49. Timing of systemic chemotherapy in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and HIPEC

ABSTRACTS Methods: From a prospective database of 120 patients affected by PMP who underwent cytoreductive surgery (CRS) plus HIPEC, we selected 70 patients with a follow-up >36 months. Overall survival (OS) according to pathological classifications (DPAM vs PMCA, low- vs high-grade PMP and G1 vs G2-3) and tumour markers levels were calculated. A Ca125 level >35 U/L, Ca19.9 >37 U/mL and CEA >5 ng/mL were considered threshold values. Survival curves were compared using the log-rank test. From this cohort of patients, samples of peritoneal metastases (14 PMP, 4 CRC) were selected to perform microarray-based global mRNA expression profiling. Results: Survival analysis performed according with three different histopathological classification systems (Ronnet, p ¼ 0.2358; WHO, p ¼ 0.8017 and AJCC, p ¼ 0.9148) and with the levels of three independent tumor markers (Ca125, p ¼ 0.5983; Ca19.9, p ¼ 0.7164 and CEA, p ¼ 0.2255) do not show any significant correlation with patient OS. Gene expression profiling was then exploited to stratify samples accordingly with Levine transcriptional criteria. We found that genes distinctive of cluster 3 properly distinguish CRC carcinomatosis from PMP, while only few genes of cluster 1 are expressed in our samples. The stratification of PMP according with genes of cluster 2, highlighted the presence of two subgroups. This preliminary analysis, based on a small-sized dataset, suggests that these two groups do not show significant differences in terms of OS. Conclusions: Histopathological and biochemical classification don’t reliably predict long-term OS. Transcriptome analysis confirmed that CRC and PMP are two different tumor types characterized by distinctive molecular features. Preliminary data suggest that the prognostic values of previously defined gene expression signatures may not faithfully predict patient prognosis. We are considering other transcriptional traits to improve patient stratification and prognosis prediction. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.053

48. MicroRNA prognostic signature for distant relapse in early stage colon cancer M. Bobowicz1, M. Skrzypski2, P. Czapiewski3, M. Marczyk4, A. Maciejewska5, M. Jankowski6, A. Szulgo-Paczkowska7, W. Zegarski6, R. Pawłowski5, J. Pola nska4, W. Biernat3, 1 2 J. Jaskiewicz , J. Jassem 1 Medical University of Gdansk, Department of Surgical Oncology, Gdansk, Poland 2 Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland 3 Medical University of Gdansk, Department of Pathomorphology, Gdansk, Poland 4 Silesian University of Technology, Data Mining Group, Gliwice, Poland 5 Medical University of Gdansk, Institute of Forensic Medicine, Gdansk, Poland 6 Collegium Medicum of Nicolaus Copernicus University, Chair of Oncological Surgery, Bydgoszcz, Poland 7 Centre of Oncology, Department of Clinical Oncology, Bydgoszcz, Poland Background: The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse. We searched for microRNA-based signature with prognostic significance in this group. Material and methods: We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumor samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between 40 patients who did and 45 who did not develop distant metastases in the first four years after resection. Additionally, miRNA expression was compared between 85 cancer and 14 normal colon mucosa

S85 samples and between the mismatch repair (MMR) competent and deficient tumors. Results: We developed 5-miRNA signature (miR-1296, miR-135b, miR539, miR-572 and miR-185), which was found prognostic (p ¼ 1.28E07, HR8.4 [95% CI 3.81e18.52]) for distant metastasis-free survival (DMFS) and further cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74% and 78%, respectively. Additionally, low expression of miR-1300 and miR-939 was significantly correlated with shorter DMFS in Cox univariate analysis (p ¼ 0.049) after correction for multiple testing. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of miR-888 and miR-1243 was specific for CC (p.adjusted <0.05). Conclusions: We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage colon cancer. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.054

49. Timing of systemic chemotherapy in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and HIPEC H. Van Eden1, N. Kok1, K. Jozwiak2, G. Beets1, M. Van Leerdam3, H. Boot3, A. Aalbers1 1 Netherlands Cancer Institute e Antoni van Leeuwenhoek Hospital, Surgical Oncology, Amsterdam, Netherlands 2 Netherlands Cancer Institute e Antoni van Leeuwenhoek Hospital, Epidemiology and Biostatistics, Amsterdam, Netherlands 3 Netherlands Cancer Institute e Antoni van Leeuwenhoek Hospital, Medical Oncology and Gastroenterology, Amsterdam, Netherlands Background: Timing of systemic chemotherapy in patients with colorectal peritoneal carcinomatosis (PC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. Neoadjuvant systemic chemotherapy may offer benefits, including selection of patients with early progressive disease and an increase of the rate of patients treated with multimodal therapy. The aim of this study was to evaluate the effect of neoadjuvant systemic chemotherapy on survival. Materials and methods: Data of patients undergoing CRS-HIPEC in a tertiary referral centre from January 2004 to June 2015 were registered. The influence of patient-related, tumor-related and treatment-related factors on disease free survival (DFS) and overall survival (OS) were investigated using Cox regression models. Timing and number of cycles of systemic chemotherapy were included in the multivariate model. Main outcome was OS. Results/Discussion: Two hundred eighty consecutive patients underwent CRS-HIPEC. In group A 78 patients (28%) were treated with neoadjuvant or perioperative chemotherapy and CRS-HIPEC. In group B 169 patients (60%) were intentionally treated with CRS-HIPEC and adjuvant chemotherapy. In group C 33 patients (12%) had received their chemotherapy before PC was diagnosed. Median follow-up time was 29.8 months (IQR 17.4e52.5). Median disease free survival was 20.3 months (IQR 13.3e40.4) and did not significantly differ between the treatment groups (P ¼ 0.29). Median OS was 36.9 months (IQR 20.6e79.7) in group A, 43.1 months (IQR 25.7e95.9) in group B and 34.0 months (IQR 20.0e53.7) in group C (P ¼ 0.19). Extent of PC (region count of 3e5 (HR 1.58 (95% CI 1.02e2.45)) and 6e7 (HR 3.34 (95% CI 1.66e6.72)) vs 1e2 regions), a higher lymph node ratio (HR 7.96 (95% CI 2.16e29.31) and cycles of systemic chemotherapy (0 cycles (HR 2.52 (95% CI 1.48e4.29) and partial chemotherapy (HR 2.15 (95% CI 1.27e3.65) vs complete chemotherapy) were associated with poorer OS. Conclusion: Timing of systemic chemotherapy does not appear to have impact on survival in patients with colorectal PC undergoing CRS-HIPEC. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.055