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917 poster RADIATION-INDUCED CHRONIC-OXIDATIVE RENAL DAMAGE CAN BE REDUCED BY AMIFOSTINE
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the rectal mucosa in the present study. The results indicated late radiation proctitis followed acute proctitis. We could establish an animal experimental model of late radiation proctitis, and also established a novel method to evaluate the severity of late radiation proctitis focusing microangiopathy. Our animal experimental model may be also used as an animal experimental model of radiation induced microangiopathy. 915 poster MORBIDITY PROFILES FOLLOWING CONFORMAL VS. INTENSITYMODULATED RADIOTHERAPY FOR URINARY BLADDER CANCER. J. Søndergaard1 , M. Holmberg2 , A. R. Jakobsen3 , L. P. Muren4 , C. Grau1 ,
irradiated individually with a single dose of 8 Gy. 2, 2, 4 and 1 deaths were occurred in groups, respectively. Animals underwent both Tc99m DTPA (Diethylene triamine pentaacetic acid) dynamic renal imaging and Tc99m DMSA (Dimercaptosuccinic acid) static renal imaging at the end of three months follow-up period. Proximal tubular degeneration, tubular atrophy, interstitial fibrosis and glomerular degeneration were assessesed histopathologically. Results: The mean Tmax and T1/2 values in the RT group were 4.2 ± 0.8 and 14.5 ± 4.1, respectively. In the L-Carnitine + RT group, those values were 2.8 ± 0.4 and 12.8 ± 1.7 and significantly lower than those in the RT group (p=0.03, p=0.04). In L-Carnitine + RT group, the glomerular structures were well protected compared to RT group (0.78 ± 0.22 vs. 1.88 ± 0.58, p=0.04) (Table 1).
M. Hoyer1 1 A ARHUS U NIVERSITY H OSPITAL, Department of Oncology, Aarhus C, Denmark 2 A ALBORG U NIVERSITY H OSPITAL, Department of Oncology, Aalborg, Denmark 3 A ALBORG U NIVERSITY H OSPITAL, Department of Medical Physics, Aalborg, Denmark 4 A ARHUS U NIVERSITY H OSPITAL, Department of Medical Physics, Aarhus C, Denmark Purpose: The improved dose distributions of intensity modulated radiotherapy (IMRT) compared to conformal radiotherapy (CRT) is well characterized in radiotherapy (RT) of pelvic tumours. Moreover, previous studies in particular for prostate cancer have reported a reduction of toxicity enabling treatment intensification and improved outcome. In RT of bladder cancer large intestinal volumes are irradiated in particular when pelvic lymph nodes are included in the target. The purpose of the present study was to evaluate acute and late toxicity following RT for bladder cancer and to correlate these to dose-volume parameters. This analysis was performed in patients treated in the same time period at two different RT centres where patients according to local policy received IMRT in one centre and CRT in the other. Materials: 116 consecutively treated patients with muscle invasive bladder cancer who received either CRT (n=66) or IMRT (n=50) in the time period 2007-2010 were analysed. Patient charts and treatment plans were retrospectively evaluated. A cross-sectional evaluation of late toxicity was performed by telephone interview of 44 surviving and recurrence free patients. Acute and late toxicity was scored according to the Common Terminology Criteria for Adverse Event version 3.0 (CTCAE). The toxicity scores were dichotomized, and comparisons between the groups were analyzed by twosided Fishers exact test and logistic regression modelling where appropriate. Results: Acute diarrhoea grade 2+ occurred more frequently in patients treated by CRT (56%) compared to IMRT (30%) (p=0.008). There were no differences in other acute gastrointestinal (GI) toxicities such as bowel pain or the use of anti-diarrhoea medication. The acute genitourinary (GU) toxicities were not different in the two groups receiving IMRT or CRT. Logistic regression analysis revealed a statistically significant correlation between acute diarrhoea and volume of bowel cavity exposed to irradiation. Severe late toxicity (CTCAE grade 3+) was recorded in 10% in the total patient cohort; there was no difference between the IMRT and CRT groups. In the cross-sectional study any late grade 2+ GI toxicity occurred in 17% and 40% of patients receiving IMRT and CRT, respectively (p=0.1), while the corresponding no. for any late grade 2+ GU toxicity were 63% and 48% of the patients (p=0.4). Conclusions: Patients treated with IMRT experienced significantly less acute diarrhoea compared to those treated with CRT, whereas there was no significant difference in late morbidity. The increased occurrence of acute diarrhoea in CRT patients could be explained by the high bowel volume receiving irradiation by this treatment. 916 poster PROTECTIVE ROLE OF CARNITINE AGAINST RADIATIONINDUCED KIDNEY DAMAGE IN INFANT RATS: SCINTIGRAPHIC AND HISTOPATHOLOGIC EVALUATION C. Rusen1 , G. Durmus Altun2 , F. Oz Puyan3 , M. Saynak1 , K. Ibis1 , A. Özen1 , G. Bayir-Angin1 , F. Ustun4 , B. Denizli1 , S. Parlar1 , M. Caloglu1 , V. Yurut-Caloglu1 , M. C. Uzal1 , Z. Koçak1 1 T RAKYA U NIVERSITY M EDICAL FACULTY, Radiation Oncology, Edirne, Turkey 2 T RAKYA U NIVERSITY M EDICAL FACULTY, Nuclear Medicine, Edirne, Turkey 3 T RAKYA U NIVERSITY M EDICAL FACULTY, Pathology, Edirne, Turkey 4 C ANAKKALE U NIVERSITY FACULTY OF M EDICINE, Nuclear Medicine, Canakkale, Turkey Purpose: The aim of this paper is to clarify, whether L-carnitine has a protective effect in prevention of radiation induced nefrotoxicity (RIN) during late phase following radiation therapy in an infant rat model. Materials: Thirty-one two-week-old male Wistar albino rats divided into four groups. Group 1 (n=10): Control, Group 2 (n=10): L-Carnitine alone, Group 3 (n=10): Irradiation alone (RT), Group 4 (n=10): L-Carnitine before irradiation (L-Carnitine + RT), injected with L-Carnitine (LC) (300 mg/kg) i.p., 30 minutes before the irradiation. The rats in the RT and L-Carnitine + RT groups were
Conclusions: The use of radioprotective drug is more important for children where there is probability of long-term survival. L-Carnitine is a natural substance, which is well tolerated and can be given by oral administration. L-Carnitine may have protective effects on RT-induced late nephrotoxicity in infantile period. 917 poster RADIATION-INDUCED CHRONIC-OXIDATIVE RENAL DAMAGE CAN BE REDUCED BY AMIFOSTINE C. Rusen1 , V. Yurut-Caloglu1 , S. Eskiocak2 , A. Özen1 , K. Ibis1 , N. Turan3 , B. Denizli1 , M. C. Uzal1 , M. Kaldir4 , M. Saynak1 , S. Parlar1 , M. Caloglu1 , B. Uregen1 , Z. Koçak1 1 T RAKYA U NIVERSITY M EDICAL FACULTY, Radiation Oncology, Edirne, Turkey 2 T RAKYA U NIVERSITY M EDICAL FACULTY, Biochemistry, Edirne, Turkey 3 T RAKYA U NIVERSITY M EDICAL FACULTY, Biostatistics, Edirne, Turkey 4 ˘ EBV SAGLIK ÜRÜNLER˙I SAN.VE T˙IC.LTD ST ¸ ˙I, Radiation Oncology, Istanbul, Turkey Purpose: In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Materials: Thirty Wistar-Albino 3-4 months old, female rats, were randomly divided into Group I (n=10): Control, Group II (n=10): Irradiation-alone, Group III (n=10): Amifostine before irradiation. In group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a Co60 treatment unit. Rats in group III received 200 mg/kg amifostine intraperitoneally, 30 minutes prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One way ANOVA, Post-hoc Bonferroni, Dunnett T3 and Mann-Whitney U tests. Results: Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (p=0.004, p=0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (p=0.02, p=0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (p=0.002, p=0.016; respectively). Tissue GSH activity was increased following amifostine administration (p=0.001) (Table 1). Conclusions: Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy. 918 poster RENAL FUNCTION AFTER PREOPERATIVE CHEMORADIATION FOR T3-PANCREATIC CANCER S. NAKAMURA1 , Y. Kawaguchi1 , O. Suzuki1 , K. Nishiyama1 1 O SAKA M EDICAL C ENTER FOR C ANCER AND C ARDIOVASCULAR D IS EASES, Radiation Oncology, Osaka, Japan Purpose: We performed a combination of preoperative concurrent chemoradiotherapy (CRT) with full-dose gemcitabine (GEM) and postoperative liver
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the rectal mucosa in the present study. The results indicated late radiation proctitis followed acute proctitis. We could establish an animal experimental model of late radiation proctitis, and also established a novel method to evaluate the severity of late radiation proctitis focusing microangiopathy. Our animal experimental model may be also used as an animal experimental model of radiation induced microangiopathy. 915 poster MORBIDITY PROFILES FOLLOWING CONFORMAL VS. INTENSITYMODULATED RADIOTHERAPY FOR URINARY BLADDER CANCER. J. Søndergaard1 , M. Holmberg2 , A. R. Jakobsen3 , L. P. Muren4 , C. Grau1 ,
irradiated individually with a single dose of 8 Gy. 2, 2, 4 and 1 deaths were occurred in groups, respectively. Animals underwent both Tc99m DTPA (Diethylene triamine pentaacetic acid) dynamic renal imaging and Tc99m DMSA (Dimercaptosuccinic acid) static renal imaging at the end of three months follow-up period. Proximal tubular degeneration, tubular atrophy, interstitial fibrosis and glomerular degeneration were assessesed histopathologically. Results: The mean Tmax and T1/2 values in the RT group were 4.2 ± 0.8 and 14.5 ± 4.1, respectively. In the L-Carnitine + RT group, those values were 2.8 ± 0.4 and 12.8 ± 1.7 and significantly lower than those in the RT group (p=0.03, p=0.04). In L-Carnitine + RT group, the glomerular structures were well protected compared to RT group (0.78 ± 0.22 vs. 1.88 ± 0.58, p=0.04) (Table 1).
M. Hoyer1 1 A ARHUS U NIVERSITY H OSPITAL, Department of Oncology, Aarhus C, Denmark 2 A ALBORG U NIVERSITY H OSPITAL, Department of Oncology, Aalborg, Denmark 3 A ALBORG U NIVERSITY H OSPITAL, Department of Medical Physics, Aalborg, Denmark 4 A ARHUS U NIVERSITY H OSPITAL, Department of Medical Physics, Aarhus C, Denmark Purpose: The improved dose distributions of intensity modulated radiotherapy (IMRT) compared to conformal radiotherapy (CRT) is well characterized in radiotherapy (RT) of pelvic tumours. Moreover, previous studies in particular for prostate cancer have reported a reduction of toxicity enabling treatment intensification and improved outcome. In RT of bladder cancer large intestinal volumes are irradiated in particular when pelvic lymph nodes are included in the target. The purpose of the present study was to evaluate acute and late toxicity following RT for bladder cancer and to correlate these to dose-volume parameters. This analysis was performed in patients treated in the same time period at two different RT centres where patients according to local policy received IMRT in one centre and CRT in the other. Materials: 116 consecutively treated patients with muscle invasive bladder cancer who received either CRT (n=66) or IMRT (n=50) in the time period 2007-2010 were analysed. Patient charts and treatment plans were retrospectively evaluated. A cross-sectional evaluation of late toxicity was performed by telephone interview of 44 surviving and recurrence free patients. Acute and late toxicity was scored according to the Common Terminology Criteria for Adverse Event version 3.0 (CTCAE). The toxicity scores were dichotomized, and comparisons between the groups were analyzed by twosided Fishers exact test and logistic regression modelling where appropriate. Results: Acute diarrhoea grade 2+ occurred more frequently in patients treated by CRT (56%) compared to IMRT (30%) (p=0.008). There were no differences in other acute gastrointestinal (GI) toxicities such as bowel pain or the use of anti-diarrhoea medication. The acute genitourinary (GU) toxicities were not different in the two groups receiving IMRT or CRT. Logistic regression analysis revealed a statistically significant correlation between acute diarrhoea and volume of bowel cavity exposed to irradiation. Severe late toxicity (CTCAE grade 3+) was recorded in 10% in the total patient cohort; there was no difference between the IMRT and CRT groups. In the cross-sectional study any late grade 2+ GI toxicity occurred in 17% and 40% of patients receiving IMRT and CRT, respectively (p=0.1), while the corresponding no. for any late grade 2+ GU toxicity were 63% and 48% of the patients (p=0.4). Conclusions: Patients treated with IMRT experienced significantly less acute diarrhoea compared to those treated with CRT, whereas there was no significant difference in late morbidity. The increased occurrence of acute diarrhoea in CRT patients could be explained by the high bowel volume receiving irradiation by this treatment. 916 poster PROTECTIVE ROLE OF CARNITINE AGAINST RADIATIONINDUCED KIDNEY DAMAGE IN INFANT RATS: SCINTIGRAPHIC AND HISTOPATHOLOGIC EVALUATION C. Rusen1 , G. Durmus Altun2 , F. Oz Puyan3 , M. Saynak1 , K. Ibis1 , A. Özen1 , G. Bayir-Angin1 , F. Ustun4 , B. Denizli1 , S. Parlar1 , M. Caloglu1 , V. Yurut-Caloglu1 , M. C. Uzal1 , Z. Koçak1 1 T RAKYA U NIVERSITY M EDICAL FACULTY, Radiation Oncology, Edirne, Turkey 2 T RAKYA U NIVERSITY M EDICAL FACULTY, Nuclear Medicine, Edirne, Turkey 3 T RAKYA U NIVERSITY M EDICAL FACULTY, Pathology, Edirne, Turkey 4 C ANAKKALE U NIVERSITY FACULTY OF M EDICINE, Nuclear Medicine, Canakkale, Turkey Purpose: The aim of this paper is to clarify, whether L-carnitine has a protective effect in prevention of radiation induced nefrotoxicity (RIN) during late phase following radiation therapy in an infant rat model. Materials: Thirty-one two-week-old male Wistar albino rats divided into four groups. Group 1 (n=10): Control, Group 2 (n=10): L-Carnitine alone, Group 3 (n=10): Irradiation alone (RT), Group 4 (n=10): L-Carnitine before irradiation (L-Carnitine + RT), injected with L-Carnitine (LC) (300 mg/kg) i.p., 30 minutes before the irradiation. The rats in the RT and L-Carnitine + RT groups were
Conclusions: The use of radioprotective drug is more important for children where there is probability of long-term survival. L-Carnitine is a natural substance, which is well tolerated and can be given by oral administration. L-Carnitine may have protective effects on RT-induced late nephrotoxicity in infantile period. 917 poster RADIATION-INDUCED CHRONIC-OXIDATIVE RENAL DAMAGE CAN BE REDUCED BY AMIFOSTINE C. Rusen1 , V. Yurut-Caloglu1 , S. Eskiocak2 , A. Özen1 , K. Ibis1 , N. Turan3 , B. Denizli1 , M. C. Uzal1 , M. Kaldir4 , M. Saynak1 , S. Parlar1 , M. Caloglu1 , B. Uregen1 , Z. Koçak1 1 T RAKYA U NIVERSITY M EDICAL FACULTY, Radiation Oncology, Edirne, Turkey 2 T RAKYA U NIVERSITY M EDICAL FACULTY, Biochemistry, Edirne, Turkey 3 T RAKYA U NIVERSITY M EDICAL FACULTY, Biostatistics, Edirne, Turkey 4 ˘ EBV SAGLIK ÜRÜNLER˙I SAN.VE T˙IC.LTD ST ¸ ˙I, Radiation Oncology, Istanbul, Turkey Purpose: In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Materials: Thirty Wistar-Albino 3-4 months old, female rats, were randomly divided into Group I (n=10): Control, Group II (n=10): Irradiation-alone, Group III (n=10): Amifostine before irradiation. In group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a Co60 treatment unit. Rats in group III received 200 mg/kg amifostine intraperitoneally, 30 minutes prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One way ANOVA, Post-hoc Bonferroni, Dunnett T3 and Mann-Whitney U tests. Results: Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (p=0.004, p=0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (p=0.02, p=0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (p=0.002, p=0.016; respectively). Tissue GSH activity was increased following amifostine administration (p=0.001) (Table 1). Conclusions: Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy. 918 poster RENAL FUNCTION AFTER PREOPERATIVE CHEMORADIATION FOR T3-PANCREATIC CANCER S. NAKAMURA1 , Y. Kawaguchi1 , O. Suzuki1 , K. Nishiyama1 1 O SAKA M EDICAL C ENTER FOR C ANCER AND C ARDIOVASCULAR D IS EASES, Radiation Oncology, Osaka, Japan Purpose: We performed a combination of preoperative concurrent chemoradiotherapy (CRT) with full-dose gemcitabine (GEM) and postoperative liver