Hyperthermic Intraperitoneal Chemotherapy After Cytoreductive Surgery; Experience and Short Term Outcomes

BackgroundSelection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent.MethodsA retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed.ResultsA total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05).ConclusionsPatients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

BackgroundSelection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent.MethodsA retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed.ResultsA total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04).Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05).ConclusionsPatients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Background: Peritoneal metastasis (PM) is an advanced stage of intra-abdominal malignancy with a very poor prognosis. In recent years, hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) has been utilized as an active treatment in the prevention and treatment of PM, with encouraging results. However, compared with CRS alone, the results of the CRS plus HIPEC strategy in the treatment of patients with intra-abdominal malignancies are still controversial. This study sought to determine the impact of HIPEC + CRS on patient survival and adverse events (AEs) by reviewing randomized controlled trials (RCTs) for all types of intra-abdominal malignancies.Methods: A PubMed, Embase, Cochrane Library, Web of Science and Clinical Trials.gov search extracted all RCTs until 12 October 2022, examining the CRS + HIPEC vs. CRS alone strategies in the treatment of various types of intra-abdominal malignancies. The outcomes included overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS) and AEs. The dichotomous data were pooled and reported as odds ratios (ORs) with 95% confidence intervals (CIs). The survival outcome data were pooled using hazard ratios (HRs) and corresponding 95% CIs. The Cochrane Collaboration’s Risk of Bias Tool was used to assess the risk of bias in the included studies.Results: A total of 12 RCTs were included in this meta-analysis, including 873 patients in the CRS + HIPEC group and 878 patients in the CRS alone group. The studies included 3 (617 patients) on colorectal cancer, 4 (416 patients) on gastric cancer, and 5 (718 patients) on ovarian cancer. Our analysis showed no difference in OS between the CRS + HIPEC and CRS alone groups (HR: 0.79, 95% CI 0.62–1.01). Subgroup analysis showed that CRS + HIPEC improved the OS of gastric cancer patients (HR: 0.49, 95% CI 0.32–0.76) compared with CRS alone. However, CRS + HIPEC did not significantly improve the OS of colorectal cancer (HR: 1.06, 95% CI 0.81–1.38) and ovarian cancer (HR: 0.82, 95% CI 0.62–1.07) patients. In addition, there was no significant difference in DFS/RFS (HR: 0.78, 95% CI 0.57–1.07) or PFS (HR: 1.03, 95% CI 0.77–1.38) between the two groups. Compared with CRS alone, CRS with HIPEC had greater nephrotoxicity (OR: 0.45, 95% CI 0.21–0.98), while other AEs did not differ significantly between the two groups.Conclusion: Our results suggest that CRS + HIPEC may improve OS in gastric cancer patients compared with CRS alone, but we did not observe a benefit for DFS/RFS. For patients with ovarian and colorectal cancers, our results suggest that HIPEC + CRS does not appear to improve survival outcomes. In addition, CRS + HIPEC has higher nephrotoxicity than CRS alone. More evidence from RCTs is needed to evaluate whether the use of CRS + HIPEC is an appropriate option.

Peritoneal malignancies (PM) are observed in about 1030% of patients suffering from gastrointestinal malignant diseases, both in connection with the primary surgical management or as metachronous metastases due to cancer recurrence. In the 1980s a new method of cytoreductive surgery (CRS) + HIPEC (hyperthermic intraperitoneal chemotherapy) was introduced. Today, we consider this method to be the gold standard for treatment of pseudomyxoma peritonei and peritoneal mesothelioma. The method increases overall survival (OS) of patients diagnosed with colorectal cancer, primary peritoneal and ovarian cancers. However, the disease recurs after this demanding treatment in the certain group of patients, approximately in 2544% of patients treated for pseudomyxoma peritonei, and in 40% and up to 82% of those treated for mesothelioma and colorectal cancer, respectively. Based on literary data (PubMed-Medline, last 5 years) and our own experience we present the basic factors associated with tumor recurrence, possibility of treatment using repeated CRS + HIPEC, data regarding second-look operations, and as applicable, prophylactic HIPEC. The method CRS + HIPEC provides an effective treatment of peritoneal carcinomatosis even in cases of recurrence. The second-look operations and prophylactic HIPEC may favorably affect the prognosis after primary R0 resections.

Simple SummaryThe vast majority of patients with epithelial ovarian carcinoma (OC) will relapse during the natural history of their disease. The role of cytoreductive surgery (CRS) in the treatment of recurrent disease has been emphasized by current studies. Adding hyperthermic intraperitoneal chemotherapy (HIPEC) has been evolved to improve DFS and OS. There are currently two convincing studies of HIPEC after complete cytoreduction in the treatment of primary OC, but there is little homogenous data on the role of HIPEC in platinum-sensitive recurrent ovarian cancer, its ideal compound, and its duration. The aim of this study was to analyze the bicentric experience with CRS + HIPEC in patients with platinum-sensitive recurrent epithelial OC in order to standardize the surgical approach. Thus, multimodal therapy was feasible with acceptable morbidity and mortality. Cisplatin monotherapy as a HIPEC compound and a 90 min HIPEC application proved to be the best option for regional additive treatment.Background: This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. Methods: The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. Results: The median follow-up was 4.7 years (95%-CI 4.6–5.5). The median age was 55.8 years (IQR: 50.3–66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0–20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1–52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. Conclusion: In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer.

To evaluate the optimal candidates for hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer. Descriptive study. Place and Duration of the Study: Health Sciences University, Dr. Abdurrahman YurtasianAnkara Oncology Training and Research Hospital, Ankara, Turkey, between 2013 and 2021. Ovarian cancer patients who underwent HIPEC and CRS for peritoneal involvement were included in this study. Thermosolutions were prepared as a closed system by using HT 2000 hyperthermic perfusion device. Then, cisplatin was applied at 100 mg/m2 at 42-42.5 °C for 60 minutes after CRS. A total of 47 patients were enrolled. The median age was 54 years (27-80) at the time of diagnosis. Forty (85.1%) patients had high grade serous carcinoma and 22 (46.7%) patients had clinical stage 3C disease. The median peritoneal cancer index (PCI) was 13 (3-24) in the whole population. HIPEC was applied as first-line treatment in 25 (51%) patients. Eleven (23.4%) patients had HIPEC in the post-neoadjuvant interval whereas 10 (21.3%) patients had it in platinum sensitive relapse. Median progression free survival (PFS) was 31(95% CI:11-50), 33 (95% CI:1-67), and 18 (95% CI:8-27) months in the primary, post-neoadjuvant interval, and platinum-sensitive relapse HIPEC groups, respectively. The patients with lower PCI (PCI<13) had significantly better OS than others with higher PCI (PCI>13, 145 months versus 42 months, p=0.034). HIPEC with CRS should be considered in selected serous carcinoma patients with peritoneal involvement, especially for the patients with primary ovarian cancer with lower PCI (PCI<13). Ovarian cancer, HIPEC, Peritoneal cancer index.

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with curative intent for selected patients with peritoneal carcinomatosis (PC). CRS and HIPEC have been implemented in Denmark at a single centre since 2006. Six years of data on these patients were analysed. Patients with PC from colorectal or appendiceal cancer, pseudomyxoma peritonei or malignant peritoneal mesothelioma referred to the single national HIPEC centre were prospectively registered from June 2006 to July 2012. Morbidity, 30-day mortality and long-term survival of patients who underwent CRS and HIPEC were analysed. In total, 80 patients underwent CRS and HIPEC. PC originated from colorectal cancer in 34 patients, pseudomyxoma peritonei in 29, appendiceal cancer in 13 and malignant peritoneal mesothelioma in four patients. Thirty-two patients had one or more complications during the hospital stay. The 30-day mortality rate was 1.3%. The predicted 2-, 3- and 5-year survival was 60%, 47% and 38% in patients with PC from colorectal cancer, and 100%, 93% and 73% in pseudomyxoma peritonei patients. CRS and HIPEC is a safe procedure when centralized as in Denmark. Favourable long-term outcome was achieved in selected patients with PC from colorectal cancer and pseudomyxoma peritonei. Short-term and long-term outcomes were comparable to results from international centres.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients. Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS. Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n=39), colorectal cancer (n=28), primary peritoneal (n=6), appendiceal cancer (n=20), and mesothelioma (n=7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3% and OS was 50.9%. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56%, and there were no 30-day mortalities. CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.

BackgroundMore information is needed for selection of patients with peritoneal metastases from endometrial cancer (EC) to undergo cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsThis study analyzed clinical, pathologic, and treatment data for patients with peritoneal metastases from EC who underwent CRS plus HIPEC at two tertiary centers. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS) during a median 5 year follow-up period. Uni- and multivariate analyses were performed to identify significant factors related to outcome.ResultsA total of 33 patients met the inclusion criteria and completed the follow-up period. At laparotomy, the median peritoneal cancer index (PCI) was 15 (range 3–35). The CRS procedure required a mean 8.3 surgical procedures per patient, and for 22 patients (66.6%), a complete cytoreduction was achieved. The mean hospital stay was 18 days, and major morbidity developed in 21% of the patients. The operative mortality was 3%. When surgery ended, HIPEC was administered with cisplatin 75 mg/m2 for 60 min at 43 °C. During a median follow-up period of 73 months, Kaplan–Meier analysis indicated a 5 year OS of 30% (median 33.1 months) and a PFS of 15.5% (median 18 months). Multivariate analysis identified the completeness of cytoreduction (CC) score as the only significant factor independently influencing OS. Logistic regression for the clinicopathologic variables associated with complete cytoreduction (CC0) for patients with metachronous peritoneal spread from EC who underwent secondary CRS plus HIPEC identified the PCI as the only outcome predictor.ConclusionsFor selected patients with peritoneal metastases from EC, when CRS leaves no residual disease, CRS plus HIPEC achieves outcomes approaching those for other indications such as colon and ovarian carcinoma.

Introduction: There is a need for more exhaustive data concerning the use of prophylactic ureteral stenting for extended debulking and cytoreductive procedures in the literature. Material and Methods: A retrospective analysis of the CARPEPACEM study protocol database was performed. The trial protocol schedules the positioning of bilateral ureteral stents before cytoreductive surgery + hyperthermic intraperitoneal chemotherapy (HIPEC). Results: Fifty-one operated patients: 31 (59.6%) with peritoneal dissemination from ovarian cancer, 8 (15.3%) from colorectal cancer, 4 (7.9%) from pseudomyxoma peritonei, 3 (5.7%) from gastric cancer, 2 (3.8%) from peritoneal mesothelioma, 1 (1.9%) from appendiceal cancer, 1 (1.9%) from endometrial cancer, and 1 (1.9%) from leiomyosarcoma. Mean and median peritoneal cancer index: 11 and 10 (range: 0–28). CC-score: CC-0 in 45 (86.5%) patients, CC-1 in 5 (9.6%) and CC-2 in 1 (1.9%). HIPEC was performed with platinum + taxol in 22 patients (42.3%), platinum + adriablastin in 10 (19.2%), mitomycin in 9 (17.3%), platinum + mitomycin in 7 (13.4%), platinum + doxorubicin in 2 (3.8%), and taxol + adriablastin in 1 (1.9%). Two major ureteral complications were observed (3.9%). Discussion: Prophylactic ureteral stenting could reduce the risk of postoperative ureteral complications without an increase in stent placement-related complications; however, a randomized clinical trial is needed.

This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60min or 90min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. The median follow-up was 5.0years (95%-CI 4.6-5.5). The median age was 59.2years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60min and 14 patients (16.7%) received it for 90min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.

Background: Early Post-operative Intra-Peritoneal Chemotherapy (EPIC) following Cytoreductive Surgery (CRS) and Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC) in high-grade appendiceal peritoneal cancer remains controversial with unclear survival benefit. The following study evaluates the survival outcomes in highgrade appendiceal cancer patients receiving varying days of EPIC in addition to CRS and HIPEC, and if survival varied between different appendiceal cancer subtypes. Patients and Methods: A monocentric retrospective analysis of patients with high-grade appendiceal cancers managed from 1994 to 2018 was undertaken. An analysis was performed comparing survival between patients who received HIPEC, HIPEC+EPIC, HIPEC+EPIC &lt;3 days and HIPEC+EPIC ≥3days. All patients received CRS. Results: 212 patients were included in the study. The 5years overall survival was 60% and 55% in the HIPEC+EPIC and HIPEC groups respectively. Patients who received ≥3days of EPIC had an 8% reduction in risk of death compared to those who had &lt;3 days (HR 0.92, CI 0.89-0.94), with a 5-year survival of 62% in the ≥3days group compared to 55% in the &lt;3day group. Patients with signet cell carcinoma had the greatest 5year survival advantage when both HIPEC and EPIC were given (HR 01.23, CI 01.21-01.26). Conclusion: EPIC in combination with HIPEC and CRS offers survival benefit at 5years in high-grade appendiceal peritoneal cancer and is most advantageous in signet cell carcinoma. Completing a ≥3day course of EPIC increases chance of survival at 5years compared to a &lt;3 days course.