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515 Background: Although radical cystectomy (RC) has been a standard treatment for muscle invasive bladder cancer (MIBC), some patients are unfit or refuse RC. Intraarterial chemotherapy combined with radiotherapy (IAC-RT) is one of the bladder preservation techniques, but there are a few data in patients who performed IAC-RT without salvage RC. The aim of this study was to evaluate the efficacy and tolerability of IAC-RT without RC compared to RC in patients with MIBC. Methods: We retrospectively reviewed patients with MIBC (T2-4N0M0) who had received either IAC-RT or RC in our hospital between January 1999 and December 2019. Intraarterial chemotherapy consisted of cisplatin (30mg/m2) and adriamycin (20mg/m2) on day 1 of each 1st, 2nd, 5th, 6th week. Concomitant radiotherapy (2 Gy/session, total 60 Gy) to whole pelvis was performed during chemotherapy. Salvage RC was not performed in all patients. Overall survival (OS), disease-specific survival (DSS), and metastasis-free survival (MFS) were compared between patients who received IAC-RT and RC. The prognostic factors of IAC-RT associated with OS were also investigated. Results: Forty-two and 143 patients received IAC-RT and RC, respectively. Of 42 patients who received IAC-RT, 28 (67%) and 14 (33%) were elective (refused RC) and imperative (comorbidity:7 poor PS:6 unresectable:1) cases, respectively. The patients who underwent IAC-RT were older (median; 77 vs 69 years old) and had poorer PS (≥2; 43% vs 4.9%) and shorter follow-up time (median; 21.9 vs 40.0 months) than those of RC. During follow up periods, metastasis, bladder cancer death, death of any cause was observed in 20, 19, and 27 patients with IAC-RT, 59, 55, and 49 patients with RC. In survival analyses, median OS was 38.7 months (95%CI, 16.9-74.7) with IAC-RT versus 154.0 months (95%CI, 70.6- not estimable (NE)) with RC, these OS curves were significantly different (P=0.001). There were not significant differences between two groups in DSS (median 46.5 vs not reached, P=0.06) and MFS (median 38.7 vs not reached, P=0.21). In multivariate analysis, clinical stage (≥T3; HR, 1.89; 95% CI, 1.04-3.46; P=0.04) and PS (≥2; HR, 2.24; 95% CI, 1.16-4.33; P=0.02) were suggested as risk factors associated with poor OS, however, treatment procedure (IAC-RT or RC) did not associate with OS. Forty of 42 (95%) patients with IAC-RT had any adverse events (AEs). Although grade3 AEs were observed in 21 (50%) patients, most of them were hematological AEs and Grade 4/5 AEs was not observed. Conclusions: IAC-RT was a useful and tolerable treatment option for patients with MIBC who were unfit or refused RC.

511 Background: The best method of venous thromboembolism (VTE) prevention after surgery for colorectal cancer remains unclear. It is reported that about 20-40% of high-risk patients were diagnosed as DVT and 2-4% was diagnosed as PE and its mortality rate is 0.5-1.0%. The aim of this study is to evaluate the incidence of postoperative VTE patients with colorectal adenocarcinoma and to evaluate the efficacy of VTE preventive strategy. Methods: A total of 264 patients who had undergone curative surgical resection for colorectal cancer at Tokushima University Hospital were included in this study (n = 264 colon: rectum = 1:0.57). All patients were measured D-dimer preoperatively. When D-dimer was ≥ 1.1, lower extremities ultrasonography (US) was performed. All patients were treated with Heparin (10,000U/24h) continuously intravenous injection from the day of surgery, and administered Enoxaparin (2,000U/24h) subcutaneous injection after 24h of the operation. Results: In all 264 patients, 74 (28%) were D-dimer ≥ 1.1 and 16 (6%) diagnosed VTE in US (proximal:distal type n = 6:1). 239 (91%) were treated with postoperative anticoagulant therapy. 2 developed perioperative VTE (symptomatic: asymptomatic = 1:1) and after discharge 12 developed postoperative VTE and mortality rate of VTE was 0%. Univariate analysis indicated that obesity (BMI ≥ 25), hyperlipidemia and preoperative PE were risk factors for deep venous thrombosis (DVT) (p < 0.0001, 0.014, 0.0135, respectively) and multivariate analysis revealed that obesity was an independent risk factor for postoperative DVT (p < 0.0001). Conclusions: Obesity (BMI ≥ 25) was independent risk factor for postoperative VTE. Our preventive protocol including screening using D-dimer and lower extremities US and treatment with Enoxaparin is considered as effective for prevention of postoperative VTE.

584 Background: Clinical and molecular characteristics are different between Right-side and left-sided colorectal cancer (CRC). The aim of this study was to clarify the significance of the correlation of the Sidedness of CRC and tumor immunity. Methods: A total of 116 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of PD-1, PD-L1, FoxP3, TGF-b, and IDO was examined by immunohistochemistry and the relationship of sidedness to several prognostic factors was examined. Results: In clinicopathological factors, there were no significant difference between right sided and left sided CRC except for differentiation. Regarding tumor immunity, there were no significant difference in PD-1 and IDO expression. However, Fox P3 (right side 72% vs. left side 59%) and TGFβ (right side 72% vs. left side 57%) tended to be highly expressed in right side(p < 0.1). PDL1 was significantly highly expressed in right side(right side 65% vs. left side 35%, p < 0.05). In OS and DFS, the patients with right sided tumor tended to have poor prognosis compared with left side (p < 0.1). The PD-L1 positive patients of right-sided tumor had poor prognosis (p < 0.05). Conclusions: Sidedness is associated with tumor immunity in colorectal cancer.

464 Background: In colorectal liver metastasis (CRLM), the difference of tumor malignancy between primary and metastatic lesion has been elucidated. Hypoxia inducible factor-1 (HIF-1) represent tumor malignancy including angiogenesis, tumor growth and epithelial mesenchymal transition (EMT). The aim of this study was to investigate the difference of tumor malignancy between metastatic and primary lesion of CRLM and its impact for patient’s prognosis. Methods: In an initial curative hepatectomy of 75 cases in CRLM, HIF-1 expression in primary and metastatic lesion was evaluated by immunostaining method (Sigma-Aldrich, HPA 001275). Staining score was classified as follows, staining intensity (0: negative, 1: low, 2: medium, 3: high) and staining area (0: 0%, 1: -25%, 2: 26-50%, 3: ≥ 51%), and defined more than 4 points as positive expression. We evaluated the clinicopathological features according to HIF-1 expression. Results: Regarding HIF-1 expression of metastatic site, we divided into the positive group (n = 54) and the negative group (n = 21). There was no difference between metastatic HIF-1 expression and clinicopathological factors. Nevertheless, in overall survival, multivariate analysis revealed that HIF-1 positive in metastasis (HR: 2.850, p = 0.042) and poor differentiation type of primary lesion (HR: 20.873, p = 0.001) were independent prognostic factors. HIF-1 positive and negative patients were 3 year survival of 95.2% and 58.6%, respectively. Also, in disease free survival, HIF-1 positive in metastasis (HR: 2.608, p = 0.004), Synchronous (HR: 1.794, p = 0.049), Grade BC (HR: 2.145, p = 0.008), and lymph node metastasis in primary lesion (HR: 2.070, p = 0.016) was identified. Regarding HIF-1 expression of primary site, we divided into 51 cases of positive group and 24 cases of negative group. There was no relationship to clinicopathological factors as well as HIF-1 expression in metastasis, besides HIF-1 expression of prognosis was not associated. Conclusions: In CRLM, HIF-1 expression in the metastatic lesion is not associated with the primary lesion and may be useful as prognostic marker.

75 Background: Indoleamine 2,3-dioxygenase (IDO) downregulates T cell activation and is related to immune tolerance. The aim of this study was to clarify the significance of IDO expression and to analyze the relationships among the expression of IDO, TGF-b, and Foxp3 in gastric cancer (GC). Methods: Sixty patients who underwent curative gastrectomy for stage III gastric cancer were included in this study. The expressions of IDO, TGF-b, and Foxp3 were examined by immunohistochemistry. The patients were divided into two groups: the IDO-positive group (n = 23) and negative group (n = 37). Clinicopathological factors were compared between the two groups. Univariate analysis was used to assess overall (OS) and disease-free survival (DFS) in several prognostic factors. Multivariate analysis was used to identify the independent prognostic factors. Results: IDO expression was not positively correlated with any clinicopathological factors. IDO expression was positively correlated with TGF-b expression (p < 0.05) and TGF-b expression was positively correlated with FoxP3 expression (p < 0.05). Overall survival (OS) rates were significantly poorer in the IDO-positive group compared with the IDO-negative group (3-year OS, 78.5% vs. 90%, respectively; p < 0.05). Multivariate analysis identified IDO expression as independent prognostic factors in OS. Disease-free survival (DFS) was significantly poorer in the IDO-positive group compared with the IDO-negative group (3-year DFS, 59.3% vs. 69.3%, respectively; p < 0.05). Conclusions: IDO is associated with poor prognosis and immuno-tolerance through Treg in Stage III GC.

88 Background: Thrombospondin-1 (TSP1) correlated with the carcinogenesis in the intestinal inflammation. TSP1 binding CD36 evoked inflammation via the activation of TGFβ and STAT3. The aim of this study is to clarify the role of TSP1 in gastric carcinogenesis. Methods: Thirty-nine patients with gastric cancer who underwent gastrectomy were enrolled. The expression of TSP1 mRNA in non-cancer tissue was determined in clinicopathological factors (including mucosal inflammation and atrophy based on Sydney system). The expressions of CD36, STAT3 and TGFβR2 mRNA in the TSP1 high and low expression group in non-cancer tissue were examined. Results: TSP1 expression was high in mucosal atrophy group and tended to be high in Helicobacter pylori (H.pylori) (+) and multiple cancer group. In TSP1 high group, CD36, STAT3 and TGFβR2 mRNA showed significantly high. The expressions of TSP1 signaling pathway in multiple cancer or atrophy (+) or H.pylori (+) showed high compared with that in single cancer and atrophy (-) and H.pylori (-). The expressions associated TSP1 signaling pathway in non-cancer tissue with multiple gastric cancer showed higher than that with single gastric cancer. Conclusions: Our results indicated TSP1 expressions in non-cancer tissue correlated with gastric carcinogenesis.

249 Background: Heat shock factor 1 (HSF1) is a master regulator of heat shock response. HSF1 is recently identified to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 in intrahepatic cholangiocarcinoma (IHCC) remain unknown. The aim of this study was to investigate the relationship between HSF1 expression and clinicopathological factors in IHCC patients after hepatic resection, and its possible mechanism for malignant behavior. Methods: Forty-nine patients with IHCC who undergo hepatic resection were enrolled in this study. HSF1 expressions in tumor tissue were determined by immunohistochemistry. Patients were divided into two groups, the HSF1 high and low expression group. Clinicopathological factors including prognosis were compared between the high group (n = 20) and low expression groups (n = 29) in tumor tissues. Furthermore, the correlation between HSF1 with Fbxw7 or Ki-67 expressions was also examined. Results: HSF1 expression in tumor tissues was significantly higher than that in normal tissues. HSF1 expression was not significantly correlated with any clinicopathological characteristics, including age, sex, tumor markers, maximum tumor size, tumor number, and tumor staging curability . The overall survival rate in the HSF1 high expression group was significantly worse than that in the HSF1 low expression group ( p= 0.018). On multivariate analysis, HSF1 high expression was detected as the independent prognostic factor. There was a significant inverse correlation between HSF1 and Fbxw7 expression ( p= 0.008). Ki67 labeling index was significantly higher in the high than in the low HSF1 expression group ( p= 0.030). Conclusions: HSF1 high expression in tumor tissues may be prognostic biomarker in IHCC. Targeting the Fbxw7/HSF1 axis might be a critical therapeutic strategy in IHCC.

406 Background: Recently, the perihilar cholangiocarcinoma was defined as a tumor existing perihilar region between the right side of the umbilical portion of the left portal vein and the left side of the origin of the right posterior portal vein, in the General Rules for Clinical and Pathological Studies on Cancer of the Biliary Tract (The 6th edition). The study was aimed to investigate characteristics of intrahepatic cholangiocarcinoma (IHCC) according to tumor location. Methods: Study 1: Sixty-two IHCC patients who underwent hepatic resection were divided into the following 3 groups; peripheral type (n=41), perihilar type (n=10) and unclassified type (peripheral type with perihilar invasion: n=11). Clinicopathological data including CA19-9 and immnohistochemical staining of Ki67 and hypoxia inducible factor-1 (HIF-1) were compared. Study 2: The effect of 2 cycles of adjuvant gemcitabine combined with 5-FU and cisplatin (GFP) (Morine and Shimada. Hepatogastroenterology 2009) was retrospectively investigated, in advanced IHCC with one of 3 prognostic factors of LN metastasis, intrahepatic metastasis and R2 resection. Results: Study 1: There was no difference in background variables except for more frequent hilar biliary invasion in perihilar and unclassified types, and the largest tumor size in unclassified-type. The 5-year survival rate in the peripheral, perihilar and unclassified-types were 44%, 20% and 0%, respectively. In addition, CA19-9 level, Ki67 labelling index and positive rate of HIF-1 expression in the unclassified type were higher than those in other 2 types. Multivariate analysis revealed the unclassified type as an independent prognostic factor. Study 2: In 29 patients (47%) having one of the 3 prognostic factors, 9 patients including 4 unclassified-type IHCCs received the adjuvant GFP. The prognosis in GFP group tended to be better than that in non-GFP group (3-year survival rate: 38% vs. 6%, p = 0.07). Two patients with unclassified-type IHCC in non-GFP group died within 1 year after surgery. Conclusions: The unclassified-type IHCC indicated the most aggressive tumor biology, and the adjuvant GFP may be a useful strategy for such a highly malignant tumor with poor prognostic factors.

708 Background: We have performed preoperative CRT for advanced lower rectal cancer patients using S-1 or UFT. To improve response rate, we are performing phase 2 trial of preoperative CRT using S-1/ Oxaliplatin /Bevacizumab (SOX+Bev) regimen. In this study, we show the results of the trial and the promising predictive factor. Methods: Twenty-five patients (SOX+Bev) and 59 patients (S-1 or UFT) were included in this study. S-1(80mg/m2), UFT(300mg/m2) were administered orally every day on radiation therapy, and S-1(80mg/m2,Oxaliplatin(40-60mg/m2),Bevacizumab(5mg/kg) were administered in SOX+Bev group. Total dose of radiation was 40Gy with four field technique. As a predictive factor, we measured miR-223 with real-time PCR using pre CRT biopsy specimens. Results: Clinical response by RECIST were as follows: SOX+Bev group: CR/PR/SD/PD = 1/21/3/0, S-1/UFT group: CR/PR/SD/PD = 1/32/26/0. Clinical response rate were 88% in SOX+Bev group, higher than 56.0% in S-1/UFT group. Pathological response grade were as follows: SOX+Bev group: 1a/1b/2/3 = 5/4/10/6,S-1/UFT group :1a/1b/2/3 = 13/16/27/3. Pathological response rate was 64% in SOX+Bev group, 51% in S-1/UFT group and there was no significant difference. The pCR rate was 24% in SOX+Bev group, significantly higher than 5% in S-1/UFT group (p < 0.05)B In S-1 group, miR-223 in responder group tended to be higher than non-responder group (p = 0.06). And in SOX+Bev group, miR-223 in Grade 3 group(8.89±9.41) was significantly higher than other group (3.19±4.64) (p = 0.05). Conclusions: Preoperative CRT with SOX+Bev regimen can improve response rate and bring high pCR rate. miR-223 may be promising predictive factor and useful to perform order made therapy. Clinical trial information: 13267.

780 Background: Recent advances in systemic chemotherapy, including molecular target agents, can introduce “Conversion surgery” and achieve R0 resection even for initially unresectable colorectal liver metastasis (CRLM). We investigated the optimal indication for initial surgical induction and treatment strategy for unresectable CRLM. Methods: Our current surgical indication for CRLM as follows: i) curative resection is achievable, ii) no limitation of tumor size and number, and iii) future remnant liver volume over 35%. Additionally, same indication is applied even after chemotherapy.Two hundreds forty-one cases from 1994 to 2015, consisted of 134 initially resectable case and 107 unresectable cases, were included. Among 107 unresectable cases, 55 cases received current chemotherapy such as FOLFOX, FOLFILI, XEROX and FOLFOXIRI. Results: 1) Optimal indication for initially resectable case:Multivariate analysis revealed MDN (Maximum Diameter × Number) index more than 30 of metastatic liver tumor (HR3.06), non-curative resection of metastatic liver tumor (HR4.082) and poor differentiation of primary tumor (HR11.14).2) Treatment strategy of unresectable case for “Conversion surgery” (FOLFOXIRI vs. other regimen): Forty-two unresectable cases with MDN > 30 were included. Of those 14 cases, FOLFOXIRI regimen was applied. Regarding clinicopathological factors, the use of molecular targeted drug was introduced in all patients of FOLFOXIRI group, but 67.9% patients of other regimen group. The “Conversion” rate in FOLFIXIRI group and other regimen group were 64.3% and 39.3% (p = 0.126), and median period until “Conversion” were 6.2 courses and 11.8 courses (p = 0.038). Regarding tumor necrotic rate, FOLFOXIRI regimen induced higher necrotic rate than other regimen group (77.9% vs. 50.4%, p = 0.073). Overall survival in FOLFOXIRI group has been better than that in other regimen group and 3-years survival rates were 83.3% and 48.0% (p = 0.044). Also, relapse free survival in FOLFOXIRI group was significantly better than that in other regimen group (p = 0.002). Conclusions: MDN can predict surgical outcome for CRLM. FOLFOXIRI plus molecular target drug may be a promising option for CRLM with MDN > 30.

767 Background: Recent studies demonstrate the efficacy of irradiation from light emitting diodes (LED) for wound healing and anti-inflammation and anti-cancertherapies. In this study, the blue LED (465nm) suppressed the tumor growth in various cancers. Methods: < Experiment 1, Effect of blue LED on colon cancer > Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were put on LED irradiation equipment with a blue LED (465 nm). Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. Cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. < Experiment 2, Effect of blue LED on pancreas cancer > Human colon cancer cells (SUIT2) were examined by same way and additionally cell cycle was checked. < Experiment 3, Effect of LED on CSCs > Cancer sphere were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-LED. Stemness gene and cell surface markers of CSCs expressions were analyzed by RT-PCR. Results: < Experiment 1 > Viability of HT29 and HCT116 cells was lower in blue LED irradiated cultures than in control cultures. Moreover, the expression of FAS, caspase3, capase8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue LED-irradiated cells. < Experiment 2 > Viability of SUIT2 cells was lower in blue LED irradiated cultures than in control cultures. And the CCND1 mRNA expression was significantly lower in blue LED group (p < 0.05). The cells of phase G2/M was decreased. < Experiment 3 > Cell viability of cancer sphere were significantly decreased by LED irradiation(p < 0.05). And, stemness gene and cell surface markers of CSCs expressions were significantly decreased by LED irradiation (p < 0.05) Conclusions: Blue LED irradiation inhibited tumor growth in various cancer cell lines.

31 Background: PD-1 (Programmed Death 1), a member of the B7-CD28 family, is a cell surface coinhibitory receptor expressed on T cells, B cells, monocytes, and natural killer T cells, following activation. Recently, PD-1 expression is involved with malignancy have been reported in cancer cells and virus-infected cells. The aim of this study is to clarify the impact of PD-1 expression on long term outcome of gastric cancer. Methods: Total of 105 patients who were performed gastrectomy in Stage 2/3 gastric cancer. For resected specimen was performed immunostaining of PD-1. We counted PD-1 positive T cells in the tumor across five adjoining high power fields (×400 magnification level). And, we calculated the percentage of the total cell number, it was considered PD-1 positive more than 40%. We investigated clinicopathological factors and survival. Results: 28 cases were PD-1 positive expression. There was no significant difference between the two groups in the clinicopathological factors (age, gender, tumor size, differentiation, depth of invasion, lymph node metastasis, stage, lymphatic invasion and venous invasion). There was no difference in overall survival rate at 3 years (PD-1 positive vs. negative 76% vs. 81%, p=0.552). PD-1 positive expression was significantly poorer in disease-free survival rate (36% vs. 65%, p=0.022). 10 cases were Foxp3 positive expression, and Foxp3 positive expression was related with PD-1 expression. Conclusions: The PD-1 expression in the tumor could be a potential prognostic factor in gastric cancer.

416 Background: In our principle, hepatectomy is the first choice for liver metastases (mets) from colorectal cancer whenever future remnant liver is over 40% in volume. Recently, FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab (Bev) regimen was reported to be high rates of pathologic responses and necrosis of colorectal liver metastases (CLMs) without increasing liver toxicity (Br J Cancer 2013). The aim of this retrospective study is to clarify impact of FOLFXIRI plus molecular targeted drugs on initially unresectable CLMs. Methods: Among 81 patients with initially unresectable liver mets, 59 had chemotherapy (CTx), including 10 old CTx (-2003) and 49 new CTx (2004- ) using new drugs such as oxaliplatin. Regimen of FOLFOXIRI + molecular target drugs, consisting of Bev in 12 and C/P-mab in 2, was applied to 14 patients. “Conversion” rate and the period until “Conversion”, and overall survival (OS) were compared between FOLOFOXIRI group and other regimen group. Pathological and morphological responses were also examined. Results: “Conversion” was not obtained in old CTx group. In new CTx group, “Conversion” was achieved in 21 patients (43%). OS in “Convresion” group was better than “non-conversion” group (3-year survival: 70 % vs. 15 %). “Conversion” rate in FOLFOXIRI group was higher than that in other regimen group (64% vs. 34%). The period until “Conversion” in FOLFOXIRI group was shorter than that in other regimen group (6.2 cycles vs. 16.1 cycles). Furthermore, tumor necrosis rate in FOLFOXIRI group (80 %) was higher than that in other regimen group (47 %), and morphologic response (optimal/partial) in FOLFOXIRI group (33 % / 44 %) was higher than in other regimen group (8 % / 33 %). Prognosis after “Conversion” in FOLFOXIRI group was better than that in other regimen group (3-year survival: 80 % vs. 33 %). In addition, time to surgical failure (TSF) in FOLFOXIRI group tended to be better than that in other regimen group. Conclusions: FOLFOXIRI + molecular target drugs is highly effective in order to obtain early conversion and better long-term outcome after ”Conversion” for initially unresectable CLMs.

271 Background: Recent studies demonstrate the efficacy of irradiation from light emitting diodes (LED) for wound healing and anti-inflammation and anti-cancertherapies. However, little is known about the effects of LED in colon cancer cells. Furthermore, most solid cancers are believed to be initiated from and maintained by cancer stem cells (CSCs). The purpose of this study was to evaluate the biological response of human colon cancer cells and CSCs to LED irradiation. Methods: Human colon cancer cells (HT29 or HCT116) were seeded onto laboratory dishes that were put on LED irradiation equipment with a 465 nm-, 525 nm-, or 635 nm-LED. Irradiation at 15 or 30 mW was performed 10 min/day, each day for 5 days. Cell counting kit8 was then used to measure cell viability. Apoptosis and expression of several mRNAs (caspase, MAPK and autophagy pathway) in HT29 cultures irradiated with 465 nm LED were evaluated via AnnexinV/PI and RT-PCR, respectively. HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Cancer sphere were seeded onto laboratory dishes that were then put on LED irradiation equipment with a 465 nm-LED. Stemness gene and cell surface markers of CSCs expressions (Oct4, CD44, Nanog, EPCAM) were analyzed by RT-PCR. Results: Viability of HT29 and HCT116 cells was lower in 465 nm-LED irradiated cultures than in control cultures, but viability of HT29 cells did not differ between control cultures and 525 nm-LED or 635 nm-LED irradiated cultures. Moreover, the expression of FAS, caspase3, capase8, and JUK were significantly higher in 465 nm-LED irradiated cultures than in control cultures, and expression of ERK1/2 and LC3 was lower in blue-irradiated cells. Cell viability of cancer sphere were significantly decreased by LED irradiation(p

620 Background: Oxaliplatin(Ox) based regimen is widely used in colorectal cancer patients.One of the major adverse effects of Ox is a neuropathy. There is no useful biomarker predicting such adverse effect. The aim of this study is to evaluate platinum concentration as a biomarker predicting the adverse effect. Methods: Ten patients who underwent curative colectomy were included in this study. Final stage of all patients was UICC stage III. All patients underwent adjuvant chemotherapy by CapeOX regimen for eight cycles (or six months). Blood samples were collected after fourth cycle and last cycle. Ox concentration was measured in red blood cells (RBC) and serum, and evaluated the kinetics of platinum (PL) in blood. In addition, we investigated relationship between Ox concentration and adverse effects. Results: 1) Kinetics of PL concentration: PL concentration in RBC tended to be correlated with the difference of RBC numbers between pre- and post-chemotherapy (R2=0.358, p=0.068). The PL concentration in RBC siginificantly correlated with the difference of mean corpuscular volume (MCV) between pre- and post-chemotherapy (R2=0.661, p=0.004). After four cycle, the platinum concentration in RBC siginificantly correlated with the hemoglobin and hematocrit (R2=0.447, p=0.004 and R2=0.425, p=0.041). There was no siginificant difference in PL concentration in both RBC and serum between the points after four cycle and last cycle points (RBC: 1380.5±495.2 ng/ml vs. 1107.0±699.2 ng/ml Aserum: 210.1±38.9 ng/ml vs. 221.2±99.2 ng/ml). 2) PL concentration and adverse effects: PL concentration did not elevate depending on cycle number. There was no siginificant correlations between PL concentrations in RBC or serum and the grade of neuropathy. Conclusions: The PL concentration was significantly related with the difference of RBC numbers and MCV between pre- and post-chemotherapy. However, there was no siginificant relationship between Ox concentration in blood and side effects including neuropathy. So Ox concentration in blood could not be a reliable biomarker for predicting the grade of neuropathy. Clinical trial information: 000009128.

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

432 Background: Preoperative chemoradiotherapy (CRT) in rectal cancer reduces the local recurrence rate after operation and preserves the anus, but it is difficult to predict the effects of CRT. Our purpose of this study was to determine the effects and adverse events of CRT (S-1 or UFT) and to predict the response to CRT in rectal cancer by using both miRNA and DNA expression patterns. Methods: Rectal cancer patients (n=60) who underwent preoperative CRT were randomly divided into two groups (40Gy radiotherapy combined with S-1: 31 patients or UFT: 29 patients). The effects and adverse events of CRT were compared between S-1 group and UFT group. Additionally, RNA and DNA isolated from biopsy specimens of rectal cancer before preoperative CRT were hybridized to miRNA and DNA microarrays. Response to CRT was determined by histopathologic examination of surgically resected specimens. Results: Response to CRT determined by histopathologic examination of surgically resected specimens and RECIST were as follows: responders (grade 2 or 3) were 60%(S-1) and 52%(UFT) (p=0.52). Adverse events of CRT did not differ significantly between the 2 groups, and there was no adverse event of grade 3 or 4. As candidate predictive genes, 184 genes (S-1 group) and 193 genes (UFT group) were identified by DNA microarray, while 6 miRNA (S-1 group) and 16 miRNA (UFT group) were isolated by miRNA microarray as candidate predictive miRNA. Conclusions: Preoperative CRT using S-1 or UFT to rectal cancer is effective and the adverse events were acceptable. Expression profiling of both gene and miRNA may predict the effects of preoperative CRT, implicating the possible personalized therapy for patients with rectal cancer.

524 Background: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. In ASCO 2008 Gastrointestinal Cancers Symposium, we reported that the patients with up-regulation of 17 genes were suggested to be good responder of CRT. Our purpose of this study was to evaluate the toxicity and efficacy of CRT using UFT versus S-1 and explore biomarkers for response in patients with locally advanced rectal cancer. Methods: Fifty patients who received preoperative CRT (40Gy radiotherapy) were randomly assigned to either UFT or S-1. UFT and S-1 were administered during the radiotherapy course. S-1 was a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase and had potent radiosensitizing property. Biopsy specimens were obtained from rectal cancer before preoperative CRT and were analyzed by focused DNA microarray (132 genes). To pick up the predictive factors, the 132 genes were selected in the view of sensitivity of 5FU. Response to CRT was determined by RECIST and histopathologic examination of surgically resected specimens and classified as responders (CR, PR and grade 2, 3) or nonresponders (SD, PD and grade 0, 1). Results: UFT group (n=25) and S-1 group (n=25) were enrolled. Response rate (grade 2 or 3) to CRT determined by histopathologic examination of surgically resected specimens was 58% in the UFT group and was 75% in the S-1 group. Response rate evaluated by RECIST criteria was 62% in the UFT group and was 77% in the S-1 group. National Cancer Institute Common Toxicity Criteria grade 2 or 3 toxicity was observed in 8% of the patients in the UFT group and 23% of patients in the S-1 group. Grade 2 or 3 toxicity in the UFT group was neutropenia and was diarrhea, neutropenia and dermatitis in the S-1 group. In ASCO 2010, we will report each candidate biomarker genes for response to CRT in the UFT and S-1 group. Conclusions: The results have suggested that CRT using UFT or S-1 is feasible and effective for patients with locally advanced rectal cancer. [Table: see text]

e15056 Background: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but sensory neurotoxicity is its dose-limiting toxicity. The OPTIMOX (stop and go) approach offers a reasonable strategy, but preventive agent is not established. It is reported that Gosha-jinki-gan (a blended herbal medicine) is recently considered as an effective agent for the neurotoxicity of taxanes and for vibration sensation in patients with diabetic neuropathy. Patients and Methods: From 2007, 32 patients treated with modified FOLFOX6 for advanced or unresectable colorectal cancer were randomized. Fifteen patients received oral administration of 7.5 g/day of Gosha-jinki-gan (G group) every days from first course and 17 patients (Control group) did not. Neurotoxicities were evaluated every course according to DEB-NTC (Neurotoxicity Criteria of DEBIOPHARM) and NCI-CTCAE Ver.3.0 using self-check sheet. Results: The median number of cycles of per patient of G group was 14 (range, 4–26), and that of C Group was 9 (range, 1–20). Cumulative dose of oxaliplatin of two groups was 1,190 mg/m2 (G group) and 765 mg/m2 (C Group). Peripheral neurotoxicity evaluated by DEB-NTC in Group G was grade 0 in 0 patients (0%), grade 1 in 11 (73%), grade 2 in 4 (27%) and grade 3 in 0 (0%) and, in C group, respectively, 1 (6%), 6 (35%), 7 (41%), 3 (18%). According to NCI-CTCAE, neurotoxicity was lower in G group than that of C group. Fifteen patients in G group were evaluated by RECIST criteria with a PR rate of 66.7%, SD rate of 20.0% and PD rate of 13.3%. Seventeen patients in C group were evaluated by RECIST criteria with a PR rate of 52.9%, SD rate of 35.3% and disease control rate of 11.8%. Conclusion: Gosha-jinki-gan is effective for preventing oxaliplatin-induced neuropathy in advanced or unresectable colorectal cancer patients. [Table: see text]