The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: HIPEC Technologies.

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

Cytoreduction and HIPEC in the Netherlands: nationwide long-term outcome following the Dutch protocol.

PURPOSE: This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol. METHODS: In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival. RESULTS: Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III-V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0-166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36-46 months). Median progression-free survival was 15 months (95 % CI 13-17 months) for CRC patients and 53 months (95 % CI 40-66 months) for PMP patients. Overall median survival was 33 (95 % CI 28-38 months) months for CRC patients and 130 months (95 % CI 98-162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients. CONCLUSIONS: The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.

Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study.

The aim of our study was to provide population-based data on incidence and prognosis of synchronous peritoneal carcinomatosis and to evaluate predictors for its development. Diagnosed in 1995-2008, 18,738 cases of primary colorectal cancer were included. Predictors of peritoneal carcinomatosis were analysed by multivariable logistic regression analysis. Median survival in months was calculated by site of metastasis. In the study period, 904 patients were diagnosed with synchronous peritoneal carcinomatosis (4.8% of total, constituting 24% of patients presenting with M1 disease). The risk of peritoneal carcinomatosis was increased in case of advanced T stage [T4 vs. T1,2: odds ratio (OR) 4.7, confidence limits 4.0-5.6), advanced N stage [N0 vs. N1,2: OR 0.2 (0.1-0.2)], poor differentiation grade [OR 2.1 (1.8-2.5)], younger age [<60 years vs. 70-79 years: OR 1.4 (1.1-1.7)], mucinous adenocarcinoma [OR 2.0 (1.6-2.4)] and right-sided localisation of primary tumour [left vs. right: OR 0.6 (0.5-0.7)]. Median survival of patients with peritoneum as single site of metastasis remained dismal [1995-2001: 7 (6-9) months; 2002-2008: 8 (6-11) months], contrasting the improvement among patients with liver metastases [1995-2001: 8 (7-9) months; 2002-2008: 12 (11-14) months]. To conclude, synchronous peritoneal metastases from colorectal cancer are more frequent among younger patients and among patients with advanced T stage, mucinous adenocarcinoma, right-sided tumours and tumours that are poorly differentiated. The prognosis of synchronous peritoneal carcinomatosis remains poor with a median survival of 8 months and even worse if concomitant metastases in other organs are present.

The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases: A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI).

INTRODUCTION: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. MATERIALS AND METHODS: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. RESULTS: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. CONCLUSION: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.

8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer.

INTRODUCTION: The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy. In 2003, a randomized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. This trial showed a positive result favoring the studied treatment. This trial has now been updated to a minimal follow-up of 6 years to show long-term results. PATIENTS AND METHODS: For all patients still alive, the follow-up was updated until 2007. In the original study, four patients were excluded-two because of no eligible histology/pathology and two because of major protocol violations. After randomization, four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy, one patient because of withdrawal, one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment. During the follow-up, one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease, after the assigned treatment was completed. The data from these patients were censored at the moment of the cross-over. Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method. The long-term results were studied in more detail to evaluate efficacy and toxicity. RESULTS: At the time of this update, the median follow-up was almost 8 years (range 72-115 months). In the standard arm, 4 patients were still alive, 2 with and 2 without disease; in the "HIPEC' arm, 5 patients were still alive, 2 with and 3 without disease. The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm (P = 0.020). The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm (P = 0.028). The 5-year survival was 45% for those patients in whom a R1 resection was achieved. CONCLUSION: With 90% of all events having taken place up to this time, this randomized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin. For a selected group, there is a possibility of long-term survival.

The eligibility for local-regional treatment of peritoneal surface malignancy.

At the Fifth International Workshop on Peritoneal Surface Malignancy, held in Milan, the consensus on technical aspects of cytoreductive surgery (CRS) for peritoneal surface malignancy was obtained through the Delphi process. General conflicting points concerning the eligibility to the local-regional therapy were discussed and voted.

Short-term outcome in patients treated with cytoreduction and HIPEC compared to conventional colon cancer surgery.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an extensive procedure with considerable morbidity. Since only few hospitals perform CRS + HIPEC, this might lead to confounded outcomes between hospitals when audited. This study aims to compare outcomes between peritoneally metastasized (PM) colon cancer patients treated with CRS + HIPEC and patients undergoing conventional colon surgery. Furthermore, the impact of CRS + HIPEC on the risk of postoperative complications will be assessed, probably leading to better insight into how to report on postoperative outcomes in this distinct group of patients undergoing extensive colon surgery.All patients with primary colon cancer who underwent segmental colon resection in a tertiary referral hospital between 2011 and 2014 were included in this prospective cohort study. Outcome after surgery was compared between patients who underwent additional CRS + HIPEC treatment or conventional surgery.Consequently, 371 patients underwent surgery, of which 43 (12%) underwent CRS + HIPEC. These patients were younger and healthier than patients undergoing conventional surgery. Tumor characteristics were less favorable and surgery was more extensive in CRS + HIPEC patients. The morbidity rate was also higher in CRS + HIPEC patients (70% vs 41%; P < 0.001). CRS + HIPEC was an independent predictor of postoperative complications (odds ratio 6.4), but was not associated with more severe postoperative complications or higher treatment-related mortality.Although patients with colonic PM undergoing CRS + HIPEC treatment were younger and healthier, the postoperative outcome was worse. This is most probably due to less favorable tumor characteristics and more extensive surgery. Nevertheless, CRS + HIPEC treatment was not associated with severe complications or increased treatment-related mortality. These results stress the need for adequate case-mix correction in colorectal surgery audits.

Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.

PURPOSE: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin. PATIENTS AND METHODS: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival. RESULTS: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001). CONCLUSION: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.

Peritoneal metastases from small bowel cancer: Results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in The Netherlands.

INTRODUCTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is currently considered the standard of care for pseudomyxoma peritonei, mesothelioma and peritoneal metastases (PM) from colorectal cancer. CRS + HIPEC has also been suggested as a potential treatment option in PM of the much rarer small bowel cancer. Therefore, the current study was undertaken to investigate the results of CRS + HIPEC in all HIPEC centers in The Netherlands. METHODS: From the 4 tertiary referral centers for peritoneal surface malignancies in The Netherlands, data from all patients with peritoneally metastasized small bowel carcinoma intended to undergo CRS and HIPEC were collected between January 2005 and July 2014. Primary tumor characteristics, operative details, and survival outcomes were collected. RESULTS: Sixteen of 19 patients (84.2%) who underwent explorative laparotomy underwent CRS + HIPEC. Of these patients, 81.3% were female, and primary tumors were mainly located in the ileum (50%). A complete macroscopic resection was achieved in 93.8%. Serious adverse events requiring re-intervention occurred in 25%, and no in-hospital mortality was observed. Recurrent disease was observed in 50% of patients and median survival after CRS and HIPEC was 31 months. CONCLUSION: In a select group of patients in whom a complete macroscopic resection can be achieved, survival rates comparable with those in colorectal PM are attainable with acceptable morbidity. The role of adjuvant chemotherapy needs further research.

Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy.

BACKGROUND: During recent years, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin has been used for various malignancies. OBJECTIVE: To characterise the population pharmacokinetics and pharmacodynamics of mitomycin during HIPEC. METHODS: Forty-seven patients received mitomycin 35 mg/m2 intraperitoneally as a perfusion over 90 minutes. Mitomycin concentrations were determined in both the peritoneal perfusate and plasma. The observed concentration-time profiles were used to develop a population pharmacokinetic model using nonlinear mixed-effect modelling (NONMEM). The area under the plasma concentration-time curve (AUC) was related to the haematological toxicity. RESULTS: Concentration-time profiles of mitomycin in perfusate and plasma were adequately described with one- and two-compartment models, respectively. The average volume of distribution of the perfusate compartment (V1) and rate constant from the perfusate to the systemic circulation (k12) were 4.5 +/- 1.1L and 0.014 +/- 0.003 min(-1), respectively (mean +/- SD, n = 47). The average volume of distribution of the central plasma compartment (V2), clearance from the central compartment (CL) and volume of distribution of the peripheral plasma compartment (V3) were 28 +/- 16L, 0.55 +/- 0.18 L/min and 36 +/- 8L, respectively. The relationship between the AUC in plasma and degree of leucopenia was described with a sigmoidal maximum-effect (Emax) model. CONCLUSIONS: The pharmacokinetics of mitomycin during HIPEC could be fitted successfully to a multicompartment model. Relationships between plasma exposure and haematological toxicity were quantified. The developed pharmacokinetic-pharmacodynamic model can be used to simulate different dosage schemes in order to optimise mitomycin administration during HIPEC.

Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: a near pathologic complete response does not translate into good clinical outcome.

BACKGROUND: After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum. AIM: The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients. METHODS: Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6-8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators. RESULTS: The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators. CONCLUSION: The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that "watch-and-wait" in LARC patients should be applied with care.

Long-term results of cytoreduction and HIPEC followed by systemic chemotherapy.

Cytoreduction followed by hyperthermic intraperitoneal chemotherapy is a treatment option for peritoneal surface malignancies in The Netherlands. This treatment has been available for more than 10 years. Therefore, long-term results on survival and quality of life can now be studied. With these results, the true long-term benefits of this new management strategy can be determined.

Survival analysis of pseudomyxoma peritonei patients treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE: To evaluate the survival of patients with pseudomyxoma peritonei (PMP) treated by cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and to identify factors with prognostic value. SUMMARY BACKGROUND DATA: PMP is a clinical syndrome characterized by progressive intraperitoneal accumulation of mucous and mucinous implants, usually derived from a ruptured mucinous neoplasm of the appendix. Survival is dominated by pathology. METHODS: A total of 103 patients (34 men and 69 women) treated at The Netherlands Cancer Institute between 1996 and 2004 were identified. Survival was calculated from date of initial treatment and corrected for a second procedure. PMP was pathologically categorized into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and an intermediate subtype (PMCA-I). Clinical and pathologic factors were analyzed to identify their prognostic value for survival. RESULTS: Median follow-up was 51.5 months (range, 0.1-99.5 months). Recurrence developed in 44%. A second procedure for recurrence was performed in 11 patients. The median disease-free interval was 25.6 months (95% confidence interval [CI], 14.8-43.6 months). The 3-year and 5-year disease-free survival probability was 43.6% (95% CI, 34.4%-55.2%) and 37.4% (95% CI, 28.2%-49.5%), respectively. The disease-specific 3-year and 5-year survival probability was 70.9% (95% CI, 62.0%-81.2%) and 59.5% (95% CI 48.7%-72.5%), respectively. Factors associated with survival were pathological subtype, completeness of cytoreduction, and degree and location of tumor load (P < 0.05). The main prognostic factor, independently associated with survival, was the pathologic subtype (P < 0.01). CONCLUSION: Cytoreductive surgery in combination with intraoperative HIPEC is a feasible treatment strategy for PMP in terms of survival. The pathologic subtype remains the dominant factor in survival. Patients should be centralized to improve survival by a combination of surgical experience and adequate patient selection.

Progression of pseudomyxoma peritonei after combined modality treatment: management and outcome.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment strategy for pseudomyxoma peritonei (PMP) with curative intent. The aim of this study was to determine the patterns of failure in patients who underwent such a procedure and to evaluate management and outcome of progressive disease. METHODS: After exclusion of patients with overt malignancy, progression was studied in 96 PMP patients treated primarily by CRS with HIPEC. Location, pathology, management and outcome were recorded. RESULTS: Median follow-up was 51.5 months (0.1-99.5). Median progression free survival (PFS) was 28.2 months (95% CI 18.3->). Progressive disease was mainly located sub hepatic (38%) or in multiple regions (36%). Pathological dedifferentiation was observed in 8 patients (20%). The choice of treatment depended on pathology, extent of disease and PFS. Seventeen patients were treated for progression by second CRS with (n=8) or without HIPEC (n=10). The 3-years overall survival (OS) probability after this treatment was 100% and 53.3% (95% CI 28.2-100%), respectively. Fifteen patients with (slow) progression were observed. Three-years OS probability of these patients was 66.0% (95% CI 43.4-100%). All patients treated for progression by systemic chemotherapy only (n=6) had died of disease after a median follow up of 14.8 (9.8-33.6) months. A longer PFS after primary treatment was associated with longer OS after progression (P = 0.04). CONCLUSIONS: Progressive PMP after primary CRS with HIPEC is probably the result of technical failure and/or tumor biology. Management of progressive PMP can be valuable for selected patients and should depend primarily on the PFS.

Long-term survival of peritoneal carcinomatosis of colorectal origin.

BACKGROUND: Peritoneal carcinomatosis of colorectal cancer is probably best treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). In The Netherlands Cancer Institute, this treatment has been performed since 1995. The long tradition of this treatment enabled us to study long-term survival in detail. METHODS: Between 1995 and 2003, 117 patients were treated by cytoreduction and HIPEC. The aim of the cytoreduction was to remove all visible tumor. After the cytoreduction, the abdomen was perfused with mitomycin C (35 mg/m2) at 40 degrees C to 41 degrees C for 90 minutes. Survival was calculated by the Kaplan-Meier method. Survival was also analyzed for the following subgroups: no residual tumor, residual tumor < or = 2.5 mm, and more residual tumor. Hazard ratios for each of the seven abdominal regions were calculated to determine the influence on survival. RESULTS: The median survival was 21.8 months. The 1-, 3-, and 5-year survival rates were 75%, 28%, and 19%, respectively. The Kaplan-Meier curve reached a plateau of 18% at 54 months. In 59 patients a complete cytoreduction was achieved, and in 41 patients there was minimal residual disease. The median survival of these patient groups was 42.9 and 17.4 months, respectively. When gross macroscopic tumor was left behind, as was the case in 17 patients, the median survival was 5 months. Involvement of the small bowel before cytoreduction was associated with poorer outcome. CONCLUSIONS: Cytoreduction followed by HIPEC showed a median survival of 21 months. From 3 years on, a consistent group of 18% of patients stayed alive.

Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Cytoreduction with hyperthermic intra-peritoneal chemotherapy (HIPEC) is a treatment with a high morbidity. Optimal patients selection can possible reduce toxicity and complications. PATIENTS AND METHODS: Complications and toxicity of 102 patients were studied. Toxicity was graded according National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A complication was defined as any post-operative event that needed re-intervention. Potential patients, tumor, and treatment factors were studied on their relation to complications. RESULTS: Grade 3, 4, or 5 toxicity was observed in 66 patients (65%). Eight patients died of treatment-related causes. Surgical complications occurred in 36 patients (35%). Fistulae were frequently encountered (18 patients). The risk of a complicated recovery was higher in carcinomatosis with recurrent colorectal cancer (P = 0.009) and in the case of more than five regions affected (P = 0.044), who had a Simplified Peritoneal Cancer (SPC) score of 13 (P = 0.012) and with an incomplete initial cytoreduction (P = 0.035). Patients with blood loss exceeding 6 L (P = 0.028) and those with three or more anastomoses also had an increased post-operative complication rate (P = 0.018). CONCLUSIONS: Toxicity of cytoreduction followed by HIPEC was 65% (Grade 3-5 NCI CTC), with a surgical complication rate of 35%. Patients with six or seven regions involved and those in whom complete cytoreduction cannot be reached are probably better off without this treatment.