Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases.

BACKGROUND: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population. This study investigates to what extent systemic anti-cancer therapy crosses the peritoneal barrier. METHODS: In a Phase I study, eighteen patients received systemic oxaliplatin, 5-FU, and bevacizumab. Plasma and peritoneal fluid samples were collected to measure drug concentrations. A non-compartmental analysis determined the Area Under the Curve (AUC) for oxaliplatin and 5-FU in both matrices. Intraperitoneal (IP) and intravenous (IV) exposure ratios were calculated, along with the bevacizumab concentration IP/IV ratio. The relationship between tumour load and IP/IV ratios and the correlation between the IP/IV ratios of different treatments were assessed statistically. RESULTS: A total of 438 5-FU samples and 578 oxaliplatin samples were analysed in plasma and peritoneal fluid. Bevacizumab was quantified with 17 measurements in plasma and 15 measurements IP. Median IP/IV ratios were 0.143, 0.352 and 0.085 for 5-FU, oxaliplatin and bevacizumab, respectively. Oxaliplatin exhibited a longer IP half-life than 5-FU. A correlation was found between oxaliplatin and bevacizumab IP/IV ratios (R=0.69, p=0.01). No statistical correlations were found between the other investigated drugs. CONCLUSIONS: Our findings indicate that only a small percentage of systemically administered anti-cancer treatment reaches the IP cavity, questioning their efficacy against PM. This strengthens the hypothesis for repeated intraperitoneal chemotherapy to reach adequate anti-cancer drug levels.

Population pharmacokinetics of intraperitoneal irinotecan and SN-38 in patients with peritoneal metastases from colorectal origin.

Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS-HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN-38 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2 weeks in combination with systemic FOLFOX-bevacizumab. Irinotecan and SN-38 were measured in plasma (588 samples) and SN-38 was measured in peritoneal fluid (267 samples). Concentration-Time data were log-transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter-individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN-38 plasma volume of distribution and GGT was found to influence the SN-38 plasma clearance. This population PK model adequately described the irinotecan and SN-38 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN-38 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.

The importance of integrating diagnostic modalities in patient selection for CRS-HIPEC in colorectal peritoneal metastases.

BACKGROUND: Despite thorough preoperative work-up for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), so called open-close (OC) procedures as a result of irresectable disease remain common. Currently, diagnostic laparoscopy (DLS) is considered the gold standard, and consequently overrules the results of computed tomography (CT) scans; however, certain regions of the abdomen are difficult to assess and postoperative adhesion formation may further compromise staging during DLS. PURPOSE: To determine whether better clinical assessment could be achieved by combining the results of DLS and preoperative CT scans during a multidisciplinary team (MDT) meeting. MATERIAL AND METHODS: All patients who were eligible for CRS-HIPEC after DLS, but eventually underwent an OC procedure between 2010 and 2018 were selected. Radiological reassessment of CT scans was performed and combined with assessment of the DLS during a MDT meeting. The MDT was blinded for the outcome of the procedure (OC vs. CRS-HIPEC). RESULTS: The majority of the OC procedures (69%) was correctly predicted by the MDT. In most patients (88%), this conclusion was based on the combination of the radiological and surgical peritoneal cancer index (PCI). CT was particularly accurate for detection of larger tumor deposits in the abdominal regions, as 84%-86% was detected. Assessment of lesions in the small bowel regions is troublesome; 72% of lesions are missed on the preoperative CT scan. CONCLUSIONS: A combination of radiological and surgical assessment of the PCI may lead to improved preoperative patient selection for CRS-HIPEC.

Adjuvant dendritic cell-based immunotherapy after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with malignant peritoneal mesothelioma: a phase II clinical trial.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is an aggressive malignancy with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival outcomes, but recurrence rates remain high. Dendritic cell-based immunotherapy (DCBI) showed promising results in patients with pleural mesothelioma. The primary aim of this trial was to determine feasibility of adjuvant DCBI after CRS-HIPEC. METHODS: This open-label, single-center, phase II clinical trial, performed in the Erasmus MC Cancer Institute Rotterdam, the Netherlands, included patients with epithelioid MPM. 4-6 weeks before CRS-HIPEC leukapheresis was performed. 8-10 weeks after surgery, DCBI was administered three times biweekly. Feasibility was defined as administration of at least three adjuvant vaccinations in 75% of patients. Comprehensive immune cell profiling was performed on peripheral blood samples prior to and during treatment. RESULTS: All patients who received CRS-HIPEC (n=16) were successfully treated with adjuvant DCBI. No severe toxicity related to DCBI was observed. Median progression-free survival (PFS) was 12 months (IQR 5-23) and median overall survival was not reached. DCBI was associated with increased proliferation of circulating natural killer cells and CD4+ T-helper (Th) cells. Co-stimulatory molecules, including ICOS, HLA-DR, and CD28 were upregulated predominantly on memory or proliferating Th-cells and minimally on CD8+ cytotoxic T-lymphocytes (CTLs) after treatment. However, an increase in CD8+ terminally differentiated effector memory (Temra) cells positively correlated with PFS, whereas co-expression of ICOS and Ki67 on CTLs trended towards a positive correlation. CONCLUSIONS: Adjuvant DCBI after CRS-HIPEC in patients with MPM was feasible and safe, and showed promising survival outcomes. DCBI had an immune modulatory effect on lymphoid cells and induced memory T-cell activation. Moreover, an increase of CD8+ Temra cells was more pronounced in patients with longer PFS. These data provide rationale for future combination treatment strategies. TRIAL REGISTRATION NUMBER: NTR7060; Dutch Trial Register (NTR).

Phase I study of intraperitoneal irinotecan combined with palliative systemic chemotherapy in patients with colorectal peritoneal metastases.

BACKGROUND: Patients with colorectal peritoneal metastases who are not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) owing to extensive peritoneal disease have a poor prognosis. It was hypothesized that these patients may benefit from the addition of intraperitoneal irinotecan to standard palliative systemic chemotherapy. METHODS: This was a classical 3 + 3 phase I dose-escalation trial in patients with colorectal peritoneal metastases who were not eligible for CRS-HIPEC. Intraperitoneal irinotecan was administered every 2 weeks, concomitantly with systemic FOLFOX (5-fluorouracil, folinic acid, oxaliplatin)-bevacizumab. The primary objective was to determine the maximum tolerated dose and dose-limiting toxicities. Secondary objectives were to elucidate the systemic and intraperitoneal pharmacokinetics, safety profile, and efficacy. RESULTS: Eighteen patients were treated. No dose-limiting toxicities were observed with 50 mg (4 patients) and 75 mg (9 patients) intraperitoneal irinotecan. Two dose-limiting toxicities occurred with 100 mg irinotecan among five patients. The maximum tolerated dose of intraperitoneal irinotecan was established to be 75 mg, and it was well tolerated. Intraperitoneal exposure to SN-38 (active metabolite of irinotecan) was high compared with systemic exposure (median intraperitoneal area under the curve (AUC) to systemic AUC ratio 4.6). Thirteen patients had a partial radiological response and five had stable disease. Four patients showed a complete response during post-treatment diagnostic laparoscopy. Five patients underwent salvage resection or CRS-HIPEC. Median overall survival was 23.9 months. CONCLUSION: Administration of 75 mg intraperitoneal irinotecan concomitantly with systemic FOLFOX-bevacizumab was safe and well tolerated. Intraperitoneal SN-38 exposure was high and prolonged. As oncological outcomes were promising, intraperitoneal administration of irinotecan may be a good alternative to other, more invasive and costly treatment options. A phase II study is currently accruing.

Patients with extensive colorectal peritoneal metastases who are not eligible for surgery and heated intraperitoneal chemotherapy have poor survival. The authors tried to improve the survival of these patients by adding intraperitoneal (inside the abdominal cavity) chemotherapy to standard palliative chemotherapy which is administered into the bloodstream. In this trial, irinotecan (a type of chemotherapy) was administered into the abdomen of patients with extensive colorectal peritoneal metastases. The authors investigated which dose could be administered safely in combination with standard palliative chemotherapy. They also looked into toxicity, safety, benefit, and movement of the drug in the body. Eighteen patients were treated in this study. The maximum tolerated dose of intraperitoneal irinotecan was 75 mg. It was well tolerated and could be administered safely. The intra-abdominal amount of irinotecan was high, whereas the amount of irinotecan in the blood remained low. The benefits of intra-abdominal irinotecan were promising. Because of this, a new study has been started to further investigate this new combination chemotherapy for colorectal cancer.

Nasogastric- vs. percutaneous gastrostomy tube for prophylactic gastric decompression after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

OBJECTIVES: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with postoperative gastroparesis and ileus. In 2015, our practice shifted from using percutaneous gastrostomy tubes (PGT), to nasogastric tubes (NGT) for prophylactic gastric decompression after CRS-HIPEC. This study aimed to compare these methods for length of stay (LOS) and associated complications. METHODS: Patients that underwent CRS-HIPEC for peritoneal metastases from colorectal cancer between 2014 and 2019 were included. Cases were grouped based on receiving NGT or PGT postoperatively. Multivariable linear regression determined the independent effect of decompression method on LOS, thereby adjusting for confounders. RESULTS: In total, 179 patients were included in the analyses. Median age was 64 years [IQR:54-71]. Altogether, 135 (75.4%) received a NGT and 44 (24.6%) received a PGT. Gastroparesis occurred significantly more often in the PGT group (18.2 vs. 7.4%, p=0.039). Median LOS was significantly shorter for patients with a NGT (15 [IQR:12-19] vs. 18.5 [IQR:17-25.5], p<0.001). PGT was independently associated with longer LOS in multivariable analysis (Beta=4.224 [95%CI 1.243-7.204]). There was no difference regarding aspiration, pneumonia and postoperative mortality between groups. CONCLUSIONS: NGT should be preferred over PGT for gastric decompression after CRS-HIPEC as it is associated with fewer gastroparesis and shorter LOS.

The Accuracy of the Surgical Peritoneal Cancer Index in Patients with Peritoneal Metastases of Colorectal Cancer.

INTRODUCTION: The peritoneal cancer index (PCI) is one of the most important prognostic factors in patients with peritoneal metastases from colorectal cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by 2 experienced surgeons and plays a major role in the decision to proceed with CRS-HIPEC. The primary objective of this study was to determine the accuracy of the surgical PCI (sPCI) by comparing it with the PCI confirmed by the pathologist (pPCI). METHODS: All consecutive patients who underwent CRS-HIPEC for colorectal peritoneal metastases between February 2015 and June 2018 were identified. Relevant patient- and tumor-related characteristics were collected. RESULTS: In total, 119 patients were included, 60 males (50.4%). The median age was 64 (IQR 55-71). The median sPCI (sPCI = 11, IQR 6-16) was significantly higher than the median pPCI (pPCI = 8, IQR 3-13, p < 0.001). The total pPCI was lower than the total sPCI in 80 patients (67.2%). In 21 patients (17.6%), the sPCI was overestimated with ≥5 points. Small lesions are more likely to be negative. In patients that underwent resection of their primary tumor prior to CRS-HIPEC, the difference between the sPCI and pPCI was significantly larger (p < 0.05). CONCLUSIONS: Surgical calculation of the PCI often results in overestimation. Far-reaching consequences are tied to the macroscopic evaluation of the sPCI, but this evaluation seems not very reliable.

Predictive Ability of C-Reactive Protein in Detecting Short-Term Complications After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Retrospective Cross-Sectional Study.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment for peritoneal carcinomatosis. OBJECTIVE: The aim of this study was to determine the predictive value of postoperative inflammatory biomarkers in assessing complications after CRS and HIPEC. METHODS: A prospective database of 181 patients, who underwent CRS-HIPEC between March 2014 through April 2018 in the Erasmus MC, was retrospectively analyzed. Postoperative complications were defined according to the serious adverse event (SAE) grading system. Levels of C-reactive protein (CRP) and white blood cell (WBC) count were compared between patients with SAE grade < 3 and SAE grade ≥ 3. The area under the receiver operating characteristic curve (AUC) was calculated for CRP and WBC against SAE ≥ 3 and various intra-abdominal complications. RESULTS: SAE ≥ 3 postoperative complications occurred in 50 patients. From the second until the fifth postoperative day (POD), CRP levels were significantly higher (p = 0.023, p < 0.001, p = 0.002, and p = 0.002, respectively) in these patients. CRP concentrations above 166 mg/L on POD3 (AUC 0.75) and 116 mg/L on POD4 (AUC 0.70) were associated with the highest risk of an SAE ≥ 3. Postoperative WBC levels were not significantly different between patients with SAE < 3 and SAE ≥ 3 complications. CONCLUSION: Data from our hospital suggest that CRP levels that continue to rise after POD2 or that are ≥ 166 mg/L at POD3 or ≥ 116 mg/L at POD4, indicate a considerable risk for developing high-grade SAEs. The cut-off values we found can potentially be used as a threshold for additional diagnostic interventions, after they have been validated in external data.

A population-based study on the prognostic impact of primary tumor sidedness in patients with peritoneal metastases from colon cancer.

Primary tumor location is an established prognostic factor in patients with (metastatic) colon cancer. Colon tumors can be divided into left-sided and right-sided tumors. The aim of this study was to determine the impact of primary tumor location on treatment and overall survival (OS) in patients with peritoneal metastases (PM) from colon cancer. This study is a retrospective, population-based cohort study. Records of patients diagnosed with colon cancer and synchronous PM, from 1995 through 2016, were retrieved from the Netherlands Cancer Registry (NCR). Data on diagnosis, staging, and treatment were extracted from the medical records by specifically trained NCR personnel. Information on survival status was updated annually using a computerized link with the national civil registry. In total, 7930 patients were included in this study; 4555 (57.4%) had a right-sided and 3375 (42.6%) had a left-sided primary tumor. In multivariable analysis right-sided primary tumor was associated with worse OS (HR: 1.11, 95% CI 1.03-1.19, P = .007). Of all patients diagnosed with PM, 564 (7.1%) underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with left-sided primary tumors were more often candidates for CRS-HIPEC (6.5% vs. 8.0%, P = .008). OS of patients with right- and left-sided tumors who underwent CRS-HIPEC did not significantly differ. In conclusion, primary right-sided colon cancer was an independent prognostic factor for decreased OS in patients diagnosed with synchronous PM. In patients treated with CRS-HIPEC location of the primary tumor did not influence survival.

Malignant Peritoneal Mesothelioma: Patterns of Care and Survival in the Netherlands: A Population-Based Study.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. Recently, focus has shifted toward a more aggressive and multimodal treatment approach. This study aimed to assess the patterns of care and survival for MPM patients in the Netherlands on a nationwide basis. METHODS: The records of patients with a diagnosis of MPM from 1993 to 2016 were retrieved from the Dutch Cancer Registry. Data regarding diagnosis, staging, treatment, and survival were extracted. Cox regression analyses and Kaplan-Meier survival curves were used to study overall survival. RESULTS: Between 1993 and 2016, MPM was diagnosed for 566 patients. Overall, the prognosis was very poor (24% 1-year survival). The most common morphologic subtype was the epithelioid subtype (88%), followed by the biphasic (8%) and sarcomatoid (4%) subtypes. Surgical treatment has become more common in recent years, which most likely has resulted in improved survival rates. In this study, improved survival was independently associated with hyperthermic intraperitoneal chemotherapy (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.21-0.55) and surgery with adjuvant systemic chemotherapy (HR, 0.33; 95% CI, 0.23-0.48). Nonetheless, most patients (67%) do not receive any form of anti-cancer treatment. CONCLUSION: This study indicated that MPM still is a rare and fatal disease. The survival rates in the Netherlands have improved slightly in the past decade, most likely due to more aggressive treatment approaches and increased use of surgery. However, most patients still do not receive cancer-directed treatment. To improve MPM management, and ultimately survival, care should be centralized in expert medical centers.

Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial.

INTRODUCTION: Malignant peritoneal mesothelioma (MPM) is an uncommon but aggressive neoplasm and has a strong association with asbestos exposure. MPM has low survival rates of approximately 1 year even after (palliative) surgery and/or systemic chemotherapy. Recent advances in treatment strategies focusing on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have resulted in improved median survival of 53 months and a 5 year survival of 47%. However, recurrence rates are high. Current systemic chemotherapy in the adjuvant setting is of limited efficacy, while immunotherapy with dendritic cell based immunotherapy (DCBI) has yielded promising results in murine models with peritoneal mesothelioma and in patients with pleural mesothelioma. METHODS AND ANALYSIS: The MESOPEC trial is an open-label single centre phase II study. The study population are adult patients with histological/cytological confirmed diagnosis of epithelioid malignant peritoneal mesothelioma. INTERVENTION: 4 to 6 weeks before CRS-HIPEC a leukapheresis is performed of which the monocytes are used for differentiation to dendritic cells (DCs). Autologous DCs pulsed with allogeneic tumour associated antigens (MesoPher) are re-injected 8 to 10 weeks after surgery, three times biweekly. Additional booster vaccinations are given at 3 and 6 months.Primary objective is to determine the feasibility of administering DCBI after CRS-HIPEC in patients with malignant peritoneal mesothelioma. Secondary objectives are to assess safety of DCBI in patients with peritoneal mesothelioma and determine whether a specific immunological response against the tumour occurs as a result of this adjuvant immunotherapy. ETHICS AND DISSEMINATION: Permission to carry out this study protocol has been granted by the Central Committee on Research Involving Human Subjects (CCMO in Dutch) and the Research Ethics Committee (METC in Dutch). The results of this trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NTR7060. EudraCT: 2017-000897-12; Pre-Results.

Perioperative systemic therapy and cytoreductive surgery with HIPEC versus upfront cytoreductive surgery with HIPEC alone for isolated resectable colorectal peritoneal metastases: protocol of a multicentre, open-label, parallel-group, phase II-III, randomised, superiority study (CAIRO6)

BACKGROUND: Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. METHODS: This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0-10 or 11-20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician's discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. DISCUSSION: This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. TRIAL REGISTRATION: Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016-001865-99 .

Short-term complications in elderly patients undergoing CRS and HIPEC: A single center's initial experience.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-established curative treatment for patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP). The study's aim was to present a single center's initial experience with CRS and HIPEC and report the postoperative morbidity in elderly patients. METHODS: A retrospective observational study was conducted of all patients with peritoneally disseminated colorectal cancer or pseudomyxoma peritonei undergoing CRS and HIPEC between March 2014 and March 2017. Patient characteristics and the peri- and postoperative course were reviewed. Elderly patients were defined as those aged ≥ 65 years. Postoperative complications were classified according to the Serious Adverse Event (SAE) grading system. RESULTS: 122 patients undergoing CRS and HIPEC were split into two groups based on age (< 65 years versus ≥ 65 years) at the time of surgery. Both groups were comparable for ASA score, Peritoneal Cancer Index (PCI), procedure time and blood loss. Serious Adverse Event (SAE) grade > 3 morbidity was 26.7% in the elderly group as opposed to 10.4% in the younger group (p = 0.034). Both univariate and multivariate logistic regression analysis demonstrated that age was a significant risk factor (OR = 3.2, 95% CI 1.1-9.4, p = 0.033) for severe postoperative morbidity (SAE > 3). CONCLUSION: This retrospective study showed advanced age to be a significant risk factor for SAE > 3, after undergoing CRS and HIPEC. The initial institutional experience resembles previously published literature in terms of severe postoperative morbidity in elderly patients.

Acute malignant obstruction in patients with peritoneal carcinomatosis: The role of palliative surgery.

INTRODUCTION: Patients with peritoneal carcinomatosis who do not have curative treatment options often develop acute obstructive symptoms and when conservative management fails, surgical treatment is the remaining option. However, palliative surgery is associated with high morbidity and mortality and the chance of success is unclear. The aim of this study was to evaluate outcomes of palliative surgery and to provide guidance for surgeons, medical oncologists and patients in their decision-making. METHODS: All consecutive patients who underwent palliative surgery for acute obstruction caused by peritoneal carcinomatosis between January 2005 and October 2017 where identified. RESULTS: In total 148 patients underwent surgery. Primary malignancy was colorectal cancer (28.4%), neuroendocrine tumor (20.3%), ovarian cancer (14.2%) or 'other' (37.2%). Median length of postoperative hospital stay was 16 days (IQR 9-24). More than half (58.1%) of the patients developed postoperative complications, 29.1% developed ≥2 complications. In-hospital mortality was 8.8%. Readmission (56.1%) and re-obstruction (35.0%) were common. Median overall survival was 119 days (IQR 48-420). Patients with a neuroendocrine tumor had a significantly better overall survival compared to other primary malignancies (p < 0.001). Patients who developed an obstruction during or within 6 months after treatment with chemotherapy had a worse overall survival (p < 0.001), compared to patients treated with chemotherapy longer than 6 months ago, or patients not treated with chemotherapy. CONCLUSION: Palliative surgery is associated with high rates of complications and readmission and re-obstruction are common. Comfort care is often a better option than surgery, especially in patients with disease progression under recent treatment with chemotherapy.