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11069 Background: Objective parameters identifying ideal pts for MT from pts with a/mSTS remain scarce. Here, we analysed the impact of sacropenia in a/mSTS pts on treatment outcome of MT, retrospectively. Methods: Pts. with a/m STS treated at our centre (12/98-5/16ere identified. 89/181 pts were evaluable for analysis (CT-scans: -14 days before MT onset). Lumbar skeletal muscle index (SMI) was measured with MeVisLab 2.7 by manually segmentation of preinterventional CTs. SMI cut-off were defined through optimal fitting method (sarcopenia = SMI(+) in male: < 44 , in female: 38). Progression was defined by clinical or radiological judgment. Descriptive statistics, Kaplan-Meier-analysis and Cox-regression were administered. Results: At MT onset 28/89 pts (31%) suffered from sarcopenia, and SMI(+) pts were older than SMI(-) pts (p = 0.025). SMI(+) pts tends to receive lower numbers of medical treatments, received less often surgery, and more frequently radiotherapy, although differences were not significant. Further on, SMI(+) pts tends to profit less from first line medical treatment, compared to SMI(-) pts (objective responses: 14,3% vs. 27.9%, p = .161, clinical benefit rate: 25% vs. 65.6%, p = .032, PFS: 1 (95%-CI:.35-1.65) vs. 16 (95%CI:8.8-23.2) months, p = .002). OS was inferior in SMI(+) compared to SMI(-) pts. (4 (95%CI:2-6) vs. 16 (95%CI:8.8-23.2), p = .002). Multivariable analysis showed a trend for SMI(+) to be associated with PFS (HR: 1.7 (95%CI: 0.9-2.8), p = .067) and were independently associated with OS (HR: 2.53 (95%CI: 1.5-4.2), p < .001). Conclusions: In our cohort sarcopenia tends to be associated with less aggressive therapy in a/mSTS pts. However, sarcopenia tends to be associated with inferior PFS and was identified as independent risk factor for inferior OS. Although this analysis is limited due to its sample size sarcopenia might offer an attractive tool as guidance for treatment intensity modulation in a/mSTS patients, avoiding overtreatment in this cohort with dismal prognosis.

e23566Background: MT applies to a selected group of pts with a/m STS. The impact of MT on prognosis remains undefined. We report results on palliative medical treatment (Rx) with MT(+) or without M...

e13039 Background: Lipocalin-2 is a pleiotropic protein synthesized under acute phase conditions. The source of increased serum levels and the major organ responsible for its production are still unknown. The aim of our study was to prospectively evaluate the Lipocalin-2 (LCN-2) expression in rat liver exposed to single dose x-irradiation. Methods: A single dose of 25 Gy was administered percutaneously to the liver of randomly paired rats after a planning CT scan. Male Wistar rats were sacrificed 1, 3, 6, 12, 24 and 48 hours after irradiation along with sham irradiated control. Blood was taken for ELISA of LCN-2, and organs were removed and deep-frozen for RT-PCR and Western Blot or prepared for immunostaining. Furthermore, hepatocytes, myofibroblasts and Kupffer cells were isolated from the liver of healthy rats and irradiated with 2 Gy ex-vivo. Results: LCN-2 serum levels increased significantly (2.5 mg/ml) within 24 hours after direct liver irradiation. In the liver, LCN-2 specific transcripts increased significantly up to 552 ±109-fold at 24 hours which was further confirmed by Western blot analysis. Immunohistology of liver sections detected positivity in recruited granulocytes within 1 hour after irradiation around the central and portal areas. Ex-vivo irradiated hepatocytes showed a significantly higher LCN-2 expression as compared to myofibroblasts and Kupffer cells. Treatment of isolated, irradiated hepatocytes with acute phase cytokines (IL-6, IL-1b, TNFa, IL-6+TNFa) showed that the main inducer of LCN-2 was IL-1β. Conclusions: Single dose liver irradiation, induces a fast and significant increase of LCN-2 serum level. Hepatocytes are the major producers of LCN-2 in oxidative stress conditions. LCN-2 may represent a new serum-biomarker when the liver is hit by irradiation.

e21128 Background: Radiotherapy alone or in combination with systemic therapies, is a major tool for local tumor control. Although organ-targeting techniques have greatly been improved over the past years, radiation enteropathy is a dose-limiting factor for effective radiotherapy. The out-of-field effects on the intestine, caused by radiation treatment of a parenchymatous organ, have not previously been studied. Methods: A single dose of 25 Gray was administered percutaneously to the liver of male Wistar rats after a planning CT-scan. Sham-irradiated animals served as controls. At 1, 6, 24, 96 hours, 1.5 and 3 months the duodenum, jejunum, ileum and distal colon were removed, washed and deep-frozen or prepared for paraffin staining. Results: All animals survived the treatment. Epithelial cell damage occurred in all small-intestinal segments. However, prolonged denudation of the villi together with destruction of the crypt lining was only observed in the ileum, which only received scattered radiation. Whilst the intestinal lining in the duodenum and jejunum was restored at the end of the study, in the ileum, tissue regeneration was deficient. In the colon, changes were minor. Immunhistochemical staining showed radiation mucositis with granulocyte (MP0+) infiltration from 1 to 24 hours in the duodenum and jejunum, when ED1+ macrophages, CD3+ T-lymphocytes, and CD34+ hematopoietic precursor cells were recruited, accompanied by an increase in the chemokines MCP-1, MIP-1α, MIP3α and Il-8. In the ileum, early granulocyte infiltration was delayed but continuous. Recruitment of macrophages and lymphocytes was deficient and induction of chemokines as of the adhesion molecules PECAM-1, ICAM-1 was lacking. Conclusions: Post-irradiation damage to the ileum was delayed and followed by an altered repair process with structural changes of the villi. The observed changes might result from a higher sensitivity to oxidative stress mechanisms with subsequent damage of the regenerative capacity of the crypt-villus axis, accompanied by a sustained “inflammatory response” and vascular damage with a lack of regeneratory cell recruitment.

LBA3505 Background: The German CAO/ARO/AIO-94 trial established preoperative chemoradiotherapy (CRT), surgery, and postoperative chemotherapy with 5-FU as standard treatment for locally advanced rectal cancer. With this approach local relapse rates are below 10%. The development of distant metastasis is the predominant mode of failure. Integrating more effective systemic treatment into combined modality therapy was the goal of CAO/ARO/AIO-04. Methods: Between 7/2006-2/2010, patients with rectal cancer within 12 cm from the anal verge and clinical evidence of perirectal fat or lymph node involvement were randomly assigned to receive preoperative CRT, surgery, and adjuvant chemotherapy with 5-FU according to CAO/ARO/AIO-94 (arm 1), or preoperative CRT (50.4 Gy in 28 fractions) with 5-FU (250 mg/m2/days 1-14 and 22-35) and oxaliplatin (50 mg/m2/days 1, 8, 22, 29), surgery, and 8 cycles of adjuvant chemotherapy according to modified FOLFOX6 regimen (arm 2). Disease-free survival was the primary endpoint. We present early secondary endpoints, including acute toxicity, treatment compliance, and pCR-rates. Results: 637 patients were randomly assigned to arm 1 and 628 to arm 2. Full dose preoperative RT and full dose concurrent chemotherapy was delivered in 97% and 74% of patients in both arms, respectively. Preoperative grade 3/4 toxicity occurred in 21.6% in arm 1 and in 22.9% in arm 2. The R0-resection rate was 95.4% in both arms, and abdominoperineal resections were limited to 11.9% and 12.2% in arms 1 and 2, respectively. Overall postoperative complications were not different between both arms (21.0% and 21.9%). The pCR rate (ypT0N0) was 13.1% in arm 1 and 17.6% in arm 2 (p = 0.033, Cochran-Mantel-Haenszel Chi-Squared Test without continuity correction for conditional independence of pCR rate in the two treatment arms in each stratum). Conclusions: Inclusion of oxaliplatin to 5-FU based CRT was well tolerated and associated with increased pCR-rates compared with 5-FU-CRT alone. Longer follow-up is necessary to evaluate the primary endpoint, disease-free survival.

e21107 Background: Primary liver tumors or liver metastasis are treated by gamma-irradiation. However, the liver is considered to be a radio-sensitive organ. Methods: Rats were exposed to single-do...