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4065 Background: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) was recently introduced in the palliative treatment of peritoneal metastases (PM). Results from preclinical experiments suggest that intraperitoneal (IP) Nab-PTX may result in superior efficacy compared to solvent based paclitaxel (PTX). We performed a phase I first-in-human trial of PIPAC using Nab-PTX in patients with PM from upper gastrointestinal, breast, or ovarian cancer. Methods: Eligible patients with biopsy-proven PM underwent up to three PIPAC treatments using Nab-PTX with a four-week interval at two university hospitals. Patients underwent laparoscopy with IP nebulization of Nab-PTX over 5 min; the procedure was completed after 30 min. The dose of Nab-PTX was escalated from 35 to 140 mg/m2 using a Bayesian approach until the maximally tolerated dose (MTD) was reached. Secondary endpoints included surgical morbidity, pharmacokinetics (PK), histological treatment response, and overall survival. Blood and tissue samples were taken after each PIPAC procedure. Population PK analysis was performed using Monolix version 2020R1. Quality of life was measured using the EORTC QLQ-C30 questionnaire and visual analogue pain scales (VAS). Results: Twenty-three patients were included. The primary tumor was gastric cancer (55%), ovarian cancer (20%), hepatobiliary or pancreatic cancer (15%), breast cancer (5%), and miscellaneous (5%). No dose limiting toxicity was observed. Grade 3 thrombopenia was observed in one patient allocated to a dose of 90 mg/m2. One patient allocated to the highest dose experienced grade 3 neutropenia one week after each PIPAC. The most frequent treatment-related toxicities were liver toxicity (grade 1 to 3, 75%) and anemia (grade 1 to 3, 70%). Eight patients (40%) showed surgical site infections including wound infection and wound dehiscence (grade 1 to 3), four of whom required treatment with antibiotics. Treatment was associated with histological response in 35% of patients, while stable disease and progressive disease were found in 35% and 30%, respectively. The absorption of PTX continued long after the end of the procedure (30 min), with the Tmax reached between 2 and 6 h after initiation of the procedure. Median tumor PTX concentrations suggested accumulation: 9.37 ng/mg, 14.78 ng/mg and 25.75 ng/mg after the first, second and third PIPAC, respectively. EORTC global health, functional, and symptom scores as well as VAS scores remained stable throughout the treatment period. Overall survival after one year was 57%. Conclusions: PIPAC with Nab-PTX may be applied safely up to a dose of 140 mg/m2 and results in a favorable PK profile and promising anticancer activity. At the MTD of 140 mg/m2, considerable surgical site infections and liver toxicity were observed. Therefore, the recommended dose for future phase II trials is 112.5 mg/m2. Clinical trial information: NCT03304210.

3587Background: Metastasis to locoregional lymph nodes (LN) is one of the most powerful predictors of recurrence free survival (RFS) in colon cancer (CC). Debate persists on the prognostic value of...

e13524 Background: Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) to treat mucinous intra-abdominal tumors began in 1980.1 More recently, the combination of complete cytoreductive surgery and ...

4033 Background: We built nomograms for predicting overall (OS) and progression-free survivals (PFS) in patients with pseudomyxoma peritonei (PMP) treated with cytoreductive surgery (CRS)+/-intraperitoneal chemotherapy (IPCT). Methods: Data from 1,715 PMP patients in 31 centers from 1993 to 2012 constituted the developing set. The covariates were previous systemic chemotherapy (sCT), histologic subtype (Ronnett’s criteria), peritoneal cancer index (PCI), completeness of cytoreduction (CC), IPCT (Hyperthermic intraperitoneal chemotherapy [HIPEC], early postoperative chemotherapy [EPIC], or both), lymph node status (LN), G3-5 morbidity (NCI CTCAE v3), and surgical proficiency. Centers with >100 procedures for PMP were considered proficient. Continuous variables were transformed using restricted cubic splines. We handled missing data using multiple imputation with chained equations (MICE) approach. We fitted a Cox model in each of the different completed developing datasets generated by MICE. Pooled estimate...

e14067 Background: Mucinous colorectal adenocarcinoma (MAC) has been known and studied for many years. The prognostic significance of this histological subtype remains controversial. We reviewed th...

15040 Background: Peritoneal carcinomatosis (PC) has a dismal prognosis. Cytoreductive surgery with HIPEC has been introduced in the management of PC with biologically favourable features. Methods: In an eight year period, 130 patients were treated (53% female, mean age 56±1 years). The origin of PC was colorectal cancer (CRC, 58%), pseudomyxoma peritonei (PMP, 9%), ovarian cancer (17%), primary peritoneal mesothelioma (10%) and gastric cancer (6%). Surgery was followed by HIPEC with mitomycin C (90 min, 35 mg/m2), oxaliplatin (30 min, 460 mg/m2) or cisplatin (90 min, 100–250 mg /m2) depending on tumour histology and previous systemic chemotherapy. The extent of disease was scored using a scale ranging from 0–9, while completeness of cytoreduction (CC) was scored as complete (CC0), nearly complete (CC1, miliary residual disease) or incomplete (CC2, gross residual disease). Target intraperitoneal temperature was 41°C-42°C. Actuarial survival was calculated using the Kaplan Meier method and univariate analysis performed using the log rank method. Results: Open perfusion (coliseum technique) was used in 41% of procedures. Macroscopically complete resection was achieved in 41%. Postoperative 30 day mortality was 1.5% while major morbidity developed in 18% of patients. Morbidity was mainly related to the extent of surgery. Median overall survival (months) was as follows: CRC, 20; PMP, 38; ovarian cancer, 19; gastric cancer, 10; mesothelioma, 9. Median survival was significantly better in CC0 patients (40 months) compared to CC1 (17 months) or CC2 (12 months). Survival was significantly worse in patients with ascites at surgery (p No significant financial relationships to disclose.

3550 Background: Neoadjuvant therapy is an integral part of rectal cancer management. Prediction of response to radiotherapy (RT) is highly relevant for both further surgery and prognosis in these patients. In a rat colorectal cancer model, we studied the use of DCE-MRI with a new macromolecular rapid clearance contrast agent (P792) to visualize tumor vascular permeability as a surrogate marker for angiogenesis and evaluate the effect of RT. Methods: Male WAG/Rij rats were injected with 2x106 CC531 cells in the hind leg. Once the tumor reached a diameter of 1 cm, DCE-MRI with high temporal resolution was performed before and 5 days after 5x500 cGy of external RT. The DCE-MRI data were used to generate parametric tissue permeability maps of the endothelial transfer constant (Ktrans) according to the Tofts-Kermode two compartment mathematical model. Separate region of interest (ROI) analyses were performed of the entire tumor (T), periferal vascular rim (P) and tumor core (C). In order to differentiate perm...