013) S1S22 S19 with glioblastoma multiforme (GBM) treated at Ramthibodi Hospital. Methods. A total of 47 medical records of patients diagnosed with GBM who were older than 18 years old and treated at the radiotherapy unit of Ramathibodi hospital from 2000 to 2010 were reviewed and included in a survival analysis. Results. Of the 47 patients, all were diagnosed with histologically confirmed GBM. Mean age of patients at diagnosis was 51.91 years (range 18−82). All patients received postoperative radiotherapy with 2D or 3D technique. Twenty- nine patients received chemotherapy, 15 with concurrent and adjuvant temozolomide to 6 months. Mean follow-up was 656.52 days. The median survival time was 2.14 years (95% confidence interval (CI) 1.08–7.36). In univariate analysis, the following unfavourable prognostic factors were identified: age 50 years, higher recursive partitioning analysis (RPA), presentation with headache, persistent neurological deficit after surgery, and lower total tumour dose. In multivariate analysis, patients who received total radiotherapy dose more than 4500 cGy and those with younger age had significantly better overall survival. The type of surgery or time before start of radiation did not appear to improve overall survival. Patients who received temozolomide concurrently and adjuvantly with radiation had a significantly higher survival rate (p = 0.04). The mean total radiation dose in the survival group was 5790 cGy while in the mortality group it was 5147 cGy (p = 0.005). Discussion. GBM has a poor prognosis. Clinical symptoms after surgery, radiotherapy, and chemotherapy significantly affected survival. Younger age of patient and higher doses of radiation had a survival impact, while technique of radiation or time before start of radiation did not. However, due to small numbers of patients, further study is needed. Funding. None declared. The author declared no conflicts of interest. AOSP36 PREVALENCE OF DMMR IN SPORADIC COLORECTAL CANCER PATIENTS AT SIRIRAJ HOSPITAL K. Korphaisarn, A. Manuyakorn, E. Roothumnong, W. Klaisuban, A. Nimmannit, A. Jinawath, C. Limwongse, C. Akewanlop *. Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Introduction. The presence of defective DNA mismatch repair (dMMR) is one of the predominant carcinogenic pathways in colorectal cancer (CRC). It accounts for 15−20% of sporadic CRC and seems to be a favourable prognostic marker. However, there are no existing data in Thai patients. This study aimed to determine the prevalence of dMMR and association with various clinicopathological features and outcome in sporadic CRC patients at Siriraj Hospital. Methods. Paraffin-embedded tumour blocks of patients with stage I−IV CRC diagnosed at Siriraj Hospital between 2006 and 2007 were analysed for dMMR by either loss of protein expression for MMR proteins detected by immunohistochemistry (IHC) or microsatellite instability (MSI) using the PCR-DHPLC method. The association between patient characteristics and MMR status with overall survival (OS) and disease-free survival (DFS) were analysed using Kaplan–Meier estimation and log-rank test with Cox’s proportional hazard regression. Results. IHC for MMR proteins and MSI detection was analysed in 164 and 44 tumours, respectively. dMMR was identified in ten of 164 and 21 of 44 tumours (total 15%). dMMR was more commonly found in patients with colon primary rather than rectal cancer (20.4% vs 7.6%, p = 0.01). It was associated with lower grade tumours (p = 0.005). Patients with dMMR tumours had significantly better DFS (hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.11–0.76, p = 0.012) and OS (HR 0.3, 95% CI 0.10–0.88, p = 0.028) compared with those with proficient MMR tumours. Discussion. The prevalence of dMMR in sporadic CRC at Siriraj Hospital was 15% and was also associated with better survival in our patients. Funding. None declared. The authors declared no conflicts of interest. AOSP37 HUMANISED ANTI-VEGF AND ANTI-IL-6 RECEPTOR MONOCLONAL ANTIBODY SUPPRESSED IN-VIVO FLUID RETENTION IN PRIMARY EFFUSION LYMPHOMA H. Goto, E. Kudo, M. Taura, K. Matuda, R. Kariya, S. Okada*. Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Japan Introduction. Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma that is universally associated with Kaposi’s sarcoma-associated herpes virus (KSHV)/human herpesvirus-8 (HHV-8). PEL shows malignant effusions without tumour mass most commonly in advanced AIDS patients. In this study, we clarified the potential role of VEGF and IL-6 in the fluid retention of PEL and evaluated the efficacy of humanised anti-VEGF monoclonal antibody, bevacizumab, and anti-IL-6 receptor monoclonal antibody, tocilizumab, against PEL. Methods. We measured the production of VEGF and IL-6 in PEL cell lines by ELISA. The expression of VEGFR-1, VEGFR-2, and IL-6Ra in PEL cell lines were analysed by flow cytometry. The inhibitory effect of bevacizumab or tocilizumab on the proliferation of PEL cell lines was evaluated by tetrazolium dye methylthiotetrazole (MTT) assay.The effect of tocilizumab on VEGF was evaluated by quantitative PCR and ELISA. We assessed the in-vivo effect of bevacizumab or tocilizumab using a PEL mouse model. Results. Although we found the production of VEGF and IL-6, and the expression of VEGF-R1, VEGF-R2, IL-6 Ra in PEL cell lines, bevacizumab or tocilizumab did not inhibit the proliferation of PEL cells in vitro. Tocilizumab decreased VEGF mRNA and VEGF production via inhibiting Stat3 phosphorylation. Both bevacizumab and tocilizumab suppressed ascites formation significantly and improved overall survival in vivo. Discussion. The production of VEGF and IL-6 contributed to the fluid retention, and bevacizumab and tocilizumab could be effective molecular targeting therapies for PEL. Funding. This work was supported in part by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan (H22-AIDS-I-002), and Grants-in- Aid for Science Research (No. 23107725) from the Ministry of Education, Science, Sports, and Culture of Japan. The authors declared no conflicts of interest.

AOSP37 HUMANISED ANTI-VEGF AND ANTI-IL-6 RECEPTOR MONOCLONAL ANTIBODY SUPPRESSED IN-VIVO FLUID RETENTION IN PRIMARY EFFUSION LYMPHOMA

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Abstracts, 5th AOS and 9th Annual Conference of OOTR, 2013 / European Journal of Cancer 49S1 (2013) S1−S22 S19

with glioblastoma multiforme (GBM) treated at RamthibodiHospital.Methods. A total of 47 medical records of patients diagnosedwith GBM who were older than 18 years old and treated atthe radiotherapy unit of Ramathibodi hospital from 2000 to2010 were reviewed and included in a survival analysis.Results. Of the 47 patients, all were diagnosed withhistologically confirmed GBM. Mean age of patients atdiagnosis was 51.91 years (range 18−82). All patients receivedpostoperative radiotherapy with 2D or 3D technique. Twenty-nine patients received chemotherapy, 15 with concurrent andadjuvant temozolomide to 6 months. Mean follow-up was656.52 days. The median survival time was 2.14 years (95%confidence interval (CI) 1.08–7.36). In univariate analysis, thefollowing unfavourable prognostic factors were identified:age �50 years, higher recursive partitioning analysis (RPA),presentation with headache, persistent neurological deficitafter surgery, and lower total tumour dose. In multivariateanalysis, patients who received total radiotherapy dose morethan 4500 cGy and those with younger age had significantlybetter overall survival. The type of surgery or time before startof radiationdidnot appear to improveoverall survival. Patientswho received temozolomide concurrently and adjuvantlywithradiation had a significantly higher survival rate (p=0.04). Themean total radiation dose in the survival group was 5790 cGywhile in the mortality group it was 5147 cGy (p=0.005).Discussion. GBM has a poor prognosis. Clinical symptomsafter surgery, radiotherapy, and chemotherapy significantlyaffected survival. Younger age of patient and higher doses ofradiation had a survival impact, while technique of radiationor time before start of radiation did not. However, due to smallnumbers of patients, further study is needed.Funding. None declared.The author declared no conflicts of interest.

AOSP36 PREVALENCE OF DMMR IN SPORADICCOLORECTAL CANCER PATIENTS AT SIRIRAJ HOSPITALK. Korphaisarn, A. Manuyakorn, E. Roothumnong,W. Klaisuban, A. Nimmannit, A. Jinawath, C. Limwongse,C. Akewanlop*. Faculty of Medicine Siriraj Hospital, MahidolUniversity, Bangkok, Thailand

Introduction. The presence of defective DNA mismatch repair(dMMR) is one of the predominant carcinogenic pathwaysin colorectal cancer (CRC). It accounts for 15−20% of sporadicCRC and seems to be a favourable prognosticmarker. However,there are no existing data in Thai patients. This study aimedto determine the prevalence of dMMR and association withvarious clinicopathological features and outcome in sporadicCRC patients at Siriraj Hospital.Methods. Paraffin-embedded tumour blocks of patients withstage I−IV CRC diagnosed at Siriraj Hospital between2006 and 2007 were analysed for dMMR by either lossof protein expression for MMR proteins detected byimmunohistochemistry (IHC) or microsatellite instability(MSI) using the PCR-DHPLC method. The association betweenpatient characteristics and MMR status with overall survival(OS) and disease-free survival (DFS) were analysed usingKaplan–Meier estimation and log-rank test with Cox’sproportional hazard regression.Results. IHC forMMR proteins andMSI detectionwas analysedin 164 and 44 tumours, respectively. dMMR was identified

in ten of 164 and 21 of 44 tumours (total 15%). dMMRwas more commonly found in patients with colon primaryrather than rectal cancer (20.4% vs 7.6%, p=0.01). It wasassociated with lower grade tumours (p=0.005). Patients withdMMR tumours had significantly better DFS (hazard ratio (HR)0.3, 95% confidence interval (CI) 0.11–0.76, p=0.012) and OS(HR 0.3, 95%CI 0.10–0.88, p=0.028) compared with those withproficient MMR tumours.Discussion.The prevalence of dMMR in sporadic CRC at SirirajHospital was 15% and was also associated with better survivalin our patients.Funding. None declared.The authors declared no conflicts of interest.

AOSP37 HUMANISED ANTI-VEGF AND ANTI-IL-6RECEPTOR MONOCLONAL ANTIBODY SUPPRESSED IN-VIVOFLUID RETENTION IN PRIMARY EFFUSION LYMPHOMAH. Goto, E. Kudo, M. Taura, K. Matuda, R. Kariya, S. Okada*.Division of Hematopoiesis, Center for AIDS Research, KumamotoUniversity, Japan

Introduction. Primary effusion lymphoma (PEL) is an aggressivesubtype of non-Hodgkin lymphoma that is universallyassociated with Kaposi’s sarcoma-associated herpes virus(KSHV)/human herpesvirus-8 (HHV-8). PEL shows malignanteffusions without tumour mass most commonly in advancedAIDS patients. In this study, we clarified the potential roleof VEGF and IL-6 in the fluid retention of PEL and evaluatedthe efficacy of humanised anti-VEGF monoclonal antibody,bevacizumab, and anti-IL-6 receptor monoclonal antibody,tocilizumab, against PEL.Methods. We measured the production of VEGF and IL-6 inPEL cell lines by ELISA. The expression of VEGFR-1, VEGFR-2,and IL-6Ra in PEL cell lines were analysed by flow cytometry.The inhibitory effect of bevacizumab or tocilizumab on theproliferation of PEL cell lines was evaluated by tetrazoliumdyemethylthiotetrazole (MTT) assay.The effect of tocilizumabon VEGF was evaluated by quantitative PCR and ELISA. Weassessed the in-vivo effect of bevacizumab or tocilizumabusing a PEL mouse model.Results. Although we found the production of VEGF andIL-6, and the expression of VEGF-R1, VEGF-R2, IL-6 Rain PEL cell lines, bevacizumab or tocilizumab did notinhibit the proliferation of PEL cells in vitro. Tocilizumabdecreased VEGF mRNA and VEGF production via inhibitingStat3 phosphorylation. Both bevacizumab and tocilizumabsuppressed ascites formation significantly and improvedoverall survival in vivo.Discussion. The production of VEGF and IL-6 contributed tothe fluid retention, and bevacizumab and tocilizumab couldbe effective molecular targeting therapies for PEL.Funding. This work was supported in part by a Health andLabour Sciences Research Grant from the Ministry of Health,Labour, andWelfare of Japan (H22-AIDS-I-002), and Grants-in-Aid for Science Research (No. 23107725) from the Ministry ofEducation, Science, Sports, and Culture of Japan.The authors declared no conflicts of interest.